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Sample records for rat hearts discrimination

  1. Method of Discriminant Gravity Tolerance using Heart Rate Variability

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    Yoshida, Yutaka; Yokoyama, Kiyoko; Takada, Hiroki; Iwase, Satoshi

    When returning on the earth by the space flight, the space deconditioning may be developed. As this countermeasure, the artificial gravity load device using the centrifuge is proposed in the space station. But the gravity load might cause the faint, and safe gravity load is uncertainty. We proposed that discriminate strength of gravity tolerance using heart rate variability time series. Step function was inputted to AR model estimated from heart rate variability time series during rest or under light gravity load, and strength of the gravity tolerance was discriminated by the step response function. On the result, discriminant accuracy was 87.5% by using heart rate variability time series when gravity load of 1.0 G was added to the human lying on the supine. Therefore, possibility of discriminant of gravity tolerance was obtained by using heart rate variability time series when sympathetic hyperactivity. Discriminant of the gravity tolerance is expected before countermeasure of space deconditioning is executed.

  2. Postextrasystolic potentiation in the isolated rat heart

    NARCIS (Netherlands)

    Meijler, F.L.; Boogaard, F. van de; Tweel, H. van der; Durrer, D.

    1962-01-01

    “Postextrasystolic potentiation" of isotonic contractions of the intact isolated rat heart was studied. It was found that the Frank-Starling mechanism does not participate in the increase of the contraction following a premature beat and a compensatory pause. A linear relationship could be demonstra

  3. Effects of Metallothionein on Isolated Rat Heart

    Institute of Scientific and Technical Information of China (English)

    SUN Zhongdong; XIA Jiahong; DONG Nianguo; DU Xinling; CHI Yifan; YANG Tienan; YANG Chenyuan

    2007-01-01

    To investigate the effects of metallothionein (MT) on isolated rat heart, 16 Wistar rats were randomly divided into 2 groups. In control group (group C), distilled water was injected intraperitoneally and 24 h later isolated hearts were perfused with Langendorff and stored at 4℃ for 3 h with histidine-tryptophan-ketoglutarate (HTK) solutions, and then isolated hearts were perfused for 2 h by Langendorff. In experimental group (group E), 3.6% ZnSO4 was injected intraperitoneally, 24 h later isolated hearts were perfused by Langendorff and stored at 4℃ for 3 h with HTK solutions, and then the isolated herts were perfused for 2 h with Langendorff. MT content, the recovery of hemodynamics, myocardial water content (MWC), lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, adenosine triphosphate (ATP) and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, myocardial cell Ca2+ content, Ca2+-ATPase activity of mitochondria ([Ca2+-ATPase]m) and its Ca2+ content ([Ca2+]m), synthesizing ATP activity of mitochondria ([ATP]m), and the ultrastructure of cells were examined. There were a significant increase in group E in hemodynamic recovery, ATP content, SOD activity, [Ca2+-ATPase]m activity, [ATP]m activity, and substantial reduction in MWC, LDH and CK leakage, MDA content, myocardial cell Ca2+ content, [Ca2+]m content,and the ultrastructural injury were obviously milder than that of group C. This study demonstrated that MT has protective effects on isolated rat heart.

  4. Hypercholesterolemia downregulates autophagy in the rat heart.

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    Giricz, Zoltán; Koncsos, Gábor; Rajtík, Tomáš; Varga, Zoltán V; Baranyai, Tamás; Csonka, Csaba; Szobi, Adrián; Adameová, Adriana; Gottlieb, Roberta A; Ferdinandy, Péter

    2017-03-23

    We have previously shown that efficiency of ischemic conditioning is diminished in hypercholesterolemia and that autophagy is necessary for cardioprotection. However, it is unknown whether isolated hypercholesterolemia disturbs autophagy or the mammalian target of rapamycin (mTOR) pathways. Therefore, we investigated whether isolated hypercholesterolemia modulates cardiac autophagy-related pathways or programmed cell death mechanisms such as apoptosis and necroptosis in rat heart. Male Wistar rats were fed either normal chow (NORM; n = 9) or with 2% cholesterol and 0.25% cholic acid-enriched diet (CHOL; n = 9) for 12 weeks. CHOL rats exhibited a 41% increase in plasma total cholesterol level over that of NORM rats (4.09 mmol/L vs. 2.89 mmol/L) at the end of diet period. Animals were sacrificed, hearts were excised and briefly washed out. Left ventricles were snap-frozen for determination of markers of autophagy, mTOR pathway, apoptosis, and necroptosis by Western blot. Isolated hypercholesterolemia was associated with a significant reduction in expression of cardiac autophagy markers such as LC3-II, Beclin-1, Rubicon and RAB7 as compared to controls. Phosphorylation of ribosomal S6, a surrogate marker for mTOR activity, was increased in CHOL samples. Cleaved caspase-3, a marker of apoptosis, increased in CHOL hearts, while no difference in the expression of necroptotic marker RIP1, RIP3 and MLKL was detected between treatments. This is the first comprehensive analysis of autophagy and programmed cell death pathways of apoptosis and necroptosis in hearts of hypercholesterolemic rats. Our data show that isolated hypercholesterolemia suppresses basal cardiac autophagy and that the decrease in autophagy may be a result of an activated mTOR pathway. Reduced autophagy was accompanied by increased apoptosis, while cardiac necroptosis was not modulated by isolated hypercholesterolemia. Decreased basal autophagy and elevated apoptosis may be responsible for the

  5. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine, CA 92612 (United States); Fisher, Robyn L. [Vitron Inc., Tucson, AZ (United States); Vickers, Alison E.M., E-mail: vickers_alison@allergan.com [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine, CA 92612 (United States)

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  6. Pseudoketogenesis in the perfused rat heart

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    Fink, G.; Desrochers, S.; Des Rosiers, C.; Garneau, M.; David, F.; Daloze, T.; Landau, B.R.; Brunengraber, H.

    1988-12-05

    Ketogenesis is usually measured in vivo by dilution of tracers of (3R)-hydroxybutyrate or acetoacetate. We show that, in perfused working rat hearts, the specific activities of (3R)-hydroxybutyrate and acetoacetate are diluted by isotopic exchanges in the absence of net ketogenesis. We call this process pseudoketogenesis. When hearts are perfused with buffer containing 2.3 mM of (4-3H)- plus (3-14C)acetoacetate, the specific activities of (4-3H) and (3-14C)acetoacetate decrease while C-1 of acetoacetate becomes progressively labeled with 14C. This is explained by the reversibility of reactions catalyzed by mitochondrial 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase. After activation of labeled acetoacetate, the specific activity of acetoacetyl-CoA is diluted by unlabeled acetoacetyl-CoA derived from endogenous fatty acids or glucose. Acetoacetyl-CoA thiolase partially exchanges 14C between C-1 and C-3 of acetoacetyl-CoA. Finally, 3-oxoacid-CoA transferase liberates weakly labeled acetoacetate which dilutes the specific activity of extracellular acetoacetate. An isotopic exchange in the reverse direction is observed when hearts are perfused with unlabeled acetoacetate plus (1-14C)-, (13-14C)-, or (15-14C)palmitate; here also, acetoacetate becomes labeled on C-1 and C-3. Computations of specific activities of (3R)-hydroxybutyrate, acetoacetate, and acetyl-CoA yield minimal rates of pseudoketogenesis ranging from 19 to 32% of the net uptake of (3R)-hydroxybutyrate plus acetoacetate by the heart.

  7. Examining the association between perceived discrimination and heart rate variability in African Americans.

    Science.gov (United States)

    Hill, LaBarron K; Hoggard, Lori S; Richmond, Ashley S; Gray, DeLeon L; Williams, Dewayne P; Thayer, Julian F

    2017-01-01

    Previous research attempting to delineate the role of discrimination in racial/ethnic disparities in hypertension has focused largely on blood pressure, which is chiefly governed by the sympathetic branch of the autonomic nervous system. Consequently, few studies have considered the role of the parasympathetic branch and particularly its regulation of the heart via the vagus nerve. In the present cross-sectional study, we employed hierarchical linear regressions to examine associations between perceived ethnic discrimination and resting heart rate variability (HRV), an important biomarker of parasympathetic cardiac modulation and overall health, in a sample (N = 103) of young, healthy African American participants (58% female, Mage = 19.94 years, SD = 2.84). After accounting for demographic factors and health status characteristics, lifetime discrimination emerged as an inverse predictor of HRV. When subdomains of discrimination were considered, discrimination attributable to threats or actual acts of aggression was also predictive of lower HRV. Our findings suggest that a greater lifetime burden of discrimination and discriminatory harassment and/or assault is associated with lower resting HRV in African Americans. The implications of these findings are discussed in the context of past, present and emerging research emphasizing biological linkages between discrimination and health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Cortical area in the rat that mediates visual pattern discrimination

    DEFF Research Database (Denmark)

    Wörtwein, Gitta; Mogensen, Jesper; Williams, Gregg

    1994-01-01

    Neurobiologi, visuel discrimination, delayed alternation, rotte, inferotemporal cortex, artssammenligning......Neurobiologi, visuel discrimination, delayed alternation, rotte, inferotemporal cortex, artssammenligning...

  9. Perceived discrimination is associated with health behaviours among African-Americans in the Jackson Heart Study.

    Science.gov (United States)

    Sims, Mario; Diez-Roux, Ana V; Gebreab, Samson Y; Brenner, Allison; Dubbert, Patricia; Wyatt, Sharon; Bruce, Marino; Hickson, DeMarc; Payne, Tom; Taylor, Herman

    2016-02-01

    Using Jackson Heart Study data, we examined associations of multiple measures of perceived discrimination with health behaviours among African-Americans (AA). The cross-sectional associations of everyday, lifetime and burden of discrimination with odds of smoking and mean differences in physical activity, dietary fat and sleep were examined among 4925 participants aged 35-84 years after adjustment for age and socioeconomic status (SES). Men reported slightly higher levels of everyday and lifetime discrimination than women and similar levels of burden of discrimination as women. After adjustment for age and SES, everyday discrimination was associated with more smoking and a greater percentage of dietary fat in men and women (OR for smoking: 1.13, 95% CI 1.00 to 1.28 and 1.19, 95% CI 1.05 to 1.34; mean difference in dietary fat: 0.37, pdiscrimination were associated with fewer hours of sleep in men and women (mean difference for everyday discrimination: -0.08, pdiscrimination: -0.08, pdiscrimination was associated with more smoking and fewer hours of sleep in women only. Higher levels of perceived discrimination were associated with select health behaviours among men and women. Health behaviours offer a potential mechanism through which perceived discrimination affects health in AA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Exposure to Discrimination and Heart Rate Variability Reactivity to Acute Stress among Women with Diabetes.

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    Wagner, Julie; Lampert, Rachel; Tennen, Howard; Feinn, Richard

    2015-08-01

    Exposure to racial discrimination has been linked to physiological reactivity. This study investigated self-reported exposure to racial discrimination and parasympathetic [high-frequency heart rate variability (HF-HRV)] and sympathetic (norepinephrine and cortisol) activity at baseline and then again after acute laboratory stress. Lifetime exposure to racial discrimination was measured with the Schedule of Racist Events scale. Thirty-two women (16 Black and 16 White) with type 2 diabetes performed a public speaking stressor. Beat-to-beat intervals were recorded on electrocardiograph recorders, and HF-HRV was calculated using spectral analysis and natural log transformed. Norepinephrine and cortisol were measured in blood. Higher discrimination predicted lower stressor HF-HRV, even after controlling for baseline HF-HRV. When race, age, A1c and baseline systolic blood pressure were also controlled, racial discrimination remained a significant independent predictor of stressor HF-HRV. There was no association between lifetime discrimination and sympathetic markers. In conclusion, preliminary data suggest that among women with type 2 diabetes mellitus (T2DM), exposure to racial discrimination is adversely associated with parasympathetic, but not sympathetic, reactivity. Copyright © 2013 John Wiley & Sons, Ltd.

  11. Do discrimination tasks discourage multi-dimensional stimulus processing? Evidence from a cross-modal object discrimination in rats.

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    Jeffery, Kathryn J

    2007-11-02

    Neurobiologists are becoming increasingly interested in how complex cognitive representations are formed by the integration of sensory stimuli. To this end, discrimination tasks are frequently used to assess perceptual and cognitive processes in animals, because they are easy to administer and score, and the ability of an animal to make a particular discrimination establishes beyond doubt that the necessary perceptual/cognitive processes are present. It does not, however, follow that absence of discrimination means the animal cannot make a particular perceptual judgement; it may simply mean that the animal did not manage to discover the relevant discriminative stimulus when trying to learn the task. Here, it is shown that rats did not learn a cross-modal object discrimination (requiring association of each object's visual appearance with its odour) when trained on the complete task from the beginning. However, they could eventually make the discrimination when trained on the component parts step by step, showing that they were able to do the necessary cross-modal integration in the right circumstances. This finding adds to growing evidence that discrimination tasks tend to encourage feature-based discrimination, perhaps by engaging automatic, habit-based brain systems. Thus, they may not be the best way to assess the formation of multi-dimensional stimulus representations of the kind needed in more complex cognitive processes such as declarative memory. Instead, more natural tasks such as spontaneous exploration may be preferable.

  12. Rat heart: a site of oxytocin production and action.

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    Jankowski, M; Hajjar, F; Kawas, S A; Mukaddam-Daher, S; Hoffman, G; McCann, S M; Gutkowska, J

    1998-11-24

    We report here that the rat heart is a site of oxytocin (OT) synthesis and release. Oxytocin was detected in all four chambers of the heart. The highest OT concentration was in the right atrium (2128 +/- 114 pg/mg protein), which was 19-fold higher than in rat uterus but 3.3-fold lower than in the hypothalamus. OT concentrations were significantly greater in the right and left atria than in the corresponding ventricles. Furthermore, OT was released into the effluent of isolated, perfused rat heart (34.5 +/- 4.7 pg/min) and into the medium of cultured atrial myocytes. Reverse-phase HPLC purification of the heart extracts and heart perfusates revealed a main peak identical with the retention time of synthetic OT. Southern blots of reverse transcription-PCR products from rat heart revealed gene expression of specific OT mRNA. OT immunostaining likewise was found in atrial myocytes and fibroblasts, and the intensity of positive stains from OT receptors paralleled the atrial natriuretic peptide stores. Our findings suggest that heart OT is structurally identical, and therefore derived from, the same gene as the OT that is primarily found in the hypothalamus. Thus, the heart synthesizes and processes a biologically active form of OT. The presence of OT and OT receptor in all of the heart's chambers suggests an autocrine and/or paracrine role for the peptide. Our finding of abundant OT receptor in atrial myocytes supports our hypothesis that OT, directly and/or via atrial natriuretic peptide release, can regulate the force of cardiac contraction.

  13. Neural discriminability in rat lateral extrastriate cortex and deep but not superficial primary visual cortex correlates with shape discriminability.

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    Vermaercke, Ben; Van den Bergh, Gert; Gerich, Florian; Op de Beeck, Hans

    2015-01-01

    Recent studies have revealed a surprising degree of functional specialization in rodent visual cortex. It is unknown to what degree this functional organization is related to the well-known hierarchical organization of the visual system in primates. We designed a study in rats that targets one of the hallmarks of the hierarchical object vision pathway in primates: selectivity for behaviorally relevant dimensions. We compared behavioral performance in a visual water maze with neural discriminability in five visual cortical areas. We tested behavioral discrimination in two independent batches of six rats using six pairs of shapes used previously to probe shape selectivity in monkey cortex (Lehky and Sereno, 2007). The relative difficulty (error rate) of shape pairs was strongly correlated between the two batches, indicating that some shape pairs were more difficult to discriminate than others. Then, we recorded in naive rats from five visual areas from primary visual cortex (V1) over areas LM, LI, LL, up to lateral occipito-temporal cortex (TO). Shape selectivity in the upper layers of V1, where the information enters cortex, correlated mostly with physical stimulus dissimilarity and not with behavioral performance. In contrast, neural discriminability in lower layers of all areas was strongly correlated with behavioral performance. These findings, in combination with the results from Vermaercke et al. (2014b), suggest that the functional specialization in rodent lateral visual cortex reflects a processing hierarchy resulting in the emergence of complex selectivity that is related to behaviorally relevant stimulus differences.

  14. Hippocampal damage causes retrograde but not anterograde memory loss for context fear discrimination in rats.

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    Lee, Justin Q; Sutherland, Robert J; McDonald, Robert J

    2017-09-01

    There is a substantial body of evidence that the hippocampus (HPC) plays and essential role in context discrimination in rodents. Studies reporting anterograde amnesia (AA) used repeated, alternating, distributed conditioning and extinction sessions to measure context fear discrimination. In addition, there is uncertainty about the extent of damage to the HPC. Here, we induced conditioned fear prior to discrimination tests and rats sustained extensive, quantified pre- or post-training HPC damage. Unlike previous work, we found that extensive HPC damage spares context discrimination, we observed no AA. There must be a non-HPC system that can acquire long-term memories that support context fear discrimination. Post-training HPC damage caused retrograde amnesia (RA) for context discrimination, even when rats are fear conditioned for multiple sessions. We discuss the implications of these findings for understanding the role of HPC in long-term memory. © 2017 Wiley Periodicals, Inc.

  15. Requirement of the auditory association cortex for discrimination of vowel-like sounds in rats.

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    Kudoh, Masaharu; Nakayama, Yoko; Hishida, Ryuichi; Shibuki, Katsuei

    2006-11-27

    We investigated the roles of the auditory cortex in discrimination learning of vowel-like sounds consisting of multiple formants. Rats were trained to discriminate between synthetic sounds with four formants. Bilateral electrolytic lesions including the primary auditory cortex and the dorsal auditory association cortex impaired multiformant discrimination, whereas they did not significantly affect discrimination between sounds with a single formant or between pure tones. Local lesions restricted to the dorsal/rostral auditory association cortex were sufficient to attenuate multiformant discrimination learning, and lesions restricted to the primary auditory cortex had no significant effects. These findings indicate that the dorsal/rostral auditory association cortex but not the primary auditory cortex is required for discrimination learning of vowel-like sounds with multiple formants in rats.

  16. Discrimination of brief speech sounds is impaired in rats with auditory cortex lesions.

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    Porter, Benjamin A; Rosenthal, Tara R; Ranasinghe, Kamalini G; Kilgard, Michael P

    2011-05-16

    Auditory cortex (AC) lesions impair complex sound discrimination. However, a recent study demonstrated spared performance on an acoustic startle response test of speech discrimination following AC lesions (Floody et al., 2010). The current study reports the effects of AC lesions on two operant speech discrimination tasks. AC lesions caused a modest and quickly recovered impairment in the ability of rats to discriminate consonant-vowel-consonant speech sounds. This result seems to suggest that AC does not play a role in speech discrimination. However, the speech sounds used in both studies differed in many acoustic dimensions and an adaptive change in discrimination strategy could allow the rats to use an acoustic difference that does not require an intact AC to discriminate. Based on our earlier observation that the first 40 ms of the spatiotemporal activity patterns elicited by speech sounds best correlate with behavioral discriminations of these sounds (Engineer et al., 2008), we predicted that eliminating additional cues by truncating speech sounds to the first 40 ms would render the stimuli indistinguishable to a rat with AC lesions. Although the initial discrimination of truncated sounds took longer to learn, the final performance paralleled rats using full-length consonant-vowel-consonant sounds. After 20 days of testing, half of the rats using speech onsets received bilateral AC lesions. Lesions severely impaired speech onset discrimination for at least one-month post lesion. These results support the hypothesis that auditory cortex is required to accurately discriminate the subtle differences between similar consonant and vowel sounds. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. The changes of vaccinia related kinase 1 in grafted heart after rat heart transplantation

    Science.gov (United States)

    Qian, Shiguo; Yang, Xuechao; Wu, Kunpeng; Lv, Qiangsheng; Zhang, Yuanyuan; Dai, Jiahong; Chen, Cheng

    2014-01-01

    Objective To assess the expression and significance of vaccinia-related kinase 1 (VRK1) after rat heart transplantation. Materials and methods Lewis and Wistar rats weighing 250 to 300 g were used as donors and recipients. Allografts were from Wistar transplanted into Lewis, and isografts were transplanted from Lewis into Lewis. Grafts were harvested at 1, 3, 5, and 7 days after transplantation. We performed Western Blot of heart tissues after cardiac transplantation. To analyze VRK1 express between the isografts and allografts for immunohistochemical staining. At 5th day after heart transplantation use related cytokines VRK1 for immunohistochemical. We used double immunofluorescent staining on transverse cryosections of graft tissues by co-labeling with different markers, including those for VRK1, activate caspase-3, α-actinin, VCAM-1, CD4. Results Compared with rare expression in syngeneic Lewis rat hearts, VRK1 protein level in allogeneic hearts were detected at various survival times after heterotopic heart transplantation, which observably expressed on day 5 postoperative. In addition, we examined the expression of activate caspase-3 in allogeneic hearts, which has a similar expression with VRK1. Immunohistochemical and immunofluorescent method displayed that VRK1 was widely expressed in cytoplasm of cardiac tissue and activate caspase-3 was also expressed in cardiomyocytes. However, the VRK1 wasn’t express in inflammation. Conclusions The VRK1 expression has increased after heart transplantation in allograft and isograft, and VRK1 may play a significant role in myocardial apoptosis after heterotopic heart transplantation in rats. PMID:25589968

  18. Ventricular repolarization in a rat model of global heart failure.

    Science.gov (United States)

    Krandycheva, Valeria; Kharin, Sergey; Strelkova, Marina; Shumikhin, Konstantin; Sobolev, Aleksey; Shmakov, Dmitry

    2013-07-01

    Isoproterenol in high doses induces infarction-like myocardial damage and structural and functional remodelling of the ventricular myocardium. The purpose of the present study was to investigate ventricular repolarization in a rat model of isoproterenol-induced heart failure. Isoproterenol was administered twice to female Wistar rats (170 mg/kg, s.c., 24 h apart). Four weeks after the injections, cardiac output was measured and unipolar epicardial ventricular electrograms were recorded in situ. Activation-recovery intervals were calculated to assess repolarization. Histological examination of the heart ventricles was also performed. Heart failure in rats treated with isoproterenol was indicated by myocardial histopathological damage and reduced cardiac output. In rats with heart failure, the regional differences in activation-recovery interval prolongation over the ventricular epicardium resulted in increasing heterogeneity in the activation-recovery interval distribution and increasing repolarization heterogeneity of the ventricular subepicardium. Myocardial damage and haemodynamic changes in heart failure induced by isoproterenol were accompanied by significant changes in ventricular repolarization, which were not associated with myocardial hypertrophy.

  19. Regional uptake of iodine-125-metaiodobenzylguanidine in the rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Matsunari, Ichiro (Dept. of Radiology, Fukui Prefectural Hospital, Fukui-City (Japan)); Bunko, Hisashi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Taki, Junichi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Nakajima, Kenichi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Muramori, Akira (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Kuji, Ichiei (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Miyauchi, Tsutomu (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Tonami, Norihisa (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Hisada, Kinichi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan))

    1993-11-01

    Regional uptake of iodine-125-metoiodobenzylguanidine was evaluated in normal (n=12) and reserpinized (n=12) rat hearts. At 15 min and 1, 3 and 6 h after injection of [sup 125]IMIBG, tissue activities were calculated for the right ventricular myocardium (RV), the whole left ventricular myocardium (whole LV), the epicardial layer of the left ventricular myocardium (Ep LV), the endocardial layer of the left ventricular myocardium (En LV), the basal segment of the left ventricular myocardium and the apical segment of the left ventricular myocardium. The uptake of [sup 125]IMIBG at 6 h after injection in the normal rat heart was higher in RV than in whole LV (0.45 [+-]0.09% vs 0.03 [+-]0.06% kg dose/g), and in Ep LV than in En LV (0.32 [+-]0.07% vs 0.25 [+-]0.05%). In the reserpinized rat heart, the difference in the uptake between Ep LV and En LV was smaller. This suggests that the difference in the regional [sup 125]IMIBG uptake might reflect different intravesicular uptake in the layers of the heart. To our knowledge, the low uptake in the endocardial layer was a new finding which seems to indicate a difference in innervation between the epicardial and endocardial layers of the left ventricle in the rat heart. Autoradiographic study also showed the low uptake of [sup 125]IMIBG in the endocardial layer, while homogeneous perfusion was observed with thallium-201, supporting the tissue uptake study. Thus, the endocardial and epicardial layers of the left ventricle in the rat heart were considered to be differently innervated. (orig.)

  20. Incidence of heart failure in infarcted rats that die spontaneously

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    R.L.G. Flumignan

    2006-10-01

    Full Text Available The present study reports for the first time the incidence of congestive heart failure (CHF in previously infarcted rats that died spontaneously. Previously, pulmonary (PWC and hepatic (HWC water contents were determined in normal rats: 14 control animals were evaluated immediately after sacrifice, 8 placed in a refrigerator for 24 h, and 10 left at room temperature for 24 h. In the infarcted group, 9 rats died before (acute and 28 died 48 h after (chronic myocardial infarction. Thirteen chronic animals were submitted only to autopsy (N = 13, whereas PWC and HWC were also determined in the others (N = 15. Seven rats survived 48 h and died during anesthesia. Notably, PWC differed in normal rats: ambient (75.7 ± 1.3% < control (77.5 ± 0.7% < refrigerator (79.1 ± 1.4% and there were no differences with respect to HWC. No clinical signs of CHF (dyspnea, lethargy or foot edema were observed in infarcted rats before death. PWC was elevated in all chronic and anesthetized rats. HWC was increased in 48% of chronic and in all anesthetized rats. Our data showed that PWC needs to be evaluated before 24 h post mortem and that CHF is the rule in chronic infarcted rats suffering natural death. The congestive syndrome cannot be diagnosed correctly in rats by clinical signs alone, as previously proposed.

  1. Gender and post-ischemic recovery of hypertrophied rat hearts

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    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

  2. Comparison of the discriminative stimulus effects of dimethyltryptamine with different classes of psychoactive compounds in rats.

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    Gatch, Michael B; Rutledge, Margaret A; Carbonaro, Theresa; Forster, Michael J

    2009-07-01

    There has been increased recreational use of dimethyltryptamine (DMT), but little is known of its discriminative stimulus effects. The present study assessed the similarity of the discriminative stimulus effects of DMT to other types of hallucinogens and to psychostimulants. Rats were trained to discriminate DMT from saline. To test the similarity of DMT to known hallucinogens, the ability of (+)-lysergic acid diethylamide (LSD), (-)-2,5-dimethoxy-4-methylamphetamine (DOM), (+)-methamphetamine, or (+/-)3,4-methylenedioxymethyl amphetamine (MDMA) to substitute in DMT-trained rats was tested. The ability of DMT to substitute in rats trained to discriminate each of these compounds was also tested. To assess the degree of similarity in discriminative stimulus effects, each of the compounds was tested for substitution in all of the other training groups. LSD, DOM, and MDMA all fully substituted in DMT-trained rats, whereas DMT fully substituted only in DOM-trained rats. Full cross-substitution occurred between DMT and DOM, LSD and DOM, and (+)-methamphetamine and MDMA. MDMA fully substituted for (+)-methamphetamine, DOM, and DMT, but only partially for LSD. In MDMA-trained rats, LSD and (+)-methamphetamine fully substituted, whereas DMT and DOM did not fully substitute. No cross-substitution was evident between (+)-methamphetamine and DMT, LSD, or DOM. DMT produces discriminative stimulus effects most similar to those of DOM, with some similarity to the discriminative stimulus effects of LSD and MDMA. Like DOM and LSD, DMT seems to produce predominately hallucinogenic-like discriminative stimulus effects and minimal psychostimulant effects, in contrast to MDMA which produced hallucinogen- and psychostimulant-like effects.

  3. Carvedilol protected diabetic rat hearts via reducing oxidative stress

    Institute of Scientific and Technical Information of China (English)

    HUANG He; SHAN Jiang; PAN Xiao-hong; WANG Hui-ping; QIAN Ling-bo

    2006-01-01

    Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that earvedilol partly improves cardiac function via its antioxidant properties in diabetic rats.

  4. Heart Morphometry in Rats with Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Claudia Joffre Fríaz

    2015-12-01

    Full Text Available Background: epidemiological and experimental studies suggest that cardiovascular disease in adulthood is influenced by prenatal or early postnatal events, regardless of lifestyle-related risk factors. Objective: to characterize the heart morphometry in Wistar rats with intrauterine growth restriction and to determine the differences between adolescents and adults of both sexes as well as the association with some morphometric variables at birth. Methods: a total of 80 rats in the control group and 80 in the experimental group were studied. The following morphometric variables were analyzed in the newborns: weight, height in addition to size, weight and volume of the heart, all in millimeters. Results: low birth weight resulting from intrauterine growth restriction caused changes in heart morphometry, especially in heart weight and thickness of the left ventricle. These changes were observed in both sexes during adolescence and showed a slight predominance in adult males. Conclusions: these results led to an increased knowledge of the events involved in heart development in response to nutrient restriction in utero, which could contribute to the design of health strategies to reduce morbidity and perinatal mortality from heart diseases.

  5. Manganese depresses rat heart muscle respiration

    Science.gov (United States)

    It has previously been reported that moderately high dietary manganese (Mn) in combination with marginal magnesium (Mg) resulted in ultrastructural damage to heart mitochondria. Manganese may replace Mg in biological functions, including the role of enzyme cofactor. Manganese may accumulate and subs...

  6. Social discrimination of cage-mates and non-cage-mates by rats.

    Science.gov (United States)

    Jones, Samantha; Burman, Oliver; Mendl, Michael

    2014-07-01

    The ability to discriminate between group-mates and non-group-mates likely underpins the occurrence of affiliative and aggressive behaviour towards 'in-group' and 'out-group' individuals. Here we present two experiments aimed at testing the ability of rats (Rattus norvegicus) to discriminate between cage-mate (CM: animals residing in the subject's home cage) and non-cage-mate (NCM) conspecifics. In experiment 1, rats were trained to discriminate between different exemplars of CM and NCM using a lever pressing task employing symmetrical reinforcement. Subjects did not reach performance criterion, but they did show some evidence of discrimination between the two types of stimuli. In experiment 2, we employed a digging task to determine if rats can discriminate between odour cues from CM and NCM presented simultaneously on two sand-filled bowls. Subjects reached performance criterion on the first pair of odours, and on three more different pairs of CM and NCM odours. The results of a reversal task, using a fifth pair of odours, indicate that the rats were using a common factor to discriminate between social cues from CM and NCM conspecifics, rather than learning each pair independently. Possible candidates include a group-specific odour cue, or the development of a CM/NCM category concept. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Psychometric curve and behavioral strategies for whisker-based texture discrimination in rats.

    Directory of Open Access Journals (Sweden)

    Takeshi Morita

    Full Text Available The rodent whisker system is a major model for understanding neural mechanisms for tactile sensation of surface texture (roughness. Rats discriminate surface texture using the whiskers, and several theories exist for how texture information is physically sensed by the long, moveable macrovibrissae and encoded in spiking of neurons in somatosensory cortex. However, evaluating these theories requires a psychometric curve for texture discrimination, which is lacking. Here we trained rats to discriminate rough vs. fine sandpapers and grooved vs. smooth surfaces. Rats intermixed trials at macrovibrissa contact distance (nose >2 mm from surface with trials at shorter distance (nose <2 mm from surface. Macrovibrissae were required for distant contact trials, while microvibrissae and non-whisker tactile cues were used for short distance trials. A psychometric curve was measured for macrovibrissa-based sandpaper texture discrimination. Rats discriminated rough P150 from smoother P180, P280, and P400 sandpaper (100, 82, 52, and 35 µm mean grit size, respectively. Use of olfactory, visual, and auditory cues was ruled out. This is the highest reported resolution for rodent texture discrimination, and constrains models of neural coding of texture information.

  8. The effect of excitotoxic hippocampal lesions on simple and conditional discrimination learning in the rat.

    Science.gov (United States)

    Murray, T K; Ridley, R M

    1999-02-15

    The effect of excitotoxic lesions of the hippocampus on acquisition and reversal of simple and conditional tasks was investigated using a Y-maze. Hippocampal-lesioned rats were severely impaired on acquisition and reversal of a conditional visuo-spatial task (where different pairs of visually distinctive choice arms indicated whether a left or right arm choice was correct on that trial) and were unable to acquire a visuo-visual conditional discrimination (where the appearance of the start arm indicated which of the visually distinctive choice arms was correct irrespective of their left/right position). They were not impaired on acquisition or reversal of a simple spatial left/right discrimination task (where all arms had the same visual appearance) nor on acquisition of a visual discrimination (where the correct, visually distinctive, choice arm varied in its left/right position). Hippocampal-lesioned rats were, however, impaired on reversal of this visual discrimination task and on acquisition and reversal of another visual discrimination task in which the visually distinctive choice arms were less different from each other than in the first version of this task. The degree of impairment in the lesioned rats was related to task difficulty for the sham-operated rats and was not specific to tasks requiring spatial choices, visual discrimination or conditional responding. The impairment on conditional tasks was greater than the impairment on those non-conditional tasks which happened to be matched for task difficulty for the sham-operated rats, suggesting that the conditional demand may target the function of the hippocampus rather closely. Statistically worse than chance performance by hippocampal-lesioned (and sham-operated) rats at the beginning of reversal testing, which was given 24 h after achieving criterion on acquisition of that task, indicated that hippocampal-lesioned rats simultaneously exhibited good memory but impaired learning for the type of

  9. Differential substitution for the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine and methylphenidate in rats.

    Science.gov (United States)

    Mori, Tomohisa; Uzawa, Naoki; Kazawa, Haruyo; Watanabe, Hirohiko; Mochizuki, Ayano; Shibasaki, Masahiro; Yoshizawa, Kazumi; Higashiyama, Kimio; Suzuki, Tsutomu

    2014-08-01

    Previous studies have demonstrated that methylphenidate, MDMA (3,4-methylenedioxymethamphetamine), and other psychostimulants exert stimulant-like subjective effects in humans. Furthermore, MDMA and methylphenidate substitute for the discriminative stimulus effects of psychostimulants, such as amphetamine and cocaine, in animals, which suggests that MDMA and methylphenidate may produce similar discriminative stimulus effects in rats. However, there is no evidence regarding the similarities between the discriminative stimulus effects of MDMA and methylphenidate. To explore this issue, cross-substitution, substitution, and combination tests were conducted in rats that had been trained to discriminate between MDMA (2.5 mg/kg) or methylphenidate (5.0 mg/kg) and saline. In the cross-substitution tests, MDMA and methylphenidate did not cross-substitute for each other. In the substitution test, methamphetamine substituted for the discriminative stimulus effects of methylphenidate, but not for those of MDMA. Furthermore, ephedrine and bupropion, which activate dopaminergic and noradrenergic systems, substituted for the discriminative stimulus effects of methylphenidate. On the other hand, serotonin (5-HT) receptor agonists 5-HT1A and 5-HT2 fully substituted for the discriminative stimulus effects of MDMA. These results suggest that activation of the noradrenergic and dopaminergic systems is important for the discriminative stimulus effects of methylphenidate, whereas activation of the serotonergic system is crucial for the discriminative stimulus effects of MDMA. Even though MDMA, like psychostimulants, exerts stimulant-like effects, our findings clearly indicate that the discriminative stimulus effects of MDMA are distinctly different from those of other psychostimulants in rats.

  10. Effects of ouabain on ultrastructure and function in rat heart

    Institute of Scientific and Technical Information of China (English)

    JIANG Xing; GUO Ning; REN Yan-ping; Lü Zhuo-ren

    2006-01-01

    Objective:To investigate the ouabain's effects on the ultrastructure and function of the rat heart. Methods: Male Sprague-Dawley (SD) rats were treated with ouabain and systolic blood pressure (SBP) were recorded weekly. After 4 weeks, echocardiography was performed, hemodynamic parameters were measured by invasive cardiac catheterization and hanges in heart ultrastructure were analyzed using transmission electron microscopy. Results :After treated by ouabain for 4 weeks, there were no significant differences in the mean SBP of the two groups. However, cardiac systolic and diastolic performances were both worsened with ouabain treatment by echocardiography, left ventricular chamber diameters and wall thickness were significantly increased in the rats of ouabain group. Invasive monitoring indicated that left ventricular systolic pressures (LVSP), rate of pressure development (+dp/dt) and rate of pressure decay (-dp/dt) were significantly attenuated and left ventricular end-diastolic pressures (LVEDP) were increased in ouabain group (P<0. 05). Disorganization of myofilaments, mitochondrial swelling, disruption and vacuolation, hyperplastic collagen fibers were found in ouabain group by transmission electron microscopy. Conclusion:It is suggested that ouabain induces alterations in cardiac ultrastructure and function, and the effects happened before the increase of blood pressure, which indicates that ouabain might damage rat heart independent of blood pressure.

  11. A Survey of Ofloxacin Histopathological Effect on Fetus Rat Heart

    Directory of Open Access Journals (Sweden)

    Zahedi Afshin

    2014-01-01

    Full Text Available Objective: Ofloxacin is an antibiotic of the fluoroquinolone group consisting of broad-spectrum antibiotics widely used in various infectious diseases. Nearly 600 teratogenic factors are known that cause congenital disease in laboratory animals. One of these factors is drugs. The aim of this study was to determine the effect of ofloxacin on the development of fetus rat heart. Materials and Methods: In this study, 4-month-old Wistar rats with 300 gram weight were used and were housed in an environmentally controlled room. A group of 3 females were caged with a single male of proven fertility overnight. Finding of vaginal plug on the following morning was regarded as a gestational day 0. Pregnant rats were divided into 2 groups (control and experimental. The first were fed with rodent food and the second with rodent food plus 50 mg/kg ofloxacin every day. After collection of tissue specimen from rat newborns the heart was dissected and prepared for light microscopy. Results: The results showed that in the group receiving ofloxacin, in comparison with the control group, myocardial cells were smaller and contain highly dense nuclei. Conclusion: In conclusion, the results show that the above mentioned drug could be transferred through placenta and affect the normal development of myocardial cells. These changes could have negative effects on the function of the heart after birth.

  12. Olfactory repeated discrimination reversal in rats: effects of chlordiazepoxide, dizocilpine, and morphine.

    Science.gov (United States)

    Galizio, Mark; Miller, Laurence; Ferguson, Adam; McKinney, Patrick; Pitts, Raymond C

    2006-10-01

    Effects of a benzodiazepine (chlordiazepoxide), an N-methyl-D-aspartate receptor antagonist (dizocilpine), and an opiate agonist (morphine) were studied with a procedure designed to assess effects of drugs and other manipulations on nonspatial learning in rats. In each session, rats were exposed to 2 different 2-choice odor-discrimination problems with food reinforcement for correct responses. One problem (performance discrimination) remained the same throughout the study. That is, 1 odor was always correct (S+) and the other was never correct (S-). For the other problem (reversal discrimination), stimuli changed every session. Six different odors were used to program the reversal discrimination; on any given session, S+ was a stimulus that had served as S- the last time it had appeared, S- was a stimulus that had been S+ on its last appearance. Thus, in each session, learning a discrimination reversal could be studied along with the performance of a comparable, but previously learned, discrimination. Chlordiazepoxide interfered with reversal learning at doses that had no effect on the performance discrimination. Morphine and dizocilpine also impaired reversal learning but only at doses that also affected performance of the well-learned performance discrimination.

  13. Melatonin protects against ischemic heart failure in rats.

    Science.gov (United States)

    Şehirli, Ahmet Özer; Koyun, Derya; Tetik, Şermin; Özsavcı, Derya; Yiğiner, Ömer; Çetinel, Şule; Tok, Olgu Enis; Kaya, Zehra; Akkiprik, Mustafa; Kılıç, Ertugrul; Şener, Göksel

    2013-09-01

    Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β-D-glucuronidase, β-galactosidase, β-D-N-acetyl-glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase-3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin-3 levels were also determined by histological analyses. In the vehicle-treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure.

  14. Discrimination

    National Research Council Canada - National Science Library

    Midtbøen, Arnfinn H; Rogstad, Jon

    2012-01-01

    ... of discrimination in the labour market as well as to the mechanisms involved in discriminatory hiring practices. The design has several advantages compared to -‘single-method’ approaches and provides a more substantial understanding of the processes leading to ethnic inequality in the labour market.

  15. Cardioprotective effects of morphine on rat heart suffering from ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    师恩祎; 江晓菁; 白菡; 谷天祥; 常业恬; 王俊科

    2003-01-01

    Objective To investigate the cardioprotective effects of morphine on ischemic reperfused rat heart in vitro and its mechanism.Methods The isolated rat heart was perfused in a Langendorff apparatus. Infarct myocardium was determined by TTC. Coronary flow (CF), heart rate (HR), left ventricular pressure (LVP), the first derivative of ventricular pressure (LVP/dtmax) and infarct size after ischemia and reperfusion in rat heart given 0.3 μmol/L morphine were observed. The effects of naloxone and glibenclamide on the cardioprotection of morphine were also measured.Results After ischemia and reperfusion, CF, HR, LVP and LVP/dtmax of isolated rat hearts decreased significantly (P0.05). The cardioprotective effects of morphine were abolished by naloxone or glibenclamide completely.Conclusions Morphine can reduce ischemia-reperfusion injuries in isolated rat heart. The cardioprotective effects of morphine are mediated by a local opioid receptor-KATP channel linked mechanism in rat hearts.

  16. Learning discriminative distance functions for valve retrieval and improved decision support in valvular heart disease

    Science.gov (United States)

    Voigt, Ingmar; Vitanovski, Dime; Ionasec, Razvan I.; Tsymal, Alexey; Georgescu, Bogdan; Zhou, Shaohua K.; Huber, Martin; Navab, Nassir; Hornegger, Joachim; Comaniciu, Dorin

    2010-03-01

    Disorders of the heart valves constitute a considerable health problem and often require surgical intervention. Recently various approaches were published seeking to overcome the shortcomings of current clinical practice,that still relies on manually performed measurements for performance assessment. Clinical decisions are still based on generic information from clinical guidelines and publications and personal experience of clinicians. We present a framework for retrieval and decision support using learning based discriminative distance functions and visualization of patient similarity with relative neighborhood graphsbased on shape and derived features. We considered two learning based techniques, namely learning from equivalence constraints and the intrinsic Random Forest distance. The generic approach enables for learning arbitrary user-defined concepts of similarity depending on the application. This is demonstrated with the proposed applications, including automated diagnosis and interventional suitability classification, where classification rates of up to 88.9% and 85.9% could be observed on a set of valve models from 288 and 102 patients respectively.

  17. Development of neuropeptide Y-mediated heart innervation in rats.

    Science.gov (United States)

    Masliukov, Petr M; Moiseev, Konstantin; Emanuilov, Andrey I; Anikina, Tatyana A; Zverev, Alexey A; Nozdrachev, Alexandr D

    2016-02-01

    Neuropeptide Y (NPY) plays a trophic role in the nervous and vascular systems and in cardiac hypertrophy. However, there is no report concerning the expression of NPY and its receptors in the heart during postnatal development. In the current study, immunohistochemistry and Western blot analysis was used to label NPY, and Y1R, Y2R, and Y5R receptors in the heart tissue and intramural cardiac ganglia from rats of different ages (newborn, 10 days old, 20 days old, 30 days old, 60 days old, 1 year old, and 2 years old).The obtained data suggest age-dependent changes of NPY-mediated heart innervation. The density of NPY-immunoreactive (IR) fibers was the least in newborn animals and increased in the first 20 days of life. In the atria of newborn and 10-day-old rats, NPY-IR fibers were more abundant compared with the ventricles. The vast majority of NPY-IR fibers also contained tyrosine hydroxylase, a key enzyme in catecholamine synthesis.The expression of Y1R increased between 10 and 20 days of life. Faint Y2R immunoreactivity was observed in the atria and ventricles of 20-day-old and older rats. In contrast, the highest level of the expression of Y5R was found in newborn pups comparing with more adult rats. All intramural ganglionic neurons were also Y1R-IR and Y5R-IR and Y2R-negative in all studied animals.Thus, the increasing of density of NPY-containing nerve fibers accompanies changes in relation of different subtypes of NPY receptors in the heart during development.

  18. MITOCHONDRIAL AND METABOLIC GENE EXPRESSION IN THE AGED RAT HEART

    Directory of Open Access Journals (Sweden)

    Gregory P Barton

    2016-08-01

    Full Text Available Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function and AMP-activated protein kinase (AMPK activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo, Old (33 mo, and old exercise trained (Old + EXE (34 mo FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05 expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α, peroxisome proliferator activated receptor alpha (PPARα, and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function are superfluous and decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity and mitochondrial function in the heart.

  19. Speech sound discrimination training improves auditory cortex responses in a rat model of autism

    Directory of Open Access Journals (Sweden)

    Crystal T Engineer

    2014-08-01

    Full Text Available Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes.

  20. Speech sound discrimination training improves auditory cortex responses in a rat model of autism

    Science.gov (United States)

    Engineer, Crystal T.; Centanni, Tracy M.; Im, Kwok W.; Kilgard, Michael P.

    2014-01-01

    Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA) increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field (AAF) responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes. PMID:25140133

  1. Oxidative Damage in the Aging Heart: an Experimental Rat Model

    Science.gov (United States)

    Marques, Gustavo Lenci; Neto, Francisco Filipak; Ribeiro, Ciro Alberto de Oliveira; Liebel, Samuel; de Fraga, Rogério; Bueno, Ronaldo da Rocha Loures

    2015-01-01

    Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID:27006709

  2. Morphology discrimination in implantable cardioverter-defibrillators: Consistency of template match percentage during atrial tachyarrhythmias at different heart rates

    NARCIS (Netherlands)

    D.A.M.J. Theuns (Dominic); M. Rivero-Ayerza (Maximo); D. Goedhart (Dick); M. Miltenburg (Max); L.J.L.M. Jordaens (Luc)

    2008-01-01

    textabstractBackground: Morphology discrimination (MD) in implantable cardioverter-defibrillators (ICDs) is based on the comparison of the ventricular electrogram during tachycardia with a stored reference template obtained during baseline rhythm. However, the effect of heart rate on the template ma

  3. Mechanoelectric feedback does not contribute to the Frank-Starling relation in the rat and guinea pig heart

    Directory of Open Access Journals (Sweden)

    D Kelly

    2014-12-01

    Full Text Available Mechanoelectric feedback (MEF is the process by which mechanical forces on the myocardium can alter its electrical properties. The effect can be large enough to induce ectopic beats or fibrillation. However, the role of MEF at physiological levels of mechanical stress is not clear. We have investigated alteration in action potential morphology in rat and guinea pig ventricle and in rat atrial tissue at levels of stretch near the plateau of the Frank-Starling curve. Stretch of >100 mm.Hg End Diastolic Left Ventricular Pressure (EDLVP or rapidly applied stretch (EDLVP increased by 25 mm.Hg within 100 ms often triggered ectopic beats in isolated rat and guinea-pig hearts. However, ventricular epicardial monophasic action potentials (MAPs recorded during stretch to EDLVP up to 30 mm. Hg showed no consistent changes in action potential duration (at APD20, APD50 or APD80 in either species. MAP recording detected APD prolongation with very small concentrations of 4-AP (10 μM, confirming the discrimination of the recording technique. In isolated rat atrial strips, no changes in intracellular action potential morphology or membrane potential were seen when stretched to levels producing an optimum increase in contractility. We conclude that alteration in action potential morphology with stretch does not contribute to the Frank-Starling relation in ventricle of rat or guinea-pig isolated heart, or in rat atrial tissue.

  4. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

    Science.gov (United States)

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  5. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

    Science.gov (United States)

    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  6. A grasp-related deficit in tactile discrimination following dorsal column lesion in the rat.

    Science.gov (United States)

    Ballermann, M; McKenna, J; Whishaw, I Q

    2001-01-15

    The dorsal columns of the spinal cord are a major source of haptic (sense of active touch) and proprioceptive input to the brainstem and sensory-motor cortex. Following injury in primates, there are impairments in two-point discrimination, direction of movement across the skin, and frequency of vibration, and qualitative control of the digits, but simple spatial discriminations recover. In the rat there are qualitative deficits in paw control in skilled reaching, but no sensory deficits have been reported. Because recent investigations of sensory control suggest that sensory functions may be related to specific actions, the present study investigated whether the dorsal columns contribute to hapsis during food grasping in the rat. Adult female Long-Evans rats were trained to reach with a single forepaw for a piece of uncooked pasta or for equivalent sized but tactually different nonfood items. One group was given lesions of the dorsal column ipsilateral to their preferred paw, while the second group served as a control. Postlesion, both groups were tested for skilled reaching success and force application as well as adhesive dot removal and forepaw placing. Performance levels on these tests were normal. Nevertheless, the rats with dorsal column lesions were unable to discriminate a food item from a tactually distinctive nonfood item as part of the reaching act, suggesting that the dorsal columns are important for on-line tactile discriminations, or "haptic actions," which contribute to the normal performance of grasping actions.

  7. Knockdown of Nurr1 in the Rat Hippocampus: Implications to Spatial Discrimination Learning and Memory

    Science.gov (United States)

    Colon-Cesario, Wanda I.; Martinez-Montemayor, Michelle M.; Morales, Sohaira; Felix, Jahaira; Cruz, Juan; Adorno, Monique; Pereira, Lixmar; Colon, Nydia; Maldonado-Vlaar, Carmen S.; Pena de Ortiz, Sandra

    2006-01-01

    Nurr1 expression is up-regulated in the brain following associative learning experiences, but its relevance to cognitive processes remains unclear. In these studies, rats initially received bilateral hippocampal infusions of control or antisense oligodeoxynucleotides (ODNs) 1 hour prior to training in a holeboard spatial discrimination task. Such…

  8. Knockdown of Nurr1 in the Rat Hippocampus: Implications to Spatial Discrimination Learning and Memory

    Science.gov (United States)

    Colon-Cesario, Wanda I.; Martinez-Montemayor, Michelle M.; Morales, Sohaira; Felix, Jahaira; Cruz, Juan; Adorno, Monique; Pereira, Lixmar; Colon, Nydia; Maldonado-Vlaar, Carmen S.; Pena de Ortiz, Sandra

    2006-01-01

    Nurr1 expression is up-regulated in the brain following associative learning experiences, but its relevance to cognitive processes remains unclear. In these studies, rats initially received bilateral hippocampal infusions of control or antisense oligodeoxynucleotides (ODNs) 1 hour prior to training in a holeboard spatial discrimination task. Such…

  9. TRPC1 expression and distribution in rat hearts

    Directory of Open Access Journals (Sweden)

    W. Niu

    2009-12-01

    Full Text Available Transient receptor potential canonical (TRPC proteins have been identified as a family of plasma membrane calcium-permeable channels. TRPC proteins can be activated by various stimuli and act as cellular sensors in mammals. Stretch-activated ion channels (SACs have been proposed to underlie cardiac mechano-electric feedback (MEF, although the molecular entity of SAC remains unknown. There is evidence suggesting that transient receptor potential canonical 1 (TRPC1 is a stretch-activated ion channel. As a non-selective cation channel, TRPC1 may cause stretch-induced depolarization and arrhythmia and thus may contribute to the MEF of the heart. In this study, we examined the expression patterns of TRPC1 in detail at both the mRNA and protein levels in rat hearts.We isolated total RNA from the left and right atria, and the left and right ventricles, and detected TRPC1 mRNA in these tissues using reverse-transcriptase polymerase chain reaction (RT-PCR. To study the protein localization and targeting, we performed immunohistochemistry and immunofluorescence labeling with the antibody against TRPC1. TRPC1 was detected in the cardiomyocytes of the ventricle and atrium at both the mRNA and protein levels. The cell membrane and Ttubule showed strong fluorescence labeling in the ventricular myocytes. Purkinje cells, the endothelial cells and smooth muscle cells of the coronary arterioles also displayed TRPC1 labeling. No TRPC1 was detected in fibroblasts. In conclusion, TRPC1 is widely expressed in the rat heart, including in working cells, Purkinje cells and vascular cells, suggesting that it plays an important role in the heart. The specific distribution pattern offered a useful insight into its function in adult rat ventricular cells. Further investigations are needed to clarify the role of TRPC1 in regulating cardiac activity, including cardiac MEF.

  10. Comparison of Pavlovian serial conditional discrimination in rats and hamsters in the same experimental situation

    Directory of Open Access Journals (Sweden)

    J.L.O. Bueno

    2001-12-01

    Full Text Available The present study compares behavioral changes between two distinct rodent groups, hamsters (Mesocricetus auratus and Wistar rats, when submitted in the same homogeneous experimental situations to a serial conditional discrimination procedure which involves water deprivation and the processing of temporal variables. Both hamsters and rats acquired serial positive conditional discrimination as indicated by higher frequencies of magazine-oriented behavior during the tone followed by reinforcement (T+ and preceded by the feature stimulus light (L and during the empty interval, than during the tone alone not followed by reinforcement (T-. Rats' frequencies of magazine-oriented behavior were high during T+ and T-, initially during training, and decreased during T- as the training progressed. However, the hamsters' frequencies of magazine-oriented behavior started very low and increased only during T+ as the training progressed. Comparison of the frequencies of magazine-oriented behavior during the empty interval in relation to the frequencies during the preceding L period showed that rats' frequencies remained very high and hamsters' frequencies increased during training. These results suggest that rats and hamsters have different behavioral strategies for the acquisition of a conditional discrimination. The results of the comparisons made in these experiments support the view of the importance of an ecological psychology approach to the understanding of complex learning in animals.

  11. Heroin discriminative stimulus effects of methadone, LAAM and other isomers of acetylmethadol in rats.

    Science.gov (United States)

    Newman, Jennifer L; Vann, Robert E; May, Everette L; Beardsley, Patrick M

    2002-10-01

    LAAM (alpha- l-acetylmethadol) is a derivative of the synthetic mu-opiate agonist methadone and is one of the four isomers of acetylmethadol. Methadone and LAAM have similar pharmacological properties and both are approved medications for the treatment of heroin dependency disorders. Few studies have reported on the pharmacology of acetylmethadol's other isomers and most of these have focused on their potential analgesic activity. The purpose of the present investigation was to examine the discriminative stimulus effects of LAAM, the other isomers of acetylmethadol, and methadone in rats trained to discriminate heroin from water, and to compare the duration of the discriminative stimulus effects of heroin, methadone, and LAAM. Long-Evans rats were trained to discriminate 0.3 mg/kg heroin from water under a fixed ratio 10 (FR10) schedule of food reinforcement. Dose-response functions for heroin, methadone, LAAM, three other isomers of acetylmethadol: alpha- d-acetylmethadol, beta- d-acetylmethadol, beta- l-acetylmethadol, and its precursor, beta- l-methadol were examined. Additionally, the time course effects for heroin, methadone, and LAAM were examined. LAAM and methadone dose-dependently occasioned heroin-like discriminative stimulus effects. Two of acetylmethadol's isomers, alpha- d-acetylmethadol and beta- d-acetylmethadol, were more potent than LAAM in producing heroin-like effects. The beta- l-methadol precursor and beta- l-acetylmethadol did not fully substitute for heroin's discriminative stimulus. LAAM elicited heroin-like discriminative stimulus effects for at least 6 h and generated partial generalization up to 36 h following administration. Methadone, LAAM, beta- d-acetylmethadol and alpha- d-acetylmethadol, but not beta- l-acetylmethadol and beta- l-methadol evoke heroin-like discriminative stimulus effects.

  12. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    Science.gov (United States)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

  13. Beta-adrenoceptor stimulation of alveolar fluid clearance is increased in rats with heart failure.

    Science.gov (United States)

    Maron, Michael B; Luther, Daniel J; Pilati, Charles F; Ohanyan, Vahagn; Li, Tianbo; Koshy, Shyny; Horne, Walter I; Meszaros, J Gary; Walro, Jon M; Folkesson, Hans G

    2009-09-01

    The alveolar epithelium plays a critical role in resolving pulmonary edema. We thus hypothesized that its function might be upregulated in rats with heart failure, a condition that severely challenges the lung's ability to maintain fluid balance. Heart failure was induced by left coronary artery ligation. Echocardiographic and cardiovascular hemodynamics confirmed its development at 16 wk postligation. At that time, alveolar fluid clearance was measured by an increase in protein concentration over 1 h of a 5% albumin solution instilled into the lungs. Baseline alveolar fluid clearance was similar in heart failure and age-matched control rats. Terbutaline was added to the instillate to determine whether heart failure rats responded to beta-adrenoceptor stimulation. Alveolar fluid clearance in heart failure rats was increased by 194% after terbutaline stimulation compared with a 153% increase by terbutaline in control rats. To determine the mechanisms responsible for this accelerated alveolar fluid clearance, we measured ion transporter expression (ENaC, Na-K- ATPase, CFTR). No significant upregulation was observed for these ion transporters in the heart failure rats. Lung morphology showed significant alveolar epithelial type II cell hyperplasia in heart failure rats. Thus, alveolar epithelial type II cell hyperplasia is the likely explanation for the increased terbutaline-stimulated alveolar fluid clearance in heart failure rats. These data provide evidence for previously unrecognized mechanisms that can protect against or hasten resolution of alveolar edema in heart failure.

  14. Common Deletion (CD) in mitochondrial DNA of irradiated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Raquel Gomes; Ferreira-Machado, Samara C.; Almeida, Carlos E.V. de, E-mail: raquelgsiqueira@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Ciencias Radiologicas; Silva, Dayse A. da; Carvalho, Elizeu F. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Diagnosticos por DNA; Melo, Luiz D.B. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biofisica Carlos Chagas Filho. Lab. de Parasitologia Molecular

    2014-05-15

    The purpose of this study was to map the common deletion (CD) area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy) delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days). The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rd until the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high). This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels. (author)

  15. Common Deletion (CD in mitochondrial DNA of irradiated rat heart

    Directory of Open Access Journals (Sweden)

    RAQUEL G. SIQUEIRA

    2014-06-01

    Full Text Available The purpose of this study was to map the common deletion (CD area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days. The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rduntil the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high. This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels.

  16. Heart Alterations after Domoic Acid Administration in Rats

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    Andres C. Vieira

    2016-03-01

    Full Text Available Domoic acid (DA is one of the best known marine toxins, causative of important neurotoxic alterations. DA effects are documented both in wildlife and experimental assays, showing that this toxin causes severe injuries principally in the hippocampal area. In the present study we have addressed the long-term toxicological effects (30 days of DA intraperitoneal administration in rats. Different histological techniques were employed in order to study DA toxicity in heart, an organ which has not been thoroughly studied after DA intoxication to date. The presence of DA was detected by immunohistochemical assays, and cellular alterations were observed both by optical and transmission electron microscopy. Although histological staining methods did not provide any observable tissue damage, transmission electron microscopy showed several injuries: a moderate lysis of myofibrils and loss of mitochondrial conformation. This is the first time the association between heart damage and the presence of the toxin has been observed.

  17. Effect of hypertonic saline solution on the left ventricular functions of isolated hearts from burned rats

    Institute of Scientific and Technical Information of China (English)

    周继红; 刘大维; 王正国; 朱佩芳

    2002-01-01

    To study the effect of hypertonic saline solution on the left ventricular functions of isolated hearts from burned rats. Methods: Thirty-six Wistar rats were used and divided into 4 groups: (1) normal hearts perfused with isotonic Krebs-Henseleit solution; (2) normal hearts perfused with Krebs-Henseleit solution which contained 215 mmol/L Na+; (3) hearts of rats suffered from 25% TBSA third degree burn and perfused with isotonic Krebs-Henseleit solution; (4) hearts of the burned rats perfused with Krebs-Henseleit solution which contained 215 mmol/L Na+. The systolic and diastolic functions of the left ventricle were observed. Results: During perfusion, there were very short periods of decrease in heart systolic and diastolic functions at first, but they recovered very soon and even became stronger than normal both in the normal and burned rats. The systolic and diastolic functions of the hearts increased very significantly when the perfusion solution was changed to isotonic solution from the hypertonic solutions. The effect of the hypertonic saline solution on the ventricular systolic and diastolic improvements was stronger in the hearts of the burned rats than that in the normal hearts. Conclusions: Hypertonic saline solution can directly affect myocardium and significantly improve the ventricular systolic and diastolic functions, especially in the hearts of the burned rats.

  18. Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts.

    Science.gov (United States)

    Piuhola, Jarkko; Szokodi, István; Kinnunen, Pietari; Ilves, Mika; deChâtel, Rudolf; Vuolteenaho, Olli; Ruskoaho, Heikki

    2003-01-01

    Endothelin-1 is involved in mechanical load-induced cardiac growth processes; it also has effects on contractility. The interaction of endothelin-1 and the Frank-Starling response is unknown. The present study aimed to characterize the role of endothelin-1 in the regulation of the Frank-Starling response, one of the major mechanisms regulating cardiac contractile force, in both normal and hypertrophied hearts. Nontransgenic rat hearts and hypertrophic hearts of hypertensive double transgenic rats harboring human angiotensinogen and renin genes were studied in a Langendorff isolated heart setup with a liquid-filled balloon inside the left ventricle used to measure contractile parameters. The rats were studied at compensated phase, before showing any signs of heart failure. Compensated hypertrophy in double transgenic rat hearts resulted in improved contractility at a given level of preload when compared with nontransgenic rat hearts. Hearts of both rat lines showed preserved Frank-Starling responses, that is, increased contractile function in response to increased end-diastolic pressure. The mixed endothelin A/B receptor antagonist bosentan attenuated the Frank-Starling response by 53% (P<0.01) in the double transgenic hearts but not in nontransgenic hearts. The diastolic parameters remained unaffected. The left ventricles of the double transgenic rat hearts showed an 82% higher level of endothelin type A receptor mRNA and a 25% higher level of immunoreactive endothelin-1 compared with nontransgenic rat hearts. The type 1 angiotensin II receptor antagonist CV-11974 had no significant effect on contractile function in response to load in either strain. These results show that endogenous endothelin-1 contributes to the Frank-Starling response in hypertrophied rat hearts by affecting systolic performance.

  19. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

    Science.gov (United States)

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

  20. Effect of pioglitazone on the abrogated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart

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    Dhiraj Mittal

    2016-01-01

    Conclusion: Cardioprotective effect of IPC gets lost in hyperlipidemic rat heart. The results suggest that perfusion of pioglitazone restored the cardioprotective effect of IPC in hyperlipidemic rat heart, an effect that may be via PI3K and mTOR.

  1. Metabolic changes in rat urine after acute paraquat poisoning and discriminated by support vector machine.

    Science.gov (United States)

    Wen, Congcong; Wang, Zhiyi; Zhang, Meiling; Wang, Shuanghu; Geng, Peiwu; Sun, Fa; Chen, Mengchun; Lin, Guanyang; Hu, Lufeng; Ma, Jianshe; Wang, Xianqin

    2016-01-01

    Paraquat is quick-acting and non-selective, killing green plant tissue on contact; it is also toxic to human beings and animals. In this study, we developed a urine metabonomic method by gas chromatography-mass spectrometry to evaluate the effect of acute paraquat poisoning on rats. Pattern recognition analysis, including both partial least squares discriminate analysis and principal component analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the levels of benzeneacetic acid and hexadecanoic acid of the acute paraquat poisoning group (intragastric administration 36 mg/kg) increased, while the levels of butanedioic acid, pentanedioic acid, altronic acid decreased. Based on these urinary metabolomics data, support vector machine was applied to discriminate the metabolomic change of paraquat groups from the control group, which achieved 100% classification accuracy. In conclusion, metabonomic method combined with support vector machine can be used as a useful diagnostic tool in paraquat-poisoned rats.

  2. Genomic and nongenomic effects of aldosterone in the rat heart : why is spironolactone cardioprotective?

    NARCIS (Netherlands)

    Chai, WX; Garrelds, IM; Arulmani, U; Schoemaker, RG; Lamers, JMJ; Danser, AHJ

    2005-01-01

    1 Mineralocorticoid receptor (MR) antagonism with spironolactone reduces mortality in heart failure on top of ACE inhibition. To investigate the underlying mechanism, we compared the actions of both aldosterone and spironolactone to those of angiotensin (Ang) II in the rat heart. 2 Hearts of male Wi

  3. [Dynamics of heart rate changes in rats following stepwise change of treadmill running speed].

    Science.gov (United States)

    Tarasova, O S; Borzykh, A A; Kuz'min, I V; Borovik, A S; Lukoshkova, E V; Sharova, A P; Vinogradova, O L; Grigor'ev, A I

    2012-11-01

    Amplitude and temporal responses of heart rate to stepwise increase or decrease of treadmill running intensity were investigated in rats. Heart rate amplitude response was shown to be connected mainly with the change of sympathetic nervous activity whereas heart rate temporal response was shown to be determined predominantly by parasympathetic cardiotrophic influences.

  4. Induction of immune tolerance with heart-thymus composite allotransplantation in rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Hai-bo; XIA Sui-sheng; WEN Hao; HUANG Zu-fa; YE Qi-fa

    2005-01-01

    Objective To study on the role of thymus transplantation for heart allograft in rats. Methods Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, level of IL-2, IL-4 and its mRNA expression in serum and cardiac grafts were investigated. Results Heart-thymus combined transplantation achieved effect in the prolongation of cardiac graft survival with short-term administration of cyclosporine. Conclusions Vascularized thymus transplantation induced immune tolerance in thymectomized rats.

  5. Effects of selective antagonism or depletion of the cholinergic system on visual discrimination performance in rats

    NARCIS (Netherlands)

    Drinkenburg, W.H.I.M.; Sondag, H.N.P.M.; Coenders, C.J.H.; Andrews, J.S.; Vossen, J.M.H.

    1995-01-01

    A two-lever simultaneous visual discrimination task was used to study the effects on performance in Long-Evans rats of the muscarinic antagonists scopolamine (0.0125, 0.05, 0.2 and 0.8mg/kg s.c.), the M(1) antagonist pirenzepine, the M(2) antagonist AF-DX 116, the M(3) antagonist UH-AH 37 (each 3.2,

  6. Knockdown of Nurr1 in the rat hippocampus: Implications to spatial discrimination learning and memory

    OpenAIRE

    2006-01-01

    Nurr1 expression is up-regulated in the brain following associative learning experiences, but its relevance to cognitive processes remains unclear. In these studies, rats initially received bilateral hippocampal infusions of control or antisense oligodeoxynucleotides (ODNs) 1 h prior to training in a holeboard spatial discrimination task. Such pre-training infusions of nurr1 antisense ODNs caused a moderate effect in learning the task and also impaired LTM tested 7 d later. In a second experi...

  7. Knockdown of Nurr1 in the rat hippocampus: Implications to spatial discrimination learning and memory

    OpenAIRE

    Colón-Cesario, Wanda I.; Martínez-Montemayor, Michelle M.; Morales, Sohaira; Félix, Jahaira; Cruz, Juan; Adorno, Monique; Pereira, Lixmar; Colón, Nydia; Maldonado-Vlaar, Carmen S.; Peña de Ortiz, Sandra

    2006-01-01

    Nurr1 expression is up-regulated in the brain following associative learning experiences, but its relevance to cognitive processes remains unclear. In these studies, rats initially received bilateral hippocampal infusions of control or antisense oligodeoxynucleotides (ODNs) 1 h prior to training in a holeboard spatial discrimination task. Such pre-training infusions of nurr1 antisense ODNs caused a moderate effect in learning the task and also impaired LTM tested 7 d later. In a second experi...

  8. Texture discrimination and multi-unit recording in the rat vibrissal nerve

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    Décima Emilio E

    2006-05-01

    Full Text Available Abstract Background Rats distinguish objects differing in surface texture by actively moving their vibrissae. In this paper we characterized some aspects of texture sensing in anesthetized rats during active touch. We analyzed the multifiber discharge from a deep vibrissal nerve when the vibrissa sweeps materials (wood, metal, acrylic, sandpaper having different textures. We polished these surfaces with sandpaper (P1000 to obtain close degrees of roughness and we induced vibrissal movement with two-branch facial nerve stimulation. We also consider the change in pressure against the vibrissa as a way to improve the tactile information acquisition. The signals were compared with a reference signal (control – vibrissa sweeping the air – and were analyzed with the Root Mean Square (RMS and the Power Spectrum Density (PSD. Results We extracted the information about texture discrimination hidden in the population activity of one vibrissa innervation, using the RMS values and the PSD. The pressure level 3 produced the best differentiation for RMS values and it could represent the "optimum" vibrissal pressure for texture discrimination. The frequency analysis (PSD provided information only at low-pressure levels and showed that the differences are not related to the roughness of the materials but could be related to other texture parameters. Conclusion Our results suggest that the physical properties of different materials could be transduced by the trigeminal sensory system of rats, as are shown by amplitude and frequency changes. Likewise, varying the pressure could represent a behavioral strategy that improves the information acquisition for texture discrimination.

  9. Curcumin ameliorates streptozotocin-induced heart injury in rats.

    Science.gov (United States)

    Abo-Salem, Osama M; Harisa, Gamaleldin I; Ali, Tarek M; El-Sayed, El-Sayed M; Abou-Elnour, Fatma M

    2014-06-01

    Heart failure (HF) is one of diabetic complications. This work was designed to investigate the possible modulatory effect of curcumin against streptozotocin-induced diabetes and consequently HF in rats. Rats were divided into control, vehicle-treated, curcumin-treated, diabetic-untreated, diabetic curcumin-treated, and diabetic glibenclamide-treated groups. Animal treatment was started 5 days after induction of diabetes and extended for 6 weeks. Diabetic rats showed significant increase in serum glucose, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, nitric oxide, lactate dehydrogenase, cardiac malondialdehyde, plasma levels of interleukin-6, and tumor necrosis factor-alpha, and also showed marked decrease in serum high-density lipoprotein-cholesterol, cardiac reduced glutathione, and cardiac antioxidant enzymes (catalase, superoxide dismutase, and glutathione-S-transferase). However, curcumin or glibenclamide treatment significantly mitigated such changes. In conclusion, curcumin has a beneficial therapeutic effect in diabetes-induced HF, an effect that might be attributable to its antioxidant and suppressive activity on cytokines.

  10. Social Interaction and Conditional Self-Discrimination under a Paradigm of Avoidance and Positive Reinforcement in Wistar Rats

    Science.gov (United States)

    Penagos-Corzo, Julio C.; Pérez-Acosta, Andrés M.; Hernández, Ingrid

    2015-01-01

    The experiment reported here uses a conditional self-discrimination task to examine the influence of social interaction on the facilitation of self-discrimination in rats. The study is based on a previous report (Penagos- Corzo et al., 2011) showing positive evidence of such facilitation, but extending the exposition to social interaction…

  11. Inference Based on Transitive Relation in Tree Shrews ("Tupaia belangeri") and Rats ("Rattus norvegicus") on a Spatial Discrimination Task

    Science.gov (United States)

    Takahashi, Makoto; Ushitani, Tomokazu; Fujita, Kazuo

    2008-01-01

    Six tree shrews and 8 rats were tested for their ability to infer transitively in a spatial discrimination task. The apparatus was a semicircular radial-arm maze with 8 arms labeled A through H. In Experiment 1, the animals were first trained in sequence on 4 discriminations to enter 1 of the paired adjacent arms, AB, BC, CD, and DE, with right…

  12. Early reperfusion hemodynamics predict recovery in rat hearts: a potential approach towards evaluating cardiac grafts from non-heart-beating donors.

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    Monika Dornbierer

    Full Text Available AIMS: Cardiac grafts from non-heartbeating donors (NHBDs could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. METHODS AND RESULTS: Hearts (n = 31 isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001. Coronary flow and the production of lactate and lactate dehydrogenase (LDH also correlated significantly with outcomes after 60 min reperfusion (p<0.05. Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR, developed pressure (DP and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *10(3 mmHg*beats*min(-1 (p<0.01. CONCLUSION: Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.

  13. Early Reperfusion Hemodynamics Predict Recovery in Rat Hearts: A Potential Approach towards Evaluating Cardiac Grafts from Non-Heart-Beating Donors

    Science.gov (United States)

    Dornbierer, Monika; Stadelmann, Mathieu; Sourdon, Joevin; Gahl, Brigitta; Cook, Stéphane; Carrel, Thierry P.; Tevaearai, Hendrik T.; Longnus, Sarah L.

    2012-01-01

    Aims Cardiac grafts from non-heartbeating donors (NHBDs) could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. Methods and Results Hearts (n = 31) isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C) for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV) pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001). Coronary flow and the production of lactate and lactate dehydrogenase (LDH) also correlated significantly with outcomes after 60 min reperfusion (p<0.05). Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR), developed pressure (DP) and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *103 mmHg*beats*min−1 (p<0.01). Conclusion Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation. PMID:22928009

  14. Histological analysis of heart after domoic acid administration in rats

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    Andrés Crespo Vieira

    2014-06-01

    All data were analysed with GraphPad Prism 5.0 by a one-way analysis of variance (ANOVA. Dunnett’s Multiple Comparison test was used for post hoc comparisons between control and treatment groups. Results were expressed as means ± SEM, with a P value of Zalophus californianus (Gulland et al. 2002; Zabka et al. 2009, although these effects were no studied under experimental conditions due to that they were natural intoxications. In vitro studies showed that DOM produced alterations in the metabolism of rat cardiac myoblasts (Nijjar et al. 1999; Vranyac-Tramoundanas et al. 2008, but few in vivo observations are reduced to a previous report by Vranyac-Tramoundanas (Vranyac-Tramoundanas et al. 2011, where heart lesions were seen 3 days i.p. administration. The early onset of the heart lesions, characteristic of acute damage, led us to realize the present assay, where we expected to observe some kind of heart damage or collagen alterations. The possible observed damage would be correlated with the presence of DOM by IHQ assays. The experimental dose (2.5 mg/kg and the antibody concentration (1:5000 were determined by previous experiments (Vieira et al., in press. Our previous observations showed an important presence of DOM only in hippocampus 6h and 10h after toxin i.p. administration (Vieira et al., in press. Neuropathological studies in rodents concluded that hippocampus constitutes the principal target of DOM, due to the high concentration of KA receptors in this area (Wisden 1993. In spite of the presence of GluRs in rat heart (Gill et al. 1998, the DOM affinity for these GluRs or the concentration of GluRs might not be high enough to detect DOM presence 6h, 10h or 24h after i.p. administration. The mild collagen alterations and the lack of observable damage in the first 24 h after toxin administration concluded that DOM seems to need several days in order to produce observable damage. Further experiments with long-time expositions to DOM will be done.

  15. Responding by exclusion in Wistar rats in a simultaneous visual discrimination task.

    Science.gov (United States)

    Felipe de Souza, Matheus; Schmidt, Andréia

    2014-11-01

    Responding by exclusion is to select a correct alternative by rejecting other potential alternatives. Studies describe this ability in some mammals and birds. However, this type of performance has not been reported in rodents. The aim of this study was to verify the occurrence of responding by exclusion in Wistar rats after a baseline of simple simultaneous visual discrimination. Six male Wistar learned nose-poking tunnels displaying visual stimuli (projected geometric shapes) in an operant chamber. After establishing the simultaneous discrimination baseline, three probe sessions were conducted. In each session, there was a novelty-control probe (a new stimulus was presented together with a stimulus trained as the S(+)) and an exclusion probe (a second new stimulus was presented simultaneously with a stimulus trained as the S(-)). Only one rat responded to the new stimulus in one of the three novelty probe trials. Four rats responded to the three new stimuli and one responded to the new stimulus in two of the three exclusion probes. One subject responded to the S(-) in all the exclusion probes. Five of the six subjects were therefore able to choose the new stimulus, rejecting stimuli trained as the S(-). This is the first experimental evidence for performance by exclusion in rats.

  16. Calcium Activation Profile In Electrically Stimulated Intact Rat Heart Cells

    Science.gov (United States)

    Geerts, Hugo; Nuydens, Rony; Ver Donck, Luc; Nuyens, Roger; De Brabander, Marc; Borgers, Marcel

    1988-06-01

    Recent advances in fluorescent probe technology and image processing equipment have made available the measurement of calcium in living systems on a real-time basis. We present the use of the calcium indicator Fura-2 in intact normally stimulated rat heart cells for the spatial and dynamic measurement of the calcium excitation profile. After electric stimulation (1 Hz), the activation proceeds from the center of the myocyte toward the periphery. Within two frame times (80 ms), the whole cell is activated. The activation is slightly faster in the center of the cell than in the periphery. The mean recovery time is 200-400 ms. There is no difference along the cell's long axis. The effect of a beta-agonist and of a calcium antagonist is described.

  17. Coherence between Rat Sensorimotor System and Hippocampus Is Enhanced during Tactile Discrimination.

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    Natalia Grion

    2016-02-01

    Full Text Available Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5-12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats--whisker motion, hippocampal local field potential (LFP, and barrel cortex unit firing--during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task. Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers.

  18. A luminance-based heart chip assay for assessing the efficacy of graft preservation solutions in heart transplantation in rats.

    Science.gov (United States)

    Maeda, Masashi; Kasahara, Naoya; Doi, Junshi; Iijima, Yuki; Kikuchi, Takeshi; Teratani, Takumi; Kobayashi, Eiji

    2013-01-01

    We developed a novel luciferase-based viability assay for assessing the viability of hearts preserved in different solutions. We examined whether this in vitro system could predict heart damage and survival after transplantation in rats. By our novel system, preserved heart viability evaluation and transplanted heart-graft functional research study. University basic science laboratory. Isolated Luciferase-transgenic Lewis (LEW) rat cardiac-tissue-chips were plated on 96-well tissue-culture plates and incubated in preservation solutions at 4°C. Viability was measured as photon intensity by using a bio-imaging system. Heart-grafts preserved in University of Wisconsin (UW), extracellular-trehalose-Kyoto (ETK), Euro-Collins (EC), histidin-tryptophan-ketoglutarat solution (HTK), lactated Ringer's (LR) or normal saline solution were transplanted cervically by using a cuff-technique or into the abdomens of syngeneic wild-type LEW rats by using conventional microsurgical suture techniques. Imaging an evaluation of preservation heart-graft and functional analysis. Cardiac-tissue-chips preserved with UW, HTK or ETK solution gave higher luminance than those preserved with EC, LR or normal saline (phearts in each solution at 4°C, the beating of the isolated hearts was evaluated. The success rate, evaluation of beating, of cervical heart transplants using UW and ETK solution exceeded 70%, but those using other preservation solutions were lower (UW: 100%, ETK: 75%, EC: 42.86%, HTK: 14.29%, normal saline: 0%). Histological analysis of cervical heart-grafts after 3 h preservation by myeloperoxidase (MPO), zona occludens-1(ZO-1), and caspase-3 immunostaining revealed different degrees of preservation damage in all grafts. Our novel assay system is simple and can test multiple solutions. It should therefore be a powerful tool for developing and improving new heart-graft preservation solutions.

  19. Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

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    Cheng-Chia Tsai

    2014-01-01

    Full Text Available The present study investigated the merit of ginseng in the improvement of heart failure in diabetic rats and the role of peroxisome proliferator-activated receptors δ (PPARδ. We used streptozotocin-induced diabetic rat (STZ-rat to screen the effects of ginseng on cardiac performance and PPARδ expression. Changes of body weight, water intake, and food intake were compared in three groups of age-matched rats; the normal control (Wistar rats received vehicle, STZ-rats received vehicle and ginseng-treated STZ-rats. We also determined cardiac performances in addition to blood glucose level in these animals. The protein levels of PPARδ in hearts were identified using Western blotting analysis. In STZ-rats, cardiac performances were decreased but the food intake, water intake, and blood glucose were higher than the vehicle-treated control. After a 7-day treatment of ginseng in STZ-rats, cardiac output was markedly enhanced without changes in diabetic parameters. This treatment with ginseng also increased the PPARδ expression in hearts of STZ-rats. The related signal of cardiac contractility, troponin I phosphorylation, was also raised. Ginseng-induced increasing of cardiac output was reversed by the cotreatment with PPARδ antagonist GSK0660. Thus, we suggest that ginseng could improve heart failure through the increased PPARδ expression in STZ-rats.

  20. Zinc antagonizes homocysteine-induced fetal heart defects in rats.

    Science.gov (United States)

    He, Xiaoyu; Hong, Xinru; Zeng, Fang; Kang, Fenhong; Li, Li; Sun, Qinghua

    2009-09-01

    It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In each group, two fetuses were removed on GD 13, 15, 17, and 19 and examined for cardiac malformations; maternal copper/zinc-containing-superoxide dismutase (Cu/Zn-SOD) activity and metallothionein type I (MT-1) mRNA expression were measured simultaneously. The prevalence of cardiac malformations was significantly higher in group H than in group C, and significantly lower in group Z than in group H at the studied time points. Cu/Zn-SOD activity and MT-1 mRNA levels were significantly lower in group H than in group C, and significantly higher in group Z than in group H. Our data suggest that zinc antagonizes homocysteine-induced teratogenic effects on the fetal heart, possibly via the inhibition of excessive peroxidation.

  1. Contractile force measured in unskinned isolated adult rat heart fibres.

    Science.gov (United States)

    Brady, A J; Tan, S T; Ricchiuti, N V

    1979-12-13

    A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.

  2. Development of heart failure assessed by tissue Doppler imaging in hypertensive Dahl rats

    OpenAIRE

    宮田, 聖子||ミヤタ, セイコ||Miyata, Seiko; 山田, 亜紀||ヤマダ, アキ||Yamada, Aki||Iwami Yamada, Aki; 橋本, 克徳||ハシモト, カツノリ||Hashimoto, Katsunori; 黒木, 祥子||クロキ, ショウコ||Kuroki, Shoko; 岩本, 隆司||イワモト, タカシ||Iwamoto, Takashi; 野田, 明子||ノダ, アキコ||Noda, Akiko

    2014-01-01

    Objective: Tissue Doppler imaging (TDI) has been recognized as a useful tool to assess regional myocardial function. The purpose of this study was to evaluate the development of heart failure in hypertensive Dahl rats using echocardiography with TDI. Methods: Dahl salt-sensitive (DS) rats were placed on 8% NaCl diet from 7 weeks old. As an age-matched control, DS rats were consistently placed on normal diet. In these rats, echocardiography was performed successively. We evaluated interventric...

  3. Discriminate Properties of Three Specific and Generic Health-Related Quality of Life Questionnaires in Heart Failure

    Directory of Open Access Journals (Sweden)

    M Asadi-Lari

    2005-10-01

    Full Text Available Objectives: To assess health-related quality of life (HRQL in patients with suspected heart failure (HF and to explore discriminate properties of the tools, two generic questionnaires, Short Form 36 (SF-36 and EuroQol 5D (EQ-5D and one specific, the Minnesota Living with Heart Failure questionnaire (MLHF-Q HRQL were employed and compared with New York Heart Association (NYHA functional class. Method: All patients with symptoms suggestive of heart failure referred to University Hospital, Nottingham, between June 2002 and March 2003. Confirmation of left ventricular systolic dysfunction carried out by echocardiography. Main Results: 223 patients (median age=74 were referred. HF was confirmed in 81. Lower HRQL scores were found in older patients (SF-36 and EQ-5D: P30 (P= ns; P<0.05; P= ns respectively. Among those with confirmed heart failure, lower mean scores were found in both subscales of SF-36, four of six subscales in EQ-5D and all MLHF-Q subscales, but these were not statistically significant. SF-36 Mental Component Score (MCS and the emotional subscale of MLHF-Q were more sensitive to depressive disorders than EQ-5D ((P< 0.001; p<0.001; and P< 0.05 respectively. Regression analysis indicated that only SF-36 Physical Component Score (PCS was able to differentiate significantly between NYHA functional classes (P< 0.01. The validity of MLHF-Q was confirmed by correlation with various subclasses in other HRQL measures (P< 0.001 and known group analysis with NYHA functional class (P< 0.001 in both physical and emotional subscales. Conclusion: The specific HRQL measure, MLHF-Q, was more sensitive to functional status in heart failure but emotional abnormalities and general affections were more readily identified by generic tools. Employing both generic and specific HRQL instruments seems necessary in suspected and confirmed heart failure. MLHF-Q showed appropriate construct validity in this sample.

  4. Effects of rat urotensin II on coronary flow and myocardial eNOS protein expression in isolated rat heart

    Institute of Scientific and Technical Information of China (English)

    LingLI; Wen-junYUAN; Ding-fengSU

    2004-01-01

    AIM: To examine the effects of urotensin Ⅱ, a recently discovered endogenous peptide, on coronary flow (CF),cardiac function, and endothelial nitric oxide synthase (eNOS) expression in isolated rat hearts. METHODS: Heart was isolated and perfused retrogradely via the aorta in Langendorff mode. Rat urotensin Ⅱ was administered in the perfusion solution. The eNOS content in myocardium was determined by Western blot. RESULTS: Rat urotensin Ⅱ had no effect on the heart rate, left ventricular systolic pressure, left ventricular end-diastolic pressure, or±dp/dt max. While rat urotensin Ⅱ dose-dependently increased CF. CF was increased by 11.43%, 6.67%, 6.62%,6.56%, 6.36%, and 5.86% respectively in a time-dependent manner at 5, 10, 15, 20, 25, and 30 min after injection of rat urotensin Ⅱ 6.66×10-2μg. The maximal effect on CF was found at 5 min following urotensin Ⅱ administration.NG-nitro-L-arginine methyl ester (L-NAME) did not prevent the increased CF in response to urotensin Ⅱ. Rat urotensin Ⅱ dose-dependently increased the cardiac eNOS protein expression and this effect was not inhibited by L-NAME. CONCLUSION: Rat urotensin Ⅱ did not alter cardiac function but increased CF and the amount of myocardial eNOS protein in the isolated rat heart. The increased CF was independent of the involvement of eNOS.

  5. Discrimination of the "Athlete's Heart" from real disease by electrocardiogram and echocardiogram.

    Science.gov (United States)

    Erickson, Christopher C

    2017-01-01

    Chronic physical training has been shown to produce multiple changes in the heart, resulting in the athlete's heart phenotype. Some of the changes can make it difficult to discern athlete's heart from true cardiac disease, most notably hypertrophic cardiomyopathy. Other diseases such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy may be difficult to rule in or out. In this article, the physiological cardiac changes of chronic athletic training are reviewed. A methodological approach using electrocardiography and echocardiography to differentiate between athlete's heart and cardiac disease is proposed.

  6. Stress Alters the Discriminative Stimulus and Response Rate Effects of Cocaine Differentially in Lewis and Fischer Inbred Rats

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    Therese A. Kosten

    2012-03-01

    Full Text Available Stress enhances the behavioral effects of cocaine, perhaps via hypothalamic-pituitary-adrenal (HPA axis activity. Yet, compared to Fischer 344 (F344 rats, Lewis rats have hyporesponsive HPA axis function and more readily acquire cocaine self-administration. We hypothesized that stress would differentially affect cocaine behaviors in these strains. The effects of three stressors on the discriminative stimulus and response rate effects of cocaine were investigated. Rats of both strains were trained to discriminate cocaine (10 mg/kg from saline using a two-lever, food-reinforced (FR10 procedure. Immediately prior to cumulative dose (1, 3, 10 mg/kg cocaine test sessions, rats were restrained for 15-min, had 15-min of footshock in a distinct context, or were placed in the shock-paired context. Another set of F344 and Lewis rats were tested similarly except they received vehicle injections to test if stress substituted for cocaine. Most vehicle-tested rats failed to respond after stressor exposures. Among cocaine-tested rats, restraint stress enhanced cocaine’s discriminative stimulus effects in F344 rats. Shock and shock-context increased response rates in Lewis rats. Stress-induced increases in corticosterone levels showed strain differences but did not correlate with behavior. These data suggest that the behavioral effects of cocaine can be differentially affected by stress in a strain-selective manner.

  7. Heart Rate Variability in Nonlinear Rats with Different Orientation and Exploratory Activity in the Open Field.

    Science.gov (United States)

    Kur'yanova, E V; Teplyi, D L; Zhukova, Yu D; Zhukovina, N V

    2015-12-01

    The basic behavioral activity of nonlinear rats was evaluated from the sum of crossed peripheral and central squares and peripheral and central rearing postures in the open fi eld test. This index was low (30 episodes). Male rats with high score of orientation and exploratory activity were characterized by higher indexes of total heart rate variability than rats with low or intermediate activity. Specimens with a greater contribution of VLF waves into the total power spectrum of heart rate variability were shown to dominate among the rats with high behavioral activity. Our results are consistent with the notions of a suprasegmental nature of VLF waves.

  8. Sniff adjustment in an odor discrimination task in the rat: analytical or synthetic strategy?

    Directory of Open Access Journals (Sweden)

    Emmanuelle eCourtiol

    2014-05-01

    Full Text Available A growing body of evidence suggests that sniffing is not only the mode of delivery for odorant molecules but also contributes to olfactory perception. However, the precise role of sniffing variations remains unknown. The zonation hypothesis suggests that animals use sniffing variations to optimize the deposition of odorant molecules on the most receptive areas of the olfactory epithelium. Sniffing would thus depend on the physicochemical properties of odorants, particularly their sorption. Rojas-Líbano and Kay (2012 tested this hypothesis and showed that rats used different sniff strategies when they had to target a high-sorption molecule or a low-sorption molecule in a binary mixture. Which sniffing strategy is used by rats when they are confronted to discrimination between two similarly sorbent odorants remains unanswered. Particularly, is sniffing adjusted independently for each odorant according to its sorption properties (analytical processing, or is sniffing adjusted based on the pairing context (synthetic processing? We tested these hypotheses on rats performing a two-alternative choice discrimination of odorants with similar sorption properties. We recorded sniffing in a non-invasive manner using whole-body plethysmography during the behavioral task. We found that sniffing variations were not only a matter of odorant sorption properties and that the same odorant was sniffed differently depending on the odor pair in which it was presented. These results suggest that rather than being adjusted analytically, sniffing is instead adjusted synthetically and depends on the pair of odorants presented during the discrimination task. Our results show that sniffing is a specific sensorimotor act that depends on complex synthetic processes.

  9. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

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    Alexis eFaure

    2013-09-01

    Full Text Available Huntington’s disease (HD is characterized by triad of motor, cognitive and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats, evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE. Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1 a fear cue produces a short-lived decrease of temporal precision after its termination, and (2 animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala.

  10. Effects of X-ray radiation on complex visual discrimination learning and social recognition memory in rats.

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    Catherine M Davis

    Full Text Available The present report describes an animal model for examining the effects of radiation on a range of neurocognitive functions in rodents that are similar to a number of basic human cognitive functions. Fourteen male Long-Evans rats were trained to perform an automated intra-dimensional set shifting task that consisted of their learning a basic discrimination between two stimulus shapes followed by more complex discrimination stages (e.g., a discrimination reversal, a compound discrimination, a compound reversal, a new shape discrimination, and an intra-dimensional stimulus discrimination reversal. One group of rats was exposed to head-only X-ray radiation (2.3 Gy at a dose rate of 1.9 Gy/min, while a second group received a sham-radiation exposure using the same anesthesia protocol. The irradiated group responded less, had elevated numbers of omitted trials, increased errors, and greater response latencies compared to the sham-irradiated control group. Additionally, social odor recognition memory was tested after radiation exposure by assessing the degree to which rats explored wooden beads impregnated with either their own odors or with the odors of novel, unfamiliar rats; however, no significant effects of radiation on social odor recognition memory were observed. These data suggest that rodent tasks assessing higher-level human cognitive domains are useful in examining the effects of radiation on the CNS, and may be applicable in approximating CNS risks from radiation exposure in clinical populations receiving whole brain irradiation.

  11. VITAMIN D DEFICIENCY IN THE SPONTANEOUSLY HYPERTENSIVE HEART FAILURE [SHHF] PRONE RAT

    Science.gov (United States)

    Przybylski, Robert; Mccune, Sylvia; Hollis, Bruce; Simpson, Robert U.

    2009-01-01

    Background and Aims Vitamin D deficiency has been associated with the etiology and pathogenesis of heart disease including congestive heart failure. We previously observed cardiac hypertrophy in vitamin D deficient rats and vitamin D-receptor knockout mice. These studies indicate that the absence of vitamin D-mediated signal transduction and genomic activation results in increased sensitivity of the heart to ionotropic stimuli and cardiomyocyte hypertrophy. This study’s aim is to investigate the relationship between vitamin D status and the heart failure phenotype in the rat. Methods and Results Vitamin D status was assessed by measuring 25-hydroxyvitamin D levels and related to heart weight in young, middle-aged and aging spontaneously hypertensive, heart failure-prone (SHHF) rats. We also measured the effects of the vitamin D hormone,1,25(OH)2D3, on cardiac function in SHHF rats. Cardiac hypertrophy in this model of the failing heart increased with age and related to decreasing vitamin D status. Vitamin D deficiency presented after cardiac hypertrophy was first observed. Additionally, we found that 1,25(OH)2D3 treatment between 4.0–7.0 months of age prevented cardiac hypertrophy and permits decreased workload for the heart while allowing adequate blood perfusion and pressure, resulting in reduced cardiac index. Conclusions Our findings suggest that low vitamin D status is associated with the progression and final terminal phase of the heart failure phenotype and not with initial heart hypertrophy. Also, we report that in the vitamin D sufficient SHHF rat, 1,25(OH)2D3 treatment provided protection against the progression of the heart failure phenotype. PMID:19836216

  12. Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.

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    Min Zheng

    Full Text Available BACKGROUND: The paraventricular nucleus (PVN of the hypothalamus plays an important role in the progression of heart failure (HF. We investigated whether cyclooxygenase-2 (COX-2 inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS and renin-angiotensin system (RAS in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg. On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW and lung to body weight (LW/BW ratios, heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular peak systolic pressure (LVPSP and maximum rate of change in left ventricular pressure (LV±dp/dtmax were improved in HF+CLB rats. Angiotensin II (ANG II, norepinephrine (NE, COX-2 and glutamate (Glu in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.

  13. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure

    NARCIS (Netherlands)

    Yin, Meimei; van der Horst, Iwan C. C.; van Melle, Joost P.; Qian, Cheng; van Gilst, Wiek H.; Sillje, Herman H. W.; de Boer, Rudolf A.

    2011-01-01

    Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Sillje HH, de Boer RA. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol 301: H459-H468, 2011. First published May 13, 2011; doi:10.1152/ajpheart.00054.2011.-Metformin

  14. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  15. The effect of prefixation on the quality of vascular corrosion casts of rat heart.

    Science.gov (United States)

    Reddy, P A; Douglas, J E; Schulte, M; Hossler, F E

    1995-01-01

    To help define the optimal conditions for the preparation of vascular corrosion casts of rat heart, we examined the effect of prefixation with aldehyde fixatives on the perfusion rates of rat heart and on the quality of vascular casts. For these studies, beating hearts were removed from rats, cannulated via the aortic stump, arrested with KCl, perfused retrograde with buffered saline or fixative, and infused with resin to prepare corrosion casts. Fixatives used were 2.5% glutaraldehyde or 2% paraformaldehyde, and the casting resin consisted of a Mercox-methylmethacrylate mixture (4:1). All perfusion pressures were monitored at 80 to 100 mm Hg using a mercury manometer. The perfusion rate of control hearts was 13 to 14 mL/min. Prefixation with glutaraldehyde and paraformaldehyde reduced perfusion to 8.5 and 8.1 mL/min, respectively. Cast quality was observed grossly and with the scanning electron microscope. Control hearts yielded high quality, complete casts with 2570 capillaries/mm(2+). Casts from prefixed hearts exhibited areas of incomplete vessel filling and resisted complete tissue maceration, leaving tissue remnants adhering to the vessel replicas. Casts from glutaraldehyde-fixed hearts were of very poor quality. Our results indicate that prefixation is an unnecessary step in the preparation of vascular casts of rat heart and is inconsistent with cast quality.

  16. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  17. Inhibition of Cyclooxygenase-2 Reduces Hypothalamic Excitation in Rats with Adriamycin-Induced Heart Failure

    OpenAIRE

    2012-01-01

    BACKGROUND: The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the progression of heart failure (HF). We investigated whether cyclooxygenase-2 (COX-2) inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg...

  18. Influence of microwaves on the beating rate of isolated rat hearts.

    Science.gov (United States)

    Yee, K C; Chou, C K; Guy, A W

    1988-01-01

    Previous reports have shown that microwave exposure can decrease the beating rate of isolated rat hearts. These experiments were conducted at room temperature and with the hearts exposed to air. We observed arrhythmia frequently at room temperature, and the variation of heart beat was so large that it makes the results difficult to reproduce. Therefore, we employed a double-circulating system to provide perfusion through the coronary artery and around the outside of the heart to maintain the rat hearts at 37.7 degrees C. No arrhythmias were observed in our experiments, and the hearts were beating for at least 1 h. The effects of 16-Hz modulated 2,450-MHz pulsed microwaves (10 microseconds, 100 pps) on the beating rate of 50 isolated rat hearts were studied. Results showed no statistically significant changes of heart rate in exposed groups at SARs of 2 and 10 W/kg compared with the control group. The effect seen at 200 W/kg was shown to be similar to that resulting from heating the heart.

  19. Regulation of atriopeptin release from the isolated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Currie, M.G.; Newman, W.H.

    1986-03-05

    Recent studies have demonstrated that the mammalian atria possess an endocrine function which appears to play a role in the regulation of systemic arterial pressure, fluid balance, and electrolyte homeostasis. They have begun to study the regulation of atriopeptin (atrial natriuretic factor) release into the coronary effluent of the isolated perfused rat heart. Characterization by high pressure liquid chromatography of the form of the hormone released indicates that the predominant form is the active low MW circulating hormone not the pro-hormone. The release of immunoreactive atriopeptin (iAP) was stimulated by infusion of norepinephrine (1 ..mu..M) or epinephrine (1 ..mu..M) 3.0 and 2.6-fold, respectively. The ..beta..-adrenergic agonist isoproterenol and the ..cap alpha..-2 adrenergic agonist BHT-920 lacked effects on iAP release. On the other hand, the ..cap alpha..-1 adrenergic agonist phenylephrine caused a dose-dependent increase in release of iAP. Release of iAP stimulated by phenylephrine was inhibited by the ..cap alpha.. antagonist phentolamine. Further, iAP release was stimulated 4.2-fold by phorbol ester (1 ..mu..M) but was not affected by 4-..beta.. phorbol (1 ..mu..M). From these collective data they conclude that the release of atriopeptin is stimulated by ..cap alpha..-1 receptor activation and that protein kinase C participates in the regulation of secretion. The data suggests that the sympathetic nervous system may play a physiologic role in the regulation of atriopeptin secretion.

  20. Peak oxygen uptake in relation to total heart volume discriminates heart failure patients from healthy volunteers and athletes

    Directory of Open Access Journals (Sweden)

    Buhre Torsten

    2010-12-01

    Full Text Available Abstract Background An early sign of heart failure (HF is a decreased cardiac reserve or inability to adequately increase cardiac output during exercise. Under normal circumstances maximal cardiac output is closely related to peak oxygen uptake (VO2peak which has previously been shown to be closely related to total heart volume (THV. Thus, the aim of this study was to derive a VO2peak/THV ratio and to test the hypothesis that this ratio can be used to distinguish patients with HF from healthy volunteers and endurance athletes. Thirty-one patients with HF of different etiologies were retrospectively included and 131 control subjects (60 healthy volunteers and 71 athletes were prospectively enrolled. Peak oxygen uptake was determined by maximal exercise test and THV was determined by cardiovascular magnetic resonance. The VO2peak/THV ratio was then derived and tested. Results Peak oxygen uptake was strongly correlated to THV (r2 = 0.74, p 2 = 0.0002, p = 0.95. The VO2peak/THV ratio differed significantly between control subjects and patients, even in patients with normal ejection fraction and after normalizing for hemoglobin levels (p 2peak/THV ratio was the only independent predictor of presence of HF (p Conclusions The VO2peak/THV ratio can be used to distinguish patients with clinically diagnosed HF from healthy volunteers and athletes, even in patients with preserved systolic left ventricular function and after normalizing for hemoglobin levels.

  1. Classification and discrimination of pediatric patients undergoing open heart surgery with and without methylprednisolone treatment by cytomics

    Science.gov (United States)

    Bocsi, Jozsef; Mittag, Anja; Pierzchalski, Arkadiusz; Osmancik, Pavel; Dähnert, Ingo; Tárnok, Attila

    2011-02-01

    Introduction: Methylprednisolone (MP) is frequently preoperatively administered in children undergoing open heart surgery. The aim of this medication is to inhibit overshooting immune responses. Earlier studies demonstrated cellular and humoral immunological changes in pediatric patients undergoing heart surgeries with and without MP administration. Here in a retrospective study we investigated the modulation of the cellular immune response by MP. The aim was to identify suitable parameters characterizing MP effects by cluster analysis. Methods: Blood samples were analysed from two aged matched groups with surgical correction of septum defects. Group without MP treatment consisted of 10 patients; MP was administered on 21 patients (median dose: 11mg/kg) before cardiopulmonary bypass (CPB). EDTA anticoagulated blood was obtained 24 h preoperatively, after anesthesia, at CPB begin and end (CPB2), 4h, 24h, 48h after surgery, at discharge and at out-patient followup (8.2; 3.3-12.2 month after surgery; median and IQR). Flow cytometry showed the biggest MP relevant changes at CPB2 and 4h postoperatively. They were used for clustering analysis. Classification was made by discriminant analysis and cluster analysis by means of Genes@work software. Results & conclusion: 146 parameters were obtained from analysis. Cross-validation revealed several parameters being able to discriminate between MP groups and to identify immune modulation. MP administration resulted in a delayed activation of monocytes, increased ratio of neutrophils, reduced T-lymphocytes counts. Cluster analysis demonstrated that classification of patients is possible based on the identified cytomics parameters. Further investigation of these parameters might help to understand the MP effects in pediatric open heart surgery.

  2. Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Polegato, Bertha F.; Minicucci, Marcos F.; Azevedo, Paula S.; Gonçalves, Andréa F.; Lima, Aline F.; Martinez, Paula F.; Okoshi, Marina P.; Okoshi, Katashi; Paiva, Sergio A. R.; Zornoff, Leonardo A. M., E-mail: lzornoff@fmb.unesp.br [Faculdade de Medicina de Botucatu - Universidade Estadual Paulista ' Júlio de mesquita Filho' - UNESP Botucatu, SP (Brazil)

    2016-02-15

    Heart failure prediction after acute myocardial infarction may have important clinical implications. To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset.

  3. Conditional self-discrimination enhances dendritic spine number and dendritic length at prefrontal cortex and hippocampal neurons of rats.

    Science.gov (United States)

    Penagos-Corzo, Julio C; Bonilla, Andrea; Rodríguez-Moreno, Antonio; Flores, Gonzalo; Negrete-Díaz, José V

    2015-11-01

    We studied conditional self-discrimination (CSD) in rats and compared the neuronal cytoarchitecture of untrained animals and rats that were trained in self-discrimination. For this purpose, we used thirty 10-week-old male rats were randomized into three groups: one control group and two conditioning groups: a comparison group (associative learning) and an experimental group (self-discrimination). At the end of the conditioning process, the experimental group managed to discriminate their own state of thirst. After the conditioning process, dendritic morphological changes in the pyramidal neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus were evaluated using Golgi-Cox stain method and then analyzed by the Sholl method. Differences were found in total dendritic length and spine density. Animals trained in self-discrimination showed an increase in the dendritic length and the number of dendritic spines of neurons of the prefrontal cortex and CA1 region of the dorsal hippocampus. Our data suggest that conditional self-discrimination improves the connectivity of the prefrontal cortex and dorsal CA1, which has implications for memory and learning processes.

  4. Altered neuropeptide Y Y1 responses in mesenteric arteries in rats with congestive heart failure

    DEFF Research Database (Denmark)

    Bergdahl, A; Nilsson, T; Sun, X Y;

    1998-01-01

    The aim of the present study was to elucidate if the potentiating effect of neuropeptide Y on various vasoactive agents in vitro is (1) altered in mesenteric arteries from rats with congestive heart failure and (2) mediated by the neuropeptide Y Y1 receptor. The direct vascular effects...... of the neuropeptide Y Y1 antagonist, BIBP3226 (BIBP3226¿(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl ]-D-arginine-amide¿). Neuropeptide Y, per se, had no vasoactive effect in the arteries. The potency of endothelin-1 was significantly decreased in congestive heart failure rats. Neuropeptide Y and neuropeptide Y......-(13-36) potentiated the endothelin-1-induced contraction in congestive heart failure mesenteric arteries. In 20% of the congestive heart failure rats, sarafotoxin 6c induced a contraction of 31+/-4%. Neuropeptide Y also potentiated U46619- and noradrenaline-induced contractions but not 5-HT...

  5. ENDURANCE TRAINING AND GLUTATHIONE-DEPENDENT ANTIOXIDANT DEFENSE MECHANISM IN HEART OF THE DIABETIC RATS

    Directory of Open Access Journals (Sweden)

    Mustafa Atalay

    2003-06-01

    Full Text Available Regular physical exercise beneficially influences cardiac antioxidant defenses in normal rats. The aim of this study was to test whether endurance training can strengthen glutathione-dependent antioxidant defense mechanism and decrease lipid peroxidation in heart of the streptozotocin-induced diabetic rats. Redox status of glutathione in blood of diabetic rats in response to training and acute exercise was also examined. Eight weeks of treadmill training increased the endurance in streptozotocin-induced diabetic rats. It did not affect glutathione level in heart tissue at rest and also after exercise. On the other hand, endurance training decreased glutathione peroxidase activity in heart, while glutathione reductase and glutathione S-transferase activities were not affected either by acute exhaustive exercise or endurance training. Reduced and oxidized glutathione levels in blood were not affected by either training or acute exercise. Conjugated dienes levels in heart tissue were increased by acute exhaustive exercise and also 8 weeks treadmill training. Longer duration of exhaustion in trained group may have contributed to the increased conjugated dienes levels in heart after acute exercise. Our results suggest that endurance type exercise may make heart more susceptible to oxidative stress. Therefore it may be wise to combine aerobic exercise with insulin treatment to prevent its adverse effects on antioxidant defense in heart in patients with diabetes mellitus

  6. Enhanced Ca2+-induced contractions and attenuated alpha-adrenoceptor responses in resistance arteries from rats with congestive heart failure

    DEFF Research Database (Denmark)

    Bergdahl, A; Valdemarsson, S; Sun, X Y;

    2001-01-01

    AIM: The aim of the present study was to examine the role of Ca2+-mediated contractile responses in isolated mesenteric resistance arteries from rats with congestive heart failure (CHF). METHODS: Heart failure was induced by ligation of the left coronary artery. Rats exposed to the same surgical......-adrenoceptors and a difference of Ca2+-mediated vascular contractility in resistance arteries of congestive heart failure rats....

  7. Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.

    Science.gov (United States)

    Zhang, Hongmei; Dong, Yan; Su, Qing

    2017-02-01

    In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

  8. Long-term physiological T3 supplementation in hypertensive heart disease in rats.

    Science.gov (United States)

    Weltman, Nathan Y; Pol, Christine J; Zhang, Youhua; Wang, Yibo; Koder, Adrienne; Raza, Sarah; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Gerdes, A Martin

    2015-09-15

    Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function. Copyright © 2015 the American Physiological Society.

  9. Effects of anabolic steroid nandrolone decanoate on ischemic preconditioning in isolated heart of sedentary rats

    Directory of Open Access Journals (Sweden)

    Zahra Akbari

    2014-11-01

    Full Text Available Background: Previous studies have shown that use of supraphysiologocal doses of anabolic adrogenic steroids (AAS associated with detrimental cardiovascular effects including ventricular hypertrophy, increased susceptibility to ischaemia/reperfusion injury, impairment of exercise-induced cardioprotection and sudden cardiac death. The aim of the present study was to evaluate the impact of 8 weeks treatment of AAS nandrolone decanoate (10 mg/kg/week, on ischemic preconditioning (IPC phenomena in isolated hearts of sedentary rats. Materials and Methods: Three groups of animals were studied in the present study. Control ischemia/reperfusion injury group (IR, 2- Ischemic preconditioned group before main test ischemia and reperfusion (IPC+IR, and 3- Nandrolone treated ischemic preconditioned group before main test ischemia and reperfusion (Nan+IPC+IR. After two months of nandrolone and/or its solvent, the isolated Langendorff perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion. The IPC was induced by three cycles of 3-min occlusion and 3-min reperfusion of the left anterior descending coronary artery (LAD before main test ischemia. Heart rate, left ventricular developed pressure (LVDP, rate pressure product (RPP, Max dp/dt, Min dp/dt and coronary flow were recorded during experiment. Infarction size was measured after 120 min reperfusion by TTC staining. Results: Eight weeks’ nandrolone treatment decreased body weight and increased cardiac to body weight ratio in treated rats. Nandrolone increased pre-ischemic base line cardiac function parameters in the rat hearts. Cardiac function recovery parameters in different time points during reperfusion were also greater in nandrolone treated rats compared to their respective controls. IPC decreased infarct size in the rats (P<0.05. Nandrolone could not significantly change the infarct size lowering effect of IPC in the rat heart. Conclusion: The present study revealed

  10. Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight.

    Science.gov (United States)

    Engle, Steven K; Watson, David E

    2016-02-01

    Cardiovascular (CV) toxicity is an important cause of failure during drug development. Blood-based biomarkers can be used to detect CV toxicity during preclinical development and prioritize compounds at lower risk of causing such toxicities. Evidence of myocardial degeneration can be detected by measuring concentrations of biomarkers such as cardiac troponin I and creatine kinase in blood; however, detection of functional changes in the CV system, such as blood pressure, generally requires studies in animals with surgically implanted pressure transducers. This is a significant limitation because sustained changes in blood pressure are often accompanied by changes in heart rate and together can lead to cardiac hypertrophy and myocardial degeneration in animals, and major adverse cardiovascular events (MACE) in humans. Increased concentrations of NPs in blood correlate with higher risk of cardiac mortality, all-cause mortality, and MACE in humans. Their utility as biomarkers of CV function and toxicity in rodents was investigated by exploring the relationships between plasma concentrations of NTproANP and NTproBNP, blood pressure, heart rate, and heart weight in Sprague Dawley rats administered compounds that caused hypotension or hypertension, including nifedipine, fluprostenol, minoxidil, L-NAME, L-thyroxine, or sunitinib for 1-2 weeks. Changes in NTproANP and/or NTproBNP concentrations were inversely correlated with changes in blood pressure. NTproANP and NTproBNP concentrations were inconsistently correlated with relative heart weights. In addition, increased heart rate was associated with increased heart weights. These studies support the use of natriuretic peptides and heart rate to detect changes in blood pressure and cardiac hypertrophy in short-duration rat studies. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. The Effect of Treadmill Exercise on Antioxidant Status in the Hearts of the Diabetic Rats

    Directory of Open Access Journals (Sweden)

    I. Salehi

    2009-07-01

    Full Text Available Introduction & Objective: Diabetes is a metabolic disorder caused by low secretion or resistance to the insulin action. Oxidative stress, as a result of imbalance between the free radical production and antioxidant defense systems is strongly related to diabetes and its complications. The aim of the present study is to evaluate the effect of experimental diabetes and forced treadmill exercise on oxidative stress indexes in heart tissue.Materials & Methods: 40 male wistar rats (20020g were divided into four groups(n=10: control, control with exercise, diabetic, diabetic with exercise. Diabetes was induced by a single dose injection of streptozotocin (50 mg/Kg-1, i.p. Treadmill was performed for 1 hour, 5 days in 8 weeks. At the end of the experiments, the rats were anesthetized by sodium pentobarbital (50 mg/Kg-1, i.p and left ventricle dissociate from heart and maintenance in -80 ºC. Supernatant from homogenization were used to determine the superoxide dismutase (SOD, gluthatione peroxidase (GPX, gluthatione reductase (GR and catalase (CAT activities as enzymatic antioxidant status. Also Maolnyldealdehyde (MDA level as index of lipid peroxidation and total glutathione (T.GSH of the heart tissue were measured.Results: Diabetes significantly reduced CAT and GR activities in diabetic rats compared with control rats. SOD and GPX activities weren't changed in the hearts of the diabetic rats. MDA level, as a lipid peroxidation index, increased in non exercised diabetic rats. In response to exercise, MDA level, CAT, GR and SOD activities showed a significant increase in exercise diabetic rats compared with non exercise diabetic rats.Conclusion: Forced treadmill with moderate severity has harmful effects on cardiovascular system in diabetes because it increases MDA level of heart tissue in exercised diabetic rats.

  12. Combined effects of niacin and chromium treatment on heart of hyperlipidemic rats.

    Science.gov (United States)

    Döger, M Mutluhan; Sokmen, Bahar B; Yanardag, Refiye

    2011-10-01

    The present study was undertaken to investigate the effects of the combination of niacin and chromium(III)-chloride on heart glutathione (GSH), lipid peroxidation (LPO) levels, serum paraoxonase (PON), gamma-glutamyl transferase (GGT) activities and protein carbonyl contents (PCC) of hyperlipidemic rats. In this study, female Swiss albino rats were used. They were divided into four groups. The animals of the first group (group I) were fed with pellet chow. The rats (group II) were fed with a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 20% sunflower oil added to the pellet chow, and given 3% alcoholic water for 60 days. The rats (group III) were fed with the same lipogenic diet and treated by gavage technique with CrCl(3) 6H(2)O to a dose of 250 µg/kg and 100 mg/kg niacin for 45 days, 15 days after experimental animals were done hyperlipidemic. Group IV was fed with pellet chow and treated with 250 µg/kg CrCl(3) 6H(2)O and 100 mg/kg niacin for 45 days. On the 60th day, the heart tissue and blood samples were taken from animals. As a result, heart LPO, serum GGT activity and serum PCC were increased; serum PON activity and heart GSH levels were decreased in hyperlipidemic rats. Treatment with combined niacin and chromium reversed these effects. In conclusion, the combined treatment with niacin and chromium might induce a protective effect on heart tissue.

  13. Modulation of the cardioprotective effect of ischemic preconditioning in hyperlipidaemic rat heart.

    Science.gov (United States)

    Yadav, Harlokesh Narayan; Singh, Manjeet; Sharma, Pyare Lal

    2010-09-15

    Ischemic preconditioning (IPC) produces cardioprotection by phosphorylation of glycogen synthaes kinase-3beta (GSK-3beta) that inhibits the opening of mitochondrial permeability transition pore (MPTP), and this cardioprotective action of IPC is attenuated by hyperlipidaemia. The present study investigated the role of GSK-3beta in attenuation of cardioprotective effect of IPC, by hyperlipidaemia in the rat heart. Hyperlipidaemia was produced in rat by feeding high fat diet for six weeks. Isolated perfused rat heart was subjected to 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) was analyzed from coronary effluent. IPC significantly decreased the myocardial infarct size and the release of LDH and CK-MB from normal rat heart. IPC induced myocardial protection was attenuated in hyperlipidaemic rat heart. However, cardioprotective effect of pharmacological preconditioning with GSK-3beta inhibitors i.e. Lithium Chloride (LiCl) (20mM), Indirubin - 3 Monooxime (1 microM) and 3-(2, 4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2, 5-dione (SB216763) (3 microM), was not attenuated. This differential attenuation by hyperlipidaemia, of IPC and pharmacological preconditioning induced cardioprotection is a new finding in our study. GSK-3beta inhibition is reported to increase the threshold of opening for MPTP during reperfusion. Administration of atractyloside (20 microM), an opener of MPTP, significantly attenuated the cardioprotective effect of IPC in normal heart, and pharmacological preconditioning in the hyperlipidaemic rat heart. Thus, the attenuation of cardioprotective effect of IPC in hyperlipidaemic heart may be due to inhibition of protective signaling pathways upstream of GSK-3beta and inhibition of opening of MPTP.

  14. The effects of noribogaine and harmaline in rats trained with ibogaine as a discriminative stimulus.

    Science.gov (United States)

    Helsley, S; Rabin, R A; Winter, J C

    1997-01-01

    In the present investigation, Fischer-344 rats were trained to discriminate 10.0 mg/kg of ibogaine from water using a pretreatment time of 60 minutes. Analysis of dose response data generated an ED50 of 4.6 mg/kg. The time course of the ibogaine (10.0 mg/kg) cue was also determined. The stimulus reached a maximum level of 94% ibogaine-appropriate responding at the 60-min pretreatment time. This was followed by a time-dependent decrease in ibogaine-appropriate responding. At a pretreatment time of 8 hrs only 6.4% drug-appropriate responding was observed. In substitution experiments, intermediate generalization was observed with a metabolite of ibogaine, 12-hydroxyibogamine [noribogaine] (71.6%) whereas complete generalization was seen with harmaline (83.5%).

  15. A comparison of event-related potential of humans and rats elicited by a serial feature-positive discrimination task

    NARCIS (Netherlands)

    Sambeth, A.; Maes, J.H.R.

    2006-01-01

    The purpose of this experiment was to compare components of the human and rat auditory event-related potential (ERP) in a serial feature-positive discrimination task. Subjects learned to respond to an auditory target stimulus when it followed a visual feature (X→A+), but to not respond when it was

  16. The effect of endotoxin on heart rate dynamics in diabetic rats.

    Science.gov (United States)

    Meamar, Morvarid; Dehpour, Tara; Mazloom, Roham; Sharifi, Fatemeh; Raoufy, Mohammad R; Dehpour, Ahmad R; Mani, Ali R

    2015-05-01

    The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic and controls rats using a telemetric system. Endotoxin induced a reduction in sample entropy of cardiac rhythm in control animals. However, this effect was significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling of cardiac pacemaker from cholinergic control is linked to reduced HRV in endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed in isolated atria. Endotoxemia was associated with impaired responsiveness to carbacholine in control rats. However, endotoxemia did not impair cholinergic responsiveness in diabetic atria. These findings corroborates with development of endotoxin tolerance in diabetic rats. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Aortic banding in rat as a model to investigate malnutrition associated with heart failure.

    Science.gov (United States)

    Héliès-Toussaint, Cécile; Moinard, Christophe; Rasmusen, Carole; Tabbi-Anneni, Imène; Cynober, Luc; Grynberg, Alain

    2005-05-01

    Heart failure is a severe pathology, which has displayed a dramatic increase in the occurrence of patients with chronic heart disease in developed countries, as a result of increases in the population's average age and in survival time. This pathology is associated with severe malnutrition, which worsens the prognosis. Although the cachexia associated with chronic heart failure is a well-known complication, there is no reference animal model of malnutrition related to heart failure. This study was designed to evaluate the nutritional status of rats in a model of loss of cardiac function obtained by ascending aortic banding. Cardiac overload led to the development of cardiac hypertrophy, which decompensates to heart failure, with increased brain natriuretic peptide levels. The rats displayed hepatic dysfunction and an associated renal hypotrophy and renal failure, evidenced by the alteration in renal function markers such as citrullinemia, creatininemia, and uremia. Malnutrition has been evidenced by the alteration of protein and amino acid metabolism. A muscular atrophy with decreased protein content and increased amino acid concentrations in both plasma and muscle was observed. These rats with heart failure displayed a multiorgan failure and malnutrition, which reflected the clinical situation of human chronic heart failure.

  18. Sensory discrimination between innocuous and noxious cold by TRPM8-expressing DRG neurons of rats

    Directory of Open Access Journals (Sweden)

    Sarria Ignacio

    2012-10-01

    Full Text Available Abstract The TRPM8 channel is a principal cold transducer that is expressed on some primary afferents of the somatic and cranial sensory systems. However, it is uncertain whether TRPM8-expressing afferent neurons have the ability to convey innocuous and noxious cold stimuli with sensory discrimination between the two sub-modalities. Using rat dorsal root ganglion (DRG neurons and the patch-clamp recording technique, we characterized membrane and action potential properties of TRPM8-expressing DRG neurons at 24°C and 10°C. TRPM8-expressing neurons could be classified into TTX-sensitive (TTXs/TRPM8 and TTX-resistant (TTXr/TRPM8 subtypes based on the sensitivity to tetrodotoxin (TTX block of their action potentials. These two subtypes of cold-sensing cells displayed different membrane and action potential properties. Voltage-activated inward Na+ currents were highly susceptible to cooling temperature and abolished by ~95% at 10°C in TTXs/TRPM8 DRG neurons, but remained substantially large at 10°C in TTXr/TRPM8 cells. In both TTXs/TRPM8 and TTXr/TRPM8 cells, voltage-activated outward K+ currents were substantially inhibited at 10°C, and the cooling-sensitive outward currents resembled A-type K+ currents. TTXs/TRPM8 neurons and TTXr/TRPM8 neurons were shown to fire action potentials at innocuous and noxious cold temperatures respectively, demonstrating sensory discrimination between innocuous and noxious cold by the two subpopulations of cold-sensing DRG neurons. The effects of cooling temperatures on voltage-gated Na+ channels and A-type K+ currents are likely to be contributing factors to sensory discrimination of cold by TTXs/TRPM8 and TTXr/TRPM8 afferent neurons.

  19. Odor Memory and Discrimination Covary as a Function of Delay between Encoding and Recall in Rats.

    Science.gov (United States)

    Hackett, Chelsea; Choi, Christina; O'Brien, Brenna; Shin, Philip; Linster, Christiane

    2015-06-01

    Nonassociative odor learning paradigms are often used to assess memory, social recognition and neuromodulation of olfactory pathways. We here use a modified object recognition paradigm to investigate how an important task parameter, delay between encoding and recall trials, affects the properties of this memory. We show that both memory for a previously investigated odorant and discrimination of a novel odorant decay with delay time and that rats can remember an odorant for up to 45min after a single trial encoding event. The number of odorants that can be encoded, as well as the specificity of the encoded memory, decrease with increased delay and also depend on stimulus concentration. Memory for an odorant and discrimination of a novel odorant decay at approximately the same rate, whereas the specificity of the formed memory decays faster than the memory itself. These results have important implications for the interpretation of behavioral data obtained with this paradigm. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Age-associated changes in hearts of male Fischer 344/Brown Norway F1 rats.

    Science.gov (United States)

    Walker, Ernest M; Nillas, Michael S; Mangiarua, Elsa I; Cansino, Sylvestre; Morrison, Ryan G; Perdue, Romaine R; Triest, William E; Wright, Gary L; Studeny, Mark; Wehner, Paulette; Rice, Kevin M; Blough, Eric R

    2006-01-01

    Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other recordings from parasternal long- and short-axis views were obtained using a Phillips 5500 ECHO system with a 12 megahertz transducer. Hearts and aortas from sacrificed rats were evaluated grossly and microscopically. The ECHO studies revealed persistent cardiac arrhythmias (chiefly PVCs) in 72% (13/18) of 36-mo rats, 10% (1/10) of 30-mo rats, and none in 6-mo rats (0/16). Gross and microscopic studies showed left ventricular (LV) dilatation, borderline to mild hypertrophy, and areas of fibrosis that were common in 36-mo rats, less evident in 30-mo rats, and absent in 6-mo rats. Aging was associated with mild to moderate decreases of LV diastolic and systolic function. Thus, male F344/BN F1 rats demonstrated progressive age-related (a) decline in cardiac function (diastolic and systolic indices), (b) LV structural changes (chamber dimensions, volumes, and wall thicknesses), and (c) persistent arrhythmias. These changes are consistent with those in humans. The noninvasive ECHO technique offers a means to monitor serial age-related cardiac failure and therapeutic responses in the same rats over designated time intervals.

  1. Heart rate and blood pressure during initial LBNP do not discriminate higher and lower orthostatic tolerant men

    DEFF Research Database (Denmark)

    Simonson, Shawn R; Norsk, Peter; Greenleaf, John E

    2003-01-01

    High (n = 7, 25 +/- 2 yr) and low (n = 8, 26 +/- 3 yr) lower body negative pressure (LBNP) tolerant men were exposed to -15 mmHg (for 12 min) followed by -50 mmHg (for 21 min) to test the hypothesis that heart rate (HR) and blood pressure (BP) data from acute exposure to LBNP would not discriminate...... groups. Diastolic blood pressure changed by +7.6 % (NS) in the high group and by -3.3% (NS) in the low group; the initial exposure to -50 mmHg resulted in a significant difference between groups for the first 45 s. Central venous pressure decreased significantly at -15 mmHg (high group by -33%, low group...... between the higher and lower tolerance men. Central venous pressure (CVP), HR, and systolic (SBP) and diastolic (DBP) blood pressures measured before and at 15-s intervals during LBNP and calculated mean arterial pressure (MAP), pulse pressure (PP), and work of the heart (HW) were analyzed using ANOVA (p...

  2. EVOLUTION OF NEUROENDOCRINE CELL POPULATION AND PEPTIDERGIC INNERVATION, ASSESSED BY DISCRIMINANT ANALYSIS, DURING POSTNATAL DEVELOPMENT OF THE RAT PROSTATE

    Directory of Open Access Journals (Sweden)

    Rosario Rodríguez

    2011-05-01

    Full Text Available Serotonin immunoreactive neuroendocrine cells and peptidergic nerves (NPY and VIP could have a role in prostate growth and function. In the present study, rats grouped by stages of postnatal development (prepubertal, pubertal, young and aged adults were employed in order to ascertain whether age causes changes in the number of serotoninergic neuroendocrine cells and the length of NPY and VIP fibres. Discriminant analysis was performed in order to ascertain the classificatory power of stereologic variables (absolute and relative measurements of cell number and fibre length on age groups. The following conclusions were drawn: a discriminant analysis confirms the androgen-dependence of both neuroendocrine cells and NPYVIP innervation during the postnatal development of the rat prostate; b periglandular innervation has more relevance than interglandular innervation in classifying the rats in age groups; and c peptidergic nerves from ventral, ampullar and periductal regions were more age-dependent than nerves from the dorso-lateral region.

  3. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    Directory of Open Access Journals (Sweden)

    Sajad Jeddi

    2015-02-01

    Full Text Available Background: Ischemic postconditioning (IPost is a method of protecting the heart against ischemia-reperfusion (IR injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. Objective: The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Methods: Propylthiouracil in drinking water (500 mg/L was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Results: Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP and peak rates of positive and negative changes in left ventricular pressure (±dp/dt during reperfusion in control rats (p < 0.05. However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NOx levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05 and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05. Heart NOx concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05 higher and lower after IR and IPost, respectively, in the control groups. Conclusion: Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

  4. Effects of Ischemic Postconditioning on the Hemodynamic Parameters and Heart Nitric Oxide Levels of Hypothyroid Rats

    Energy Technology Data Exchange (ETDEWEB)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar, E-mail: ghasemi@endocrine.ac.ir [Endocrine Physiology Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Endocrine Research Center - Research Institute for Endocrine Sciences - Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2015-02-15

    Ischemic postconditioning (IPost) is a method of protecting the heart against ischemia-reperfusion (IR) injury. However, the effectiveness of IPost in cases of ischemic heart disease accompanied by co-morbidities such as hypothyroidism remains unclear. The aim of this study was to determine the effect of IPost on myocardial IR injury in hypothyroid male rats. Propylthiouracil in drinking water (500 mg/L) was administered to male rats for 21 days to induce hypothyroidism. The hearts from control and hypothyroid rats were perfused in a Langendorff apparatus and exposed to 30 min of global ischemia, followed by 120 min of reperfusion. IPost was induced immediately following ischemia. Hypothyroidism and IPost significantly improved the left ventricular developed pressure (LVDP) and peak rates of positive and negative changes in left ventricular pressure (±dp/dt) during reperfusion in control rats (p < 0.05). However, IPost had no add-on effect on the recovery of LVDP and ±dp/dt in hypothyroid rats. Furthermore, hypothyroidism significantly decreased the basal NO metabolite (NO{sub x}) levels of the serum (72.5 ± 4.2 vs. 102.8 ± 3.7 μmol/L; p < 0.05) and heart (7.9 ± 1.6 vs. 18.8 ± 3.2 μmol/L; p < 0.05). Heart NO{sub x} concentration in the hypothyroid groups did not change after IR and IPost, whereas these were significantly (p < 0.05) higher and lower after IR and IPost, respectively, in the control groups. Hypothyroidism protects the heart from IR injury, which may be due to a decrease in basal nitric oxide (NO) levels in the serum and heart and a decrease in NO after IR. IPost did not decrease the NO level and did not provide further cardioprotection in the hypothyroid group.

  5. Treatment with alpha-melanocyte stimulating hormone preserves calcium regulatory proteins in rat heart allografts.

    Science.gov (United States)

    Colombo, Gualtiero; Sordi, Andrea; Lonati, Caterina; Carlin, Andrea; Turcatti, Flavia; Leonardi, Patrizia; Gatti, Stefano; Catania, Anna

    2008-08-01

    Prevention of graft dysfunction is a major objective in transplantation medicine. Previous research on experimental heart transplantation indicated that treatment with the immunomodulatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) improves histopathology, prolongs allograft survival, and reduces expression of the main tissue injury mediators. Because calcium-handling is critical in heart graft function, we determined the effects of transplantation injury and influences of alpha-MSH treatment on representative calcium regulatory proteins in rat heart allografts. Hearts from Brown Norway rats were transplanted heterotopically into MHC incompatible Lewis rats. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), protein kinase C epsilon (PKC epsilon), sarcoplasmic/endoplasmic reticulum calcium-ATPase 2 (SERCA2a), arrestin-beta1 (Arrb1), cholinergic receptor M2 (Chrm2), and inositol 1,4,5-triphosphate receptor 1 (InsP(3)R1) were examined in: (1) non-transplanted donor hearts; (2) allografts from saline-treated rats; and (3) allografts from rats treated with the synthetic alpha-MSH analog Nle4-DPhe7-alpha-MSH (NDP-alpha-MSH) (100 microg i.p. every 12h). Transplantation injury was associated with severe reduction in calcium regulatory protein transcription and expression level. NDP-alpha-MSH administration partly reversed inhibition of protein transcription and almost completely prevented protein loss. Finally, because certain effects of cyclic 3'-5'-adenosine monophosphate (cAMP) signaling on calcium handling in cardiac myocytes depend on activation of exchange protein directly activated by cAMP 1 (Epac1), we determined Epac1 mRNA and protein expression in heart allografts. Transplantation injury markedly reduced Epac1. NDP-alpha-MSH treatment significantly preserved both Epac1 protein and mRNA in the allografts. Administration of alpha-MSH or related melanocortins could reduce transplantation-induced dysfunction through protection of heart calcium

  6. Improved Discriminability of Spatiotemporal Neural Patterns in Rat Motor Cortical Areas as Directional Choice Learning Progresses

    Directory of Open Access Journals (Sweden)

    Hongwei eMao

    2015-03-01

    Full Text Available Animals learn to choose a proper action among alternatives to improve their odds of success in food foraging and other activities critical for survival. Through trial-and-error, they learn correct associations between their choices and external stimuli. While a neural network that underlies such learning process has been identified at a high level, it is still unclear how individual neurons and a neural ensemble adapt as learning progresses. In this study, we monitored the activity of single units in the rat medial and lateral agranular (AGm and AGl, respectively areas as rats learned to make a left or right side lever press in response to a left or right side light cue. We noticed that rat movement parameters during the performance of the directional choice task quickly became stereotyped during the first 2-3 days or sessions. But learning the directional choice problem took weeks to occur. Accompanying rats’ behavioral performance adaptation, we observed neural modulation by directional choice in recorded single units. Our analysis shows that ensemble mean firing rates in the cue-on period did not change significantly as learning progressed, and the ensemble mean rate difference between left and right side choices did not show a clear trend of change either. However, the spatiotemporal firing patterns of the neural ensemble exhibited improved discriminability between the two directional choices through learning. These results suggest a spatiotemporal neural coding scheme in a motor cortical neural ensemble that may be responsible for and contributing to learning the directional choice task.

  7. Uptake of /sup 67/Ga in the heart of rats treated with isoproterenol

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, T.; Kojima, S.; Kubodera, A.

    1982-12-01

    Gallium-67 citrate (/sup 67/Ga) accumulation and various enzyme activities during the repair of rat heart with infarct-like lesions induced by isoproterenol (ISP) treatment were measured for 10 days after treatment. Serum creatine phosphokinase (CPK) and glutamic oxalacetic transaminase (GOT) activities were increased immediately after ISP treatment, reaching maximum levels of activity of 545+-64 U/ml and 542+-94 KU/ml, respectively, within 12 h. Uptake of /sup 67/Ga in the rat heart was elevated 12 h after ISP treatment, reaching a maximum on day 1 (0.267+-0.020% dose/g heart). This pattern was essentially similar to the pattern of uronic acid content in the 1.2 M NaCl fraction, which contained mainly heparan sulfate (HS). The activity of glucose-6-phosphate dehydrogenase (G-6-PDH), a marker enzyme for fibrogenesis of damaged tissues, was also elevated 12 h after the ISP treatment, reaching a maximum of approximately 2.47 times that of the control heart on day 1. On the other hand, there were no significant changes in the /sup 67/Ga uptake and uronic acid content in any of the fractions of the liver and kidneys. These findings suggested that HS might be an acceptor for /sup 67/Ga accumulation during the repair of rat heart with infarct-like lesions, in accord with our previous results on CCl/sub 4/-damaged rat liver.

  8. Behavior of silica particles introduced into an isolated rat heart as potential drug carriers

    Energy Technology Data Exchange (ETDEWEB)

    Borak, B [Institute of Material Sciences and Applied Mechanics, Wroclaw University of Technology, Smoluchowskiego 25, 50-370 Wroclaw (Poland); Arkowski, J [Chair and Department of Cardiology, Medical University of Wroclaw, Pasteura 4, 50-367 Wroclaw (Poland); Skrzypiec, M [Chair and Department of Pharmacology, Medical University of Wroclaw, Mikulicza-Radeckiego 2, 50-345 Wroclaw (Poland); Ziolkowski, P [Chair and Department of Patomorphology, Medical University of Wroclaw, Marcinkowskiego 1, 50-368 Wroclaw (Poland); Krajewska, B [Chair and Department of Histology, Medical University of Wroclaw, Chalubinskiego 6a, 50-369 Wroclaw (Poland); Wawrzynska, M [Chair and Department of Cardiology, Medical University of Wroclaw, Pasteura 4, 50-367 Wroclaw (Poland); Grotthus, B [Chair and Department of Pharmacology, Medical University of Wroclaw, Mikulicza-Radeckiego 2, 50-345 Wroclaw (Poland); Gliniak, H [Chair and Department of Pharmacology, Medical University of Wroclaw, Mikulicza-Radeckiego 2, 50-345 Wroclaw (Poland); Szelag, A [Chair and Department of Pharmacology, Medical University of Wroclaw, Mikulicza-Radeckiego 2, 50-345 Wroclaw (Poland); Mazurek, W [Chair and Department of Cardiology, Medical University of Wroclaw, Pasteura 4, 50-367 Wroclaw (Poland); Bialy, D [Chair and Department of Cardiology, Medical University of Wroclaw, Pasteura 4, 50-367 Wroclaw (Poland); Maruszewski, K [Institute of Material Sciences and Applied Mechanics, Wroclaw University of Technology, Smoluchowskiego 25, 50-370 Wroclaw (Poland)

    2007-12-15

    Silica powders consisting of small spherical particles (50-200 nm) have been obtained by the sol-gel method. A suspension of such particles in the Krebs-Hanseleit solution has been introduced into the coronary circulation of a beating perfused rat heart. The influence of the suspension on the heart muscle and the coronary vessels in the rat body has been histopathologically examined. The particles have not left the lumen of the vessels and have not caused any side effects. These observations suggest the possibility of using such silica particles as a carrier for selected drugs.

  9. Changes in oxidative status of the heart in rats receiving vitamin C supplements

    Directory of Open Access Journals (Sweden)

    Đurašević S.F.

    2007-01-01

    Full Text Available We studied the oxidative status of the heart in rats receiving by two doses of vitamin C over a period of four weeks. The activities of copper zinc superoxide dismutase (CuZnSOD, manganese superoxide dismutase (MnSOD, and catalase, hydrogen peroxide concentration, the level of lipid peroxidation, and total vitamin C content were determined in the heart of the experimental animals, as well as the concentration of vitamin C in their serum. Our results indicate that, apart from the ability of rats to synthesize vitamin C, supplementation leads to additional antioxidative protection.

  10. Metabolic adaptations of skeletal muscle to voluntary wheel running exercise in hypertensive heart failure rats

    DEFF Research Database (Denmark)

    Schultz, R L; Kullman, E L; Waters, Ryan

    2013-01-01

    The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female...... SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function...... and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (Pmuscle citrate synthase and beta-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group...

  11. Effect of acute nitric oxide synthase inhibition in the modulation of heart rate in rats

    Directory of Open Access Journals (Sweden)

    A.L. Fellet

    2003-05-01

    Full Text Available Acute nitric oxide synthase inhibition with N G-nitro-L-arginine methyl ester (L-NAME on chronotropic and pressor responses was studied in anesthetized intact rats and rats submitted to partial and complete autonomic blockade. Blood pressure and heart rate were monitored intra-arterially. Intravenous L-NAME injection (7.5 mg/kg elicited the same hypertensive response in intact rats and in rats with partial (ganglionic and parasympathetic blockade and complete autonomic blockade (38 ± 3, 55 ± 6, 54 ± 5, 45 ± 5 mmHg, respectively; N = 9, P = NS. L-NAME-induced bradycardia at the time when blood pressure reached the peak plateau was similar in intact rats and in rats with partial autonomic blockade (43 ± 8, 38 ± 5, 46 ± 6 bpm, respectively; N = 9, P = NS. Rats with combined autonomic blockade showed a tachycardic response to L-NAME (10 ± 3 bpm, P<0.05 vs intact animals, N = 9. Increasing doses of L-NAME (5.0, 7.5 and 10 mg/kg, N = 9 caused a similar increase in blood pressure (45 ± 5, 38 ± 3, 44 ± 9 mmHg, respectively; P = NS and heart rate (31 ± 4, 34 ± 3, 35 ± 4 bpm, respectively; P = NS. Addition of L-NAME (500 µM to isolated atria from rats killed by cervical dislocation and rats previously subjected to complete autonomic blockade did not affect spontaneous beating or contractile strength (N = 9. In vivo results showed that L-NAME promoted a tachycardic response in rats with complete autonomic blockade, whereas the in vitro experiments showed no effect on intrinsic heart rate, suggesting that humoral mechanisms may be involved in the L-NAME-induced cardiac response.

  12. Cardioprotective Effects of Melatonin on Recovery of Rat Donor Hearts after 12-Hour Preservation

    Institute of Scientific and Technical Information of China (English)

    高思海; 李平; 潘铁成; 杨辰垣

    2003-01-01

    The cardioprotective effects of melatonin on recovery of rat donor hearts after 12 h of preservation were investigated. Wistar rats weighing 200 to 250 g (n= 24) were randomly divided into 3 groups. In the non-storage group (n= 8), donor hearts were not stored. In the melatonin group (n=8), donor hearts were stored in 4 ℃ St. Thomas solution with melatonin (0. 1 mmol/L). In the control group (n=8), donor hearts were stored in 4 C St. Thomas solution only. The coronary flow (CF), cardiac function, coronary vasodilatory response, creatine kinase (CK) and high energy phosphate levels were measured after the hearts had been preserved for 12 h. Transmission electron microscopy was used to examine the microstructural changes after 12 h of preservation. The recovery of cardiac function and coronary vasodilatory response were significantly improved in the melatonin group (P<0.01). CK release decreased greatly in the melatonin group (P<0.01). High energy phosphate levels were significantly better preserved in the melatonin group (P<0. 01). Histological findings were much better in the melatonin group than in the control group. These results suggest that melatonin has cardioprotective effects on the recovery of rat donor hearts after 12 h of preservation.

  13. Solubilized musarinic recognition sites from rat brain and heart: evidence in favor of a homogeneous population of sites

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.; Roeske, W.R.; Yamamura, H.I.

    1986-03-01

    The binding characteristics of muscarinic receptors (MAChR) from rat brain and heart (membrane (m-) and 0.5% digitonin solubilized (s-)) were studied at 4/sup 0/C. (/sup 3/H)(-)QNB possessed the same affinity to both m- and s-MAChR (Kd = 20 pM). Pirenzepine (PZ) discriminated two affinities for brain m-MAChR and revealed a single low affinity in heart m-MAChR. S-MAChR from brain and heart displayed similar affinities for PZ ( Ki = 10 and 15 nM). High affinity (/sup 3/H)PZ binding was also found for s-MAChR from both tissues. The receptor affinity for carbachol (CARB) was decreased after solubilization. There was a decrease in the proportion of high affinity state (from 40% to 20% in the brain and from 60% to 15% in the heart) with a 4-fold decrease in the high affinity Ki for CARB. Gpp(NH)p no longer had an effect on the CARB/(/sup 3/H)(-)QNB competition in s-MAChR. Increasing the temperature to 37/sup 0/C caused a 3-6 fold decrease in PZ's affinity to both m- and s-MAChR without altering the ratio of high/low affinity sites. The reduction of PZ's affinity was completely reversible with temperature in m-MAChR and partially reversible in s-MAChR. The authors results suggests that a homogeneous muscarinic recognition site has been solubilized. Solubilization with digitonin results in a separation of the binding site from effector systems and membrane constituents responsible for the tissue specific receptor heterogeneity.

  14. Discrimination between Healthy and Sick Cardiac Autonomic Nervous System by Detrended Heart Rate Variability Analysis

    CERN Document Server

    Ashkenazy, Yu; Levitan, J; Havlin, S; Saermark, K; Moelgaard, H; Bloch-Thomsen, P E

    1998-01-01

    Multiresolution Wavelet Transform and Detrended Fluctuation Analysis have been recently proven as excellent methods in the analysis of Heart Rate Variability, and in distinguishing between healthy subjects and patients with various dysfunctions of the cardiac nervous system. We argue that it is possible to obtain a distinction between healthy subjects/patients of at least similar quality by, first, detrending the time-series of RR-intervals by subtracting a running average based on a local window with a length of around 32 data points, and then, calculating the standard deviation of the detrended time-series. The results presented here indicate that the analysis can be based on very short time-series of RR-data (7-8 minutes), which is a considerable improvement relative to 24-hours Holter recordings.

  15. Effect of low thyroid function on cardiac structure and function in spontaneously hypertensive heart failure rats.

    Science.gov (United States)

    Kisso, Bassel; Patel, Ankit; Redetzke, Rebecca; Gerdes, A Martin

    2008-03-01

    Although low thyroid function is known to have detrimental effects on the cardiovascular system, including microvascular impairment, little is known about the pathophysiologic consequences of hypothyroidism in the background of hypertension. Hypothyroidism was induced in female spontaneously hypertensive heart failure (SHHF) rats by treatment with propylthiouracil (PTU) for 6 months. Untreated SHHF and normotensive Wistar Furth (WF) rats served as controls. In terminal experiments, heart weight, echocardiographic measurements, hemodynamics, and arteriolar morphometry were performed. Left ventricular internal diameter in systole and diastole were increased and wall thickness, ejection fraction, heart rate, systolic blood pressure, and +/-dP/dt were significantly decreased in the treatment group. Surprisingly, there were no observed differences in arteriolar density among the 3 groups. As expected, PTU treatment of SHHF rats led to systolic dysfunction and chamber dilation. However, PTU treatment did not lead to arteriolar loss as previously observed in normotensive rats treated with PTU. These finding suggest that induced hypothyroidism leads to detrimental changes in SHHF rats, but the overall effects were no worse than those previously observed in normotensive rats treated with PTU.

  16. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Taghi Razavi Tousi

    2016-11-01

    Full Text Available Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs in rats with heart failure (HF.Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each as 1- Control 2- Heart Failure (HF 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT. Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×106 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done.Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001. Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001. Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001 compared with the animals in the HF group.Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

  17. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    Science.gov (United States)

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

  18. Cardiotoxic effects of the Vipera ammodytes ammodytes venom fractions in the isolated perfused rat heart.

    Science.gov (United States)

    Karabuva, Svjetlana; Brizić, Ivica; Latinović, Zorica; Leonardi, Adrijana; Križaj, Igor; Lukšić, Boris

    2016-10-01

    The nose-horned viper (Vipera ammodytes ammodytes) is the most venomous European snake. Its venom is known as haematotoxic, myotoxic and neurotoxic but it exerts also cardiotoxic effects. To further explore the cardiotoxicity of the venom we separated it into four fractions by gel filtration chromatography. Three fractions that contain polypeptides (A, B, and C) were tested for their effects on isolated rat heart. Heart rate (HR), incidence of arrhythmias (atrioventricular (AV) blocks, ventricular tachycardia, ventricular fibrillation, and asystolia), coronary flow (CF), systolic, developed and diastolic left ventricular pressure (LVP) were measured before, during, and after the application of venom fractions in three different concentrations. Fraction A, containing proteins of 60-100 kDa, displayed no effect on the rat heart. Fractions B and C disturbed heart functioning in similar way, but with different potency that was higher by the latter. This was manifested by significant decrease of HR and CF, the increase of diastolic, and the decrease of systolic and developed LVPs. All hearts treated with fraction C in the final CF concentrations 22.5 and 37.5 μg/mL suffered rapid and irreversible asystolia without AV blockade. They underwent also ventricular fibrillation and ventricular tachycardia. Fraction B affected hearts only at the highest dose inducing asystolia in all hearts, ventricular fibrillation in 80% and ventricular tachycardia in 70% of the hearts. Venom fraction C induced 71% of all recorded heart rhythm disturbances, significantly more than fraction B, which induced 29%. Most abundant proteins in fraction C were secreted phospholipases A2 among which the venom component acting on the heart is most probably to be looked for. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Multiscale entropy analysis of heart rate variability in heart failure, hypertensive, and sinoaortic-denervated rats: classical and refined approaches.

    Science.gov (United States)

    Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; da Silva, Carlos Alberto Aguiar; Valencia, Jose Fernando; Murta, Luiz Otavio; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto

    2016-07-01

    The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation.

  20. Chemical sympathectomy restores baroreceptor-heart rate reflex and heart rate variability in rats with chronic nitric oxide deficiency.

    Science.gov (United States)

    Chaswal, M; Das, S; Prasad, J; Katyal, A; Fahim, M

    2015-01-01

    Nitric oxide (NO) plays a crucial role not only in regulation of blood pressure but also in maintenance of cardiac autonomic tone and its deficiency induced hypertension is accompanied by cardiac autonomic dysfunction. However, underlying mechanisms are not clearly defined. We hypothesized that sympathetic activation mediates hemodynamic and cardiac autonomic changes consequent to deficient NO synthesis. We used chemical sympathectomy by 6-hydroxydopamine to examine the influence of sympathetic innervation on baroreflex sensitivity (BRS) and heart rate variability (HRV) of chronic N(G)-nitro-L-arginine methyl ester (L-NAME) treated adult Wistar rats. BRS was determined from heart rate responses to changes in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. Time and frequency domain measures of HRV were calculated from 5-min electrocardiogram recordings. Chronic L-NAME administration (50 mg/kg per day for 7 days orally through gavage) in control rats produced significant elevation of blood pressure, tachycardia, attenuation of BRS for bradycardia and tachycardia reflex and fall in time as well as frequency domain parameters of HRV. Sympathectomy completely abolished the pressor as well as tachycardic effect of chronic L-NAME. In addition, BRS and HRV improved after removal of sympathetic influence in chronic L-NAME treated rats. These results support the concept that an exaggerated sympathetic activity is the principal mechanism of chronic L-NAME hypertension and associated autonomic dysfunction.

  1. Effects of the nicotinic receptor partial agonists varenicline and cytisine on the discriminative stimulus effects of nicotine in rats.

    Science.gov (United States)

    LeSage, Mark G; Shelley, David; Ross, Jason T; Carroll, F Ivy; Corrigall, William A

    2009-01-01

    The nicotinic partial agonist varenicline (VCL) is a recently approved medication for the treatment of tobacco dependence, yet very little preclinical research on this drug has been published. The present experiment examined the nicotinic partial agonist properties of VCL and its parent compound, cytisine (CYT), in a nicotine discrimination assay. Rats were trained to discriminate nicotine (0.4 mg/kg, s.c.) from saline using a two-lever discrimination procedure, followed by generalization and antagonism tests with VCL and CYT. Antagonism was examined across a range of nicotine doses. In generalization tests, VCL produced a maximum of 63% responding on the nicotine-appropriate lever, indicating partial generalization. In antagonism tests, VCL decreased the % responding on the nicotine-appropriate lever at 0.2 and 0.4 mg/kg nicotine, indicating antagonism of nicotine's discriminative stimulus effects. No dose of VCL produced significant effects on response rate. The two highest doses of CYT weakly substituted for nicotine, producing a maximum of 23% nicotine-appropriate responding. CYT produced a weak antagonism of the discrimination of moderate nicotine doses, but not of the training dose. These results demonstrate that VCL and CYT partially generalize to and partially antagonize nicotine's discriminative stimulus effects, consistent with a partial agonist mechanism of action.

  2. Expressions of Estrogen Receptorαand β in the Development and Maturation of Rat Heart

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionPhysiological effects of estrogen on myocardium are mediated by two intracellular estrogen receptors (ER), alpha (ERα) and beta (ERβ). Their role in cardiovascular physiology is not well understood. For this reason,we investigated the expressions of ERα and ERβ in the development and maturation of rat heart.2 Materials and Methods2.1 Experimental animals The study on changes of ERs was performed in six newborn rats with both sexes and six adult female Wistar rats respedively.2.2 Semiquantitati...

  3. Myocardial {sup 99m}Tc-sestamibi extraction and washout in hypertensive heart failure using an isolated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Fukushima, Kenji [Department of Cardiology, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Department of Radiology, Johns Hopkins University, Baltimore, MD (United States); Momose, Mitsuru, E-mail: mmomose@rad.twmu.ac.j [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Kondo, Chisato [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Higuchi, Takahiro [Department of Radiology, Johns Hopkins University, Baltimore, MD (United States); Kusakabe, Kiyoko [Department of Diagnostic Imaging and Nuclear Medicine, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan); Hagiwara, Nobuhisa [Department of Cardiology, Tokyo Women' s Medical University, Tokyo 162-8666 (Japan)

    2010-11-15

    Purpose: Myocardial mitochondria are the primary part of energy production for healthy cardiac contraction. And mitochondrial dysfunction would play an important role in progressive heart failure. In the recent years, myocardial washout of {sup 99m}Tc-sestamibi [({sup 99m}Tc-hexakis-2-methoxy-2-methylpropyl isonitrile (MIBI)] has been introduced to be a potential marker in patients with heart failure. The objective of this study was to clarify MIBI extraction and washout kinetics using isolated perfusion system in hypertension induced model of myocardial dysfunction. Methods: Six-week-old Dahl-salt sensitive rats, allotted to 4 groups; a 5-week high-salt group (5wk-HS), 12-week high-salt group (12wk-HS) and two age-matched, low-salt diet control groups (5wk-LS and 12wk-LS). The rats in 5wk-HS and 12wk-HS groups were fed a high-salt diet (containing 8% NaCl). Cardiac function was examined by echocardiography before removing heart. Hearts were perfused according to the Langendorff method at a constant flow rate, in which 20-min MIBI washin was conducted followed by 25-min MIBI washout. Whole heart radioactivity was collected every sec by an external gamma detector. The myocardial extraction, K{sub 1} (ml/min) and washout rate, k{sub 2} (min{sup -1}) were generated. Results: High-salt diet groups showed significant high-blood pressure. Echocardiography revealed thickened LV walls in 5wk-HS, and reduced cardiac function in 12wk-HS, compared to each age-matched control group. K{sub 1} showed no significant difference among all groups (5wk-HS: 2.36{+-}1.07, 5wk-control: 2.59{+-}0.28, 12wk-HS: 1.91{+-}0.90, and 12wk-control: 2.84{+-}0.57). k{sub 2} in 5wk-HS was comparable to that in the age matched control group (0.00030{+-}0.00039 vs -0.000010{+-}0.00044), but it was increased remarkably in 18wk-HS compared to the age matched control group (0.0025{+-}0.0011 vs 0.000025{+-}0.000041, P<.01), and 5wk-HS (P<.01). Conclusion: In the course of hypertensive heart disease, MIBI

  4. Self-reported racial discrimination, response to unfair treatment, and coronary calcification in asymptomatic adults - the North Texas Healthy Heart study

    Directory of Open Access Journals (Sweden)

    Young Richard

    2010-05-01

    Full Text Available Abstract Background Accruing evidence supports the hypothesis that psychosocial factors are related to cardiovascular disease. However, a limited number of studies have investigated the pathophysiologic pathways through which these associations occur. The purpose of this study was to assess whether experiences of self-reported racial discrimination and reactions to unfair treatment were associated with coronary artery calcification (CAC, an indicator of subclinical coronary heart disease (CHD. Methods This cross-sectional study recruited 571 subjects (45 years and older who were asymptomatic of CHD from Fort Worth, Texas from 2006 to 2008. Subjects completed a questionnaire, a multi-slice computed tomography scan to assess for CAC presence (measured as Agatston score >0, and serum chemistries. Logistic regression was used to estimate odds ratios (ORs and 95% confidence intervals (CIs for the association between self-reported discrimination and CAC. Results were stratified by response to unfair treatment as it was found to significantly modify the relationship between discrimination and CAC. Results Among those who passively responded to unfair treatment, the odds of having CAC present were approximately 3 times higher for those experiencing discrimination (OR, 2.95; 95% CI, 1.19-7.32 after adjusting for age, gender, race/ethnicity, education, body mass index, hyperlipidemia, smoking status, hypertension, diabetes, and first degree relative with heart disease. Conclusions This is the first multi-racial/ethnic study to find racial discrimination associated with CAC, which differs based on how one responds to unfair treatment.

  5. Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI.

    Science.gov (United States)

    Marona-Lewicka, Danuta; Chemel, Benjamin R; Nichols, David E

    2009-04-01

    Lysergic acid diethylamide (LSD) differs from other types of hallucinogens in that it possesses direct dopaminergic effects. The exact nature of this component has not been elucidated. The present study sought to characterize the effects of several dopamine D(4) agonists and antagonists on the discriminative stimulus effect of LSD at two pretreatment times and 2,5-dimethoxy-4-iodoamphetamine (DOI), a selective 5-HT(2A/2C) agonist. Male Sprague-Dawley rats were trained in a two-lever, fixed ratio (FR) 50, food-reinforced task with LSD-30 (0.08 mg/kg, i.p., 30-min pretreatment time), LSD-90 (0.16 mg/kg, i.p., 90-min pretreatment time), and DOI (0.4 mg/kg, i.p., 30-min pretreatment time) as discriminative stimuli. Substitution and combination tests with the dopamine D(4) agonists, ABT-724 and WAY 100635, were performed in all groups. Combination tests were run using the dopamine D(4) antagonists A-381393 and L-745,870 and two antipsychotic drugs, clozapine and olanzapine. WAY 100635 produced full substitution in LSD-90 rats, partial substitution in LSD-30 rats, and saline appropriate responding in DOI-trained rats. ABT-724 partially mimicked the LSD-90 and LSD-30 cues, but produced no substitution in DOI-trained rats. In combination tests, both agonists shifted the dose-response curve of LSD leftward, most potently for the LSD-90 cue. The D(4) antagonists significantly attenuated both the LSD-90 and LSD-30 cue, but had no effect on the DOI cue. Dopamine D(4) receptor activation plays a significant modulatory role in the discriminative stimulus effects in LSD-90-trained rats, most markedly for the later temporal phase of LSD, but has no effect on the cue produced by DOI.

  6. Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Berry, C.R.; Garg, P.K.; Zalutsky, M.R. [North Carolina State Univ., Raleigh, NC (United States)]|[Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1996-12-01

    Para-[{sup 18}F]fluorobenzylguanidine ([{sup 18}F]PFBG) is a newly developed tracer for imaging myocardial sympathetic neuronal innervation. This study investigated the uptake and retention mechanisms of [{sup 18}F]PFBG in perfused, isolated rat heart. 31 refs., 3 figs., 2 tabs.

  7. Myocardial infarction with aortic banding - A combined rat model of heart failure

    NARCIS (Netherlands)

    Anthonio, RL; vanVeldhuisen, DJ; vanBekkum, C; deBoer, E; vanGilst, WH

    1997-01-01

    The effect of additional abdominal aortic banding on parameters of heart failure was studied in male Wistar rats with myocardial infarction. Contractile function was studied 8-9 weeks after operation, with an isoprenaline dose response protocol, in a retrograde Langendorff perfusion. Also, plasma no

  8. EFFECT OF MULTIGLYCOSIDES OF TRIPTERYGIUM WILFORDH (GTW) ON RAT TESTIS, HEART, LIVER AND KIDNEY

    Institute of Scientific and Technical Information of China (English)

    ZHOULan-Fang; LEIHai-Peng

    1989-01-01

    Adult male Wistar rats were given GTW orally at 50 rag/kg or 20 mg / kg for 4 or 5 weeks. Control animals were given the vehicle only. ARer treatment, testis, heart, liver and kidney were removed and examined. The scminiferous tubules of the treated

  9. Hydrogen ion changes and contractile behavior in the perfused rat heart

    NARCIS (Netherlands)

    Cingolani, H.E.; Maas, A.H.J.; Zimmerman, A.N.E.; Meijler, F.L.

    1975-01-01

    The effect of acid-base alterations was analyzed using isolated rat hearts perfused at constant coronary perfusion pressure, and stimulated to contract at constant rate. The amount of shortening in the major axis and its derivative were measured to assess myocardial contractility. Both the 'respirat

  10. Myocardial infarction with aortic banding - A combined rat model of heart failure

    NARCIS (Netherlands)

    Anthonio, RL; vanVeldhuisen, DJ; vanBekkum, C; deBoer, E; vanGilst, WH

    The effect of additional abdominal aortic banding on parameters of heart failure was studied in male Wistar rats with myocardial infarction. Contractile function was studied 8-9 weeks after operation, with an isoprenaline dose response protocol, in a retrograde Langendorff perfusion. Also, plasma

  11. Depression of the inotropic action of isoprenaline by nitric oxide synthase induction in rat isolated hearts

    NARCIS (Netherlands)

    Wei, S; Szabo, C; Dusting, GJ

    1997-01-01

    The mechanisms involved in myocardial dysfunction during septic shock are not well understood. We have investigated the effects of endotoxin and the role of nitric oxide (NO) in the P-adrenoceptor responsiveness of rat isolated, ejecting hearts perfused at 60 mmHg of head pressure. In vivo pretreatm

  12. Copper Transporter 2 Content Is Lower in Liver and Heart of Copper-Deficient Rats

    Directory of Open Access Journals (Sweden)

    Jesse Bertinato

    2010-11-01

    Full Text Available Copper (Cu transporter 2 (Ctr2 is a transmembrane protein that transports Cu across cell membranes and increases cytosolic Cu levels. Experiments using cell lines have suggested that Ctr2 expression is regulated by Cu status. The importance of changes in Ctr2 expression is underscored by recent studies demonstrating that lower Ctr2 content in cells increases the cellular uptake of platinum-containing cancer drugs and toxicity to the drugs. In this study, we examined whether Ctr2 expression is altered by a nutritional Cu deficiency in vivo. Ctr2 mRNA and protein in liver and heart from rats fed a normal (Cu-N, moderately deficient (Cu-M or deficient (Cu-D Cu diet was measured. Rats fed the Cu-deficient diets showed a dose-dependent decrease in liver Ctr2 protein compared to Cu-N rats. Ctr2 protein was 42% and 85% lower in Cu-M and Cu-D rats, respectively. Liver Ctr2 mRNA was 50% lower in Cu-D rats and unaffected in Cu-M rats. In heart, Ctr2 protein was only lower in Cu-D rats (46% lower. These data show that Cu deficiency decreases Ctr2 content in vivo.

  13. Alterations of cardiac and lymphocyte β-adrenoceptors in rat with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    张萍; 韩启德; 张幼怡; 许开明; 田斌; 吕志珍; 郭静萱; 陈明哲

    1997-01-01

    The alterations of cardiac and lymphocyte β-adrenoceptors were observed in the rats with chronic heart failure produced by constriction of both abdominal aorta and renal artery. The results showed that β1-adrenocep-tor density and mRNA levels were increased, whereas these levels remained unchanged for β2 The concentration-contractile response curve for isoproterenol was shifted to the right in cardiac atrium, whereas the concentration-cAMP accumulation response curve for isoproterenol in myocardium was not changed. The number of β-adrenoceptors in blood lymphocyte was markedly reduced. Thus in the heart-failure rats the density of cardiac β-adrenoceptor was increased accompanying reduced β-adrenoceptor-mediated positive inotropic response, suggesting a post adenylate cyclase dys-function or impaired contractile components. In contrast, the alteration of β-adrenoceptor in lymphocyte is consistent with the reduced β-adrenoceptor-mediated inotropic response in heart.

  14. Effects of rapeseed oil on fatty acid oxidation and lipid levels in rat heart and liver.

    Science.gov (United States)

    Kienle, M G; Cighetti, G; Spagnuolo, C; Galli, C

    1976-09-01

    The comparative rates of oxidation of erucic and oleic acids and of their CoA esters were studied in heart and liver mitochondria of rats fed a standard diet or semisynthetic diets containing 25% of the calories as either rapeseed oil (46.6% erucic and 10.4% eicosenoic acid) or olive oil, for a period of 5 months. The long exposure to the diet containing 25% rapeseed oil did not alter the oxidative activity of mitochondria and did not induce morphological changes in the heart. It is confirmed that erucic acid is oxidized in mitochondria at lower rates than other long chain fatty acids and that its activation as CoA derivative may be one of the rate limiting steps of the overall oxidationprocess. Total lipids and triglycerides do not significantly change in the heart whereas they increase in the liver of rats fed the diet containing rapeseed oil.

  15. Exercise training upregulates nitric oxide synthases in the kidney of rats with chronic heart failure.

    Science.gov (United States)

    Ito, Daisuke; Ito, Osamu; Mori, Nobuyoshi; Cao, Pengyu; Suda, Chihiro; Muroya, Yoshikazu; Hao, Kiyotaka; Shimokawa, Hiroaki; Kohzuki, Masahiro

    2013-09-01

    There is an interaction between heart and kidney diseases, which is a condition termed cardiorenal syndrome. Exercise training has cardioprotective effects, involving upregulation of endothelial (e) nitric oxide synthase (NOS) in the cardiovascular system. However, the effects of exercise training on NOS in the kidney with heart disease are unknown. The aim of the present study was to investigate whether exercise training upregulates NOS in the kidney, left ventricle and aorta of rats with chronic heart failure (CHF). Male Sprague-Dawley rats underwent left coronary artery ligation (LCAL) to induce CHF and were randomly assigned to sedentary or treadmill exercise groups 4 weeks after LCAL. Three days after exercising for 4 weeks, urine samples were collected for 24 h and blood samples were collected following decapitation. Nitric oxide synthase activity and protein expression were examined. Significant interactions between CHF and exercise training were observed on parameters of cardiac and renal function. Exercise training improved cardiac function, decreased plasma B-type natriuretic peptide levels, decreased urinary albumin excretion and increased creatinine clearance in CHF rats. Nitric oxide synthase activity, eNOS expression and neuronal (n) NOS expression were significantly decreased in the left ventricle and kidney of CHF rats. Exercise training significantly increased NOS activity and eNOS and nNOS expression. Upregulation of NOS in the kidney and left ventricle may contribute, in part, to the renal and cardiac protective effects of exercise training in cardiorenal syndrome in CHF rats.

  16. Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications.

    Directory of Open Access Journals (Sweden)

    Maresha S Gay

    Full Text Available The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1, 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner.

  17. Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart.

    Science.gov (United States)

    Patrick, Casey B; McHowat, Jane; Rosenberger, Thad A; Rapoport, Stanley I; Murphy, Eric J

    2005-06-01

    Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 muCi/kg of either [1-(14)C]palmitic acid ([1-(14)C]16:0) or [1-(14)C]arachidonic acid ([1-(14)C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient lambda was increased in [1-(14)C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-(14)C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-(14)C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60-84%) and turnover value (56-85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A(2) activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A(2) activity.

  18. Testing declarative memory in laboratory rats and mice using the nonconditioned social discrimination procedure.

    Science.gov (United States)

    Engelmann, Mario; Hädicke, Jana; Noack, Julia

    2011-07-14

    Testing declarative memory in laboratory rodents can provide insights into the fundamental mechanisms underlying this type of learning and memory processing, and these insights are likely to be applicable to humans. Here we provide a detailed description of the social discrimination procedure used to investigate recognition memory in rats and mice, as established during the last 20 years in our laboratory. The test is based on the use of olfactory signals for social communication in rodents; this involves a direct encounter between conspecifics, during which the investigatory behavior of the experimental subject serves as an index for learning and memory performance. The procedure is inexpensive, fast and very reliable, but it requires well-trained human observers. We include recent modifications to the procedure that allow memory extinction to be investigated by retroactive and proactive interference, and that enable the dissociated analysis of the central nervous processing of the volatile fraction of an individual's olfactory signature. Depending on the memory retention interval under study (short-term memory, intermediate-term memory, long-term memory or long-lasting memory), the protocol takes ~10 min or up to several days to complete.

  19. Metabolic changes in rat serum after administration of suberoylanilide hydroxamic acid and discriminated by SVM.

    Science.gov (United States)

    Yu, J; Wu, H; Lin, Z; Su, K; Zhang, J; Sun, F; Wang, X; Wen, C; Cao, H; Hu, L

    2017-01-01

    Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg(-1) SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography-mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.

  20. Radiation-induced changes in the ultrastructure and mechanical function of the rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Cilliers, G.D. (Johannesburg Hospital and Witwatersrand University, Johannesburg (South Africa). Department of Radiotherapy); Harper, I.S. (MRC Research Institute for Medical Biophysics, Tygerberg (South Africa)); Lochner, A. (Stellenbosch University Medical School, Tygerberg (South Africa). MRC Centre for Molecular and Cellular Biology)

    1989-12-01

    A time sequence study was performed to study the early effects of radiation on the ultrastructure of the rat heart. Wistar rats were exposed to 20 Gy electron irradiation to a field including the heart and a third of the lung. The hearts were excised at varying time intervals (1 h-180 days), and the ultrastructure of perfusion-fixed subepicardium and subendocardium studied. Changes were observed in both myocytes and interstitium at all time intervals. The most pronounced change observed in the myocyte was that of intercalated disc damage which reached a peak at 30 days post-irradiation. Mitochondrial damage, characterized by swelling and fenstration in areas of myofibrillar contracture, was focal and relatively scarce. Swelling of the capillary endothelial cells and ollapse of the capillaries were marked up to 60 days. Of significance was the observation that the damage to both myocytes and interstitium receded after 60 days and the hearts exhibited an almost normal ultrastructure from 100 to 180 days post-irradiation. Mechanical function of these hearts followed a similar pattern: maximal depression was observed 60 days after irradiation. Thereafter the work performance of these hearts improved significantly, almost reaching control level after 180 days. (author). 34 refs.; 21 figs.; 1 tab.

  1. Estimation of Early Postmortem Interval Through Biochemical and Pathological Changes in Rat Heart and Kidney.

    Science.gov (United States)

    Abo El-Noor, Mona Mohamed; Elhosary, Naema Mahmoud; Khedr, Naglaa Fathi; El-Desouky, Kareema Ibraheem

    2016-03-01

    Accurate estimation of time passed since death is a complicated task in forensic medicine especially in homicide or unwitnessed death investigations. Changes in oxidant/antioxidant parameters were investigated if it can be relied upon in estimating the early postmortem interval (EPI) in rat heart and kidney, and whether these changes were correlated with histopathological findings in these tissues. Heart and kidney tissues of 84 male albino rats were divided into 2 parts. One part used for estimation of levels of malondialdehyde (MDA), nitric oxide (NO), and total thiol as well as the activity of glutathione reductase (GR), glutathione S transferase, and catalase. The second part was examined histopathologically. It was found that MDA and NO were significantly increased earlier in the heart than kidney tissues. Meanwhile, total thiol, catalase, glutathione S transferase, and GR were commenced to be significantly decreased in the heart before kidney tissues. Linear regression analysis of independent variables of heart was found to be of a high predictive value of 97.2% (EPI = 8.607 - 0.240 GR + 0.002 MDA + 0.014 NO). Structural deterioration of heart started 3 to 4 hours compared with renal sections that began 5 to 6 hours after death. The relationship between oxidant and antioxidant parameters is crucial in determining the EPI. The kidney was found to be more resistible to oxidative damage. Further research on humans is needed.

  2. Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

    Directory of Open Access Journals (Sweden)

    Guberski Dennis

    2008-10-01

    Full Text Available Abstract We investigated the role of polyol pathway enzymes aldose reductase (AR and sorbitol dehydrogenase (SDH in mediating injury due to ischemia-reperfusion (IR in Type 2 diabetic BBZ rat hearts. Specifically, we investigated, (a changes in glucose flux via cardiac AR and SDH as a function of diabetes duration, (b ischemic injury and function after IR, (c the effect of inhibition of AR or SDH on ischemic injury and function. Hearts isolated from BBZ rats, after 12 weeks or 48 weeks diabetes duration, and their non-diabetic littermates, were subjected to IR protocol. Myocardial function, substrate flux via AR and SDH, and tissue lactate:pyruvate (L/P ratio (a measure of cytosolic NADH/NAD+, and lactate dehydrogenase (LDH release (a marker of IR injury were measured. Zopolrestat, and CP-470,711 were used to inhibit AR and SDH, respectively. Myocardial sorbitol and fructose content, and associated changes in L/P ratios were significantly higher in BBZ rats compared to non-diabetics, and increased with disease duration. Induction of IR resulted in increased ischemic injury, reduced ATP levels, increases in L/P ratio, and poor cardiac function in BBZ rat hearts, while inhibition of AR or SDH attenuated these changes and protected hearts from IR injury. These data indicate that AR and SDH are key modulators of myocardial IR injury in BBZ rat hearts and that inhibition of polyol pathway could in principle be used as a therapeutic adjunct for protection of ischemic myocardium in Type 2 diabetic patients.

  3. Transient downregulation of glomerular atrial natriuretic factor receptors in high output heart failure in the rat.

    Science.gov (United States)

    Gauquelin, G; Bonhomme, M C; Garcia, R

    1995-03-01

    The renal response to exogenous atrial natriuretic factor (ANF) is blunted in chronic heart failure. The aim of the present studies was to investigate whether renal ANF receptor regulation in chronic heart failure is a time related event. Glomerular ANF receptors were analysed in radioligand binding experiments at 0, 1, 2, 6, 12, 24, and 48 h, as well as at 1, 2, 4, and 8 weeks after the induction of an aortocaval shunt. Rats with aortocaval shunts had lower packed cell volume and body weight and higher relative heart weight than sham operated controls. Plasma ANF C and N terminal levels were increased in shunt rats as early as 5 min after establishment of the shunt. Right and left atrial ANF concentrations were decreased and ventricular ANF concentration was increased in shunt rats at 6 and 12 h respectively. Competitive inhibition of 125I-ANF binding showed that at 6 h the density (Bmax) of glomerular ANF receptors was significantly lower than in the controls [518(SEM 10) v 759(12) fmol.mg-1 protein] without differences in their affinity (Kd). The low Bmax in shunt animals persisted at 12, 24, and 48 h, even at 1 week [Bmax: 400(29) and 713(28) fmol.mg-1 protein; Kd: 80(2) and 70(4) pM, for AC rats and controls, respectively]. Bmax values were not significantly different at 2, 4, and 8 weeks. In 24 h animals, C-ANF displaced 65% of total binding, with both total and C ANF binding sites being 38% lower in shunt animals. Downregulation of glomerular ANF receptors is a transient event during the development of high output heart failure in the rat. Thus the blunted renal response to ANF during chronic heart failure is not likely to be due to a decrease in renal ANF receptor density or affinity.

  4. Protective effect of the calcium antagonist nimodipine on discrimination learning deficits and impaired retention behavior caused by prenatal nitrite exposure in rats

    NARCIS (Netherlands)

    Nyakas, Csaba; Markel, Éva; Bohus, Béla; Schuurman, Teun; Luiten, Paulus

    1990-01-01

    Discrimination learning behavior and retention of a passive avoidance response were studied in male adult offspring of gestating rats exposed to drinking water containing 2 g/l sodium nitrite, throughout the second half of pregnancy. Both in an auditory and visual discrimination learning paradigm Na

  5. Increased expression of myocardial semaphorin 3A in isoproterenol-induced heart failure rats

    Institute of Scientific and Technical Information of China (English)

    SUN Shu-qin; WANG Xin-tao; QU Xiu-fen; LI Yang; YU Yang; SONG Ying; WANG Shao-jun

    2011-01-01

    Background Maintenance of normal cardiac function is controlled by the autonomic nervous system. In congestive heart failure (CHF), sympathetic nerve denervation is increasingly recognized. The sympathetic fiber density depends on the balance between neurotrophins and neural guidance molecules. Semaphorin 3A (sema3a), a secreted neural guidance factor, is a well characterized member of the newly found semaphorin family. It can induce sympathetic growth cone collapse and axon repulsion. We conducted this study to investigate cell sources of sema3a in the heart, the expression level of sema3a in CHF and discuss the possible role of sema3a in CHF.Methods Rats were divided into four groups: 30 days control group rats, 30 days CHF rats, 60 days control group rats,60 days CHF rats. The heart failure model was induced by injection of isoproterenol (ISO) 340 mg/kg continuously two days. All animals underwent echocardiography and haemodynamics measurements. Cardiac expression of sema3a was determined by real time polymerase chain reaction (RT-PCR) and Western blotting analysis. Immunohistochemical analysis was used to determine the cell source of sema3a in the heart.Results Isoproterenol induced 30 days and 60 days CHF rats displayed left ventricular dilation, systolic and diastolic function decrease. Sema3a was secreted by the cardiocytes and increased significantly in 30 days and 60 days CHF rats compared with the controls (RT-PCR: 30 days group: 0.32±0.05 vs. 0.58±0.06, P <0.01; 60 days group: 0.34±0.08 vs.0.71±0.07, P<0.01. Western blotting: 30 days group: 0.25±0.10 vs. 0.46±0.10, P<0.05; 60 days group: 0.29±0.10 vs.0.55±0.16, P<0.01. Immunohistochemical analysis: 30 days group: 2.91±0.20 vs. 5.31±0.30, P<0.01; 60 days group:2.94±0.30 vs. 5.80±0.30, P<0.01).Conclusions Sema3a was expressed in the heart by cardiocytes. Increased expression of sema3a may partly account for sympathetic denervation in CHF; modulation of this pathway may prove

  6. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    Science.gov (United States)

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  7. Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles.

    Science.gov (United States)

    Giricz, Zoltán; Varga, Zoltán V; Baranyai, Tamás; Sipos, Péter; Pálóczi, Krisztina; Kittel, Ágnes; Buzás, Edit I; Ferdinandy, Péter

    2014-03-01

    Remote ischemic preconditioning (RIPC) of the heart is exerted by brief ischemic insults affected on a remote organ or a remote area of the heart before a sustained cardiac ischemia. To date, little is known about the inter-organ transfer mechanisms of cardioprotection by RIPC. Exosomes and microvesicles/microparticles are vesicles of 30-100 nm and 100-1000 nm in diameter, respectively (collectively termed extracellular vesicles [EVs]). Their content of proteins, mRNAs and microRNAs, renders EV ideal conveyors of inter-organ communication. However, whether EVs are involved in RIPC, is unknown. Therefore, here we investigated whether (1) IPC induces release of EVs from the heart, and (2) EVs are necessary for cardioprotection by RIPC. Hearts of male Wistar rats were isolated and perfused in Langendorff mode. A group of donor hearts was exposed to 3 × 5-5 min global ischemia and reperfusion (IPC) or 30 min aerobic perfusion, while coronary perfusates were collected. Coronary perfusates of these hearts were given to another set of recipient isolated hearts. A group of recipient hearts received IPC effluent depleted of EVs by differential ultracentrifugation. Infarct size was determined after 30 min global ischemia and 120 min reperfusion. The presence or absence of EVs in perfusates was confirmed by dynamic light scattering, the EV marker HSP60 Western blot, and electron microscopy. IPC markedly increased EV release from the heart as assessed by HSP60. Administration of coronary perfusate from IPC donor hearts attenuated infarct size in non-preconditioned recipient hearts (12.9 ± 1.6% vs. 25.0 ± 2.7%), similarly to cardioprotection afforded by IPC (7.3 ± 2.7% vs. 22.1 ± 2.9%) on the donor hearts. Perfusates of IPC hearts depleted of EVs failed to exert cardioprotection in recipient hearts (22.0 ± 2.3%). This is the first demonstration that EVs released from the heart after IPC are necessary for cardioprotection by RIPC, evidencing the importance of vesicular

  8. Patterns of heart rate responses to hydralazine in normotensive and hypertensive rats.

    Science.gov (United States)

    Vidrio, H

    1996-01-01

    Hydralazine (H) induces hypotension accompanied by cardiac stimulation due to activation of the arterial baroreflex. Both clinical and experimental observations suggest, however, that in certain conditions H hypotension can be accompanied by unchanged or even depressed cardiac performance. The present study determined whether varying patterns of heart rate responses could be detected in large populations of conscious normotensive (n = 61) and renal hypertensive (n = 59) rats receiving a single dose of H. These patterns were compared with those of normotensive pentobarbital-anesthetized rats (n = 43). In the three groups, hypotension was accompanied by either tachycardia, unchanged heart rate or bradycardia. Tachycardia was found in 52% of normotensive conscious rats, in 51% of hypertensives and in only 14% of anesthetized animals. Heart rate did not change in 26, 35 and 23%, while bradycardia was detected in 22, 14 and 63%, respectively. These results were explained by postulating the initiation by H of two reflexes with opposite effects on heart rate: the arterial baroreflex producing tachycardia and a cardiac mechanoreceptor reflex producing bradycardia. These reactions would compete with each other, with results depending on their relative sensitivity in a given animal.

  9. Cardioprotective properties of citicoline against hyperthyroidism-induced reperfusion damage in rat hearts.

    Science.gov (United States)

    Hernández-Esquivel, Luz; Pavón, Natalia; Buelna-Chontal, Mabel; González-Pacheco, Héctor; Belmont, Javier; Chávez, Edmundo

    2015-06-01

    Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria.

  10. Effects of olmesartan therapy on the expression of lung adrenoceptors in rats with chronic heart failure.

    Science.gov (United States)

    Li, Y F; Jiang, Z L; Cao, F F; Liu, F

    2015-03-01

    Adrenergic receptors (AR) play important roles in regulating lung function. However, there are few reports concerning AR expression and the protective effect of angiotensin II receptor blockers (ARB) on the lung in chronic heart failure (CHF). In this study, we aimed to investigate the protective effects of the ARB olmesartan on the lung in CHF. Wistar rats were randomly divided into four groups: normal control, sham-operated rats, rats with CHF induced by ligating the left anterior descending coronary arteries, and rats with CHF treated with olmesartan (1 mg/kg) once daily for 8 weeks. Heart function, plasma renin activity (PRA) and angiotensin II (Ang II) levels, lung microscopic structure inspection and mRNA and protein expressions of α1A-, β1- and β2-AR in lung were tested. Compared with the CHF group, PRA and Ang II levels were decreased while heart function and mRNA and protein expression of α1A-AR, β1-AR and β2-AR were up-regulated in the olmesartan group (polmesartan group. Olmesartan may play a beneficial role in protecting lung in CHF by up-regulating AR and decreasing levels of PRA and Ang II. © The Author(s) 2014.

  11. The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat

    Science.gov (United States)

    Wang, Yunru; Xu, Peng; Wang, Yang; Liu, Haiyan; Zhou, Yuwen; Cao, Xuebin

    2013-01-01

    Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dt max under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside. PMID:24454984

  12. The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat

    Directory of Open Access Journals (Sweden)

    Yunru Wang

    2013-01-01

    Full Text Available Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dtmax under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside.

  13. Protective Effects of Ginger ( Extract against Diabetes-Induced Heart Abnormality in Rats

    Directory of Open Access Journals (Sweden)

    Behrouz Ilkhanizadeh

    2016-02-01

    Full Text Available BackgroundDiabetic cardiomyopathy is an important causal factor in morbidity and mortality among diabetic patients, and currently, no effective means are available to reverse its pathological progress. The purpose of the present study was to investigate the effect of ginger extract on apolipoproteins (apo A and B, hyperhomocysteinemia, cathepsin G and leptin changes, as well as cardiac fibrosis and heart muscle cell proliferation under hyperglycemic conditions in vivo.MethodsTwenty-four male Wistar rats were divided into three groups, namely: control, non-treated diabetic, and ginger extract-treated diabetic groups. The ginger extract-treated diabetic group received a 50 mg daily dose of ginger extract intragastrically for 6 weeks.ResultsThe results revealed concurrent significant increases in plasma C-reactive protein (CRP, homocysteine (Hcy, cathepsin G and apoB levels and decreases in apoA and leptin levels in the non-treated diabetic group compared to the control group. Moreover, heart structural changes, including fibrosis and heart muscle cell proliferation, were observed in non-treated diabetic rats compared to the control rats. Significant amelioration of changes in the heart structure together with restoration of the elevated levels of Hcy and CRP, leptin, cathepsin G, and apoA and B were found in the ginger extract-treated diabetic group compared to the non-treated diabetic group.ConclusionThe findings indicated that ginger extract significantly reduces heart structural abnormalities in diabetic rats and that these effects might be associated with improvements in serum apo, leptin, cathepsin G, and Hcy levels and with the antioxidant properties of ginger extract.

  14. Endurance training in early life results in long-term programming of heart mass in rats.

    Science.gov (United States)

    Wadley, Glenn D; Laker, Rhianna C; McConell, Glenn K; Wlodek, Mary E

    2016-02-01

    Being born small for gestational age increases the risk of developing adult cardiovascular and metabolic diseases. This study aimed to examine if early-life exercise could increase heart mass in the adult hearts from growth restricted rats. Bilateral uterine vessel ligation to induce uteroplacental insufficiency and fetal growth restriction in the offspring (Restricted) or sham surgery (Control) was performed on day 18 of gestation in WKY rats. A separate group of sham litters had litter size reduced to five pups at birth (Reduced litter), which restricted postnatal growth. Male offspring remained sedentary or underwent treadmill running from 5 to 9 weeks (early exercise) or 20 to 24 weeks of age (later exercise). Remarkably, in Control, Restricted, and Reduced litter groups, early exercise increased (P heart mass in adulthood. This was despite the animals being sedentary for ~4 months after exercise. Later exercise also increased adult absolute and relative heart mass (P early or later exercise. Phosphorylation of Akt Ser(473) in adulthood was increased in the early exercise groups but not the later exercise groups. Microarray gene analysis and validation by real-time PCR did not reveal any long-term effects of early exercise on the expression of any individual genes. In summary, early exercise programs the heart for increased mass into adulthood, perhaps by an upregulation of protein synthesis based on greater phosphorylation of Akt Ser(473).

  15. Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart.

    Science.gov (United States)

    Otani, H; Prasad, M R; Engelman, R M; Otani, H; Cordis, G A; Das, D K

    1988-11-01

    In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an isolated and perfused rat heart. When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly in the heart reperfused with [3H]inositol after 30 minutes of ischemia compared with that perfused with [3H]inositol after 30 minutes of nonischemic perfusion. However, isotopic incorporation of [3H]glycerol into diacylglycerol, phosphatidic acid, and all of the three phosphoinositides was diminished in the reperfused hearts. Reperfusion of the ischemic heart prelabeled with [14C]arachidonic acid resulted in significant increases in [14C]diacylglycerol and [14C]phosphatidic acid. The enhanced accumulations of [3H]inositol phosphates during reperfusion were not affected by treatment with prazosin plus atropine or indomethacin, but were inhibited by hypoxic reperfusion, reperfusion with Ca2+-free buffer, or by mepacrine. These results suggest that myocardial reperfusion stimulates phosphodiesteratic breakdown and turnover of phosphoinositides, and increased Ca2+ influx caused by reperfusion may be involved in the mechanism of stimulation of phosphatidylinositol-specific phospholipase C activity in the rat heart.

  16. Ellagic acid prevents cisplatin-induced oxidative stress in liver and heart tissue of rats.

    Science.gov (United States)

    Yüce, Abdurrauf; Ateşşahin, Ahmet; Ceribaşi, Ali Osman; Aksakal, Mesut

    2007-11-01

    Cisplatin is one of the most active cytotoxic agents in the treatment of cancer. High doses of cisplatin have also been known to produce hepatotoxicity, and several studies suggest that supplemental antioxidants can reduce cisplatin-induced hepatotoxicity. The present study was designed to determine the effects on the liver and heart oxidant/antioxidant system and the possible protective effects of ellagic acid on liver and heart toxicity induced by cisplatin. The control group received 0.9% saline; animals in the ellagic acid group received only ellagic acid (10 mg/kg); animals in the cisplatin group received only cisplatin (7 mg/kg); animals in cisplatin + ellagic acid group received ellagic acid for 10 days after cisplatin. The rats were killed at the end of the treatment period. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione-peroxidase (GSH-Px) and catalase (CAT) activities were determined in liver and heart tissue. While administration of cisplatin increased the MDA levels in liver and heart tissues, it decreased the GSH, GSH-Px and CAT in these samples when compared to the control group. The administration of ellagic acid to cisplatin-treated rats decreased the MDA levels, and increased GSH, GSH-Px and CAT in these samples. Cisplatin caused marked damages in the histopathological status of liver and heart tissues. These damages were ameliorated by ellagic acid administration. In conclusion, ellagic acid may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters.

  17. The Effects of Velvet Antler of Deer on Cardiac Functions of Rats with Heart Failure following Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Ming-Jing Shao

    2012-01-01

    Full Text Available Velvet antler of deer (VAD is a commonly-used kidney-Yang supplementing traditional Chinese medication. According to the heart-kidney-related theory, heart Yang originates in kidney Yang and heart failure due to heart Yang deficiency can be treated by tonifying kidney Yang. In this study, we investigated therapeutic effects of VAD on cardiac functions in rats with heart failure following myocardial infarction. Forty-eight male Wistar rats were subjected either to left coronary artery ligation (N=36 or to sham operation (N=12. One week after the surgery, rats with heart failure received daily treatment of double-distilled water, captopril or VAD by gavage for consecutively four weeks, while sham-operated animals were given double-distilled water. Ultrasonic echocardiography was adopted to examine cardiac structural and functional parameters and serum brain natriuretic peptide (BNP concentration was measured using radioimmunoassay. We found that VAD partially reversed changes in cardiac functional parameters and serum BNP levels in rats with heart failure. These results provide further evidence for the heart-kidney-related theory and suggest that VAD might be a potentially alternative and complementary medicine for the treatment of heart failure.

  18. Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

    DEFF Research Database (Denmark)

    Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard;

    2013-01-01

    of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...

  19. Toxic effect of the glycoalkaloids solanine and tomatine on cultured neonatal rat heart cells.

    Science.gov (United States)

    Bergers, W W; Alink, G M

    1980-06-01

    The toxic effects of the glycoalkaloids, alpha-solanine and tomatine, were studied in beating heart cell cultures from 1--2-day-old rats. After addition of alpha-solanine (80 microgram/ml) and tomatine (40 microgram/ml) to the culture medium, the cells ceased beating within a few minutes. At a concentration of 40 microgram/ml alpha-solanine and 20 microgram/ml tomatine, both compounds caused a pronounced increase of the contraction frequency, lasting for at least 2h. K-strophantin, a reference heart glycoside, caused arrhythmic beating at 20 microgram/ml and complete cessation of contractions at 160 microgram/ml.

  20. Intermedin in the paraventricular nucleus attenuates cardiac sympathetic afferent reflex in chronic heart failure rats.

    Directory of Open Access Journals (Sweden)

    Xian-Bing Gan

    Full Text Available BACKGROUND AND AIM: Intermedin (IMD is a member of calcitonin/calcitonin gene-related peptide (CGRP family together with adrenomedullin (AM and amylin. It has a wide distribution in the central nervous system (CNS especially in hypothalamic paraventricular nucleus (PVN. Cardiac sympathetic afferent reflex (CSAR is enhanced in chronic heart failure (CHF rats. The aim of this study is to determine the effect of IMD in the PVN on CSAR and its related mechanisms in CHF rats. METHODOLOGY/PRINCIPAL FINDINGS: Rats were subjected to left descending coronary artery ligation to induce CHF or sham-operation (Sham. Renal sympathetic nerve activity (RSNA, mean arterial pressure (MAP and heart rate (HR were recorded. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. Acute experiments were carried out 8 weeks after coronary ligation or sham surgery under anesthesia. IMD and angiotensin II (Ang II levels in the PVN were up-regulated in CHF rats. Bilateral PVN microinjection of IMD caused greater decreases in CSAR and the baseline RSNA and MAP in CHF rats than those in Sham rats. The decrease of CSAR caused by IMD was prevented by pretreatment with AM receptor antagonist AM22-52, but not CGRP receptor antagonist CGRP8-37. Ang II in the PVN significantly enhanced CSAR and superoxide anions level, which was inhibited by PVN pretreatment with IMD or tempol (a superoxide anions scavenger in Sham and CHF rats. CONCLUSION: IMD in the PVN inhibits CSAR via AM receptor, and attenuates the effects of Ang II on CSAR and superoxide anions level in CHF rats. PVN superoxide anions involve in the effect of IMD on attenuating Ang II-induced CSAR response.

  1. Discrepant uptake of the radiolabeled norepinephrine analogues hydroxyephedrine (HED) and metaiodobenzylguanidine (MIBG) in rat hearts

    Energy Technology Data Exchange (ETDEWEB)

    Rischpler, Christoph [Johns Hopkins University, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology, Baltimore, MD (United States); Klinikum rechts der Isar, Nuklearmedizinische Klinik und Poliklinik, Munich (Germany); Fukushima, Kenji; Isoda, Takuro; Javadi, Mehrbod S.; Dannals, Robert F.; Wahl, Richard [Johns Hopkins University, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology, Baltimore, MD (United States); Abraham, Roselle [Johns Hopkins University, Division of Cardiology, Department of Medicine, Baltimore, MD (United States); Bengel, Frank M. [Johns Hopkins University, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology, Baltimore, MD (United States); Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Higuchi, Takahiro [Johns Hopkins University, Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology, Baltimore, MD (United States); Wuerzburg University, CHFC/Department of Nuclear Medicine, Wuerzburg (Germany); Universitaetsklinikum Wuerzburg, Nuklearmedizinische Klinik und Poliklinik, Wuerzburg (Germany)

    2013-07-15

    {sup 11}C-Hydroxyephedrine (HED) and radioiodinated metaiodobenzylguanidine ({sup 123}I/{sup 131}I-MIBG) are catecholamine analogue tracers for sympathetic nerve positron emission tomography/single photon emission computed tomography (PET/SPECT) imaging. In contrast to humans, rat hearts demonstrate high nonneural catecholamine uptake-2 in addition to neural uptake-1, the contributions of which to tracer accumulation are not fully elucidated. Wistar rats were studied using the following pretreatments: uptake-1 blockade with desipramine 2 mg/kg IV, both uptake-1 and -2 blockade with phenoxybenzamine 50 mg/kg IV, or control with saline IV. HED or {sup 123}I-MIBG was injected 10 min after pretreatment, and rats were sacrificed 10 min later. Heart to blood tissue count ratio (H/B ratio) was obtained using a gamma counter. To determine regional tracer uptake, dual-tracer autoradiography was performed with HED and {sup 131}I-MIBG in Wistar rats with chronic infarction by transient coronary occlusion and reperfusion and in healthy control rats. Local tracer distributions were analyzed, and the infarcted rats' local tracer distributions were compared with histology. The H/B ratios in control hearts were 34.4 {+-} 1.7 and 25.5 {+-} 2.1 for HED and {sup 123}I-MIBG, respectively. Desipramine led to a significant decrease in HED (3.2 {+-} 0.5, p < 0.0001), while there was no change in {sup 123}I-MIBG (25.5 {+-} 6.4, p = n.s.). Phenoxybenzamine led to a significant decrease in both HED and {sup 123}I-MIBG (3.5 {+-} 0.02, 4.3 {+-} 0.7, p < 0.0001). Only HED showed a subepicardium-subendocardium gradient in healthy control hearts which is consistent with physiological innervation, while {sup 131}I-MIBG was evenly distributed throughout the myocardium. {sup 131}I-MIBG uptake defect closely matched the scar area determined by histology [3.8 {+-} 2.3 % ({sup 131}I-MIBG defect) vs 4.0 {+-} 2.4 % (scar)]. However, the scar area was clearly exceeded by the HED uptake defect (9

  2. Overtraining does not induce oxidative stress and inflammation in blood and heart of rats.

    Science.gov (United States)

    Stanojevic, D; Jakovljevic, V; Barudzic, N; Zivkovic, V; Srejovic, I; Parezanovic Ilic, K; Cubrilo, D; Ahmetovic, Z; Peric, D; Rosic, M; Radovanovic, D; Djordjevic, D

    2016-01-01

    The aim of our research was to evaluate the changes in levels of cytokines and redox state parameters in blood and isolated heart of rats subjected to different swimming protocols. Rats were divided into 3 groups: 1) controls, 2) moderately trained rats that during all 12 weeks swam 1 h/day, 5 days/week, and 3) overtrained rats that in 10(th) week swam twice, 11(th) week 3 times, and in 12(th) week 4 times a day for 1 h. After sacrificing, blood from jugular vein was collected, and the heart excised and perfused on a Langendorff apparatus. Samples of the coronary effluent were collected during coronary autoregulation. Levels of superoxide anion radical (O(2)(-)), hydrogen peroxide (H(2)O(2)), nitric oxide (NO) and thiobarbituric acid reactive substances (TBARS) were measured in plasma and coronary effluent, while reduced glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT) were measured in erythrocytes. Venous blood was also used for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) determination. Moderate training protocol induced the decrease of TBARS in plasma, while both training protocols induced the decrease of O(2)(-) and H(2)O(2) in coronary effluent. There was no significant difference in levels of cytokines between groups. The results of study add evidence about beneficial effects of moderate-intensity training on blood and cardiac redox state of rats, and furthermore, shows that exercising frequently, if the intensity stays within moderate range, may not have detrimental effects.

  3. Effects of perindopril on expression of kidney aquaporin-2 and urine aquaporin-2 excretion in chronic heart failure rats

    Institute of Scientific and Technical Information of China (English)

    欧阳邵

    2013-01-01

    Objective To determine the expression of kidneyaquaporin-2(AQP2) and urine AQP2 excretion in chronic heart failure(CHF) rats and investigate effects of perindopril on the expression and excretion of AQP2.Methods

  4. Deltamethrin and Permethrin in the liver and heart of Wistar rats submitted to oral subchronic exposure

    OpenAIRE

    Santos,Mônica A. T; Rodrigues,Marili V. N; Áreas, Miguel A; Reyes,Felix G. R.

    2011-01-01

    For 28 days male Wistar rats were submitted to oral exposure with 1/10 of the LD50 value of permethrin (PMT) or deltamethrin (DMT). The aim of this study was to determine the residues of PMT and DMT in the liver and heart of the rats at the end of the exposure period, as well as to evaluate the effect of ingesting pectin and cellulose via the diet. The analytes were extracted with acetonitrile and the extracts were cleaned up by solid phase extraction with florisil before GC-ECD (gas chromato...

  5. Relationship between fibronectin expression during gastrulation and heart formation in the rat embryo.

    Science.gov (United States)

    Suzuki, H R; Solursh, M; Baldwin, H S

    1995-11-01

    By utilizing myosin immunostaining, we were able to identify early rat myocardium as a thin epithelial sheet and realized that its cohesive movement toward the midline leads to the straight heart tube formation. Localization study of fibronectin mRNA and protein was, therefore, carried out to investigate its tissue origin and possible roles in facilitating mesoderm migration and heart formation. Fibronectin mRNAs were first detected throughout the mesoderm during the early primitive streak stage, suggesting that the mesoderm is the source of fibronectin. By pre-head fold (pre-somite) and head fold (early somite) stages, the mesoderm became largely down-regulated for fibronectin mRNAs, while it was also at these stages when myosin-positive myocardium formed itself into the epithelium and was subsequently folding toward the midline. Thus, there appears to be little fibronectin synthesis during and directly relevant to early heart tube formation. Later, during the early straight heart tube stage (5 somite and older), endocardium became highly positive for fibronectin mRNAs, suggesting that the endocardium is the major source of fibronectin for the cardiac jelly. Based on the results, we present a map for the early mammalian heart in which the heart is a single crescentic band lying in front of the prechordal plate. We also suggest a process for heart tube formation based on the cohesive movement of the myocardial epithelium. During heart tube formation, fibronectin protein had been deposited previously by the mesoderm and was found uniformly in the ECM and not newly produced by any adjacent tissue. The data contradict the endodermal guidance of heart migration by fibronectin gradient and suggest, instead, a permissive role for the fibronectin substrate.

  6. TASTE DISCRIMINATION DURING THE EARLY ONTOGENY OF TASTE DISCRIMINATION DURING THE EARLY ONTOGENY OF THE RAT IN PROCEDURES INVOLVING SURPRISING CHANGES IN REINFORCEMENT

    Directory of Open Access Journals (Sweden)

    Giselle Kamenetzky

    2012-06-01

    Full Text Available This study evaluated consummatory responses in infant rats exposed to different magnitude of reward, and after the devaluation (i.e., consummatory successive negative contrast or omission (i.e., extinction of reward. In Experiment 1, 8-10 post-natal days (PND pups were intraorally infused with 12%, 10%, 5% or 2% sucrose (preshift phase, 2 daily trials. Subsequently, all groups received 2% sucrose (postshift phase. In Experiment 2, 10-14 day-old pups received 12% or 2% sucrose in 4 daily trials in the preshift phase, followed by 2% in a postshift trial. Both experiments indicated that during preshift, animals exposed to 12% sucrose exhibited higher sucrose consumption than those receiving lower concentration solutions. This phenomenon, indicative of a magnitude of reinforcement effect was not accompanied by evidence of successive negative contrast. In Experiment 3 we evaluated the magnitude of reinforcement extinction effect in 7-12 PND rats. Animals received 12% sucrose or water in preshift phase and both groups received a neutral solution (i.e., water in the second phase. A magnitude of reinforcement acquisition effect was again observed, yet there were no differences between groups in extinction phase. In Experiment 4 we used an anticipatory contrast procedure in 10-16 PND pups. A magnitude of reinforcement, but not an anticipatory contrast effect was observed. Overall the results indicate that: (a rats from - at least- 8 PND discriminate between different concentrations of sucrose, and (b until the second week of life the response to rewards is mainly regulated by their absolute value and not by their relative value. Results are discussed terms of the ontogeny of paradoxical effects of reward and its relationship to Amsel’s theory.

  7. Configurations of the interoceptive discriminative stimulus effects of ethanol and nicotine with two different exteroceptive contexts in rats: Extinction & recovery.

    Science.gov (United States)

    Troisi, Joseph R; Craig, Elizabeth M

    2015-06-01

    Interoceptive states interact with exteroceptive contexts in modulating operant behavior, which is maintained by its consequences. Evaluating discriminative stimulus control by overlapping interoceptive and exteroceptive configurations (gestalts) and the contribution of each modality may be clinically important for understanding aspects of relapsing behavior (e.g., drug abuse). With rats, the current investigation used a completely counterbalanced one-manipulandum operant drug discrimination procedure that established discriminative stimulus control between nicotine (0.3mg/kg) in one exteroceptive context and EtOH (1.0g/kg) in a differing exteroceptive context. One combined interoceptive-exteroceptive condition occasioned sessions of food reinforcement (S(D)) and the other counterbalanced condition occasioned sessions of non-reinforcement (S(Δ)). Each stimulus modality contributed to discriminative control, but to lesser extents than the combined intero-exteroceptive compound configurations (Experiments 1 & 2). In Experiment 1, responding was extinguished in the interoceptive stimulus conditions alone in a neutral exteroceptive context, but then renewed by reconfiguring the drugs with the exteroceptive contexts, and reversed in the opposing exteroceptive contexts. In Experiment 2, responding was extinguished in the interoceptive and exteroceptive contexts separately. Reconfiguration of the full intero-exteroceptive compound configurations did not promote recovery. These results suggest that interoceptive and exteroceptive discriminative control can be methodologically configured in modulating operant behavior during acquisition, extinction, and recovery of behavior; however, configuring interoceptive and exteroceptive discriminative stimuli do not appear to function as unique cues that differ from each stimulus modality alone. Clinical implications are discussed.

  8. The Effect of U50488 on the Cardiac Rhythm and Intracellular Calcium in the Rat Heart.

    Institute of Scientific and Technical Information of China (English)

    Zhang Weimin; Xin Dalin; Wong Takming

    2000-01-01

    The effect of U50488, a selective k-opioid receptor agonist, on cardiac rhythm in the isolated perfused rat heart and intracellular calcium ([Ca2+] i) in the single ventricular myocyte were studied. The results showed that U50488 can induce arrhythmias dose-dependently in the isolated perfused rat heart and increase [Ca2+] i in the single ventricular myocyte. The effect of U50488 can be blocked by a selectivek-receptor antagonist, nor-binaltorphimine.The arrhythmogenic effects and the increase of [ Ca2 + ] i induced by U50488 were blocked by U73122, neomycin and streptomycin, which are selective phospolipase C inhibitors, but not by U73433, the inactive structural analog of U73122. These results demonstrated that the arrhythmogenic effect of cardiac k-receptor is due to activation of phosphoinositol/Ca2+ pathway.

  9. Renal and cardiac neuropeptide Y and NPY receptors in a rat model of congestive heart failure.

    Science.gov (United States)

    Callanan, Ean Y; Lee, Edward W; Tilan, Jason U; Winaver, Joseph; Haramati, Aviad; Mulroney, Susan E; Zukowska, Zofia

    2007-12-01

    Neuropeptide Y (NPY) is coreleased with norepinephrine and stimulates vasoconstriction, vascular and cardiomyocyte hypertrophy via Y1 receptors (R) and angiogenesis via Y2R. Although circulating NPY is elevated in heart failure, NPY's role remains unclear. Activation of the NPY system was determined in Wistar rats with the aortocaval (A-V) fistula model of high-output heart failure. Plasma NPY levels were elevated in A-V fistula animals (115.7 +/- 15.3 vs. 63.1 +/- 17.4 pM in sham, P renal failure (urinary Na(+) excretion renal blood flow (RBF), and death within 5-7 days (DECOMP). Cardiac and renal tissue NPY decreased with heart failure, proportionate to the severity of renal complications. Cardiac and renal Y1R mRNA expression also decreased (1.5-fold, P failure. In contrast, Y2R expression increased up to 72-fold in the heart and 5.7-fold in the kidney (P failure and cardiac hypertrophy. Changes in receptor expression were confirmed since the Y1R agonist, [Leu31, Pro34]-NPY, had no effect on RBF, whereas the Y2R agonist (13-36)-NPY increased RBF to compensate for disease. Thus, in this model of heart failure, cardiac and renal NPY Y1 receptors decrease and Y2 receptors increase, suggesting an increased effect of NPY on the receptors involved in cardiac remodeling and angiogenesis, and highlighting an important regulatory role of NPY in congestive heart failure.

  10. Yiqi Huoxue Recipe Improves Heart Function through Inhibiting Apoptosis Related to Endoplasmic Reticulum Stress in Myocardial Infarction Model of Rats

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    Li-Xia Lou

    2014-01-01

    Full Text Available Objective. To explore the mechanism of cardioprotective effects of Chinese medicine, Yiqi Huoxue recipe, in rats with myocardial infarction- (MI- induced heart failure. Methods. Male Sprague-Dawley rats underwent left anterior descending artery (LAD ligation or sham operation. The surviving MI rats were divided randomly into three groups: MI (5 mL/kg/d NS by gavage, MI + Metoprolol Tartrate (MT (12 mg/kg/d MT by gavage, and MI + Yiqi Huoxue (5 mL/kg recipe by gavage. And the sham operation rats were given 5 mL/kg/d normal saline. Treatments were given on the day following surgery for 4 weeks. Then rats were detected for heart structure and function by transthoracic echocardiography. Apoptosis in heart tissues was detected by TUNEL staining. To determine whether the endoplasmic reticulum (ER stress response pathway is included in the cardioprotective function of the recipe, ER stress related proteins such as GRP78 and caspase-12 were examined. Results. Yiqi Huoxue recipe attenuated heart function injury, reversed histopathological damage, alleviated myocardial apoptosis and inhibited ER stress in MI rats. Conclusion. All the results suggest that Yiqi Huoxue recipe improves the injured heart function maybe through inhibition of ER stress response pathway, which is a promising target in therapy for heart failure.

  11. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

    Energy Technology Data Exchange (ETDEWEB)

    Umetani, K. [Japan Synchrotron Radiation Research Institute, SPring-8, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Fukushima, K. [National Cerebral and Cardiovascular Center Hospital, Fujishirodai, Suita-shi, Osaka 565-8565 (Japan)

    2013-03-15

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 {mu}m, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 {mu}m diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 {mu}m was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  12. hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure.

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    Antti Siltanen

    Full Text Available After severe myocardial infarction (MI, heart failure results from ischemia, fibrosis, and remodeling. A promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in MI is myoblast sheet transplantation. We hypothesized that in a rat model of MI-induced chronic heart failure, this therapy could be further improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF in the myoblast sheets. We studied the ability of wild type (L6-WT and human HGF-expressing (L6-HGF L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression profiles by use of microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD ligation and allowed heart failure to develop for 4 weeks. Thereafter, we administered L6-WT (n = 15 or L6-HGF (n = 16 myoblast sheet therapy. Control rats (n = 13 underwent LAD ligation and rethoracotomy without therapy, and five rats underwent a sham operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy, and analyzed cardiac angiogenesis and left ventricular architecture from histological sections at 4 weeks. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further

  13. Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ.

    Science.gov (United States)

    Baldwin, H S; Lloyd, T R; Solursh, M

    1994-02-01

    Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular matrix or "cardiac jelly," yet little is known about its role in the ontogeny of early ventricular performance. To investigate the in situ effect of hyaluronate degradation on ventricular function, whole rat embryos were cultured in rat serum alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase (treatment embryos) from gestational day 9.5 (before formation of the heart tube) through initial looping of the heart. Cardiac function was measured before looping (24 hours in culture) and immediately after looping (36 hours in culture) by video motion analysis of the external wall motion of the bulbus cordis and primitive ventricle. Degradation of hyaluronic acid in the treated embryos was confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate, circumferential shortening fraction, maximum velocity of circumferential contraction, and maximum velocity of circumferential relaxation were observed with looping in both control and treatment embryos. Although there was minimal difference in ventricular performance between control and treatment embryos before looping, there was a significant increase in all parameters of ventricular performance in the hyaluronidase-treated embryos immediately after looping of the heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an additional group of embryos cultured in the presence of Streptomyces hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These experiments are the first to (1) document a quantifiable increase in ventricular performance during early cardiac looping and (2) demonstrate that hyaluronate degradation results in abnormal endocardial cushion formation and altered ventricular performance of the postlooped heart.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

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    Kaytlyn A Gerbin

    Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

  15. Proteinous amino acids in hearts' muscle cytosol of rats pretreated with digoxin, caffeine or isoproterenol.

    Science.gov (United States)

    Gabrys, Janusz; Konecki, Janusz; Głowacka, Maria; Durczok, Katarzyna; Nowak, Przemysław; Bielaczyc, Grzegorz; Brus, Ryszard; Shani, Jashovam

    2004-01-01

    Levels of the 19 proteinous amino acids and total free amino acids were assayed by gas-liquid chromatography in cytosols of rat atrial and ventricular muscle cardiomyocytes. The tissues were assayed after the rats had been exposed to the cardioactive drugs digoxin, caffeine, and isoproterenol, each having different mechanisms of action. We demonstrated that, in the atrial and ventricular cardiac muscle cytosol of control (untreated) rats, arginine, glutamine, and cysteine existed in their highest levels: 35.1% and 17.6%; 14.8% and 51.6%; 9.9% and 0.25% of the total free amino acids, respectively. The levels of the other amino acids in the atrial and ventricular cardiac muscle cytosols ranged between 0.1% and 10.0% of the total free amino acids. Digoxin, caffeine, and isoproterenol significantly reduced the total amount of cytosolic free amino acids in the atrial heart muscle cytosol to 7.6%, 9.0%, and 9.2% of the control value (100%), and in the ventricular heart muscle cytosol to 31.1%, 43.2%, and 28.3% of the control. The three drugs tested changed the cytosols' levels of arginine, cysteine, tryptophane, asparagine, and tyrosine in atrial and ventricular heart muscle cytosol, as compared to the control groups (calculated as a percent of the total free amino acids in the experimental groups). The role of proteinous amino acids in the function of the heart muscle and in the mechanism of action of these drugs on the mammalian heart is discussed.

  16. The NO stimulator, Catestatin, improves the Frank-Starling response in normotensive and hypertensive rat hearts.

    Science.gov (United States)

    Angelone, T; Quintieri, A M; Pasqua, T; Filice, E; Cantafio, P; Scavello, F; Rocca, C; Mahata, S K; Gattuso, A; Cerra, M C

    2015-08-01

    The myocardial response to mechanical stretch (Frank-Starling law) is an important physiological cardiac determinant. Modulated by many endogenous substances, it is impaired in the presence of cardiovascular pathologies and during senescence. Catestatin (CST:hCgA352-372), a 21-amino-acid derivate of Chromogranin A (CgA), displays hypotensive/vasodilatory properties and counteracts excessive systemic and/or intra-cardiac excitatory stimuli (e.g., catecholamines and endothelin-1). CST, produced also by the myocardium, affects the heart by modulating inotropy, lusitropy and the coronary tone through a Nitric Oxide (NO)-dependent mechanism. This study evaluated the putative influence elicited by CST on the Frank-Starling response of normotensive Wistar-Kyoto (WKY) and hypertensive (SHR) hearts by using isolated and Langendorff perfused cardiac preparations. Functional changes were evaluated on aged (18-month-old) WKY rats and SHR which mimic human chronic heart failure (HF). Comparison to WKY rats, SHR showed a reduced Frank-Starling response. In both rat strains, CST administration improved myocardial mechanical response to increased end-diastolic pressures. This effect was mediated by EE/IP3K/NOS/NO/cGMP/PKG, as revealed by specific inhibitors. CST-dependent positive Frank-Starling response is paralleled by an increment in protein S-Nitrosylation. Our data suggested CST as a NO-dependent physiological modulator of the stretch-induced intrinsic regulation of the heart. This may be of particular importance in the aged hypertrophic heart, whose function is impaired because of a reduced systolic performance accompanied by delayed relaxation and increased diastolic stiffness.

  17. Design of a noninvasive face mask for ocular occlusion in rats and assessment in a visual discrimination paradigm.

    Science.gov (United States)

    Hager, Audrey M; Dringenberg, Hans C

    2012-12-01

    The rat visual system is structured such that the large (>90 %) majority of retinal ganglion axons reach the contralateral lateral geniculate nucleus (LGN) and visual cortex (V1). This anatomical design allows for the relatively selective activation of one cerebral hemisphere under monocular viewing conditions. Here, we describe the design of a harness and face mask allowing simple and noninvasive monocular occlusion in rats. The harness is constructed from synthetic fiber (shoelace-type material) and fits around the girth region and neck, allowing for easy adjustments to fit rats of various weights. The face mask consists of soft rubber material that is attached to the harness by Velcro strips. Eyeholes in the mask can be covered by additional Velcro patches to occlude either one or both eyes. Rats readily adapt to wearing the device, allowing behavioral testing under different types of viewing conditions. We show that rats successfully acquire a water-maze-based visual discrimination task under monocular viewing conditions. Following task acquisition, interocular transfer was assessed. Performance with the previously occluded, "untrained" eye was impaired, suggesting that training effects were partially confined to one cerebral hemisphere. The method described herein provides a simple and noninvasive means to restrict visual input for studies of visual processing and learning in various rodent species.

  18. Central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature of renal hypertensive rats

    NARCIS (Netherlands)

    Nijkamp, F.P.; Ezer, Joseph; Jong, Wybren de

    The central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature was studied in conscious renal hypertensive rats. Systemic administration of α-methyldopa decreased mean arterial blood pressure and body temperature and caused a short lasting increase in heart rate

  19. Central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature of renal hypertensive rats

    NARCIS (Netherlands)

    Nijkamp, F.P.; Ezer, Joseph; Jong, Wybren de

    1975-01-01

    The central inhibitory effect of α-methyldopa on blood pressure, heart rate and body temperature was studied in conscious renal hypertensive rats. Systemic administration of α-methyldopa decreased mean arterial blood pressure and body temperature and caused a short lasting increase in heart rate fol

  20. The Expression of β3-adrenoceptor of Left Ventricle and the Effect on Heart Function by Stimulating β3-AR in Rats With Experimental Heart Failure

    Institute of Scientific and Technical Information of China (English)

    Deng Yijun; Wu Wei; Yang Hui; Fang Chang; Huang Zhibing

    2005-01-01

    Objectives To observe theexpression of β3-adrenoceptor (β3-AR) of left ventricle and the effect on heart function by stimulating β3-AR in rats with experimental heart failure. Methods Rats were randomly divided into heart failure group and control group. Heart failure models were built up by ligating coronary artery in rats. The expression of β3-AR mRNA were detected with RT-PCR; The change of heart function were observed after administration of BRL37344 (βs-AR agonist) by measuring left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), the maximum pressure ascending rate of left ventricle(+dp/dtmax) and the maximum pressure descending rate of left ventricle(-dp/dtmax). Results The expression of β3-AR mRNA (β./β-actin) was 0.028±0.005 and the proportion of β3-AR (β3/β1+β2+β3) was 5.4%±0.06%in failure rats while the expression of β3-AR mRNA was 0.011 ±0.004 and the proportion was 1.2% ±0.04% in control rats; The descending percentage of LVESP, +dp/dtmax and -dp/dtmax were 16.1% , 21.7% and 13.2% respectively with administration of BRL37344 in failure rats, while 12.2%, 15.8% and 11.5% in control rats. Conclusions Compared with control group the expression of 33-AR mRNA of left ventricle was obviously increased and the negative inotropic function with exciting β3-AR was obviously enhanced in failure groups.

  1. THE EFFECT OF ACUTE MYOCARDIUM ISCHEMIC ON HEART FUNCTION OF PREGNANCY RAT

    Institute of Scientific and Technical Information of China (English)

    Zheng Xiaopu; Ma Aiqun; Niu Changmin; Dong Anping; Han Ke; Liu Yu; Zhang Wei; Geng Tao

    2006-01-01

    Objective To investigate the effect of acute myocardium ischemic on heart function of pregnancy rat.Methods 13 female SD rats and 6 early pregnancy rats were divided into normal group, unpregnant group with acute myocardial infarction and early pregnant group with acute myocardial infarction. The anterior branch of the left coronary artery was ligated. 3 weeks later, Image 1.31 software was used to measure areas of myocardial infarction,and to evaluate hemodynamics of heart with powerLAB4.12, and cardiac tissues were stained with Massion. Results Compared with unpregnant group with acute myocardial infarction , the early pregnant group with acute myocardial infarction had less myocardial infarction area (28. 86% vs. 36. 8%), and had a higher left ventricle end systolic pressure, ±dp/dt max, and lower left ventricle end diastolic pressure. Massion stain showed the amount of collagen of the lesion was less in the early pregnant group with acute myocardial infarction than that in unpregnant group.Conclusion The early pregnant group with acute myocardial infarction had better heart contractive and diastolic function.

  2. Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart.

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    Yuzhen Zhang

    Full Text Available BACKGROUND: Induced pluripotent stem cells (iPSCs are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients. METHODOLOGY/PRINCIPAL FINDINGS: We transplanted 2 × 10(4, 2 × 10(5, or 2 × 10(6 cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease.

  3. Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

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    Noritomo Fujisaki

    2016-01-01

    Full Text Available Because inhaled carbon monoxide (CO provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects.Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors.

  4. Altered heart and kidney phospholipid fatty acid composition are associated with cardiac hypertrophy in hypertensive rats.

    Science.gov (United States)

    Kim, Oh Yoen; Jung, Young-Sang; Cho, Yoonsu; Chung, Ji Hyung; Hwang, Geum-Sook; Shin, Min-Jeong

    2013-08-01

    We examined the association of cardiac hypertrophy or fibrosis with the phospholipid fatty acid (FA) composition of heart and kidney in hypertensive rats. Eight-week-old spontaneously hypertensive rats (SHRs) (n=8) and Wistar Kyoto rats (WKYs, n=8) as a normotensive control, were fed ad libitum for 6 weeks with regular AIN-76 diet. Phospholipid FA compositions in the left ventricle and kidney were measured and histological analyses were performed. Compared with WKYs, SHRs had lower proportions of γ-linolenic acid, α-linolenic acid, eicosadienoic acid, eicosatrienoic acid, dihomo-γ-linoleic acid, docosadienoic acid and nervonic acid in heart, and stearic acid (SA), γ-linolenic acid, and eicosapentaenoic acid (EPA) in kidney. After adjusting for food intake, SHRs still maintained higher proportions of SA, and total saturated FAs in the heart and a lower proportion of eicosapentaenoic acid in the kidney. Additionally, compared with WKYs, SHRs showed larger cardiomyocyte diameters in the left ventricles, indicating cardiac hypertrophy and interstitial fibrosis. Cardiomyocyte diameters also positively correlated with cardiac SA (r=0.550, pcardiac hypertrophy in a hypertensive setting, implicating the pathogenic role of tissue FAs in hypertension and related complications. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  5. Evaluation of wound healing potential of Pterocarpus marsupium heart wood extract in normal and diabetic rats

    Directory of Open Access Journals (Sweden)

    Anil Kumar Singhal

    2012-01-01

    Full Text Available Aim: The aim of the present study is to evaluate and compare the cutaneous wound healing potential of Pterocarpus marsupium in normal and diabetic rats and make inference for the cutaneous wound healing potential by possible "mode of action" P. marsupium extract. Materials and Methods: The effect of heart wood extract of P. marsupium on wound healing has been studied in diabetic and normal animals. The effect has also been compared with standard (mupirocin ointment application. In the absence of specific animal model for cutaneous diabetic wound healing, we have used common model of wound healing (excision wound model in animals having diabetes (by administration of alloxan monohydrate 120 mg/kg i.p.. Statistics Analysis: Data were analyzed by using one-way ANOVA, followed by Tukey′s post hoc tests, using the Graph Pad Software (5.0 demo version, and P value <0.05 was considered to be significant. Results and Conclusion : Rats treated with 200 mg/kg/day of P. marsupium heart wood extract had high rate of wound contraction, significantly decreased epithelization period, and significant increase in dry weight, wet weight, and hydroxyproline content of the granulation tissue when compared with the diabetic control and normal control groups. Wound contraction together with increased tensile strength and hydroxyproline content support the use of P. marsupium heart wood extract in the management of wound healing in normal and diabetic rats.

  6. Bi-ventricular finite element model of right ventricle overload in the healthy rat heart.

    Science.gov (United States)

    Masithulela, Fulufhelo

    2016-11-25

    The recognition of RV overpressure is critical to human life, as this may signify morbidity and mortality. Right ventricle (RV) dysfunction is understood to have an impact on the performance of the left ventricle (LV), but the mechanisms remain poorly understood. It is understood that ventricular compliance has the ability to affect cardiac performance. In this study, a bi-ventricular model of the rat heart was used in preference to other, single-ventricle models. Finite element analysis (FEA) of the bi-ventricular model provides important information on the function of the healthy heart. The passive myocardium was modelled as a nearly incompressible, hyperelastic, transversely isotropic material using finite element (FE) methods. Bi-ventricular geometries of healthy rat hearts reconstructed from magnetic resonance images were imported in Abaqus©. In simulating the normal passive filling of the rat heart, pressures of 4.8 kPa and 0.0098 kPa were applied to the inner walls of the LV and RV respectively. In addition, to simulate the overpressure of the RV, pressures of 2.4 kPa and 4.8 kPa were applied to the endocardial walls of the LV and RV respectively. As boundary conditions, the circumferential and longitudinal displacements at the base were set to zero. The radial displacements at the base were left free. The results show that the average circumferential stress at the mid-wall in the overloaded model increased from 2.8 kPa to 18.2 kPa. The average longitudinal stress increased from 1.5 kPa to 9.7 kPa. Additionally, in the radial direction, the average stress increased from 0.1 kPa to 0.6 kPa in the mid-wall. The average circumferential strain was found to be 0.138 and 0.100 on the endocardium of the over pressured and healthy model respectively. The average circumferential stress at the epicardium, mid-wall and endocardium in the case of a normal heart is 10 times lower than in the overloaded heart model. The finite analysis method is able to provide

  7. In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart

    DEFF Research Database (Denmark)

    Brazhe, Nadezda; Treiman, Marek; Faricelli, Barbara

    2013-01-01

    We developed a Raman spectroscopy-based approach for simultaneous study of redox changes in c-and b-type cytochromes and for a semiquantitative estimation of the amount of oxygenated myoglobin in a perfused rat heart. Excitation at 532 nm was used to obtain Raman scattering of the myocardial...... surface of the isolated heart at normal and hypoxic conditions. Raman spectra of the heart under normal pO2 demonstrate unique peaks attributable to reduced c-and b-type cytochromes and oxymyoglobin (oMb). The cytochrome peaks decreased in intensity upon FCCP treatment, as predicted from uncoupling...... mitochondrial respiration. Conversely, transient hypoxia causes the reversible increase in the intensity of peaks assigned to cytochromes c and c1, reflecting electron stacking proximal to cytochrome oxidase due to the lack of terminal electron acceptor O2. Intensities of peaks assigned to oxy...

  8. Establishment and improvement of model of vascularized heart-thymus composite transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Hai-bo; XIA Sui-sheng; WEN Hao; HUANG Zu-fa; YE Qi-fa

    2005-01-01

    Objective To establish and improve the model of heart-thymus composite transplantation. Methods Vascularized both lobes of the thymus is transplanted heterotopically with the heart as a composite graft in rats.This technique was developed and assessed, and viability of the grafts was evaluated histologically. Results Donor operation costed 38. 5 ± 3. 52 min, vascular anastomosis costed 25.0 ± 3. 28 min, operating successful rate was 90%, acute rejection was observed in SD-Wistar group, viable thymus with normal microarchitecture was maintained in Wistar-Wistar group. Conclusions The improved novel technique for combined heart-thymus transplantation is a valuable method for study of the role of thymus in transplantation immunity.

  9. Pharmacology of Casimiroa edulis; Part I. Blood pressure and heart rate effects in the anesthetized rat.

    Science.gov (United States)

    Magos, G A; Vidrio, H

    1991-02-01

    The effect of an alcoholic extract of seeds of Casimiroa edulis on blood pressure and heart rate was determined in rats anesthetized with pentobarbital and compared with that of histamine. The extract induced hypotension, accompanied at high doses by tachycardia. Hypotension after histamine was more transient and was not accompanied by changes in heart rate. Experiments with a variety of autonomic antagonists revealed that extract-induced hypotension was not mediated by histamine H2, muscarinic, or beta-adrenergic receptors, but involved an H1 mechanism. After H1 blockade, the depressor response was reversed to a pressor effect, mediated by alpha-adrenoceptor stimulation. The increase in heart rate was due in part to H1 and in part to beta-adrenergic receptor activation. It was suggested that imidazole derivatives could be responsible for the depressor effect observed. The pressor response could be caused by these or other components of the extract.

  10. Downregulation of adenosine and P2X receptor-mediated cardiovascular responses in heart failure rats

    DEFF Research Database (Denmark)

    Zhao, Xin; Sun, X Y; Erlinge, D;

    2000-01-01

    Neurohormonal changes in congestive heart failure (CHF) include an enhanced peripheral sympathetic nerve activity which results in increased release of noradrenaline, neuropeptide Y and ATP. To examine if such changes in CHF would modulate peripheral pre- and postsynaptic receptors of ATP and its...... effects mediated by the endothelial P2Y receptors are unaffected in CHF. Moreover, the adenosine-mediated inhibitory effects on heart rate and blood pressure were also attenuated in the CHF rats. The most important changes in adenosine and P2-receptor function induced by ischaemic CHF were the reduced...... pressor effect mediated by the P2X receptor and the increased heart rate due to an attenuated inhibitory effect of adenosine....

  11. Variations of Developing Conduction System in Bis-diamine Induced Malformed Rat Heart Recognized by HNK-1 Immunohistochemistry

    OpenAIRE

    Ohtani, Hiroshi

    1998-01-01

    To clarify the abnormal development of the cardiac conduction system in congenital heart anomalies, HNK-1 distribution of bis-diamine induced malformed hearts was studied in rat embryos. All the embryos showed not only conotruncal anomalies, such as persistent truncus arteriosus (PTA) and pulmonary hypoplasia with overriding aorta (comparable to tetralogy of Fallot), but also incomplete absorption of sinus venosus. In the malformed hearts, the middle internodal tract passing through the dorsa...

  12. Protective effects of calmodulin antagonists (trifluoperazine and W-7 on hypothermic ischemic rat hearts.

    Directory of Open Access Journals (Sweden)

    Sugawara,Eiji

    1991-06-01

    Full Text Available The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP and N-(6-aminohexyl-5-chloro-1-naphthalene sulfonamide (W-7 was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.

  13. Effect of Black Grape Juice against Heart Damage from Acute Gamma TBI in Rats

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    Edson Ramos de Andrade

    2013-09-01

    Full Text Available The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ on lipid peroxidation considering Total Body Irradiation (TBI in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH levels were evaluated as a marker for heart damage from acute radiation syndrome (ARS. Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH on serum and lipid peroxidation on heart tissue were evaluated. High concentration of metabolites from lipid peroxidation in heart, and high LDH level on serum were found only in gamma-irradiated group given placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD analysis, which showed resveratrol as the major constituent. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier.

  14. Effect of angiotensin(1-7 on heart function in an experimental rat model of obesity

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    Katja eBlanke

    2015-12-01

    Full Text Available Aim: Obesity is a risk factor for the development of cardiovascular diseases. Recently it was shown that overexpression of the Mas- receptor antagonist angiotensin(1-7 could prevent from diet- induced obesity. However, it remained unclear whether diet-induced obesity and angiotensin(1-7 overexpression might also have effects on the cardiovascular system in these rats.Methods: 23 male Sprague Dawley rats were fed with standard chow (SD+chow, n=5 or a cafeteria diet (SD+CD, n=6 for five months. To investigate the effect of angiotensin(1-7 transgenic rats, expressing an angiotensin(1-7-producing fusion protein in testis were used. These transgenic rats also received a five month’s feeding period with either chow (TGR+chow, n=6 or cafeteria diet (TGR+CD, n=6, respectively. Hemodynamic measurements (pressure-volume loops were carried out to assess cardiac function and blood pressure. Subsequently, hearts were explanted and investigated according to the Langendorff technique. Furthermore, cardiac remodeling in these animals was investigated histologically.Results: After five months cafeteria diet feeding rats showed a significantly increased body weight, which could be prevented in transgenic rats. However, there was no effect on cardiac performance after cafeteria diet in non-transgenic and transgenic rats. Moreover, overexpression of angiotensin(1-7 deteriorated cardiac contractility as indicated by impaired dp/dt. Furthermore, histological analysis revealed that cafeteria diet led to myocardial fibrosis in both, control and transgenic rats and this was not inhibited by an overproduction of angiotensin(1-7.Conclusion: These results indicate that an overexpression of circulating angiotensin(1-7 prevents a cafeteria diet-induced increase in body weight, but does not affect cardiac performance in this experimental rat model of obesity. Furthermore, overexpression of angiotensin(1-7 alone resulted in an impairment of cardiac function.

  15. n-Order and maximum fuzzy similarity entropy for discrimination of signals of different complexity: Application to fetal heart rate signals.

    Science.gov (United States)

    Zaylaa, Amira; Oudjemia, Souad; Charara, Jamal; Girault, Jean-Marc

    2015-09-01

    This paper presents two new concepts for discrimination of signals of different complexity. The first focused initially on solving the problem of setting entropy descriptors by varying the pattern size instead of the tolerance. This led to the search for the optimal pattern size that maximized the similarity entropy. The second paradigm was based on the n-order similarity entropy that encompasses the 1-order similarity entropy. To improve the statistical stability, n-order fuzzy similarity entropy was proposed. Fractional Brownian motion was simulated to validate the different methods proposed, and fetal heart rate signals were used to discriminate normal from abnormal fetuses. In all cases, it was found that it was possible to discriminate time series of different complexity such as fractional Brownian motion and fetal heart rate signals. The best levels of performance in terms of sensitivity (90%) and specificity (90%) were obtained with the n-order fuzzy similarity entropy. However, it was shown that the optimal pattern size and the maximum similarity measurement were related to intrinsic features of the time series.

  16. The role of α7 nicotinic acetylcholine receptor in modulation of heart rate dynamics in endotoxemic rats.

    Directory of Open Access Journals (Sweden)

    Roham Mazloom

    Full Text Available Previous reports have indicated that artificial stimulation of the vagus nerve reduces systemic inflammation in experimental models of sepsis. This phenomenon is a part of a broader cholinergic anti-inflammatory pathway which activates the vagus nerve to modulate inflammation through activation of alpha7 nicotinic acetylcholine receptors (α7nACHR. Heart rate variability represents the complex interplay between autonomic nervous system and cardiac pacemaker cells. Reduced heart rate variability and increased cardiac cycle regularity is a hallmark of clinical conditions that are associated with systemic inflammation (e.g. endotoxemia and sepsis. The present study was aimed to assess the role of α7nACHR in modulation of heart rate dynamics during systemic inflammation. Systemic inflammation was induced by injection of endotoxin (lipopolysaccharide in rats. Electrocardiogram and body temperature were recorded in conscious animals using a telemetric system. Linear and non-linear indices of heart rate variability (e.g. sample entropy and fractal-like temporal structure were assessed. RT-PCR and immunohistochemistry studies showed that α7nACHR is expressed in rat atrium and is mainly localized at the endothelial layer. Systemic administration of an α7nACHR antagonist (methyllycaconitine did not show a significant effect on body temperature or heart rate dynamics in naïve rats. However, α7nACHR blockade could further reduce heart rate variability and elicit a febrile response in endotoxemic rats. Pre-treatment of endotoxemic animals with an α7nACHR agonist (PHA-543613 was unable to modulate heart rate dynamics in endotoxemic rats but could prevent the effect of endotoxin on body temperature within 24 h experiment. Neither methyllycaconitine nor PHA-543613 could affect cardiac beating variability of isolated perfused hearts taken from control or endotoxemic rats. Based on our observations we suggest a tonic role for nicotinic acetylcholine

  17. The effects of prenatal exposure to a 900-MHz electromagnetic field on the 21-day-old male rat heart.

    Science.gov (United States)

    Türedi, Sibel; Hancı, Hatice; Topal, Zehra; Ünal, Deniz; Mercantepe, Tolga; Bozkurt, İlyas; Kaya, Haydar; Odacı, Ersan

    2015-01-01

    The growing spread of mobile phone use is raising concerns about the effect on human health of the electromagnetic field (EMF) these devices emit. The purpose of this study was to investigate the effects on rat pup heart tissue of prenatal exposure to a 900 megahertz (MHz) EMF. For this purpose, pregnant rats were divided into experimental and control groups. Experimental group rats were exposed to a 900 MHz EMF (1 h/d) on days 13-21 of pregnancy. Measurements were performed with rats inside the exposure box in order to determine the distribution of EMF intensity. Our measurements showed that pregnant experimental group rats were exposed to a mean electrical field intensity of 13.77 V/m inside the box (0.50 W/m(2)). This study continued with male rat pups obtained from both groups. Pups were sacrificed on postnatal day 21, and the heart tissues were extracted. Malondialdehyde, superoxide dismutase and catalase values were significantly higher in the experimental group rats, while glutathione values were lower. Light microscopy revealed irregularities in heart muscle fibers and apoptotic changes in the experimental group. Electron microscopy revealed crista loss and swelling in the mitochondria, degeneration in myofibrils and structural impairments in Z bands. Our study results suggest that exposure to EMF in the prenatal period causes oxidative stress and histopathological changes in male rat pup heart tissue.

  18. Selective remodeling of cardiolipin fatty acids in the aged rat heart

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    Rapoport Stanley I

    2006-01-01

    Full Text Available Abstract Background The heart is rich in cardiolipin, a phospholipid acylated in four sites, predominately with linoleic acid. Whether or not aging alters the composition of cardiolipin acyl chains is controversial. We therefore measured the fatty acid concentration of cardiolipin in hearts of 4, 12 and 24 month old rats that consumed one diet, adequate in fatty acids for the duration of their life. Results The concentration (nmol/g of linoleic acid was decreased in 24 month old rats (3965 ± 617, mean ± SD vs 4 month old rats (5525 ± 656, while the concentrations of arachidonic and docosahexaenoic acid were increased in 24 month old rats (79 ± 9 vs 178 ± 27 and 104 ± 16 vs 307 ± 68 for arachidonic and docosahexaenoic acids, 4 months vs 24 months, respectively. Similar changes were not observed in ethanolamine glycerophospholipids or plasma unesterified fatty acids, suggesting specificity of these effects to cardiolipin. Conclusion These results demonstrate that cardiolipin remodeling occurs with aging, specifically an increase in highly unsaturated fatty acids.

  19. COMMUNICATION: On variability and use of rat primary motor cortex responses in behavioral task discrimination

    Science.gov (United States)

    Jensen, Winnie; Rousche, Patrick J.

    2006-03-01

    The success of a cortical motor neuroprosthetic system will rely on the system's ability to effectively execute complex motor tasks in a changing environment. Invasive, intra-cortical electrodes have been successfully used to predict joint movement and grip force of a robotic arm/hand with a non-human primate (Chapin J K, Moxon K A, Markowitz R S and Nicolelis M A L 1999 Real-time control of a robotic arm using simultaneously recorded neurons in the motor cortex Nat. Neurosci. 2 664-70). It is well known that cortical encoding occurs with a high degree of cortical plasticity and depends on both the functional and behavioral context. Questions on the expected robustness of future motor prosthesis systems therefore still remain. The objective of the present work was to study the effect of minor changes in functional movement strategies on the M1 encoding. We compared the M1 encoding in freely moving, non-constrained animals that performed two similar behavioral tasks with the same end-goal, and investigated if these behavioral tasks could be discriminated based on the M1 recordings. The rats depressed a response paddle either with a set of restrictive bars ('WB') or without the bars ('WOB') placed in front of the paddle. The WB task required changes in the motor strategy to complete the paddle press and resulted in highly stereotyped movements, whereas in the WOB task the movement strategy was not restricted. Neural population activity was recorded from 16-channel micro-wire arrays and data up to 200 ms before a paddle hit were analyzed off-line. The analysis showed a significant neural firing difference between the two similar WB and WOB tasks, and using principal component analysis it was possible to distinguish between the two tasks with a best classification at 76.6%. While the results are dependent upon a small, randomly sampled neural population, they indicate that information about similar behavioral tasks may be extracted from M1 based on relatively few

  20. EFFECTS OF GLIBENCLAMIDE, GLIMEPIRIDE, AND GLICLAZIDE ON ISCHEMIC PRECONDITIONING IN RAT HEART

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IKATP ) of rat ventricular myocytes.Methods Isolated Langendorff perfused rat hearts were randomly assigned to five groups: ( 1 ) control group, (2)IPC group, (3) IPC + glibenclamide (GLB, 10 μmol/L) group, (4) IPC + glimepiride (GLM, 10 μmol/L) group,(5) IPC + gliclazide ( GLC, 50 μmol/L ) group. IPC was defined as 3 cycles of 5 -minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded.And the sarcolemmal IKATP of dissociated ventricular myocytes reperfused with 10 μmol/L GLB, 1 μmol/L GLM, and 1μmol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition.Results The infarct sizes of rat hearts in IPC (23.7% ± 1.3% ), IPC + GLM (24. 6% ± 1.0% ), and IPC +GLC (33. 1% ±1.3% ) groups were all significantly smaller than that in control group (43.3% ±1.8%; P <0. 01, n=6). The infarct size of rat hearts in IPC + GLB group (40.4% ± 1.4% ) was significantly larger than that in IPC group (P <0. 01, n =6). Under simulated ischemic condition, GLB ( 10 μmol/L) decreased IKATP from 20. 65 ± 7.80 to 9. 09 ± 0. 10 pA/pF (P < 0. 01, n = 6), GLM ( 1 μ mol/L) did not significantly inhibit IKATP ( n = 6 ), and GLC ( 1μmol/L) decreased IKATP from 16.73 ± 0. 97 to 11.18 ± 3.56 pA/pF ( P < 0. 05, n = 6).Conclusions GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.

  1. 3D imaging of the mitochondrial redox state of rat hearts under normal and fasting conditions

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    He N. Xu

    2014-03-01

    Full Text Available The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+ couple acting as a central electron carrier. We employed the Chance redox scanner — the low-temperature fluorescence scanner to image the three-dimensional (3D spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038. No significant change in Fp was found (p = 0.4. The NADH/Fp ratio decreased with a marginal p value (0.076. The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the

  2. Expression of manganese superoxide dismutase in rat blood, heart and brain during induced systemic hypoxia

    Directory of Open Access Journals (Sweden)

    Septelia I. Wanandi

    2011-02-01

    Full Text Available Background: Hypoxia results in an increased generation of ROS. Until now, little is known about the role of MnSOD - a major endogenous antioxidant enzyme - on the cell adaptation response against hypoxia. The aim of this study was to  determine the MnSOD mRNA expression and levels of specific activity in blood, heart and brain of rats during induced systemic hypoxia.Methods: Twenty-five male Sprague Dawley rats were subjected to systemic hypoxia in an hypoxic chamber (at 8-10% O2 for 0, 1, 7, 14 and 21 days, respectively. The mRNA relative expression of MnSOD was analyzed using Real Time RT-PCR. MnSOD specific activity was determined using xanthine oxidase inhibition assay.Results: The MnSOD mRNA relative expression in rat blood and heart was decreased during early induced systemic hypoxia (day 1 and increased as hypoxia continued, whereas the mRNA expression in brain was increased since day 1 and reached its maximum level at day 7. The result of MnSOD specific activity during early systemic hypoxia was similar to the mRNA expression. Under very late hypoxic condition (day 21, MnSOD specific activity in blood, heart and brain was significantly decreased. We demonstrate a positive correlation between MnSOD mRNA expression and specific activity in these 3 tissues during day 0-14 of induced systemic hypoxia. Furthermore, mRNA expression and specific activity levels in heart strongly correlate with those in blood.Conclusion: The MnSOD expression at early and late phases of induced systemic hypoxia is distinctly regulated. The MnSOD expression in brain differs from that in blood and heart revealing that brain tissue can  possibly survive better from induced systemic hypoxia than heart and blood. The determination of MnSOD expression in blood can be used to describe its expression in heart under systemic hypoxic condition. (Med J Indones 2011; 20:27-33Keywords: MnSOD, mRNA expression, ROS, specific activity, systemic hypoxia

  3. Low-power light and isolated rat hearts after ischemia of myocardium

    Science.gov (United States)

    Monich, Victor A.; Drugova, Olga V.; Lazukin, Valery F.; Bavrina, Anna B.

    2010-02-01

    Total ischemia of myocardium has been simulated on isolated hearts of rats. Effects of a low-power HeNe laser (λ=632.8 nm) and a fiber optic photo-luminescent radiation source of red light ( λ of the spectral peak is equal to 630 nm) on isolated heart contractile function characteristics and on lipid peroxidation (LPO) level in myocardium tissues have been investigated. Two groups of the specimens have been irradiated with red light during the postischemia (reperfusion) period of time. The first group has been treated with laser light and the second one with the luminescent radiation. More rapid restoration of the speed of contraction, of the force of contraction, of the relaxation speed and of the heart rate with respect to the data of the control group has been observed in both experimental groups. The similar tendency was observed in the laser treated specimens. The effects of fibrillation of myocardium of isolated hearts irradiated by lowpower He-Ne laser light were observed. These effects could be caused by the local light fluence rate excess in the interference pattern of laser light diffracted on the heart muscle structures.

  4. Exogenous reactive oxygen species deplete the isolated rat heart of antioxidants.

    Science.gov (United States)

    Vaage, J; Antonelli, M; Bufi, M; Irtun, O; DeBlasi, R A; Corbucci, G G; Gasparetto, A; Semb, A G

    1997-01-01

    The effects of reactive oxygen species (ROS) on myocardial antioxidants and on the activity of oxidative mitochondrial enzymes were investigated in the following groups of isolated, perfused rat hearts. I: After stabilization the hearts freeze clamped in liquid nitrogen (n = 7). II: Hearts frozen after stabilization and perfusion for 10 min with xanthine oxidase (XO) (25 U/l) and hypoxanthine (HX) (1 mM) as a ROS-producing system (n = 7). III: Like group II, but recovered for 30 min after perfusion with XO + HX (n = 9). IV: The hearts were perfused and freeze-clamped as in group III, but without XO + HX (n = 7). XO + HX reduced left ventricular developed pressure and coronary flow to approximately 50% of the baseline value. Myocardial content of hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased at the end of XO + HX perfusion, indicating that generation of ROS and lipid peroxidation occurred. Levels of H2O2 and MDA normalized during recovery. Superoxide dismutase, reduced glutathione and alpha-tocopherol were all reduced after ROS-induced injury. ROS did not significantly influence the tissue content of coenzyme Q10 (neither total, oxidized, nor reduced), cytochrome c oxidase, and succinate cytochrome c reductase. The present findings indicate that the reduced contractile function was not correlated to reduced activity of the mitochondrial electron transport chain. ROS depleted the myocardium of antioxidants, leaving the heart more sensitive to the action of oxidative injury.

  5. Persistent effects after trigeminal nerve proprioceptive stimulation by mandibular extension on rat blood pressure, heart rate and pial microcirculation.

    Science.gov (United States)

    Lapi, D; Colantuoni, A; Del Seppia, C; Ghione, S; Tonlorenzi, D; Brunelli, M; Scuri, R

    2013-03-01

    The trigemino-cardiac reflex is a brainstem reflex known to lead to a decrement in heart rate and blood pressure, whereas few data have been collected about its effects on the cerebral hemodynamic. In this study we assess the in vivo effects of trigeminal nerve peripheral stimulation by mandibular extension on pial microcirculation and systemic arterial blood pressure in rats. Experiments were performed in male Wistar rats subjected to mandibular extension obtained inserting an ad hoc developed retractor between the dental arches. Mean arterial blood pressure and heart rate were recorded and the pial arterioles were visualized by fluorescence microscopy to measure the vessel diameters before (15 minutes) during (5-15 minutes) and after (80 minutes) mandibular extension. While in control rats (sham-operated rats) and in rats subjected to the dissection of the trigeminal peripheral branches mean arterial blood pressure, heart rate and pial microcirculation did not change during the whole observation period (110 minutes), in rats submitted to mandibular extension, mean arterial blood pressure, heart rate and arteriolar diameter significantly decreased during stimulation. Afterward mean arterial blood pressure remained reduced as well as heart rate, while arteriolar diameter significantly increased evidencing a vasodilatation persisting for the whole remaining observation time. Therefore, trigeminal nerve proprioceptive stimulation appears to trigger specific mechanisms regulating systemic arterial blood pressure and pial microcirculation.

  6. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

    Science.gov (United States)

    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

    2016-10-01

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  7. Mechanism of cardioprotective effect of erythropoietin-induced preconditioning in rat heart

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    Garg Kavita

    2010-01-01

    Full Text Available Objective : The cardioprotective potential of human recombinant erythropoietin (alpha (Epo against ischemia-reperfusion-induced injury is well known. But, the underlying mechanisms are not well elucidated. The aim of this study was to characterize the mechanism involved in the cardioprotective effect of Epo-induced preconditioning in isolated rat heart. Materials and Methods : The heart was mounted on a Langendorff apparatus. After 10 min of stabilization, four cycles of ischemic preconditioning (IPC were given followed by 30 min of global ischemia and 120 min of reperfusion. Epo preconditioning was induced by four cycles of 5-min perfusion of K-H solution containing Epo (1.0 U/ml followed by 5 min perfusion with K-H solution. Myocardial infarct size was estimated macroscopically using the triphenyltetrazolium chloride staining technique. The extent of myocardial injury was measured by release of lactate dehydrogenase and creatine kinase-MB in the coronary effluent. Results : The present study demonstrates that Epo preconditioning was almost as effective as IPC. Administration of Wortmannin (100 nM, a PI-3K inhibitor, or Chelerythrine (1 μM, a protein kinase-C (PKC inhibitor, or AG490 (5 μM, a JAK-2 inhibitor, significantly attenuated the cardioprotective effects of Epo-induced preconditioning. Conclusion : Our result suggest that the cardioprotective potential of Epo-induced preconditioning in isolated rat heart was due to an interplay of the JAK-2, PI-3K and PKC pathways. Inhibition of any one of the three pathways was sufficient to block the cardioprotective effect of Epo-induced preconditioning in isolated rat heart.

  8. Propionate metabolism in the rat heart by 13C n.m.r. spectroscopy.

    Science.gov (United States)

    Sherry, A D; Malloy, C R; Roby, R E; Rajagopal, A; Jeffrey, F M

    1988-01-01

    High-resolution 13C n.m.r. spectroscopy has been used to examine propionate metabolism in the perfused rat heart. A number of tricarboxylic acid (TCA) cycle intermediates are observable by 13C n.m.r. in hearts perfused with mixtures of pyruvate and propionate. When the enriched 13C-labelled nucleus originates with pyruvate, the resonances of the intermediates appear as multiplets due to formation of multiply-enriched 13C-labelled isotopomers, whereas when the 13C-labelled nucleus originates with propionate, these same intermediates appear as singlets in the 13C spectrum since entry of propionate into the TCA cycle occurs via succinyl-CoA. An analysis of the isotopomer populations in hearts perfused with [3-13C]pyruvate plus unlabelled propionate indicates that about 27% of the total pyruvate pool available to the heart is derived directly from unlabelled propionate. This was substantiated by perfusing a heart for 2 h with [3-13C]propionate as the only available exogenous substrate. Under these conditions, all of the propionate consumed by the heart, as measured by conventional chemical analysis, ultimately entered the oxidative pathway as [2-13C] or [3-13C]pyruvate. This is consistent with entry of propionate into the TCA cycle intermediate pools as succinyl-CoA and concomitant disposal of malate to pyruvate via the malic enzyme. 13C resonances arising from enriched methylmalonate and propionylcarnitine are also detected in hearts perfused with [3-13C] or [1-13C]propionate which suggests that 13C n.m.r. may be useful as a non-invasive probe in vivo of metabolic abnormalities involving the propionate pathway, such as methylmalonic aciduria or propionic acidaemia. PMID:3178775

  9. Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis.

    Science.gov (United States)

    Arnold, Amy C; Shaltout, Hossam A; Gilliam-Davis, Shea; Kock, Nancy D; Diz, Debra I

    2011-06-01

    The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II.

  10. Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

    Science.gov (United States)

    Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

    2015-09-01

    Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

    Science.gov (United States)

    Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2014-04-10

    In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease.

  12. Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling

    Science.gov (United States)

    Fu, Xuebin; Segiser, Adrian; Carrel, Thierry P.; Tevaearai Stahel, Hendrik T.; Most, Henriette

    2016-01-01

    Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under “reloaded” conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients.

  13. Effects of ischemia and omeprazole preconditioning on functional recovery of isolated rat heart

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    Nevena Jeremic

    2015-04-01

    Full Text Available AbstractObjective:The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion.Methods:The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC hearts first underwent preconditioning lasting 5 minutes with 100μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion.Results:Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion.Conclusion:Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible.

  14. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart.

    Science.gov (United States)

    Bialy, Dariusz; Wawrzynska, Magdalena; Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Wozniak, Mieczyslaw; Cadete, Virgilio J J; Sawicki, Grzegorz

    2015-01-01

    Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP), and rate pressure product (RPP) were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2) and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6) were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury.

  15. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart

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    Dariusz Bialy

    2015-01-01

    Full Text Available Low frequency electromagnetic field (LF-EMF decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP, and rate pressure product (RPP were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2 and the contents of coronary effluent troponin I (TnI and interleukin-6 (IL-6 were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury.

  16. The hallucinogen derived from Salvia divinorum, salvinorin A, has kappa-opioid agonist discriminative stimulus effects in rats.

    Science.gov (United States)

    Willmore-Fordham, Catherine B; Krall, Daniel M; McCurdy, Christopher R; Kinder, David H

    2007-09-01

    Data from clinical and preclinical studies converge implicating the plant-derived hallucinogen salvinorin A as an important pharmacologic tool; this psychoactive compound may expand scientific understandings on mammalian kappa-opioid receptor systems. Human salvinorin A effects, consistent with kappa-opioid receptor agonism, include antinociception, sedation, dysphoria and distorted perceptions. The experiments reported here measured salvinorin A (1-3mg/kg, i.p.) discriminative stimulus properties in male Sprague-Dawley rats conditioned to recognize the discriminative stimulus cue generated by the well characterized kappa-opioid agonist U-69593 (0.56 mg/kg, i.p.). At three distinct active doses, salvinorin A fully substituted for U-69593 without altering response rates. The lever choice pattern in U-69593 trained animals reverted to vehicle lever responding when a kappa selective antagonist compound, nor-BNI (4.5 nM, i.c.v.) was administered 1h prior to salvinorin A, yet nor-BNI alone failed to impact the rate or pattern of subject responses. These findings confirm and extend results published after similar drug discrimination tests were performed in rhesus monkeys. The discussion section of this article highlights public concern over salvinorin A misuse and emphasizes several potential pharmacotherapeutic applications for salvinorin A or analogue compounds.

  17. Heart-bound adiponectin, not serum adiponectin, inversely correlates with cardiac hypertrophy in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Inoue, Takao; Takemori, Kumiko; Mizuguchi, Nobuyuki; Kimura, Masatomo; Chikugo, Takaaki; Hagiyama, Man; Yoneshige, Azusa; Mori, Tatsufumi; Maenishi, Osamu; Kometani, Takashi; Itoh, Tatsuki; Satou, Takao; Ito, Akihiko

    2017-08-25

    What is the central question of this study? An inverse correlation between circulating adiponectin and many diseases has been reported, but some studies have found no correlation. To evaluate this controversy, we investigated the relationship between heart-bound adiponectin and hypertension or cardiac hypertrophy, compared with serum adiponectin. What is the main finding and its importance? Using hypertensive and normotensive rats, we found that heart-bound adiponectin was inversely correlated with cardiac hypertrophy, suggesting that heart-bound adiponectin has a more important function in preventing cardiac hypertrophy than circulating adiponectin. Our study provides new insights regarding the role of adiponectin in diseases. The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin with hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages, as follows: normotensive Wistar-Kyoto rats (WKYs); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHRs); and stroke-prone SHRs (SHRSPs). Blood pressure, heart-to-body weight ratio, serum adiponectin and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration was not inversely correlated with blood pressure or heart-to-body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSPs than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues

  18. Cardioprotection by polysaccharide sulfate against ischemia/reperfusion injury in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    Ying YANG; Shen-jiang HU; Liang LI; Guo-ping CHEN

    2009-01-01

    Aim: Polysaccharide sulfate (PSS) is a new type of heparinoid synthesized with alginic acid as the basic material and then by chemical introduction of effective groups. Although PSS is successfully applied in ischemic cardio-cerebrovascular dis-ease, its effect on cardiac function after ischemia/reperfusion (I/R) injury has previously not been investigated. The aim of the present study was to investigate whether PSS can protect the heart from I/R injury and the underlying mechanism of protection. Methods: Isolated rat hearts were perfused (Langendorff) and subjected to 20 min global ischemia followed by 60 min rep-effusion with Kreb's Henseleit solution or PSS (0.3-100 mg/L). Myocardial contractile function was continuously recorded. Creatine kinase (CK) and lactate dehydrogenase (LDH) leakage were measured. Tumor necrosis factor-α (TNF-α) expres-sion in cardiomyocytes was investigated. Western blot analysis for extracellular regulated kinases (ERKs), c-jun amino-terminal kinase (INKs) and p38 mitogen-activated protein kinase (MAPK) activity was performed. Results: After I/R, cardiac contractility decreased, CK and LDH levels increased in the coronary effluent, and TNF-α expression increased in cardiomyocytes. PSS administration at concentrations of 1-30 mg/L improved cardiac contractility, reduced CK and LDH release and inhibited TNF-α production. Phosphorylated-p38MAPK (p-p38MAPK) and p-p54/p46-JNK increased in I/R rat hearts but diminished in PSS (1-30 mg/L) treated hearts. P-p44/p42-ERK levels were unchanged. In contrast, high concentrations of PSS (100 mg/L) had adverse effects that caused a worsening of heart function. Conclusion: PSS has dose-dependent cardioprotective effects on the rat heart after I/R injury. The beneficial effects may be mediated through normalization of the activity of p38 MAPK and JNK pathways as well as controlling the level of TNF-α expression.

  19. Effect of postnatal lead exposure on the development of sympathetic innervation of the heart. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, M.E.

    1983-01-01

    To determine possible mechanisms for this Pb-induced cardiotoxicity, several neutrochemical parameters indicative of cardiac sympathetic innervation were measured in developing rats. Presynaptic indices of nerve terminal development which were studied included steady-state levels of norepinephrine, neuronal uptake and vesicular storage of /sup 3/H-norepinephrine. Analysis of postsynaptic development was accomplished by quantitating the density of ..beta..-adrenergic receptors and by measuring the activity of adenylate cyclase. Rat pups were exposed to Pb from birth to weaning (21 days) via the milk of dams whose drinking water contained 0.2% Pb acetate. This method and level of Pb treatment had no effect on body or heart weight development, however, it did result in a seven-fold increase in the blood Pb content (70-75 ..mu..g/dl) of the treated pups during the period of exposure. Pb exposure accelerated the development of sympathetic innervation of the heart as detected by significant increases in the vesicular uptake of /sup 3/H-norepinephrine and the steady-state concentration of norepinephrine measured at postnatal day 4. On the other hand, ontogeny of the neutronal uptake of /sup 3/H-norepinephrine in the heart and in the forebrain was not affected by Pb treatment. The apparent premature development of sympathetic innervation induced by Pb treatment was not reflected in significant alterations in either the density or the affinity of ..beta..-adrenergic receptor sites determined by the binding kinetics of /sup 3/H-dihydroalprenolol.

  20. Effects Of The Direct Renin Inhibitor Aliskiren On Oxidative Stress In Isolated Rat Heart

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    Plecevic Sasa

    2015-09-01

    Full Text Available Increased activity of the renin-angiotensin-aldosterone system (RAAS plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g, were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O. Markers of oxidative stress (NO2−, TBARS, H2O2 and O2− were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM. The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2− and hydrogen peroxide (H2O2 levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.

  1. Tl(+) induces both cationic and transition pore permeability in the inner membrane of rat heart mitochondria.

    Science.gov (United States)

    Korotkov, Sergey M; Nesterov, Vladimir P; Brailovskaya, Irina V; Furaev, Viktor V; Novozhilov, Artemy V

    2013-12-01

    Effects of Tl(+) were studied in experiments with isolated rat heart mitochondria (RHM) injected into 400 mOsm medium containing TlNO3 and a nitrate salt (KNO3 or NH4NO3) or TlNO3 and sucrose. Tl(+) increased permeability of the inner membrane of the RHM to K(+) and H(+). This manifested as an increase of the non-energized RHM swelling, in the order of sucrose Tl(+)-induced opening of the mitochondrial permeability pore (MPTP) in Ca(2+)-loaded rat heart mitochondria increased both the swelling and the inner membrane potential dissipation, as well as decreased basal state and 2,4-dinitrophenol-stimulated respiration. These effects of Tl(+) were suppressed by the MPTP inhibitors (cyclosporine A, ADP, bongkrekic acid, and n-ethylmaleimide), activated in the presence of the MPTP inducer (carboxyatractyloside) or mitoKATP inhibitor (5-hydroxydecanoate), but were not altered in the presence of mitoKATP agonists (diazoxide or pinacidil). We suggest that the greater sensitivity of heart and striated muscles, versus liver, to thallium salts in vivo can result in more vigorous Tl(+) effects on muscle cell mitochondria.

  2. Hypertrophic response of the Association of Thyroid Hormone and Exercise in the Heart of Rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Fernanda Rodrigues de, E-mail: nandaeduca@yahoo.com.br; Resende, Elmiro Santos; Lopes, Leandro; Gonçalves, Alexandre; Chagas, Rafaella; Fidale, Thiago; Rodrigues, Poliana [UFU - Universidade Federal de Uberlândia, Uberlândia, MG (Brazil)

    2014-02-15

    Cardiac hypertrophy is a component of cardiac remodeling occurring in response to an increase of the activity or functional overload of the heart. Assess hypertrophic response of the association of thyroid hormone and exercise in the rat heart. We used 37 Wistar rats, male, adults were randomly divided into four groups: control, hormone (TH), exercise (E), thyroid hormone and exercise (H + E); the group received daily hormone levothyroxine sodium by gavage at a dose of 20 μg thyroid hormone/100g body weight, the exercise group took swimming five times a week, with additional weight corresponding to 20% of body weight for six weeks; in group H + E were applied simultaneously TH treatment groups and E. The statistics used was analysis of variance, where appropriate, by Tukey test and Pearson correlation test. The T4 was greater in groups TH and H + E. The total weight of the heart was greater in patients who received thyroid hormone and left ventricular weight was greater in the TH group. The transverse diameter of cardiomyocytes increased in groups TH, E and H + E. The percentage of collagen was greater in groups E and H + E Correlation analysis between variables showed distinct responses. The association of thyroid hormone with high-intensity exercise produced cardiac hypertrophy, and generated a standard hypertrophy not directly correlated to the degree of fibrosis.

  3. Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

    Energy Technology Data Exchange (ETDEWEB)

    Temma, K.; Akera, T.; Ng, Y.C.

    1985-03-01

    The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific (/sup 3/H)phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca/sup 2 +/ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K/sup +/ currents.

  4. Influence of starvation on heart contractility and corticosterone level in rats.

    Science.gov (United States)

    Lee, Sung Ryul; Ko, Tae Hee; Kim, Hyoung Kyu; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2015-11-01

    The physiological changes, including cardiac modification, that occur during starvation are not yet completely understood. The purpose of this study is to examine the effects of a 2-week starvation period on heart contractility, muscle mass, and irisin and corticosterone levels in rats. Rats in the starved group showed a significant reduction in the body, heart, kidney, and muscle weight (n = 23, p echocardiography were further compared with the body-weight-matched control group. Starvation reduced the left ventricle mass; however, this difference was not significant compared with the body-weight-matched group (p > 0.05). In the starvation group, the impairment of cardiac output was dependent on the reduction in stroke volume and heart rate. Starvation induced a severe reduction in ejection fraction and fractional shortening when compared with the body-weight-matched control group (p < 0.05). In summary, prolonged starvation, which leads to a deficiency of available nutrition, increases the stress-related corticosterone level, impairs the cardiac output, and is associated with changes in cardiac morphogeometry.

  5. Effects of ubiquinol with fluid resuscitation following haemorrhagic shock on rat lungs, diaphragm, heart and kidneys.

    Science.gov (United States)

    Bennetts, Paul; Shen, Qiuhua; Thimmesch, Amanda R; Diaz, Francisco J; Clancy, Richard L; Pierce, Janet D

    2014-07-01

    Haemorrhagic shock (HS) and fluid resuscitation can lead to increased reactive oxygen species (ROS), contributing to ischaemia-reperfusion injury and organ damage. Ubiquinol is a potent antioxidant that decreases ROS. This study examined the effects of ubiquinol administered with fluid resuscitation following controlled HS. Adult male Sprague-Dawley rats were randomly assigned to treatment [ubiquinol, 1 mg (100 g body weight)(-1)] or control groups. Rats were subjected to 60 min of HS by removing 40% of the total blood volume to a mean arterial pressure ∼45-55 mmHg. The animals were resuscitated with blood and lactated Ringer solution, with or without ubiquinol, and monitored for 120 min. At the end of the experiments, the rats were killed and the lungs, diaphragm, heart and kidneys harvested. Leucocytes were analysed for mitochondrial superoxide at baseline, end of shock and 120 min following fluid resuscitation using MitoSOX Red. Diaphragms were examined for hydrogen peroxide using dihydrofluorescein diacetate and confocal microscopy. The apoptosis in lungs, diaphragm, heart and kidneys was measured using fluorescence microscopy with acridine orange and ethidium bromide. Leucocyte mitochondrial superoxide levels were significantly lower in rats that received ubiquinol than in the control animals. Production of hydrogen peroxide and apoptosis were significantly reduced in the organs of rats treated with ubiquinol. These findings suggest that ubiquinol, administered with fluid resuscitation after HS, attenuates ROS production and apoptosis. Thus, ubiquinol is a potent antioxidant that may be used as a potential treatment to reduce organ injury following haemorrhagic events. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  6. Effects of Lipoteichoic Acid induced Delayed Preconditioning on Ischemia-reperfusion Injury in Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    马世玉; 向继洲; 吴基良; 胡本容

    2003-01-01

    To explore the potential of lipoteichoic acid (LTA) induced cardioprotection against is-chemia-reperfusion (I/R) injury in isolated rat hearts and whether endogenous nitric oxide (NO)participates-in the protection, the rats were pretreated with LTA (1 mg/kg, i. p. ) 24 h before theexperiment, and the isolated hearts were subjected to 30 min no-flow normothermic global ischemiaand 60 min reperfusion after a 20-min stabilization period by the langendorff method. Cardiac func-tions were evaluated at the end of stabilization, and at 30 min, 60 min of reperfusion. The amountsof MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase(LDH) and total NO oxidationproducts in the coronary effluent were measured spectrophotometrically at the end of reperfusion. Itwas revealed that pretreatment with LTA could significantly improve the recovery of cardiac func-tion, reduce the release of CK-MB and LDH, and increase the concentrations of NO in coronary ef-fluent. The protective effects were abrogated by pretreatment of the rats with L-NAME. It wasconcluded that LTA could induce the delayed cardioprotection against I/R injury, and endogenousNO may be involved in the mechanisms.

  7. Metformin prevents the development of chronic heart failure in the SHHF rat model.

    Science.gov (United States)

    Cittadini, Antonio; Napoli, Raffaele; Monti, Maria Gaia; Rea, Domenica; Longobardi, Salvatore; Netti, Paolo Antonio; Walser, Marion; Samà, Mariateresa; Aimaretti, Gianluca; Isgaard, Jörgen; Saccà, Luigi

    2012-04-01

    Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investigated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomized into three treatment groups as follows: 1) metformin (100 mg/kg per day), 2) rosiglitazone (2 mg/kg per day), and 3) no drug. Ten Sprague-Dawley rats served as normal controls. At the end of the treatment period (12 months), the cardiac phenotype was characterized by histology, echocardiography, and isolated perfused heart studies. Metformin attenuated left ventricular (LV) remodeling, as shown by reduced LV volumes, wall stress, perivascular fibrosis, and cardiac lipid accumulation. Metformin improved both systolic and diastolic indices as well as myocardial mechanical efficiency, as shown by improved ability to convert metabolic energy into mechanical work. Metformin induced a marked activation of AMP-activated protein kinase, endothelial nitric oxide synthase, and vascular endothelial growth factor and reduced tumor necrosis factor-α expression and myocyte apoptosis. Rosiglitazone did not affect LV remodeling, increased perivascular fibrosis, and promoted further cardiac lipid accumulation. In conclusion, long-term treatment with metformin, but not with rosiglitazone, prevents the development of severe CHF in the SHHF model by a wide-spectrum interaction that involves molecular, structural, functional, and metabolic-energetic mechanisms.

  8. Antidepressant treatment decreases daily salt intake and prevents heart dysfunction following subchronic aortic regurgitation in rats.

    Science.gov (United States)

    De Gobbi, Juliana Irani Fratucci; Omoto, Ana Carolina Mieko; Siqueira, Tamires Ferreira; Matsubara, Luiz Shigueto; Roscani, Meliza Goi; Matsubara, Beatriz Bojikian

    2015-05-15

    Depression is a predictor of poor prognosis in patients with heart failure. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) may improve these outcomes. Left ventricular volume overload induced hypertrophy that is associated with aortic regurgitation (AR) leads to ventricular dysfunction and heart failure. The aim of this study was to verify the effects of the SSRI paroxetine on cardiac function, as well as on fluid intake and excretion, in subchronic AR. Male Wistar rats (260 to 280g) received sham (SH) surgery or AR induced by retrograde puncture of the aortic valve leaflets. The presence of AR was confirmed by echocardiography (ECHO) exams. Four weeks after AR surgery, subcutaneous injections of paroxetine (PAR: 10mg/kg 3 times in a week) or saline were administered. The rats were randomly divided into the following 4 groups and treated for 4 weeks: AR-PAR, ARsaline, SH-PAR and SH-saline. At the end of the treatment period, fractional shortening was preserved in AR-PAR, compared to AR-saline (46.6±2.7% vs 38.3±2.2%, respectively). Daily 0.3 M NaCl intake was reduced in PAR-treated rats. Natriuresis was increased in weeks 2-3 after PAR treatment. Our results suggest that augmentation of central 5-HT neurotransmission has a beneficial effect on cardiovascular remodeling following volume overload. The mechanisms underlying this effect are unknown.

  9. Increase of ATP-sensitive potassium (KATP channels in the heart of type-1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Chen Zhih-Cherng

    2012-01-01

    Full Text Available Abstract Background An impairment of cardiovascular function in streptozotocin (STZ-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (KATP channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify the changes of cardiac KATP channels in diabetic disorders. Methods Streptozotocin-induced diabetic rats and neonatal rat cardiomyocytes treated with a high concentration of glucose (a D-glucose concentration of 30 mM was used and cells were cultured for 24 hr were used to examine the effect of hyperglycemia on cardiac function and the expression of KATP channels. KATP channels expression was found to be linked to cardiac tonic dysfunction, and we evaluated the expression levels of KATP channels by Western blot and Northern blot analysis. Results The result shows diazoxide produced a marked reduction of heart rate in control group. Furthermore, the methods of Northern blotting and Western blotting were employed to identify the gene expression of KATP channel. Two subunits of cardiac KATP channel (SUR2A and kir 6.2 were purchased as indicators and showed significantly decreased in both diabetic rats and high glucose treated rat cardiac myocytes. Correction of hyperglycemia by insulin or phlorizin restored the gene expression of cardiac KATP in these diabetic rats. Conclusions Both mRNA and protein expression of cardiac KATP channels are decreased in diabetic rats induced by STZ for 8 weeks. This phenomenon leads to result in desensitization of some KATP channel drugs.

  10. Effects of DPP-4 inhibitors on the heart in a rat model of uremic cardiomyopathy.

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    Lyubov Chaykovska

    Full Text Available BACKGROUND: Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD patients. Glucagon-like peptide-1 (GLP-1 may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-∞ in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-∞ values; 41% and 28% (p = 0.0001 and p = 0.0324, respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 µmol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h (p = 0.01. The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin. CONCLUSIONS/SIGNIFICANCE: DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP. Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment.

  11. Improved cardiac protection with Sabax cardioplegia in Langendorff isolated rat hearts

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    Perian M.

    2014-12-01

    Full Text Available Objective: Cardioplegia is an important step to facilitate cardiac surgery while limiting intraoperative myocardial injury. Although recent advances in cardioplegic arrest methods have significantly contributed to better postoperative outcomes, there is still controversy regarding the optimal composition and temperature of the cardioplegic solution. Accordingly, we aimed to assess whether cold or lukewarm Sabax cardioplegia offer improved myocardial protection compared with the classical Krebs-Henseleit solution. Methods: The hearts of 40 male Wistar rats were isolated and submitted to constant-flow retrograde perfusion using a Langendorff perfusion apparatus. The hearts were randomly assigned to cold Krebs-Henseleit (K-H, cold Sabax, or lukewarm Sabax cardioplegia. The ECG, heart rates, and left ventricular systolic pressures (LVSP were recorded pre- and post-cardioplegia. The time needed for cardioplegia induction and post-cardioplegia recovery were also noted. Results: Both cold and lukewarm Sabax cardioplegia insured faster induction and faster recovery following isothermic reperfusion compared to the standard K-H solution (both p< 0.01. With K-H cardioplegia, the hearts presented a 21.7% force loss after reperfusion (p< 0.001, whilst Sabax cardioplegia was associated with a slight increase in ventricular mechanical activity (3% LVSP increase with lukewarm Sabax cardioplegia, p< 0.001 and 2% LVSP increase with cold Sabax cardioplegia, p = 0.02. With Sabax cardioplegia the hearts displayed considerably less major arrhythmic events and presented less significant bradycardia. Conclusions: The present data suggest that Sabax cardioplegia may be superior to the classical cold crystalloid K-H solution in preserving mechanical activity of the heart and may provide superior protection against major arrhythmias.

  12. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    Institute of Scientific and Technical Information of China (English)

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan

    2010-01-01

    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  13. Pycnogenol® and its fractions influence the function of isolated heart in rats with experimental diabetes mellitus.

    Science.gov (United States)

    Kralova, Eva; Jankyova, Stanislava; Mucaji, Pavel; Gresakova, Eva; Stankovicova, Tatiana

    2015-02-01

    The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity "in vitro" was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC's fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components.

  14. Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study.

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    Carolyn A Carr

    Full Text Available AIMS: Endogenous cardiac progenitor cells, expanded from explants via cardiosphere formation, present a promising cell source to prevent heart failure following myocardial infarction. Here we used cine-magnetic resonance imaging (MRI to track administered cardiosphere-derived cells (CDCs and to measure changes in cardiac function over four months in the infarcted rat heart. METHODS AND RESULTS: CDCs, cultured from neonatal rat heart, comprised a heterogeneous population including cells expressing the mesenchymal markers CD90 and CD105, the stem cell marker c-kit and the pluripotency markers Sox2, Oct3/4 and Klf-4. CDCs (2 × 10(6 expressing green fluorescent protein (GFP+ were labelled with fluorescent micron-sized particles of iron oxide (MPIO. Labelled cells were administered to the infarcted rat hearts (n = 7 by intramyocardial injection immediately following reperfusion, then by systemic infusion (4 × 10(6 2 days later. A control group (n = 7 was administered cell medium. MR hypointensities caused by the MPIOs were detected at all times and GFP+ cells containing MPIO particles were identified in tissue slices at 16 weeks. At two days after infarction, cardiac function was similar between groups. By 6 weeks, ejection fractions in control hearts had significantly decreased (47 ± 2%, but this was not evident in CDC-treated hearts (56 ± 3%. The significantly higher ejection fractions in the CDC-treated group were maintained for a further 10 weeks. In addition, CDC-treated rat hearts had significantly increased capillary density in the peri-infarct region and lower infarct sizes. MPIO-labelled cells also expressed cardiac troponin I, von Willebrand factor and smooth muscle actin, suggesting their differentiation along the cardiomyocyte lineage and the formation of new blood vessels. CONCLUSIONS: CDCs were retained in the infarcted rat heart for 16 weeks and improved cardiac function.

  15. Stress facilitates late reversal learning using a touchscreen-based visual discrimination procedure in male Long Evans rats.

    Science.gov (United States)

    Bryce, Courtney A; Howland, John G

    2015-02-01

    The stress response is essential to the survival of all species as it maintains internal equilibrium and allows organisms to respond to threats in the environment. Most stress research has focused on the detrimental impacts of stress on cognition and behavior. Reversal learning, which requires a change in response strategy based on one dimension of the stimuli, is one type of behavioral flexibility that is facilitated following some brief stress procedures. The current study investigated a potential mechanism underlying this facilitation by blocking glucocorticoid receptors (GRs) during stress. Thirty-seven male Long Evans rats learned to discriminate between two images on a touchscreen, one of which was rewarded. Once a criterion was reached, rats received stress (30 min of restraint stress or no stress) and drug (GR antagonist RU38486 or vehicle) administration prior to each of the first 3 days of reversal learning. We expected that stress would facilitate reversal learning and RU38486 (10 mg/kg) would prevent this facilitation in both early (50% correct in one session) stages of reversal learning. Results showed that stressed rats performed better than unstressed rats (fewer days for late reversal, fewer correction trials, and fewer errors) in the late but not early stage of reversal learning. RU38486 did not block the facilitation of RL by stress, although it dramatically increased response, but not reward, latencies. These results confirm the facilitation of late reversal by stress in a touchscreen-based operant task in rats and further our understanding of how stress affects higher level cognitive functioning and behavior.

  16. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy

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    Fu Morgan

    2010-09-01

    Full Text Available Abstract Background We investigated whether early combined autologous adipose-derived mesenchymal stem cell (ADMSC and sildenafil therapy offers an additive benefit in preserving heart function in rat dilated cardiomyopathy (DCM. Methods Adult Lewis rats (n = 8 per group were divided into group 1 (normal control, group 2 (saline-treated DCM rats, group 3 [2.0 × 106 ADMSC implanted into left ventricular (LV myocardium of DCM rats], group 4 (DCM rats with sildenafil 30 mg/kg/day, orally, and group 5 (DCM rats with combined ADMSC-sildenafil. Treatment was started 1 week after DCM induction and the rats were sacrificed on day 90. Results The results showed that mitochondrial protein expressions of connexin43 and cytochrome-C were lowest in group 2, and lower in groups 3 and 4 than in group 5 (p Conclusion Early combined ADMSC/sildenafil is superior to either treatment alone in preserving LV function.

  17. Age- and sex-related changes in heart rate variability under conditions of blockade or stimulation of peripheral adrenoceptor in outbred rats.

    Science.gov (United States)

    Kur'yanova, E V; Teplyi, D L

    2014-07-01

    Changes in heart rhythm variability were studied in male and female mature and 5-6-week-old rats under conditions of 7-day administration of β1-adrenoreceptor blocker atenolol (2.5 mg/kg) and α1-adrenoreceptor agonist phenylephrine (0.3 mg/kg). Atenolol administration to mature rats was followed by a slight deceleration of cardiac rhythm, a tendency to heart rate variability decrease in the HF range, and moderate increase in centralization of regulation. In 6-week-old rats, increased variability of cardiointervals and significant increase of centralization of the heart rhythm regulation due to an increase in the power of low-frequency waves (specifically VLF) were observed. In both mature and young rats, changes of heart rate frequency and variability in response to atenolol administration were more pronounced in females. Phenylephrine administration was followed by a significant heart rate deceleration, increase in cardiointerval variability and centralization of heart rate regulation in mature rats and by a decrease in heart rate variability in all frequency ranges in 6-week-old rats. In mature rats, changes in heart rate frequency and variability produced by phenylephrine administration were more pronounced in males; in young rats, the most strained heart rhythm developed in females.

  18. Measurement of ultraweak chemiluminescence emitted from isolated and perfused rat hearts

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    Bottigli, U.; Camici, P.; Bellina, C.R. (Pisa Univ. (Italy). Ist. di Patologia Speciale Medica e Metodologia Clinica); Salvadori, P.A.; Mazzarisi, R.A. (Consiglio Nazionale delle Ricerche, Pisa (Italy). Lab. di Fisiologia Clinica); Barsacchi, R. (Pisa Univ. (Italy). Ist. di Chimica Biologica); Quaglia, M. (Scuola Normale Superiore, Pisa (Italy)); Ursini, F. (Padua Univ. (Italy). Ist. di Chimica Biologica)

    1984-03-01

    This paper describes the use of a single-photon counting apparatus (SPCA) for the continuous monitoring of the ultraweak chemiluminescence (UWC) emitted by isolated and perfused rat hearts and deriving from phospholipid peroxydation. Specifically the SPCA was used to assess the peroxidative stress induced in the heart by the addition of an hydroperoxide to the perfusing medium. To this purpose, different hydroperoxides were used and each one produced a typical and highly reliable temporal evolution of UWC. It was also found that the oxygen availability strongly influences the intensity and the kinetic of the UWC emission. UWC was proved to be a very interesting and promising tool for monitoring the peroxidative damage of biological membranes, both because it makes a continuous assessment possible and because the sensitivity of this method is approximately ten times greater than usual analytical chemistry methods.

  19. [L-propionylcarnitine taurine amide induces the metabolic recovery of the isolated postischemic rat heart].

    Science.gov (United States)

    Lazzarino, G; Corsico, N; Tavazzi, B; di Pierro, D; Arrigoni-Martelli, E; Giardina, B

    1992-10-01

    The effect of reperfusion with L-propionyl-carnitine-taurinammide 1 mM was evaluated on the metabolic recovery of the isolated postischemic rat heart. Data referring to the tissue concentration of the high-energy phosphates, oxypurines, nucleosides, nicotinic coenzymes, lactate and pyruvate indicate that L-propionyl-carnitine-taurinammide significantly improves the metabolism of the reperfused myocardium. In particular, ATP, creatinphosphate, GTP, sum of adenine nucleotides and the energy charge resulted 1.80, 1.83, 3.47, 1.47 and 1.20 times higher respectively than the corresponding values recorded in control reperfused heart (p < 0.01 all). These data, out of supplying the necessary biochemical support to the beneficial effects of L-propionyl-carnitine-taurinammide on hemodynamics obtained in previous studies, suggest that L-propionyl-carnitine-taurinammide might represent a useful tool for the pharmacological treatment of myocardial infarction.

  20. High fat diet aggravates arsenic induced oxidative stress in rat heart and liver.

    Science.gov (United States)

    Dutta, Mousumi; Ghosh, Debosree; Ghosh, Arnab Kumar; Bose, Gargi; Chattopadhyay, Aindrila; Rudra, Smita; Dey, Monalisa; Bandyopadhyay, Arkita; Pattari, Sanjib K; Mallick, Sanjaya; Bandyopadhyay, Debasish

    2014-04-01

    Arsenic is a well known global groundwater contaminant. Exposure of human body to arsenic causes various hazardous effects via oxidative stress. Nutrition is an important susceptible factor which can affect arsenic toxicity by several plausible mechanisms. Development of modern civilization led to alteration in the lifestyle as well as food habits of the people both in urban and rural areas which led to increased use of junk food containing high level of fat. The present study was aimed at investigating the effect of high fat diet on heart and liver tissues of rats when they were co-treated with arsenic. This study was established by elucidating heart weight to body weight ratio as well as analysis of the various functional markers, oxidative stress biomarkers and also the activity of the antioxidant enzymes. Histological analysis confirmed the biochemical investigations. From this study it can be concluded that high fat diet increased arsenic induced oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

    Science.gov (United States)

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-01-01

    Aim: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Methods: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1H-NMR-based metabolomic analysis. Results: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Conclusion: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The 1H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines. PMID:24632844

  2. Administration of aqueous extract of Desmodium gangeticum (L) root protects rat heart against ischemic reperfusion injury induced oxidative stress.

    Science.gov (United States)

    Kurian, Gino A; Paddikkala, Jose

    2009-02-01

    Myocardial reperfusion is believed to be associated with free radical injury. The present study evaluates the effect of aqueous extract of D. gangeticum (DG) on lipid peroxides and antioxidants in ischemic reperfused (IR) Wistar albino male rats. Significant elevation in lipid peroxide products (thiobarbituric acid reactive substances) and decreased activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) were observed in the rat hearts during ischemia reperfusion phase. Pre treatment of rats with aqueous extract of DG orally for 30 days showed significantly improved preservation of antioxidant enzymes and subsequent reduction in lipid peroxidation. But 2,3,5 triphenyl tetrazolium chloride (TTC) stained rat heart did not show much significant antioxidant enzyme activities and lipid peroxidation. On the other hand, TTC unstained rat heart showed significant improvement in the antioxidant activities indicating cardio protective effect of aqueous extract of DG in myocardium affected by ischemia reperfusion insult. The administration of DG to normal rats did not have any significant effect on any of the parameter studied. These results indicate that DG improves the antioxidant capacity of heart and attenuate the degree of lipid peroxidation after IR.

  3. Control of the heart rate of rat embryos during the organogenic period

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    Ritchie HE

    2016-11-01

    Full Text Available Helen E Ritchie,1 Carolina Ragnerstam,2 Elin Gustafsson,2 Johanna M Jonsson,2 William S Webster2 1Discipline of Biomedical Science, Sydney Medical School, University of Sydney, Lidcombe, 2Department of Anatomy and Histology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia Abstract: The aim of this study was to gain insight into whether the first trimester embryo could control its own heart rate (HR in response to hypoxia. The gestational day 13 rat embryo is a good model for the human embryo at 5–6 weeks gestation, as the heart is comparable in development and, like the human embryo, has no functional autonomic nerve supply at this stage. Utilizing a whole-embryo culture technique, we examined the effects of different pharmacological agents on HR under normoxic (95% oxygen and hypoxic (20% oxygen conditions. Oxygen concentrations ≤60% caused a concentration-dependent decrease in HR from normal levels of ~210 bpm. An adenosine agonist, AMP-activated protein kinase (AMPK activator and KATP channel opener all caused bradycardia in normoxic conditions; however, putative antagonists for these systems failed to prevent or ameliorate hypoxia-induced bradycardia. This suggests that the activation of one or more of these systems is not the primary cause of the observed hypoxia-induced bradycardia. Inhibition of oxidative phosphorylation also decreased HR in normoxic conditions, highlighting the importance of ATP levels. The β-blocker metoprolol caused a concentration-dependent reduction in HR supporting reports that β1-adrenergic receptors are present in the early rat embryonic heart. The cAMP inducer colforsin induced a positive chronotropic effect in both normoxic and hypoxic conditions. Overall, the embryonic HR at this stage of development is responsive to the level of oxygenation, probably as a consequence of its influence on ATP production. Keywords: embryonic heart rate, embryo, bradycardia, in vitro, ATP, hypoxia

  4. Chronic mercury exposure impairs the sympathovagal control of the rat heart.

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    Simões, M R; Azevedo, B F; Fiorim, J; Jr Freire, D D; Covre, E P; Vassallo, D V; Dos Santos, L

    2016-11-01

    Mercury is known to cause harmful neural effects affecting the cardiovascular system. Here, we evaluated the chronic effects of low-dose mercury exposure on the autonomic control of the cardiovascular system. Wistar rats were treated for 30 days with HgCl2 (1st dose 4.6 μg/kg followed by 0.07 μg/kg per day, intramuscular) or saline. The femoral artery and vein were then cannulated for evaluation of autonomic control of the hemodynamic function, which was evaluated in awake rats. The following tests were performed: baroreflex sensitivity, Von Bezold-Jarisch reflex, heart rate variability (HRV) and pharmacological blockade with methylatropine and atenolol to test the autonomic tone of the heart. Exposure to HgCl2 for 30 days slightly increased the mean arterial pressure and heart rate (HR). There was a significant reduction in the baroreflex gain of animals exposed to HgCl2 . Moreover, haemodynamic responses to the activation of the Von Bezold-Jarisch reflex were also reduced. The changes in the spectral analysis of HRV suggested a shift in the sympathovagal balance toward a sympathetic predominance after mercury exposure, which was confirmed by autonomic pharmacological blockade in the HgCl2 group. This group also exhibited reduced intrinsic HR after the double block suggesting that the pacemaker activity of the sinus node was also affected. These findings suggested that the autonomic modulation of the heart was significantly altered by chronic mercury exposure, thus reinforcing that even at low concentrations such exposure might be associated with increased cardiovascular risk. © 2016 John Wiley & Sons Australia, Ltd.

  5. Taxol inhibits stretch-induced electrophysiological alterations in isolated rat hearts with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Mechanosensitive channels have been determined to work as transducers of mechanoelectric feedback in the heart, which is associated with the generation of arrhythmias. Recent studies have investigated the role of the cytoskeleton in ion channels control. This study explored the ability of taxol to inhibit stretch-induced electrophysiological alterations in the ischemic myocardium. Thirty-two Wistar rats were randomly divided into four groups: normal control group (n=9), taxol group (n=7), myocardial infarction (MI) group (n=9), and MI+taxol group (n=7). After Langendorff perfusion, the isolated hearts were stretched for 5 s by balloon inflation to 0.2 or 0.3 mL. The effects of stretching on 90% monophasic action potential duration (MAPD90), premature ventricular beats (PVB), and ventricular tachycardia (VT) were observed for 30 s. Stretching increased MAPD90 in both the normal control and MI groups, but MAPD90 increased more in the MI group for the same degree of stretch. Taxol (5 μmol L?1) had no effect on MAPD90 under baseline, unstretched conditions, but MAPD90 in the taxol group was slightly increased after stretching compared with the normal control group (P>0.05). However, taxol reduced MAPD90 in infarcted myocardium (P<0.05 at V=0.3 mL). The incidences of PVB and VT in the MI group were higher than in the normal control group (both P<0.01). Taxol had no effect on the occurrence of arrhythmias in normal myocardium, but it inhibited PVB and VT in infarcted hearts (both P<0.01). Thus changes in MAPD and the occurrence of arrhythmias caused by mechanical stretching of the myocardium could be inhibited by taxol in isolated rat hearts during AMI, indicating the involvement of tubulin in mechanoelectric feedback in AMI.

  6. Novel Model of Pulmonary Artery Banding Leading to Right Heart Failure in Rats

    OpenAIRE

    Masataka Hirata; Daiki Ousaka; Sadahiko Arai; Michihiro Okuyama; Suguru Tarui; Junko Kobayashi; Shingo Kasahara; Shunji Sano

    2015-01-01

    Background. Congenital heart diseases often involve chronic pressure overload of the right ventricle (RV) which is a major cause of RV dysfunction. Pulmonary artery (PA) banding has been used to produce animal models of RV dysfunction. We have devised a new and easier method of constricting the PA and compared it directly with the partial ligation method. Methods. Eight-week-old male Sprague-Dawley rats (240–260 g) were divided into three groups: sham operation, partial pulmonary artery ligat...

  7. Influence of calcium preconditioning and streptomycin on ventricular dilation-induced arrhythmias in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate the mechanism of ventricular dilation-induced arrhythmias by dilating isolated rat hearts. Methods Isolated rat hearts were perfused by Langerdorff method. After equilibration, 80 hearts were randomly divided into four groups as follows: (1) control group (n=20), (2) Ca2+ preconditioning (CPC) group (n=20), (3) streptomycin group (n=20), and (4) CPC + streptomycin group (n=20). A latex balloon which can be filled with fluid was anchored in the left ventricle through the left atrium and mitral valve. Epicardial ECG of the left ventricle, left ventricular pressure, coronary flow and heart rate were recorded before and during ventricular dilation by injecting fluid into the latex balloon. The rate and duration of ventricular dilation-induced arrhythmias were recorded. Results Under the same increase in ventricular end-diastolic pressure made by inflation of the balloon, the rate of arrhythmias was 100% and duration of arrhythmias was 2.56±0.46 s in the control group. Both the rates of premature ventricular beat (90 %) and ventricular tachycardia 70 % ) were high. Compared with the control group, the total rate (60 % ) of arrhythmias was lower, and duration (1.67±0.61 s ) of arrhythmias was shorter in the CPC group. Both the rates of premature ventricular beat (60%) and ventricular tachycardia (40%) were low comparatively. The rate of arrhythmias (45 %) was lower and duration ( 1.64±0.42 s)of arrhythmias was shorter, and the rates of premature ventricular beat (30 % ) or ventricular tachycardia (35 %) were lower in the streptomycin group than in the control one. The least ventricular dilation-induced arrhythmias occurred in the CPC + streptomycin group. The rate of arrhythmias (10%) was the lowest and duration (1.01±0.37s) of arrhythmias was the shortest; both the rates of premature ventricular beat (5%) and ventricular tachycardia (10%) were the lowest. Conclusions Ventricular dilation may induce arrhythmias in isolated rat hearts. Stretch

  8. Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria

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    Ivana Kancirová

    2016-06-01

    Full Text Available Objective(s: Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Materials and Methods: Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro or administered per os to rat (in vivo on mitochondrial ATP synthase activity and membrane fluidity were monitored. Results: In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P

  9. Endomorphins decrease heart rate and blood pressure possibly by activating vagal afferents in anesthetized rats.

    Science.gov (United States)

    Kwok, E H; Dun, N J

    1998-08-24

    Endomorphin 1 (10, 30, 100 nmol/kg) administered intravenously (i.v. ) to urethane-anesthetized rats consistently and dose-dependently lowered heart rate (HR) and mean arterial pressure (MAP); the decrease in blood pressure recovered faster as compared to the HR. The effects of endomorphin 2 were qualitatively similar. Naloxone (2 mg/kg, i.v.) completely antagonized the bradycardia and hypotension caused by endomorphin 1. Pretreatment of the rats with atropine methylnitrate, atropine sulfate (2 mg/kg, i.v.) or bilateral vagotomy nearly abolished the bradycardia and attenuated the hypotensive effect of endomorphin 1. Our studies suggest that the bradycardia effect following systemic administration of the new opioid peptide may be explained by activation of vagal afferents and the hypotensive effect may be secondary to a reduction of cardiac output and/or a direct vasodilation.

  10. Effects of laboratory housing on exploratory behaviour, novelty discrimination and spatial reference memory in a subterranean, solitary rodent, the Cape mole-rat (Georychus capensis)

    OpenAIRE

    Oosthuizen, Maria Kathleen; Scheibler, Anne-Gita; Bennett, Nigel Charles; Amrein, Irmgard

    2013-01-01

    A large number of laboratory and field based studies are being carried out on mole-rats, both in our research group and others. Several studies have highlighted the development of adverse behaviours in laboratory animals and have emphasised the importance of enrichment for captive animals. Hence we were interested in evaluating how laboratory housing would affect behavioural performance in mole-rats. We investigated exploratory behaviour, the ability to discriminate between novel and familiar...

  11. Effect of β3-adrenoceptors on Ventricle Fibrillation Threshold and Effective Refractory Period in Rats With Heart Failure

    Institute of Scientific and Technical Information of China (English)

    Deng Yijun; Wu Wei; Huang Zhibing; Fang Chang

    2006-01-01

    Objectives To observe the effect of β3-Adrenoceptor (AR) on ventricle fibrillation threshold ( VFT ) and effective refractory period (ERP) in rats with heart failure. Methods Rats were randomized into control group and heart failure group.The expression of β3-ARmRNA was detected with RTPCR; The VFT, ERP, LVESP,LVEDP, +dp/dtmax and -dp/dtmax was measured at the same time with administration of BRL37344 ( 2 nmol / kg, β3- AR agonist). Results ①Both the expression of β3-AR mRNA and the proportion increased in rats with heart failure in comparison with control rats (0.028 vs.0.011 and 5.4% vs 1.2%, P < 0.05); ② ERP was longer in rats with heart failure than control group (70.5±5.5 ms vs 59.5±6.4ms, P < 0.05) and there was no difference of ERP in rats with heart failure with administration of BRL37344 (73.0±4.8 ms vs 70.5±5.5 ms, P > 0.05); ③VFT was lower in rats with heart failure than control group(10.9±0.8 mv vs 30.5±1.3 mv, P<0.05) and decreased obviously in rats with heart failure with administration of BRL37344 (7.1±0.6 mv vs 10.9±0.8 mv, P < 0.05); The decrease of VFT correlated with the effect on LVESP, +dp/dtmax,-dp/dtmax of BRL37344 and the expression of β3-AR mRNA (correlation coefficient: 0.788, 0.708,0.759, 0.787; P < 0.05). Conclusions The expression of β3-AR mRNA of left ventricle was obviously increased in rats with heart failure, and activation of β3-AR had no effect on ERP but could decreased VFT which correlated with the effect of β3-AR on LVESP, +dp/dtmax, -dp/dtmax and the expression of β3-AR mRNA.

  12. Pavlovian-Instrumental Transfer of the Discriminative Stimulus Effects of Nicotine and Ethanol in Rats

    Science.gov (United States)

    Troisi, Joseph R., II

    2006-01-01

    To date, only 1 study has evaluated the impact of a Pavlovian drug conditional stimulus (CS) on operant responding. A within-subject operant 1-lever go/no-go (across sessions) design was used to evaluate the impact of Pavlovian contingencies on the discriminative stimulus effects of nicotine (0.4 mg/kg) and ethanol (800 mg/kg) in male Sprague…

  13. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

    Directory of Open Access Journals (Sweden)

    Massimo Collino

    2013-07-01

    We and others have previously demonstrated that heme oxygenase 1 (HO-1 induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO. These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO activity, interleukin 1β (IL-1β production and tumor necrosis factor-α (TNFα production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade.

  14. Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

    Science.gov (United States)

    Nagai-Okatani, Chiaki; Minamino, Naoto

    2016-01-01

    Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl) diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl) diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

  15. Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats

    Directory of Open Access Journals (Sweden)

    Haller Hermann

    2002-01-01

    Full Text Available Abstract Background We are investigating a double transgenic rat (dTGR model, in which rats transgenic for the human angiotensinogen and renin genes are crossed. These rats develop moderately severe hypertension but die of end-organ cardiac and renal damage by week 7. The heart shows necrosis and fibrosis, whereas the kidneys resemble the hemolytic-uremic syndrome vasculopathy. Surface adhesion molecules (ICAM-1 and VCAM-1 are expressed early on the endothelium, while the corresponding ligands are found on circulating leukocytes. Leukocyte infiltration in the vascular wall accompanies PAI-1, MCP-1, iNOS and Tissue Factor expression. Furthermore we show evidence that Ang II causes the upregulation of NF-kB in our model. Methods We started PDTC-treatment on four weeks old dTGR (200 mg/kg sc and age-matched SD rats.. Blood-pressure- and albuminuria- measurements were monitored during the treatement period (four weeks. The seven weeks old animals were killed, hearts and kidneys were isolated and used for immunohistochemical-and electromobility shift assay analsis. Results Chronic treatment with the antioxidant PDTC decreased blood pressure (162 ± 8 vs. 190 ± 7 mm Hg, p = 0.02. Cardiac hypertrophy index was significantly reduced (4.90 ± 0.1 vs. 5.77 ± 0.1 mg/g, p Conclusion Our data show that inhibition of NF-κB by PDTC markedly reduces inflammation, iNOS expression in the dTGR most likely leading to decreased cytotoxicity, and cell proliferation. Thus, NF-κB activation plays an important role in ANG II-induced end-organ damage.

  16. Renal Actions of Neutral Endopeptidase Inhibition in Rats with Chronic Heart Failure

    Directory of Open Access Journals (Sweden)

    Amr M. Abbas

    2010-01-01

    Full Text Available Problem statement: We aim to evaluate the effects of acute and chronic inhibition of Neutral EndoPeptidase (NEP, by ONO-9902, on plasma and renal NEP gene expression, hemodynamic and renal parameters in rats with Chronic Heart Failure (CHF following left Coronary Artery Ligation (CAL. Approach: Forty eight male Sprague-Dawley rats (220-240 g were divided into sham and CAL groups. Myocardial infarction was induced by left CAL. All rats were further subdivided into untreated and orally treated with ONO-9902 (300 mg kg-1 day-1 from the 1st to 6th weeks after the operation. At the 1st and 6th weeks after the operation, gene expression of plasma and renal NEP, plasma ANP, cGMP and aldosterone concentrations, urine volume, Na and ANP excretion, creatinine clearance and renal cGMP generation were measured. Results: CAL leads to sodium and water retention, increased renal NEP gene expression, plasma ANP and aldosterone and decreased renal cGMP generation and plasma NEP gene expression. Acute treatment of CAL rats by ONO-9902, at the 1st week after the operation, inhibited plasma and renal NEP gene expression with increased plasma ANP, which caused diuresis, natriuresis and increased renal cGMP generation. Moreover, chronic treatment of those rats by ONO-9902 decreased plasma and renal NEP gene expression, plasma aldosterone, increased plasma ANP but non significantly, and caused diuresis, natriuresis with increased renal cGMP generation. GFR was not significantly changed before or after treatment. Conclusion: Chronic treatment with NEP inhibitor decreases Na and water retention in rats with CHF by enhancing ANP action and suppressing aldosterone secretion. So, ONO-9902 may offer a new therapeutic approach in patients with CHF.

  17. Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats.

    Science.gov (United States)

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S

    2014-08-01

    The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.

  18. Neonatal SSRI exposure improves mitochondrial function and antioxidant defense in rat heart.

    Science.gov (United States)

    Braz, Glauber Ruda F; Freitas, Cristiane M; Nascimento, Luciana; Pedroza, Anderson A; da Silva, Aline Isabel; Lagranha, Claudia

    2016-04-01

    Protein restriction during prenatal, postnatal, or in both periods has a close relationship with subsequent development of cardiovascular disease in adulthood. Elevated brain levels of serotonin and its metabolites have been found in malnourished states. The aim in the present study was to investigate whether treatment with fluoxetine (Fx), a selective serotonin reuptake inhibitor, mimics the detrimental effect of low-protein diet during the perinatal period on the male rat heart. Our hypothesis is that increased circulating serotonin as a result of pharmacologic treatment with Fx leads to cardiac dysfunction similar to that observed in protein-restricted rats. Male Wistar rat pups received daily subcutaneous injection of Fx or vehicle from postnatal day 1 to postnatal day 21. Male rats were euthanized at 60 days of age and the following parameters were evaluated in the cardiac tissue: mitochondrial respiratory capacity, respiratory control ratio, reactive oxygen species (ROS) production, mitochondrial membrane potential, and biomarkers of oxidative stress and antioxidant defense. We found that Fx treatment increased mitochondrial respiratory capacity (123%) and membrane potential (212%) and decreased ROS production (55%). In addition we observed an increase in the antioxidant capacity (elevation in catalase activity (5-fold) and glutathione peroxidase (4.6-fold)). Taken together, our results suggest that Fx treatment in the developmental period positively affects the mitochondrial bioenergetics and antioxidant defense in the cardiac tissue.

  19. 5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide.

    Science.gov (United States)

    Gresch, Paul J; Barrett, Robert J; Sanders-Bush, Elaine; Smith, Randy L

    2007-02-01

    d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.

  20. Cardioprotection Afforded by Norepinephrine-mediated Postconditioning in Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    Xinhua Huang; Dai Li; Yishuai Zhang; Nianshen Li; Benmei Chen; Jun Peng; Yuanjian Li

    2008-01-01

    Objectives Previous studies have demonstrated that endogenous norepinephrine (NE) plays an important role in the mediation of ischemic preconditioning. The present study is designed to determine whether NE is also involved in medi-ation of the protective effects of postconditioning. Methods The rat hearts were rapidly excised under anesthesia and attached to a Langendorff apparatus via the aorta for retrograde perfusion with Krebs-Henseleit buffer solution. All hearts were subjected to 30 min of left coronary artery occlusion followed by 60 rain of reperfusion, except the control group. Animals were randomly divided into 5 groups as follows: ① control group, the hearts were underwent same procedures without ischemic insult; ② ischemia reperfusion group, the left coronary artery was occluded for 30 min and followed by 60 min of reperfusion;③ ischemic postconditioning (Ipost) group, immediately at the onset of reperfusion, the heart was initiated with 1 min of full coronary flow, followed by 1 min of re-occlusion, repeated for a total of three cycles; ④ Ipost plus prazosin group, the heart was perfused with prazosin for 10 min before ischemia; ⑤ Ipost plus reserpine group, a single dose of reserpine was administered by I.m. Injection, 24 hours before the experiment. Coronary flow was measured by timed collection of coronary effluent and sample of coronary effluent at 5 rain of reperfusion were collected for the measurement of ereatine kinase (CK). Infarct size and risk area were determined at the end of experiments. Results 30 rain of ischemia and followed by 60 min of reperfusion caused a significant decrease in cardiac function and a significant increase in CK release and infarct size. Postconditioning with three cycles of 1-min ischemia and 1-min reperfusion markedly improved cardiac function and reduced CK release and infarct size. However,the cardioprotection afforded by postconditioning was abolished by prazosin (10-6M), a selective α1 adrenergic

  1. Neuromuscular electrical stimulation improves GLUT-4 and morphological characteristics of skeletal muscle in rats with heart failure.

    Science.gov (United States)

    de Leon, E B; Bortoluzzi, A; Rucatti, A; Nunes, R B; Saur, L; Rodrigues, M; Oliveira, U; Alves-Wagner, A B; Xavier, L L; Machado, U F; Schaan, B D; Dall'Ago, P

    2011-02-01

    Changes in skeletal muscle morphology and metabolism are associated with limited functional capacity in heart failure, which can be attenuated by neuromuscular electrical stimulation (ES). The purpose of the present study was to analyse the effects of ES upon GLUT-4 protein content, fibre structure and vessel density of the skeletal muscle in a rat model of HF subsequent to myocardial infarction. Forty-four male Wistar rats were assigned to one of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%- 15 s contraction/15 s rest). After this period, the left tibialis anterior muscle was collected from all the rats for analysis. HF+ES rats showed lower values of lung congestion when compared with HF rats (P = 0.0001). Although muscle weight was lower in HF rats than in the S group, thus indicating hypotrophy, 20 days of ES led to their recovery (P muscle vessel density (P muscle. © 2010 The Authors. Acta Physiologica © 2010 Scandinavian Physiological Society.

  2. Temporal profile of calcineurin phosphatase activity during acute allograft rejection in the heterotopic rat heart transplantation model

    DEFF Research Database (Denmark)

    Karamperis, N; Koefoed-Nielsen, P B; Marcussen, N

    2008-01-01

    if it can be utilized as a pharmacodynamic marker to identify and monitor the rejection process. METHODS: The heterotopic cervical rat heart transplantation model was used (dark Agouti to Lewis). We performed 25 control isogeneic and 46 allogeneic transplantations. Rats were sacrificed at various...... as a pharmacodynamic biomarker of acute allograft rejection in the heterotopic rat heart transplantation model. Further research is required in order to reveal the precise role of CaN during acute allograft rejection....... postoperative time points. CaN activity was measured in isolated peripheral blood and spleen mononuclear cells and in graft heart homogenates. CaN activity was measured as the release of radiolabeled phosphate from a previously phosphorylated 19 amino acid peptide. RESULTS: We have shown that CaN's activity...

  3. Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor precursor in the heart and hypothalamus during rat cardiopulmonary bypass.

    Science.gov (United States)

    Cheng, Chi; Xu, Jun-Mei; Yu, Tian

    2017-06-01

    To investigate whether the expression of nerve growth factor precursor (proNGF) changes during cardiopulmonary bypass (CPB) and whether neutralizing interleukin-6 (IL-6) during CPB has cardiac benefits. Thirty patients undergoing CPB were recruited and their serum proNGF and troponin-I (TNI) were detected. In addition, rats were divided into three groups: CPB group, CPB with cardiac ischemia-reperfusion (IR) group, and a control group. The pre-CPB standard deviation of N-N intervals (SDNN) and post-CPB SDNN were compared. At the end of CPB, nerve peptide Y (NPY), acetylcholinesterase, cell apoptosis, and proNGF protein expression were measured in the heart and hypothalamus. Another rat cohort undergoing CPB was divided into two groups: an anti-IL-6 group with IL-6 antibody and a control group with phosphate buffer solution. At the end of CPB, serum hs-troponin-T and cardiac caspases 3 and 9 were detected. NPY and proNGF in the heart and hypothalamus were detected. In patients, serum proNGF increased during CPB, and the concentration was positively correlated with TNI. In rats, cardiac autonomic nervous function was disturbed during CPB. More apoptotic cells and higher levels of proNGF were found in the heart and hypothalamus in the CPB groups than in the control groups. Neutralizing IL-6 was beneficial to lower cardiac injury by decreasing proNGF and apoptosis. CPB induced changes in proNGF in the heart and hypothalamus. Suppressing inflammation attenuated myocardial apoptosis and autonomic nerve function disturbance in CPB rats, likely due in part to regulation of proNGF in the heart and hypothalamus. Copyright © 2017. Published by Elsevier Inc.

  4. Dipeptidyl peptidase IV inhibition exerts renoprotective effects in rats with established heart failure

    Directory of Open Access Journals (Sweden)

    Daniel Francisco De Arruda Junior

    2016-07-01

    Full Text Available Circulating dipeptidyl peptidase IV (DPPIV activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for four weeks with vildagliptin (120 mg/kg/day or vehicle by oral gavage. Echocardiography was performed before (pretreatment and at the end of treatment (post-treatment to evaluate cardiac function. The fractional area change increased (34±5 vs. 45±3%, p<0.05, and the isovolumic relaxation time decreased (33±2 vs. 27±1 ms; p<0.05 in HF rats treated with vildagliptin (post-treatment vs. pretreatment. On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1 serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with

  5. Action of Al-ATP on the isolated working rat heart.

    Science.gov (United States)

    Korchazhkina, O; Wright, G; Exley, C

    1998-02-15

    ATP is an important extracellular messenger in the coronary vasculature of the heart. To be effective its extracellular concentration must be tightly controlled and this is achieved via ectonucleotidases located in the luminal surface of the coronary endothelium. Al-ATP is a potent inhibitor of the hydrolysis of ATP and we speculated that Al-ATP released by cells into the blood would disrupt the signalling function of extracellular ATP. We tested this hypothesis by perfusing isolated working Wistar rat hearts with buffers containing either ATP or Al-ATP. The functional parameters measured were, coronary flow, heart rate and pulsatile power. A number of control perfusions including adenosine, ATP-gamma-S and Al were used to identify those effects which might be specific to ATP and Al-ATP. Al-ATP did not appear to inhibit the function of the endothelial ectonucleotidases. Both ATP and Al-ATP produced a significant increase in coronary flow and this could be attributed to a coronary vasodilation. Interestingly, whilst the effect of ATP was reversible that of Al-ATP was not. ATP caused a reduction in heart rate which was potentiated by aluminium. The negatively chronotropic effect of Al-ATP was mediated via a mechanism which was either distinct from or in addition to the similar response known to be caused by adenosine. We have demonstrated for the first time an influence of Al-ATP on heart function. Perhaps more pertinently we present the first evidence that Al-ATP may influence the function of ATP-specific receptors.

  6. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

    Science.gov (United States)

    Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

    2013-08-19

    Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

  7. Phytanic acid disturbs mitochondrial homeostasis in heart of young rats: a possible pathomechanism of cardiomyopathy in Refsum disease.

    Science.gov (United States)

    Grings, Mateus; Tonin, Anelise Miotti; Knebel, Lisiane Aurélio; Zanatta, Angela; Moura, Alana Pimentel; Filho, Carlos Severo Dutra; Wajner, Moacir; Leipnitz, Guilhian

    2012-07-01

    Phytanic acid (Phyt) accumulates in tissues and biological fluids of patients affected by Refsum disease. Although cardiomyopathy is an important clinical manifestation of this disorder, the mechanisms of heart damage are poorly known. In the present study, we investigated the in vitro effects of Phyt on important parameters of oxidative stress in heart of young rats. Phyt significantly increased thiobarbituric acid-reactive substances levels (P Refsum disease.

  8. Meat product based on porcine hearts and aortas ameliorates serum lipid profile and inflammation in hyperlipidemic rats

    Science.gov (United States)

    Chernukha, I. M.; Kotenkova, E. A.; Fedulova, L. V.

    2017-09-01

    The biological effect of porcine hearts and aortas in a hyperlipidemic rat model was confirmed. Porcine heart and aorta mixture in a 3:1 ratio was blended, canned and sterilized at 115°C and 0.23 Mpa for 40 min. Administration of experimental meat product to the animal model decreased total cholesterol, triglycerides and cholesterol low density lipoproteins by 31.8% (Plipid disorders or atherosclerosis.

  9. Analysis of the Inhibitory Effect of Gypenoside on Na+,K+-ATPase in Rats' Heart and Brain and Its Kinetics

    Institute of Scientific and Technical Information of China (English)

    HAN Xiao-yan; WEI Hong-bo; ZHANG Fu-cheng

    2007-01-01

    ObjectiYe: To study the effects of gypenoside (Gyp) on the activity of microsomal Na+,K+-ATPase in rat's heart and brain in vitro. Methods: The microsomal Na+, K+-ATPase was prepared from rat's heart and brain by differential centrifugation. The activity of microsomal Na+, K+-ATPase was assayed by colorimetric technique. Enzyme kinetic analysis method was used to analyze the effect of Gyp on the microsomal Na+, K+-ATPase of rats. Results: Gyp reversibly inhibited the brain and heart's microsomal Na+, K+-ATPase in a concentration-dependent manner, and showed a more potent effect on enzyme in the brain. The IC50 of Gyp for the heart and brain were 58.79± 8.05 mg/L and 52.07 ±6.25 mg/L, respectively. The inhibition was enhanced by lowering the Na+, or K+ concentrations or increasing the ATP concentration. Enzyme kinetic studies indicated that the inhibitory effect of Gyp on the enzyme is like that of competitive antagonist of Na+, the counter-competitive inhibitor for the substrate ATP, and the mixed-type inhibitor for K+. Conclusion: Gyp displays its cardiotonic and central inhibitory effects by way of inhibiting heart and brain's microsomal Na+, K+-ATPase activities in rats.

  10. Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure.

    Science.gov (United States)

    Jaenisch, Rodrigo B; Hentschke, Vítor S; Quagliotto, Edson; Cavinato, Paulo R; Schmeing, Letiane A; Xavier, Léder L; Dal Lago, Pedro

    2011-12-01

    Respiratory muscle training (RMT) improves functional capacity in chronic heart-failure (HF) patients, but the basis for this improvement remains unclear. We evaluate the effects of RMT on the hemodynamic and autonomic function, arterial baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats were assigned to one of four groups: sedentary sham (n = 8), trained sham (n = 8), sedentary HF (n = 8), or trained HF (n = 8). Trained animals underwent a RMT protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas sedentary animals did not. In HF rats, RMT had significant effects on several parameters. It reduced left ventricular (LV) end-diastolic pressure (P RMT (P RMT (P RMT (P RMT protocol in HF rats promotes an improvement in hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and respiratory mechanics, all of which are benefits associated with improvements in cardiopulmonary interaction.

  11. Effective analgesic doses of tramadol or tapentadol induce brain, lung and heart toxicity in Wistar rats.

    Science.gov (United States)

    Faria, Juliana; Barbosa, Joana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Moreira, Roxana; Queirós, Odília; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

    2017-06-15

    Tramadol and tapentadol are extensively prescribed for the treatment of moderate to severe pain. Although these drugs are very effective in pain treatment, the number of intoxications and deaths due to both opioids is increasing, and the underlying toxic mechanisms are not fully understood. The present work aimed to study the potential biochemical and histopathological alterations induced by acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats. Forty-two male Wistar rats were divided into different groups: a control, administered with normal saline solution, and tramadol- or tapentadol-treated groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and maximum recommended doses, respectively). 24h after intraperitoneal administration, biochemical and oxidative stress analyses were performed in blood, and specimens from brain, lung and heart were taken for histopathological and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio, in LDH, CK and CK-MB activities in serum samples, and an increase in lactate levels in serum and brain samples. Oxidative damage, namely protein oxidation, was found in heart and lung tissues. In histological analyses, tramadol and tapentadol were found to cause alterations in cell morphology, inflammatory cell infiltrates and cell death in all tissues under study, although tapentadol caused more damage than tramadol. Our results confirmed the risks of tramadol exposure, and demonstrated the higher risk of tapentadol, especially at high doses. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Cyclic AMP-receptor proteins in heart muscle of rats flown on Cosmos 1887

    Science.gov (United States)

    Mednieks, Maija I.; Popova, Irina A.; Grindeland, Richard E.

    1991-01-01

    The cellular compartmentalization of the cyclic AMP-receptor proteins in heart ventricular tissue obtained from rats flown on the Cosmos 1887 is determined. Photoaffinity labeling of soluble and particular cell fractions with a (32P)-8-azido analog of cyclic AMP is followed by electrophoretic separation of the proteins and by autoradiographic identification of the labeled isoforms of cAPK R subunits. It is shown that RII in the particulate subcellular fraction was significantly decreased in heart cells from rats in the flight group when compared to controls. Protein banding patterns in both the cytoplasmic fraction and in a fraction enriched in chromatin-bound proteins exhibited some variability in tissues of individual animals, but showed no changes that could be directly attributed to flight conditions. No significant change was apparent in the distribution of RI or RII cyclic AMP binding in the soluble fractions. It is inferred that the cardiac cell integrity or its protein content is not compromised under flight conditions.

  13. Effect of Gαq/11 Protein and ATP-sensitive Potassium Channels on Ischemic Preconditioning in Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives To investigate the effect of Gαq/11 signaling pathway and ATP-sensitive potassium channel ( KATP channel ) on ischemic preconditioning (IPC) protection in rat hearts.Methods Two series of experiments were performed in Wistar rat hearts. In the first series of experiment,ischemic preconditioning was induced by left anterior descending occlusion (three, 5 min episodes separated by 5 min of reperfusion), ischemia-reperfusion injury was induced by 30 min coronary artery occlusion followed by 90 min reperfusion. Hemodynamics,infarct size and scores of ventricular arrhythmias were measured. The expression of Gαq/11 protein in the heart was measured by Western blot analysis in the second series. Results Ischemic preconditioning rats showed decreased infarct size and scores of ventricular arrhythmia vs non-IP control rats. The effect of IPC was significantly attenuated by glibenclamide (1 mg/kg, ip), a nonselective KATP channel inhibitor. IPC caused a significant increase in the expression of Gαq/11 protein. Conclusions Activations of Gαq/11 signal pathway and KATP channel played significant roles in the classical cardioprotection of ischemic preconditioning rat heart and might be an important mechanism of signal transduction pathway during the ischemic preconditioning.

  14. The utility of the Golgi-Cox method in the morphological characterization of the autonomic innervation in the rat heart.

    Science.gov (United States)

    Gómez-Villalobos, M J; Gordillo, Aurora Calvo; López, José Rubicel Hernández; Flores, Gonzalo

    2009-04-30

    The autonomic innervation in the heart is predominantly by postganglionic, parasympathetic, and sympathetic neurons, which are organized in a plexus of ganglions into the heart. The knowledge of the density, distribution, location, morphology, and intrinsic connection of this system that constitute the heart autonomic innervation is limited and controversial. Methods that provide clear information in this field are desirable. A widely used method to study the morphology of the nerve cells in the central nervous system (CNS) is used in this study to characterize the autonomic innervation in rat hearts. The method consisted of impregnation of the fresh whole heart of 12 adult male Wistar rats with the Golgi-Cox stain for 30 days, after which they were incubated in 30% sucrose solution for 2-3 days and then were sectioned (200 microm) with a vibratome. The tissues were mounted on gelatin-covered slides and analyzed by using the Sholl method under light microscopy adapted to a camera lucida. The results clearly show a distribution of the ganglion plexuses in the epicardium, myocardium, and endocardium, joined by an extensive network of nerve fibers in the four cardiac chambers. We also identified and characterized the morphology of an isolated cardiac nerve cell. As results similar to that in the CNS, the Golgi-Cox method is a simple, efficient, and an accessible tool to study the autonomic innervation in the rat heart and provides a good resolution of the morphology of the plexuses of the ganglions and nerve fibers.

  15. The Effects of Prenatal Protein Restriction on β-Adrenergic Signalling of the Adult Rat Heart during Ischaemia Reperfusion

    Directory of Open Access Journals (Sweden)

    Kevin J. P. Ryan

    2012-01-01

    Full Text Available A maternal low-protein diet (MLP fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR and related this to cardiac expression of β-adrenergic receptors (β-AR and their associated G proteins. Pregnant rats were fed control (CON or MLP diets (n=12 each group throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30 min ischemia and 60 min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP and dP/dtmax (P<0.01 during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of β2-AR following reperfusion and urinary excretion of noradrenaline and dopamine was lower in MLP and CON female rats versus CON males. In conclusion, the improved cardiac recovery in MLP male offspring following IR was attributed to greater membrane expression of β2-AR and reduced noradrenaline and dopamine levels. In contrast, females exhibiting both decreased membrane expression of β2-AR and catecholamine levels were protected from IR injury.

  16. The radioprotective effect and mechanism of captopril on radiation induced-heart damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Seung Hee; Lee, Kyung Ja; Koo, Hea Soo [Ewha Womans University, Seoul (Korea, Republic of)

    2004-03-15

    Captopril (angiotension converting enzyme inhibitor) is known to have a radioprotective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotective effect and mechanism of captopril in the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. The histopathological changes and immunohistochemical stains (TNF {alpha} , TGF {beta} 1, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema ({rho} = 0.082) and fibrin deposit ({rho} = 0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit ({rho} = 0.047) in the atrium, and the interstitial fibrin deposit ({rho} = 0.019) and edema ({rho} = 0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of TNF- {alpha} , TGF- {beta} 1, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial TNF- {alpha} and TGF- {beta} 1, in the radiation alone group continuously increased. The expressions of TNF- {alpha} , TGF- {beta} 1, and PDGF were decreased in the combined

  17. Characterization of the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone in male Sprague-Dawley rats.

    Science.gov (United States)

    Berquist, Michael D; Baker, Lisa E

    2017-08-01

    Recreational use of 3,4-methylenedioxypyrovalerone (MDPV) in the early 2000s prompted numerous scientific investigations of its behavioral and neurochemical effects. The purpose of this study was to further characterize the interoceptive stimulus effects of MDPV using a validated in-vivo drug-detection assay. Male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg MDPV from saline under a fixed ratio 20 (FR 20) schedule of food reinforcement. After stimulus control was established with MDPV (∼35 training sessions), substitution tests were commenced with drugs from several chemical classes, including drugs with predominantly dopaminergic actions [MDPV, D-amphetamine, (+)-methamphetamine, (-)-cocaine], drugs with predominantly serotonergic actions [(+)-lysergic acid diethylamide, (+)-fenfluramine], and drugs with both serotonergic and dopaminergic actions (3,4-methylenedioxymethamphetamine, 4-methylmethcathinone). Full substitution for the 0.3 mg/kg MDPV cue was observed with D-amphetamine, (+)-methamphetamine, and (-)-cocaine. Surprisingly, the 5-HT releaser (+)-fenfluramine fully substituted in half the subjects, but completely suppressed responding in the remaining subjects. 3,4-Methylenedioxymethamphetamine, 4-methylmethcathinone, and (+)-lysergic acid diethylamide failed to fully substitute for MDPV. These results indicate that the MDPV cue is similar to cues produced by drugs with predominantly dopamine-increasing effects and perhaps serotonin-releasing effects among individual subjects. Given these findings, further research is warranted to directly assess the contributions of dopamine and serotonin receptor isoforms to the discriminative stimulus functions of MDPV.

  18. Salvinorin A fails to substitute for the discriminative stimulus effects of LSD or ketamine in Sprague-Dawley rats.

    Science.gov (United States)

    Killinger, Bryan A; Peet, Mary M; Baker, Lisa E

    2010-09-01

    Salvia divinorum is a small perennial shrub that has gained recent popularity among the drug-using subculture as a legal alternative to hallucinogens. Salvinorin A, the main active compound found in the S.divinorum plant, is an atypical hallucinogen with pharmacological selectivity at kappa opioid (KOP) receptor sites and is a unique non-nitrogenous neoclerodane diterpene which is structurally distinct from other opioid compounds. The novel structure of salvinorin A and its specific binding affinity to KOP receptors provide a unique opportunity to investigate neurochemical mechanisms of hallucination and hallucinogenic compounds. The current investigation assessed the substitution of salvinorin A in 16 male Sprague-Dawley rats trained to discriminate either the prototypical serotonergic hallucinogen, LSD (0.08mg/kg, S.C., n=8) or the dissociative anesthetic and glutamatergic hallucinogen, ketamine (8.0mg/kg, I.P., n=8) from vehicle under a FR 20 schedule of food-reinforced responding. Results indicated that neither LSD nor ketamine discrimination generalized to salvinorin A. These findings are consistent with the growing body of evidence that salvinorin A is pharmacologically distinct from other traditional hallucinogenic compounds.

  19. THE CENTRAL DISTRIBUTION OF ADRENOMEDULLIN AND ITS EFFECTS ON BLOOD PRESSURE AND HEART RATE IN RATS

    Institute of Scientific and Technical Information of China (English)

    魏英杰; 李倩虹; 宋良文; 赵东; 张肇康; 何瑞荣; 汤健

    1996-01-01

    The present study was designed to make certairt whether there exists adrenomedullinrat central nervous system and evaluated the hemodynamic actions of in(ADM) in the administration(ICVA) of human ADM[13-52]. By immunobistochemistry (ABC method), We tound that there was a discrete localization of ADM positive immunoreactivity in the rat central system including cerebral cortex,paravent ricular tissues, hypothalamus, cerehellla cortex, mesencephalon and medulla oblongata. By reverse transcription polymerase chain reaction (RT-PCR) analysis, rat ADM mRNA was found to be expressed in rat brain. These above results of irnmunohistochemistry and RT PCR suggest that ADM exists in the rat brain. We also found that centrally administered ADM[13-52 in a dose of 0. 4 to 3.2 nmol/kg provoked marked, prolonged and dosedeioeudent increases in mean arteriBl blood pressure (MABP) and heart rate(HR). To clarify the mechanisms of the bemudynamic changes induced by centrally administered ADM[13-52], the effect of centrally administered ADM[13-52] on renal sympathetic nerve activity(RSNA)was studied, The result showed that centrally admiaaistered ADM [13-52] (1. 6 nmol/kg) provoked a marked increase in RSNA, therefore, the increases in MABP and HR induced by centrally administered ADM[13-52]might he due to the stimulation of central sympathetic mechanism. In eddtion,we also compared the relationship of activity and structure among the different fragments of ADM. In conclusion,ADM exists in the rat brain,and it may play an important role in the central control of cardiovascular system.

  20. In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart.

    Science.gov (United States)

    Brazhe, Nadezda A; Treiman, Marek; Faricelli, Barbara; Vestergaard, Jakob H; Sosnovtseva, Olga

    2013-01-01

    We developed a Raman spectroscopy-based approach for simultaneous study of redox changes in c-and b-type cytochromes and for a semiquantitative estimation of the amount of oxygenated myoglobin in a perfused rat heart. Excitation at 532 nm was used to obtain Raman scattering of the myocardial surface of the isolated heart at normal and hypoxic conditions. Raman spectra of the heart under normal pO2 demonstrate unique peaks attributable to reduced c-and b-type cytochromes and oxymyoglobin (oMb). The cytochrome peaks decreased in intensity upon FCCP treatment, as predicted from uncoupling mitochondrial respiration. Conversely, transient hypoxia causes the reversible increase in the intensity of peaks assigned to cytochromes c and c1, reflecting electron stacking proximal to cytochrome oxidase due to the lack of terminal electron acceptor O2. Intensities of peaks assigned to oxy- and deoxyhemoglobin were used for the semiquantitative estimation of oMb deoxygenation that was found to be of approximately 50[Formula: see text] under hypoxia conditions.

  1. In Situ Raman Study of Redox State Changes of Mitochondrial Cytochromes in a Perfused Rat Heart

    Science.gov (United States)

    Brazhe, Nadezda A.; Treiman, Marek; Faricelli, Barbara; Vestergaard, Jakob H.; Sosnovtseva, Olga

    2013-01-01

    We developed a Raman spectroscopy-based approach for simultaneous study of redox changes in c-and b-type cytochromes and for a semiquantitative estimation of the amount of oxygenated myoglobin in a perfused rat heart. Excitation at 532 nm was used to obtain Raman scattering of the myocardial surface of the isolated heart at normal and hypoxic conditions. Raman spectra of the heart under normal pO2 demonstrate unique peaks attributable to reduced c-and b-type cytochromes and oxymyoglobin (oMb). The cytochrome peaks decreased in intensity upon FCCP treatment, as predicted from uncoupling mitochondrial respiration. Conversely, transient hypoxia causes the reversible increase in the intensity of peaks assigned to cytochromes c and c1, reflecting electron stacking proximal to cytochrome oxidase due to the lack of terminal electron acceptor O2. Intensities of peaks assigned to oxy- and deoxyhemoglobin were used for the semiquantitative estimation of oMb deoxygenation that was found to be of approximately 50 under hypoxia conditions. PMID:24009655

  2. [The influence of inhibiting no formation on metabolic recovery of ischemic rat heart by apelin-12].

    Science.gov (United States)

    Pisarenko, O I; Pelogeĭkina, Iu A; Shul'zhenko, V S; Studneva, I M; Bespalova, Zh D; Az'muko, A A; Sidorova, M V; Pal'keeva, M E

    2012-01-01

    Apelin 12 (A-12) was synthesized by the automatic solid phase method with use of Fmoc 1H-NMR spectroscopy and mass spectrometry. Effects of apelin-12 (a peptide comprised of 12 aminoacids, A-12) on recovery of energy metabolism and cardiac function were studied in isolated working rat hearts perfused with Krebs buffer (KB) containing 11 mM glucose that were subjected to global ischemia and reperfusion. A short-term infusion of microM 140 A-12 in KB prior to ischemia enhanced myocardial ATP, the total adenine nucleotide pool (SigmaAN = ATP + ADP + AMP) and the energy charge of cardiomyocites ((ATP + 0.5ADP)/SigmaAN) at the end of reperfusion compared with control (KB infusion) and reduced lactate content and lactate/pyruvate ratio in reperfused myocardium to the initial values. This effect was accompanied by improved recovery of coronary flow and cardiac function. Coadministration of 140 microM A-12 and 100 microM L-NAME (the nonspecific NOS inhibitor) profoundly attenuated the peptide influence on metabolic and functional recovery of reperfused hearts. The results indicate involvement of NO, formed under the peptide action, in mechanisms of cardioprotection that are tightly associated with recovery of energy metabolism in postischemic heart.

  3. Mitigation Effect of Proanthocyanidin on Secondary Heart Injury in Rats Caused by Mechanical Trauma

    Science.gov (United States)

    Ma, Shuo; Chen, Chong; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Li, Xintao; Yu, Deqin; Li, Shuzhuang

    2017-01-01

    Multiple organ dysfunctional syndrome secondary to mechanical trauma (MT) has attracted considerable research attention. The heart is one of the most important organs of the body, and secondary cardiac insufficiency caused by MT seriously affects the quality of life. This study aims to investigate whether proanthocyanidin can alleviate myocardial injury and improve heart function in the process of MT leading to secondary cardiac insufficiency. Noble-Collip drum wasused to prepare MT model in rats. And myocardial apoptosis index was calculated after TUNEL staining. Ventricular intubation was employed to detect heart function. Changes in myocardial ultrastructure were observed using an electron microscope. ELISA was used to detect the content of TNF-α and reactive oxygen species generated from monocytes and cardiomyocytes. The changes in Ca2+ concentration in cardiomyocyte were observed by confocal microscope. Compared with trauma group, the administration group had a decreased apoptosis index of cardiomyocytes, and increased ±dp/dtmax. Meanwhile, proanthocyanidin can inhibit monocytes’ TNF-α production, and reduce plasma TNF-α concentration. Moreover, proanthocyanidin can attenuate the excessive oxidative stress reaction of cardiomyocyte, and inhibit calcium overload in cardiomyocytes. In conclusion, proanthocyanidin can effectively ease myocardial damage and improve cardiac function, through anti-inflammatory and antioxidant effects in secondary cardiac insufficiency caused by MT. PMID:28294148

  4. Acute effects of nandrolone decanoate on oxidative stress in isolated rat heart

    Directory of Open Access Journals (Sweden)

    Jevđević Maja

    2015-01-01

    Full Text Available Abuse of anabolic-androgenic steroids (AAS produces side effects in different tissues, with oxidative stress linked to their pathophysiology, being involved in fibrosis, cellular proliferation, and tumorigenesis. The aim of this study was to examine the acute effects of nandrolone decanoate (ND on oxidative stress in isolated rat heart. The hearts of male Wistar albino were excised and perfused according to the Langendorff technique at gradually increasing coronary perfusion pressures (40-120 cmH2O. The hearts were perfused with ND at doses of 1, 10 and 100 μM. Oxidative stress markers, including the index of lipid peroxidation (thiobarbituric acid reactive substances (TBARS, nitric oxide (nitrites; NO2-, the superoxide anion radical (O2- and hydrogen peroxide (H2O2 were measured in the coronary venous effluent. Our results showed that acute effects of ND do not promote the production of reactive oxygen species (ROS. Our finding pointed out that the highest concentration of ND may even possess some anti-oxidative potential, which should be examined further.

  5. Mitochondrial K+ channels are involved in ischemic postconditioning in rat hearts.

    Science.gov (United States)

    Jin, Chunhong; Wu, Jinrong; Watanabe, Makino; Okada, Takao; Iesaki, Takafumi

    2012-07-01

    The mitochondrial calcium-activated potassium channel (mitoK(Ca)) and the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) are both involved in cardiac preconditioning. Here, we examined whether these two channels are also involved in ischemic or pharmacological postconditioning. Using Langendorff perfusion, rat hearts were made hypoxic for 45 min and then reoxygenated for 30 min. Ischemic postconditioning (IPT) was achieved through application of 3 cycles of 10 s of reperfusion and 10 s of ischemia before reoxygenation, with and without paxilline (Pax; a mitoK(Ca) blocker) or 5-hydroxydecanoate (5-HD; a mitoK(ATP) blocker). Pharmacological postconditioning was carried out for 5 min at the onset of reoxygenation using NS1619 (a mitoK(Ca) opener) or diazoxide (Dia; a mitoK(ATP) opener). Pax and 5-HD abolished IPT-induced cardioprotection from reoxygenation injury, whereas administration of NS1619 or Dia significantly improved cardiac contractile activity and reduced aspartate aminotransferase (an index of myocyte injury) release following reoxygenation. In addition, isolated rat myocytes were loaded with tetramethylrhodamine methyl ester (TMRE; fluorescent mitochondrial membrane potential indicator) and 2',7'-dichlorofluorescein [DCFH; fluorescent reactive oxygen species (ROS) indicator] or Fluo-4-acetoxymethyl ester (Fluo-4-AM; fluorescent calcium indicator). When TMRE-loaded myocytes were laser illuminated, the DCFH and Fluo-4 fluorescence increased, and TMRE fluorescence decreased. These effects were significantly inhibited by NS1619 and Dia. We therefore conclude that IPT may protect the heart through activation of mitoK(ATP) and mitoK(Ca) channels, and that opening of these channels at the onset of reoxygenation protects the heart from reoxygenation injury, most likely by reducing excess generation of ROS and the resultant Ca(2+) overload.

  6. Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts

    Directory of Open Access Journals (Sweden)

    Song Cao

    2016-02-01

    Full Text Available Ischemia postconditioning (IPo is a promising strategy in reducing myocardial ischemia reperfusion (I/R injury (MIRI, but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP blocker 5-hydroxydecanoate (5-HD. Myocardial mitochondria were extracted and mitochondrial comparative proteomics was analyzed. IPo significantly reduces post-ischemic myocardial infarction and improved cardiac function in I/R rat hearts, while 5-HD basically cancelled IPo’s myocardial protective effect. Joint application of two-dimensional polyacrylamide gel electrophoresis (2DE and MALDI-TOF MS identified eight differentially expressed proteins between groups. Expression of cardiac succinate dehydrogenase (ubiquinone flavoprotein subunit (SDHA increased more than two-fold after I/R, while IPo led to overexpression of dihydrolipoyl dehydrogenase (DLD, NADH dehydrogenase (ubiquinone flavoprotein 1 and isoform CRA_b (NDUFV1. When the mitoKATP was blocked, MICOS complex subunit Mic60 (IMMT and Stress-70 protein (Grp75 were over expressed, while DLDH, ATPase subunit A (ATPA and rCG44606 were decreased. Seven of the differential proteins belong to electron transport chain (ETC or metabolism regulating proteins, and five of them were induced by closing mitoKATP in I/R hearts. We thus conclude that IPo’s myocardial protective effect relies on energy homeostasis regulation. DLD, SDHA, NDUFV1, Grp75, ATPA and rCG44606 may contribute to IPo’s cardial protective effect.

  7. Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts.

    Science.gov (United States)

    Cao, Song; Liu, Yun; Wang, Haiying; Mao, Xiaowen; Chen, Jincong; Liu, Jiming; Xia, Zhengyuan; Zhang, Lin; Liu, Xingkui; Yu, Tian

    2016-01-01

    Ischemia postconditioning (IPo) is a promising strategy in reducing myocardial ischemia reperfusion (I/R) injury (MIRI), but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker 5-hydroxydecanoate (5-HD). Myocardial mitochondria were extracted and mitochondrial comparative proteomics was analyzed. IPo significantly reduces post-ischemic myocardial infarction and improved cardiac function in I/R rat hearts, while 5-HD basically cancelled IPo's myocardial protective effect. Joint application of two-dimensional polyacrylamide gel electrophoresis (2DE) and MALDI-TOF MS identified eight differentially expressed proteins between groups. Expression of cardiac succinate dehydrogenase (ubiquinone) flavoprotein subunit (SDHA) increased more than two-fold after I/R, while IPo led to overexpression of dihydrolipoyl dehydrogenase (DLD), NADH dehydrogenase (ubiquinone) flavoprotein 1 and isoform CRA_b (NDUFV1). When the mitoKATP was blocked, MICOS complex subunit Mic60 (IMMT) and Stress-70 protein (Grp75) were over expressed, while DLDH, ATPase subunit A (ATPA) and rCG44606 were decreased. Seven of the differential proteins belong to electron transport chain (ETC) or metabolism regulating proteins, and five of them were induced by closing mitoKATP in I/R hearts. We thus conclude that IPo's myocardial protective effect relies on energy homeostasis regulation. DLD, SDHA, NDUFV1, Grp75, ATPA and rCG44606 may contribute to IPo's cardial protective effect.

  8. Aging-dependent changes in rat heart mitochondrial glutaredoxins—Implications for redox regulation

    Directory of Open Access Journals (Sweden)

    Xing-Huang Gao

    2013-01-01

    Full Text Available Clinical and animal studies have documented that hearts of the elderly are more susceptible to ischemia/reperfusion damage compared to young adults. Recently we found that aging-dependent increase in susceptibility of cardiomyocytes to apoptosis was attributable to decrease in cytosolic glutaredoxin 1 (Grx1 and concomitant decrease in NF-κB-mediated expression of anti-apoptotic proteins. Besides primary localization in the cytosol, Grx1 also exists in the mitochondrial intermembrane space (IMS. In contrast, Grx2 is confined to the mitochondrial matrix. Here we report that Grx1 is decreased by 50–60% in the IMS, but Grx2 is increased by 1.4–2.6 fold in the matrix of heart mitochondria from elderly rats. Determination of in situ activities of the Grx isozymes from both subsarcolemmal (SSM and interfibrillar (IFM mitochondria revealed that Grx1 was fully active in the IMS. However, Grx2 was mostly in an inactive form in the matrix, consistent with reversible sequestration of the active-site cysteines of two Grx2 molecules in complex with an iron–sulfur cluster. Our quantitative evaluations of the active/inactive ratio for Grx2 suggest that levels of dimeric Grx2 complex with iron–sulfur clusters are increased in SSM and IFM in the hearts of elderly rats. We found that the inactive Grx2 can be fully reactivated by sodium dithionite or exogenous superoxide production mediated by xanthine oxidase. However, treatment with rotenone, which generates intramitochondrial superoxide through inhibition of mitochondrial respiratory chain Complex I, did not lead to Grx2 activation. These findings suggest that insufficient ROS accumulates in the vicinity of dimeric Grx2 to activate it in situ.

  9. Effects of laboratory housing on exploratory behaviour, novelty discrimination and spatial reference memory in a subterranean, solitary rodent, the Cape mole-rat (Georychus capensis).

    Science.gov (United States)

    Oosthuizen, Maria Kathleen; Scheibler, Anne-Gita; Bennett, Nigel Charles; Amrein, Irmgard

    2013-01-01

    A large number of laboratory and field based studies are being carried out on mole-rats, both in our research group and others. Several studies have highlighted the development of adverse behaviours in laboratory animals and have emphasised the importance of enrichment for captive animals. Hence we were interested in evaluating how laboratory housing would affect behavioural performance in mole-rats. We investigated exploratory behaviour, the ability to discriminate between novel and familiar environments and reference memory in the solitary Cape mole-rat (Georychus capensis). Our data showed that both wild and captive animals readily explore open spaces and tunnels. Wild animals were however more active than their captive counterparts. In the Y maze two trial discrimination task, wild animals failed to discriminate between novel and familiar environments, while laboratory housed mole-rats showed preferential spatial discrimination in terms of the length of time spent in the novel arm. The performance of the laboratory and wild animals were similar when tested for reference memory in the Y maze, both groups showed a significant improvement compared to the first day, from the 3rd day onwards. Wild animals made more mistakes whereas laboratory animals were slower in completing the task. The difference in performance between wild and laboratory animals in the Y-maze may be as a result of the lower activity of the laboratory animals. Laboratory maintained Cape mole-rats show classic behaviours resulting from a lack of stimulation such as reduced activity and increased aggression. However, they do display an improved novelty discrimination compared to the wild animals. Slower locomotion rate of the laboratory animals may increase the integration time of stimuli, hence result in a more thorough inspection of the surroundings. Unlike the captive animals, wild animals show flexibility in their responses to unpredictable events, which is an important requirement under

  10. Myocardial infarction with aortic banding. A combined rat model of heart failure.

    Science.gov (United States)

    Anthonio, R L; van Veldhuisen, D J; Scholtens, E; van Bekkum, C; de Boer, E; van Gilst, W H

    1997-09-01

    The effect of additional abdominal aortic banding on parameters of heart failure was studied in male Wistar rats with myocardial infarction. Contractile function was studied 8-9 weeks after operation, with an isoprenaline dose response protocol, in a retrograde Langendorff perfusion. Also, plasma noradrenaline concentration, infarct size and morphology were determined. Compared with controls, myocardial infarction/aortic banding animals showed a decreased contractile function, both at baseline and after maximal isoprenaline stimulation, and elevated noradrenaline levels (1316 +/- 94) vs 1909 +/- 174 pg/ml, both p Emax was significantly decreased. In aortic banding rats, contractile parameters were not significantly impaired, compared with controls. Both myocardial infarction and the myocardial infarction/aortic banding animals, but not aortic banding rats, had a significantly increased heart weight (1.4 +/- 0.04 g for controls vs 1.7 +/- 0.08 g for myocardial infarction and 2.0 +/- 0.12 g for myocardial infarction/aortic banding), and left ventricular cavity volume (19 +/- 1.4 mm3 for controls vs 49 +/- 5.5 mm3 for myocardial infarction and 48 +/- 4.3 mm3 for myocardial infarction/aortic banding) compared to control animals. Infarct size was 36.0% and 39.4% for the myocardial infarction and myocardial infarction/aortic banding animals, respectively. We conclude that myocardial infarction/aortic banding provides a new experimental model, which may yield important information and pathophysiology which allow evaluation of changes that may mimic clinical myocardial infarction with concomitant hypertension.

  11. Significance of matrix metalloproteinases in norepinephrine-induced remodelling of rat hearts.

    Science.gov (United States)

    Briest, Wilfried; Hölzl, Alexander; Rassler, Beate; Deten, Alexander; Baba, Hideo A; Zimmer, Heinz-Gerd

    2003-02-01

    Norepinephrine (NE) induced hypertrophy and remodelling of the extracellular matrix (ECM) in the left ventricle (LV) of the rat heart with resulting fibrosis. However, there was no increased collagen deposition in the right ventricle (RV). To test the hypothesis that lack of RV fibrosis is the result of elevated cleavage of collagens we inhibited the activity of matrix metalloproteinases (MMP) by doxycycline (Doxy) and then measured function and collagen metabolism in the RV as compared to the LV. Female Sprague-Dawley rats were treated with 30 mg/kg per day doxycycline alone or in combination with i.v. infusion of NE (0.1 mg/kg per h). The activity of MMP-2 was increased both in the LV and RV after 3 days of NE infusion and reduced after concomitant doxycycline treatment which also caused inhibition when given alone. After 14 days of NE infusion in combination with doxycycline there was an additional increase in the NE-induced elevation of collagen accumulation in the LV (interstitial collagen fraction: NE-Doxy 1.797%, PDoxy: 36.4 mmHg) and RV dP/dt(max) (NE: 5500 mmHg/s, PDoxy: 2550 mmHg/s). Also in the NE-stimulated LV, the doxycycline-induced collagen accumulation was associated with reduced LV dP/dt(max) (NE-Doxy: 13169 mmHg/s; NE: 18849 mmHg/s, P<0.05). MMP inhibition leads to myocardial stiffness with negative functional consequences for the RV and LV in NE-treated rat hearts.

  12. Inositol trisphosphate and thapsigargin discriminate endoplasmic reticulum stores of calcium in rat brain

    DEFF Research Database (Denmark)

    Verma, A; Hirsch, D J; Hanley, M R

    1990-01-01

    ATP dependent Ca2+ accumulation into oxalate-loaded rat brain microsomes is potently inhibited by thapsigargin with an IC50 of 2 nM and maximal inhibition at 10 nM. Approximately 15% of the total A23187-releasable microsomal calcium store is insensitive to thapsigargin concentrations up to 100 mi...

  13. Genistein, a soy phytoestrogen, reverses severe pulmonary hypertension and prevents right heart failure in rats.

    Science.gov (United States)

    Matori, Humann; Umar, Soban; Nadadur, Rangarajan D; Sharma, Salil; Partow-Navid, Rod; Afkhami, Michelle; Amjedi, Marjan; Eghbali, Mansoureh

    2012-08-01

    Pretreatment with a phytoestrogen genistein has been shown to attenuate the development of pulmonary hypertension (PH). Because PH is not always diagnosed early, we examined whether genistein could also reverse preexisting established PH and prevent associated right heart failure (RHF). PH was induced in male rats by 60 mg/kg of monocrotaline. After 21 days, when PH was well established, rats received daily injection of genistein (1 mg/kg per day) for 10 days or were left untreated to develop RHF by day 30. Effects of genistein on human pulmonary artery smooth muscle cell and endothelial cell proliferation and neonatal rat ventricular myocyte hypertrophy were assessed in vitro. Severe PH was evident 21 days after monocrotaline, as peak systolic right ventricular pressure increased to 66.35±1.03 mm Hg and right ventricular ejection fraction reduced to 41.99±1.27%. PH progressed to RHF by day 30 (right ventricular pressure, 72.41±1.87 mm Hg; RV ejection fraction, 29.25±0.88%), and mortality was ≈75% in RHF rats. Genistein therapy resulted in significant improvement in lung and heart function as right ventricular pressure was significantly reduced to 43.34±4.08 mm Hg and right ventricular ejection fraction was fully restored to 65.67±1.08% similar to control. Genistein reversed PH-induced pulmonary vascular remodeling in vivo and inhibited human pulmonary artery smooth muscle cell proliferation by ≈50% in vitro likely through estrogen receptor-β. Genistein also reversed right ventricular hypertrophy (right ventricular hypertrophy index, 0.35±0.029 versus 0.70±0.080 in RHF), inhibited neonatal rat ventricular myocyte hypertrophy, and restored PH-induced loss of capillaries in the right ventricle. These improvements in cardiopulmonary function and structure resulted in 100% survival by day 30. Genistein restored PH-induced downregulation of estrogen receptor-β expression in the right ventricle and lung. In conclusion, genistein therapy not only rescues

  14. The ethanolic extract of Kaempferia parviflora reduces ischaemic injury in rat isolated hearts.

    Science.gov (United States)

    Malakul, Wachirawadee; Ingkaninan, Kornkanok; Sawasdee, Pattara; Woodman, Owen L

    2011-09-01

    The ethanolic extract of Kaempferia parviflora (KPE) has been reported to contain a range of flavonoids and to enhance endothelial synthesis of NO. We investigated the vascular relaxant, antioxidant and cardioprotective activities of KPE. Vascular function was assessed in rat aortic rings and superoxide generation determined using lucigenin enhanced chemiluminescence. Ischaemia and reperfusion were induced in rat isolated, perfused hearts. KPE caused vasorelaxation (R(max) 102 ± 2%), which was partly inhibited by removal of the endothelium (R(max) 91 ± 1%) or by N(G)-nitro-l-arginine (L-NNA, R(max) 83 ± 3%) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, R(max) 80 ± 2%). In addition KPE caused concentration-dependent inhibition of the contractile response to exogenous Ca(2+). KPE (10(-3)M) also significantly inhibited superoxide radical generation induced by of xanthine/xanthine oxidase (2.3 ± 0.4% of control) to a similar extent to the xanthine oxidase inhibitor allopurinol (10(-4)M, 1.6 ± 0.5%) or by rat isolated aorta in the presence of NADPH (30.0 ± 6.3% of control) similarly to the NADPH oxidase inhibitor diphenyliodonium (5 × 10(-6)M, 23.1 ± 5.6%). In the presence of oxidant stress generated by pyrogallol endothelium-dependent relaxation of rat aortic rings was impaired (ACh R(max) control 99 ± 1%; pyrogallol 44 ± 5%), an effect that was significantly reduced by KPE (10(-4)M, ACh R(max) 82 ± 4%). In addition, KPE was found to attenuate the ventricular dysfunction caused by 20 min global ischaemia and 30 min reperfusion (I/R) in rat isolated hearts (dP/dt IR 1016 ± 242, IR+KPE 2238±233 mm Hg/s). KPE is an effective vasodilator and antioxidant that is able to prevent myocardial ischaemia-reperfusion injury. We suggest that KPE may be useful as an adjunct to thrombolytic therapy in the management of reperfusion injury. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Angiotensin II type 1 receptor blockade restores angiotensin-(1-7)-induced coronary vasodilation in hypertrophic rat hearts.

    Science.gov (United States)

    Souza, Álvaro P S; Sobrinho, Deny B S; Almeida, Jônathas F Q; Alves, Gisele M M; Macedo, Larissa M; Porto, Juliana E; Vêncio, Eneida F; Colugnati, Diego B; Santos, Robson A S; Ferreira, Anderson J; Mendes, Elizabeth P; Castro, Carlos H

    2013-11-01

    The aim of the present study was to investigate the coronary effects of Ang-(1-7) [angiotensin-(1-7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1-7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (N(G)-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1-7) in control hearts. The coronary vasodilation produced by Ang-(1-7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1-7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1-7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1-7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1-7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1-7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas

  16. improvement of chronic heart failure by dexamethasone is not associated with downregulation of leptin in rats

    Institute of Scientific and Technical Information of China (English)

    Qin-gui XIA; Tao NA; Yi-min GUO; Yun-tian BI; Hai-yan ZHANG; De-zai DAI

    2007-01-01

    Aim: To demonstrate the hypothesis that dexamethasone (Dex) could improve chronic heart failure (CHF) by inhibiting the downstream signaling transduction of leptin but had no influence on the upregulation of leptin and its receptor in myocardium. Methods: CHF was induced by left coronary artery ligation for 6weeks. CHF rats were treated with Dex 50 mg.kg-1.d-1. Hemodynamics, histology,reactive oxygen species (ROS)-related parameters, and leptin concentrations in serum were measured. The mRNA expression of matrix metalloproteinases (MMP)2/9, tissue inhibitor of metalloproteinases (TIMP)1/2, tumor necrosis factor (TNF)-α, and OB-Rb were measured by RT-PCR. Results: In the CHF rats, hemodynamic functions were deteriorated, which was accompanied with myocardium remodel-ing and histological changes. CHF rats showed hyperleptinemia and excessive ROS in the serum, and the upregulation of MMP-2/9, TNF-α, and leptin receptorm RNA and downregulation of TIMP-1/2 mRNA in the myocardium compared with the sham operation group. Dex treatment significantly ameliorated CHF in association with the reversion of the abnormalities of MMP-2/9, TIMP-1/2, TNF-α, and ROS. But Dex had no influence on the hyperleptinemia and the upregulated leptin and its receptor in the myocardium during CHF. Conclusion: Dex improves CHF by inhibiting TNF-α, MMP-2, MMP-9, and ROS. Dex had no effects on upregulated leptin and its receptor expression and hyperleptinemia induced by CHF.

  17. Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts

    Directory of Open Access Journals (Sweden)

    Matsumoto Shuhei

    2012-01-01

    Full Text Available Abstract Background The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP. Methods Wistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener. Results Under normoglycemia, both 30 μg/kg milrinone (29 ± 12% and 10 μg/kg levosimendan (33 ± 13% reduced infarct size compared with that in the control (58 ± 7%. Under hyperglycemia, milrinone (34 ± 13% reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9% reduced infarct size compared with that in the hyperglycemic control (58 ± 13%. All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside. Conclusion Milrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.

  18. Oxymatrine attenuated isoproterenol-induced heart failure in rats via regulation of COX-2/PGI2 pathway.

    Science.gov (United States)

    Zhou, Ru; Xu, Qingbin; Xu, Yehua; Xiong, Aiqin; Wang, Yang; Ma, Ping

    2016-12-01

    Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA2. And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI2 pathway. Copyright © 2016. Published by Elsevier Masson SAS.

  19. Cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury in coronary artery occlusion-induced rats and Langendorff-perfused rat hearts.

    Science.gov (United States)

    Chang, Xiayun; Zhang, Kai; Zhou, Rui; Luo, Fen; Zhu, Lingpeng; Gao, Jin; He, He; Wei, Tingting; Yan, Tianhua; Ma, Chunhua

    2016-07-15

    The current study was designed to investigate the protective role of salisroside on rats through the study of energy metabolism homeostasis and inflammation both in ex vivo and in vivo. Energy metabolism homeostasis and inflammation injury were respectively assessed in global ischemia of isolated hearts and coronary artery ligated rats. Excessive release of cardiac enzymes and pro-inflammatory cytokines was inhibited by salidroside in coronary artery occlusion-induced rats. ST segment was also restored with the treatment of salidroside. Triphenyltetrazolium chloride staining (TTC) staining and pathological analysis showed that salidroside could significantly alleviate myocardial injury in vivo. Accumulated data in ex vivo indicated that salidroside improved heart function recovery, which was reflected by enhanced myocardial contractility and coronary flow in isolated hearts. The contents of ATP and glycogen both in ex vivo and in vivo were restored by salidroside compared with those in the model group. Besides, the expressions of p-AMPK, PPAR-α and PGC-1α in rats and isolated hearts subjected to salidroside were significantly elevated, while the levels of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were dramatically reduced by salidroside. The present study comprehensively elaborated the protective effects of salidroside on myocardial injury and demonstrated that AMPK/PGC-1α and AMPK/NF-κB signaling cascades were implicated in the myocardial ischemia-reperfusion injury (I/R) model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Receptors involved in moxonidine-stimulated atrial natriuretic peptide release from isolated normotensive rat hearts.

    Science.gov (United States)

    Mukaddam-Daher, Suhayla; Menaouar, Ahmed; Gutkowska, Jolanta

    2006-07-10

    Imidazoline I1-receptors are present in the heart and may be involved in atrial natriuretic peptide (ANP) release. The following studies investigated whether moxonidine (an antihypertensive imidazoline I1-receptor and alpha2-adrenoceptor agonist) acts directly on the heart to stimulate ANP release, and to characterize the receptor type involved in this action. Perfusion of rat (200-225 g) isolated hearts with moxonidine (10(-6) and 10(-5) M), for 30 min, resulted in ANP release (83+/-29 and 277+/-70 ng/30 min, above basal, respectively), significantly (Palpha1-adrenoceptors), and prazosin (alpha1>alpha2-adrenoceptors), but increased by rauwolscine (alpha2-adrenoceptors). Perfusion with 10(-5) M brimonidine (full alpha2-adrenoceptor agonist) inhibited moxonidine-stimulated ANP release. Similarly, moxonidine (10(-6) M) tended to reduce coronary flow, but significantly increased coronary flow in the presence of brimonidine, which was vasoconstrictive when perfused alone. Coronary flow was reduced by 10(-5) M each, brimonidine>clonidine>moxonidine; while similar bradycardia was observed with clonidine and moxonidine, but not with brimonidine. In conclusion, these results argue in favor of moxonidine acting primarily on imidazoline I1-receptors to release ANP, with both alpha2-adrenoceptor and imidazoline I1-receptors exerting inhibitory inter-relation. In contrast, the coronary vasodilatory effect of moxonidine requires full activation of alpha2-adrenoceptor. The sympatholytic and ANP-releasing effects of moxonidine appear to be mediated by cardiac imidazoline receptors that may be differentially localized. Most importantly, moxonidine can stimulate ANP release from the heart without contribution of the central nervous system.

  1. Protective effects of protocatechuic acid on TCDD-induced oxidative and histopathological damage in the heart tissue of rats.

    Science.gov (United States)

    Ciftci, Osman; Disli, Olcay Murat; Timurkaan, Necati

    2013-10-01

    2,3,7,8-Tetracholorodibenzo-p-dioxin (TCDD) is a highly toxic environmental contaminant that causes severe toxic effects in animal and human. In this study, we investigated the toxic effects of TCDD and the preventive effects of protocatechuic acid (PCA), a widespread phenolic compound, in the heart tissue of rats. For this purpose, 3-4 months old 28 rats with 280-310 g body weights were equally divided into 4 groups (control, TCDD, PCA, TCDD + PCA group). A 2 μg/kg dose of 2,3,7,8-TCDD and 100 mg/kg dose of PCA were dissolved in corn oil and given orally to the rats for 45 days. The results indicated that TCDD induced oxidative stress by increasing the level of thiobarbituric acid reactive substance and by decreasing the levels of glutathione, catalase, glutathione peroxidase and superoxide dismutase in the heart tissue of rats. In contrast, PCA treatment prevents the toxic effects of TCDD on oxidative stress. In addition, histopathological alterations such as necrosis and hemorrhage occurred in TCDD group, and PCA treatment partially prevents these alterations in heart tissue. In this study, it was concluded that TCDD exposure led to toxic effects in heart tissue and PCA treatment could prevent the toxicity of TCDD.

  2. Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat

    DEFF Research Database (Denmark)

    Bergdahl, A; Valdemarsson, S; Nilsson, T;

    1999-01-01

    It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status...

  3. Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

    Science.gov (United States)

    Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

  4. Different effects of thiopental in severe hypoxia, total ischemia and low-flow ischemia in rat heart muscle

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Slade, A.M.; Meer, P. van der; Moes, D. de; Sinclair, D.M.; Poole-Wilson, P.A.; Meijler, F.L.

    1985-01-01

    The effect of thiopental (100 mg .1-1) during total ischemia, low-flow ischemia, and severe hypoxia with maintained flow was investigated in the isolated perfused rat heart. During total ischemia the rate of decline of tissue creatine phosphate and adenosine triphosphate was no different in thiopent

  5. Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI.

    Science.gov (United States)

    Gilbert, Stephen H; Benoist, David; Benson, Alan P; White, Ed; Tanner, Steven F; Holden, Arun V; Dobrzynski, Halina; Bernus, Olivier; Radjenovic, Aleksandra

    2012-01-01

    It has been shown by histology that cardiac myocytes are organized into laminae and this structure is important in function, both influencing the spread of electrical activation and enabling myocardial thickening in systole by laminar sliding. We have carried out high-spatial resolution three-dimensional MRI of the ventricular myolaminae of the entire volume of the isolated rat heart after contrast perfusion [dimeglumine gadopentate (Gd-DTPA)]. Four ex vivo rat hearts were perfused with Gd-DTPA and fixative and high-spatial resolution MRI was performed on a 9.4T MRI system. After MRI, cryosectioning followed by histology was performed. Images from MRI and histology were aligned, described, and quantitatively compared. In the three-dimensional MR images we directly show the presence of laminae and demonstrate that these are highly branching and are absent from much of the subepicardium. We visualized these MRI volumes to demonstrate laminar architecture and quantitatively demonstrated that the structural features observed are similar to those imaged in histology. We showed qualitatively and quantitatively that laminar architecture is similar in the four hearts. MRI can be used to image the laminar architecture of ex vivo hearts in three dimensions, and the images produced are qualitatively and quantitatively comparable with histology. We have demonstrated in the rat that: 1) laminar architecture is consistent between hearts; 2) myolaminae are absent from much of the subepicardium; and 3) although localized orthotropy is present throughout the myocardium, tracked myolaminae are branching structures and do not have a discrete identity.

  6. Hypertensive heart disease versus hypertrophic cardiomyopathy: multi-parametric cardiovascular magnetic resonance discriminators when end-diastolic wall thickness ≥ 15 mm.

    Science.gov (United States)

    Rodrigues, Jonathan C L; Rohan, Stephen; Ghosh Dastidar, Amardeep; Harries, Iwan; Lawton, Christopher B; Ratcliffe, Laura E; Burchell, Amy E; Hart, Emma C; Hamilton, Mark C K; Paton, Julian F R; Nightingale, Angus K; Manghat, Nathan E

    2017-03-01

    European guidelines state left ventricular (LV) end-diastolic wall thickness (EDWT) ≥15mm suggests hypertrophic cardiomyopathy (HCM), but distinguishing from hypertensive heart disease (HHD) is challenging. We identify cardiovascular magnetic resonance (CMR) predictors of HHD over HCM when EDWT ≥15mm. 2481 consecutive clinical CMRs between 2014 and 2015 were reviewed. 464 segments from 29 HCM subjects with EDWT ≥15mm but without other cardiac abnormality, hypertension or renal impairment were analyzed. 432 segments from 27 HHD subjects with EDWT ≥15mm but without concomitant cardiac pathology were analyzed. Magnitude and location of maximal EDWT, presence of late gadolinium enhancement (LGE), LV asymmetry (>1.5-fold opposing segment) and systolic anterior motion of the mitral valve (SAM) were measured. Multivariate logistic regression was performed. Significance was defined as pheart disease (HHD) can be difficult to distinguish from HCM. • Retrospective case-control study showed that location and magnitude of EDWT are poor discriminators. • Increased left ventricular mass and midwall fibrosis are independent predictors of HHD. • Cardiovascular magnetic resonance parameters facilitate a better discrimination between HHD and HCM.

  7. Contribution of depressed reuptake to the depletion of norepinephrine from rat heart and spleen during endotoxin shock

    Energy Technology Data Exchange (ETDEWEB)

    Pardini, B.J.; Jones, S.B.; Filkins, J.P.

    1982-01-01

    Norepinephrine content (microgram/g) was depressed in hearts and spleens of fasted male Holtzman rats treated intravenously with Salmonella enteritidis lipopolysaccharide (14-17 mg/kg). To investigate the mechanism of norepinephrine depletion during endotoxicosis, in vivo norepinephrine reuptake was evaluated in control and severely shocked rats using the incorporation of /sup 3/H-norepinephrine into hearts and spleens. Incorporation of /sup 3/H-norepinephrine into spleens of endotoxic rats was reduced 88%. In contrast, cardiac tissue incorporation of /sup 3/H-norepinephrine was not significantly impaired. In vitro analysis of total norepinephrine retained in cardiac and splenic tissue slices incubated with /sup 3/H-norepinephrine yielded results consistent with in vivo experiments: Splenic norepinephrine reuptake was significantly decreased on the order of 50% in preparations from endotoxic rats, while myocardial norepinephrine reuptake was the same in both groups. The results indicate that depression of norepinephrine reuptake is a mechanism of norepinephrine depletion in spleens but not hearts of endotoxic rats.

  8. Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate.

    Science.gov (United States)

    Li, Ping; Luo, Shike; Pan, Chunji; Cheng, Xiaoshu

    2015-12-01

    Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)‑induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator‑activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO‑induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO‑induced rat model, possibly via promoting fatty acid oxidation.

  9. Central actions of the chemokine stromal cell-derived factor 1 contribute to neurohumoral excitation in heart failure rats.

    Science.gov (United States)

    Wei, Shun-Guang; Zhang, Zhi-Hua; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2012-05-01

    The ample expression of chemokines and their receptors by neurons in the brain suggests that they play a functional role beyond the coordination of inflammatory and immune responses. Growing evidence implicates brain chemokines in the regulation of neuronal activity and neurohormonal release. This study examined the potential role of brain chemokines in regulating hemodynamic, sympathetic, and neuroendocrine mechanisms in rats with ischemia-induced heart failure (HF). Immunohistochemical analysis revealed that the chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12 was highly expressed in the hypothalamic paraventricular nucleus and subfornical organ and that SDF-1 expression was significantly increased in HF rats compared with sham-operated (SHAM) control rats. ICV injection of SDF-1 induced substantial and long-lasting increases in blood pressure, heart rate, and renal sympathetic nerve activity in both SHAM and HF rats, but responses were exaggerated in HF rats. Bilateral microinjection of SDF-1 into the paraventricular nucleus also elicited exaggerated increases in blood pressure, heart rate, and renal sympathetic nerve activity in the HF rats. A 4-hour ICV infusion of SDF-1 increased plasma levels of arginine vasopressin, adrenocorticotropic hormone, and norepinephrine in normal rats, responses that were prevented by pretreatment with ICV SDF-1 short-hairpin RNA (shRNA). ICV administration of SDF-1 shRNA also reduced plasma arginine vasopressin, adrenocorticotropic hormone, and norepinephrine levels in HF rats. These data suggest that the chemokine SDF-1, acting within the brain, plays an important role in regulating sympathetic drive, neuroendocrine release, and hemodynamic function in normal and pathophysiological conditions and so may contribute to the neural and humoral activation in HF.

  10. Effects of simulated microgravity on circadian rhythm of caudal arterial pressure and heart rate in rats and their underlying mechanism

    Directory of Open Access Journals (Sweden)

    Li CHEN

    2016-04-01

    Full Text Available Objective  To explore the effects of simulated microgravity on the circadian rhythm of rats' caudal arterial pressure and heart rate, and their underlying mechanism. Methods  Eighteen male SD rats (aged 8 weeks were randomly assigned to control (CON and tail suspension (SUS group (9 each. Rats with tail suspension for 28 days were adopted as the animal model to simulate microgravity. Caudal arterial pressure and heart rate of rats were measured every 3 hours. The circadian difference of abdominal aorta contraction was measured by aortic ring test. Western blotting was performed to determine and compare the protein expression level of clock genes such as Per2 (Period2, Bmal1 (Aryl hydrocarbon receptor nuclear translocatorlike and dbp (D element binding protein in suprachiasmatic nucleus (SCN and abdominal aorta of rats in CON and SUS group at different time points. Results  Compared with CON group, the caudal arterial pressure, both systolic and diastolic pressure, decreased significantly and the diurnal variability disappeared, meanwhile the heart rate increased obviously and also the diurnal variability disappeared in rats of SUS group. Compared with CON group, the contraction reactivity of abdominal aorta decreased with disappearence of the diurnal variability, and also the clock genes expression in SCN and abdominal aorta showed no diurnal variability in rats of SUS group. Conclusion  Simulated microgravity may lead to circadian rhythm disorders in rats' cardiovascular system, which may be associated with the changes of the clock genes expression. DOI: 10.11855/j.issn.0577-7402.2016.04.06

  11. Nkx2.5 enhances the efficacy of mesenchymal stem cells transplantation in treatment heart failure in rats.

    Science.gov (United States)

    Deng, Bo; Wang, Jin Xin; Hu, Xing Xing; Duan, Peng; Wang, Lin; Li, Yang; Zhu, Qing Lei

    2017-08-01

    The aim of this study is to determine whether Nkx2.5 transfection of transplanted bone marrow mesenchymal stem cells (MSCs) improves the efficacy of treatment of adriamycin-induced heart failure in a rat model. Nkx2.5 was transfected in MSCs by lentiviral vector transduction. The expressions of Nkx2.5 and cardiac specific genes in MSCs and Nkx2.5 transfected mesenchymal stem cells (MSCs-Nkx2.5) were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models of rats were induced by adriamycin and were then randomly divided into 3 groups: injected saline, MSCs or MSCs-Nkx2.5 via the femoral vein respectively. Four weeks after injection, the cardiac function, expressions of cardiac specific gene, fibrosis formation and collagen volume fraction in the myocardium as well as the expressions of GATA4 and MEF2 in rats were analyzed with echocardiography, immunohistochemistry, Masson staining, quantitative real-time PCR and Western blot, respectively. Nkx2.5 enhanced cardiac specific gene expressions including α-MHC, TNI, CKMB, connexin-43 in MSCs-Nkx2.5 in vitro. Both MSCs and MSCs-Nkx2.5 improved cardiac function, promoted the differentiation of transplanted MSCs into cardiomyocyte-like cells, decreased fibrosis formation and collagen volume fraction in the myocardium, as well as increased the expressions of GATA4 and MEF2 in adriamycin-induced rat heart failure models. Moreover, the effect was much more remarkable in MSCs-Nkx2.5 than in MSCs group. This study has found that Nkx2.5 enhances the efficacy of MSCs transplantation in treatment adriamycin-induced heart failure in rats. Nkx2.5 transfected to transplanted MSCs provides a potential effective approach to heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Changes in ECG and enzyme activity in rat heart after myocardial infarction: effect of TPP and MnCl2.

    Science.gov (United States)

    Tylicki, A; Czerniecki, J; Godlewska, A; Kieliszek, M; Zebrowski, T; Bielawski, T; Wojcik, B

    2008-06-01

    Heart infarction is one of the main causes of death in the human population. Assurance of a sufficient level of bioenergetic processes is very important for the heart after infarction. Mn2+ as well as thiamine pyrophosphate (TPP) are positive effectors of the pyruvate dehydrogenase complex (PDH) and the 2-oxoglutarate dehydrogenase complex (OGDH), both of which play a very important role in the Krebs cycle. Thus, we have established the effect of MnCl2 (10mg/kg) and TPP (20mg/kg)--4 injections every 12 h--on the activity of PDH, OGDH, lactate dehydrogenase (LDH) and malate dehydrogenase (MDH). Additionally, we perform an analysis of ECG to affirm the changes in the heart electrophysiology of healthy rats after MnCl2 and TPP treatment. We then analyzed changes in the activity of these enzymes after experimental myocardial infarction in rats. We observed a decrease of OGDH and MDH activity in rat hearts after infarction in comparison with sham-operated rats. Treatment of healthy rats with MnCl2 caused an increase of OGDH activity. Moreover both MnCl2 and TPP caused an increase of PDH activity and a decrease of MDH activity (TPP revealed a stronger effect). We found no changes in LDH activity. Electrocardiography data showed a slight shortening of the QT interval and an enhanced heartbeat rate after treatment with MnCl2. TPP caused only elongation of the QT interval. In conclusion, application of MnCl2 enhanced the activity of some very important enzymes in the respiration process (PDH and OGDH). This effect, connected with enhanced heartbeat and a slightly shortened ventricle relaxation, may have potential application during the key period of convalescence following heart infarction.

  13. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses.

    Directory of Open Access Journals (Sweden)

    Nils Thomas Songstad

    Full Text Available To investigate the effects of high intensity interval training (HIIT on the maternal heart, fetuses and placentas of pregnant rats.Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85-90% of maximal oxygen consumption for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats, echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples.Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03, hypoxia-inducible factor 1α (p = 0.04 and glutathione peroxidase 4.2 (p = 0.02 in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014, superoxide dismutase 1 (p = 0.001 and tissue inhibitor of metallopeptidase 3 (p = 0.049 in the fetal heart.Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated.

  14. Olaparib protects cardiomyocytes against oxidative stress and improves graft contractility during the early phase after heart transplantation in rats.

    Science.gov (United States)

    Korkmaz-Icöz, Sevil; Szczesny, Bartosz; Marcatti, Michela; Li, Shiliang; Ruppert, Mihály; Lasitschka, Felix; Loganathan, Sivakkanan; Szabó, Csaba; Szabó, Gábor

    2017-08-14

    Olaparib, rucaparib and niraparib, potent inhibitors of poly(ADP-ribose) polymerase (PARP) are approved as anti-cancer drugs in humans. Considering the previously demonstrated role of PARP in various forms of acute and chronic myocardial injury, we tested the effects of olaparib in in-vitro models of oxidative stress in cardiomyocytes, and in an in vivo model of cardiac transplantation. H9c2-embryonic rat heart-derived myoblasts pretreated with vehicle or olaparib (10μM) were challenged with either hydrogen peroxide (H2 O2 ) or with glucose oxidase (GOx, which generates H2 O2 in the tissue culture medium). Cell viability assays (MTT, lactate dehydrogenase) and Western blotting for PARP and its product, PAR was performed. Heterotopic heart transplantation was performed in Lewis rats; recipients were treated either with vehicle or olaparib (10 mg kg(-1) ). Left ventricular function of transplanted hearts was monitored via a Millar catheter. Multiple gene expression in the graft was measured by qPCR. Olaparib blocked autoPARylation of PARP1 and attenuated the rapid onset of death in H9c2 cells, induced by H2 O2 , but did not affect cell death following chronic, prolonged oxidative stress induced by GOx. In rats, after transplantation, left ventricular systolic and diastolic function were improved by olaparib. In the transplanted hearts, olaparib also reduced gene expression for c-jun, caspase-12, catalase, and NADPH oxidase-2. Olaparib protected cardiomyocytes against oxidative stress and improved graft contractility in a rat model of heart transplantation. These findings raise the possibility of repurposing this clinically approved oncology drug, to be used in heart transplantation. © 2017 The British Pharmacological Society.

  15. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses

    Science.gov (United States)

    Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

    2015-01-01

    Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated. PMID:26566220

  16. Matrine improved the function of heart failure in rats via inhibiting apoptosis and blocking β3‑adrenoreceptor/endothelial nitric oxide synthase pathway.

    Science.gov (United States)

    Yu, Jiangbo; Yang, Shusen; Wang, Xu; Gan, Runtao

    2014-12-01

    Matrine, an alkaloid isolated from the traditional Chinese medicine Sophora flavescens AIT has exhibited a number of therapeutic effects on cardiovascular and liver diseases. The purpose of the present study was to investigate whether matrine has a protective effect on heart failure in rats. Coronary artery ligation was used to induce a heart failure (CHF) model in rats. Four weeks following the procedure, the rats were treated with different doses of matrine for one month. Histopathological examination demonstrated that matrine treatment alleviated myocardial hypertrophy and cardiac fibrosis in failing hearts. Furthermore, matrine administration also inhibited the increase of plasma aspartate amino transferase, creatine phosphokinase and lactate dehydrogenase levels in CHF rats. The rats with heart failure exhibited a significant reduction in ejection fraction and fractional shortening, as well as an increase in the left ventricular end systolic dimension, and matrine attenuated this decline in heart function. Further investigation demonstrated that matrine treatment also inhibited the upregulation of Bax and increase in the Bcl‑2 expression in the failing hearts. Furthermore, the upregulation of β3-adrenoreceptor (AR) and endothelial nitric oxide synthase proteins following heart failure were also attenuated by matrine. In conclusion, matrine had a preventive role in heart failure in rats at least in part by inhibiting myocardial apoptosis and the β3-AR pathway.

  17. Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    YAO Yun-tai; FANG Neng-xin; SHI Chun-xia; LI Li-huan

    2010-01-01

    Background Studies suggested that anesthetics administered upon the early reperfusion or "anesthetic postconditioning" could protect post-ischemic hearts against myocardial ischemia reperfusion injury (MIRI).However, the mechanism responsible for such protection was not well-elucidated.We investigated the cardioprotection induced by sevoflurane postconditioning (SpostC) in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase (PI3K), extracellular signal-regulated kinase 1 and 2 (ERK 1/2), mitochondrial KATP channels (mitoKATP) and mitochondrial permeability transition pore (mPTP), by selectively inhibiting PI3K, ERK 1/2, mitoKATP, with LY294002 (LY), PD98059 (PD), 5-hydroxydecanoate (5-HD) and by directly opening of mPTP with atractyloside (ATR), respectively.Methods Isolated rat hearts were randomly assigned to one of the 12 groups (n=15):Time control (continuous perfusion), ISCH (30 minutes of ischemia followed by 60 minutes of reperfusion alone), SpostC (3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia), ISCH+LY,ISCH+PD, ISCH+ATR, ISCH+5-HD and ISCH+ dimethyl sulfoxide (DMSO) groups (LY, PD, ATR, 5-HD and DMSO (the vehicle) was administered respectively during the first 15 minutes of reperfusion following test ischemia), SpostC+LY, SpostC+PD, SpostC+ATR and SpostC+5-HD groups (LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively).Hemodynamics was compared within and between groups.Infarction size was determined at the end of experiments using triphenyltetrazolium chloride (TTC) staining.Lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) released from necrotic myocardium, were compared among TC, ISCH and SpostC groups.To investigate the relationships between RISK and mPTP implicated in SpostC, NAD+ content in myocardium, a marker of mPTP opening, was compared among some experimental groups (TC, ISCH, ISCH

  18. Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture.

    Science.gov (United States)

    Harvey, Eric L; Baker, Lisa E

    2016-02-01

    Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances. The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA. Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg MDMA, and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA + AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine. Dose-response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA + AMPH mixture. These findings indicate that MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-hydroxytryptamine (5-HT) receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone.

  19. Oral delivery of insulin withDesmodium gangeticum root aqueous extract protects rat hearts against ischemia reperfusion injury in streptozotocin induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Gino A Kurian; Jose Paddikkala

    2010-01-01

    Objective:To evaluate the effect of insulin administered via oral route with the help of aqueous extract ofDesmodium gangeticum (DG) root in rendering cardio protection against ischemia reperfusion injury in diabetic rats.Methods: Diabetes mellitus was induced in rats by theβ-cell toxin, streptozotocin (STZ, 60 mg/kg). Isolated rat (IR) heart was used to investigate the effect of insulin mixed DG pretreatment on ischemia reperfusion injury. Mitochondrial respiratory enzymes and microsomal enzymes were used to assess the metabolic recovery of myocardium. Cardiac marker enzymes were used to find the functional recovery, which were compared with that of the STZ treated IR rats.Results: Compared with IR control group, rat treated with insulin mixed DG showed a significant functional and metabolic recovery of myocardium from the insult of ischemia reperfusion. Even though orally administered insulin mixed DG displayed a slow but prolonged hypoglycemic effect, the cardio protection it provided was more significant than when it was given intra peritoneal. Furthermore the above result indicates that insulin mixed DG can overcome the barriers in the gastrointestinal tract and be absorbed.Conclusions: The above results indicate the efficacy of insulin mixed DG in protecting the heart from ischemia reperfusion induced injury in diabetic rats. Furthermore the study gives additional information that herbal extracts can be used to transport insulin across the membrane and found to be a feasible approach for developing the oral delivery of insulin, as well as other peptide drugs.

  20. Continuous Monitoring of Intracellular Volumes in Isolated Rat Hearts during Normothermic Perfusion and Ischemia

    Science.gov (United States)

    Askenasy, Nadir; Navon, Gil

    1997-01-01

    The present study describes an experimental setup that enables continuous measurement of cellular volumes in isolated organs. The procedure is a modification of a recently reported method that uses multinuclear NMR measured by59Co NMR of cobalticyanide and1H NMR of water in isolated rat hearts at normothermia. The new apparatus contains a background flow which is shown to improve the rate of exchange of the marker between the interstitium and the external solution and allows detection of cellular shrinkage during no-flow ischemia. A series of experiments of marker loading and wash-out were performed to validate the method. In the Langendorff preparation, intracellular volumes (in units of milliliters per gram dry weight) of hearts perfused with Krebs-Henseleit solution oscillated around a mean value of 2.50 ± 0.06 ml/gdw. During 30 min of ischemia the cells swelled to 2.88 ± 0.08 ml/gdw and residual edema was observed after 30 min of reperfusion (2.62 ± 0.08 ml/gdw). A hypoosmotic shock was used to assess changes in membrane permeability at different time points of ischemia and reperfusion. Water influx induced by the hypoosmotic shock at the end of ischemia was similar to that elicited in perfused hearts. After 15 and 30 min of reperfusion, the magnitude of the response to hypoosmolarity decreased by 9 and 37%, respectively, indicating a gradual permeabilization of the membranes, presumably to ions. The experimental setup was also used to monitor intracellular volumes as a function of time in anisoosmotic conditions. Cellular swelling/shrinkage were delayed for periods of 5 and 8 min at osmolarities of ±50 and ±100 mosmol/liter, suggesting a limited capability of the heart to absorb an anisoosmotic shock. The variation in cellular volumes was proportional to the deviation of the conditions from isoosmolarity, and activation of volume-regulatory mechanisms was demonstrated. The noninvasive technique presented in this study is capable of providing quantitative

  1. Effects of D1 and D2 receptor antagonists on the discriminative stimulus effects of methylendioxypyrovalerone and mephedrone in male Sprague-Dawley rats trained to discriminate D-amphetamine.

    Science.gov (United States)

    Harvey, Eric L; Burroughs, Rachel L; Baker, Lisa E

    2017-10-01

    Psychopharmacology research has amassed substantial evidence for similarities between synthetic cathinones and other commonly abused psychostimulants. Few studies have utilized drug discrimination methods to investigate synthetic cathinones, and the precise neurochemical substrates underlying their interoceptive effects have not been examined. The present study assessed the involvement of D1 and D2 dopaminergic receptors in the stimulus effects of 3,4-methylenedioxypyrovalerone (MDPV) and mephedrone (MEPH) in rats trained to discriminate D-amphetamine. Eight male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg D-amphetamine (AMPH) from saline. Dose-response curves were then generated with AMPH (0.0-1.0 mg/kg), MDPV (0.0-1.0 mg/kg), and MEPH (0.0-2.0 mg/kg). Subsequently, Sch 39166 (0.3 mg/kg) and haloperidol (0.5 mg/kg) were administered in combination with select doses of MDPV and MEPH. Both MDPV and MEPH produced full substitution for AMPH. Sch 39166 produced a downward shift in the MDPV and MEPH dose-response curves and haloperidol produced similar results with MDPV. These preliminary findings indicate that MDPV and MEPH produce interoceptive stimuli that are similar to those produced by AMPH and that D1 and D2 dopamine receptors contribute to these effects. Additional studies are warranted to investigate the contribution of other receptor mechanisms involved in the interoceptive stimuli produced by synthetic cathinones.

  2. Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue

    Science.gov (United States)

    Cuello, Friederike; Luther, Pradeep; Schulze, Thomas; Eder, Alexandra; Streichert, Thomas; Mannhardt, Ingra; Hirt, Marc N.; Schaaf, Sebastian; Stenzig, Justus; Force, Thomas

    2016-01-01

    Introduction Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism. Methods and Results We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy). Conclusion This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux. PMID:26840448

  3. Mechanism-based modeling of reduced inotropic responsiveness to digoxin in endotoxemic rat hearts.

    Science.gov (United States)

    Baek, Myoungki; Weiss, Michael

    2005-05-02

    The mechanisms by which endotoxemia affects myocardial contractility and responsiveness to inotropic drugs are not well understood. We examined the positive inotropic effect of digoxin in single-pass Langendorff-perfused hearts from rats after in vivo pretreatment with lipopolysaccharide (LPS, 4 mg/kg, i.p., 4 h before heart isolation). Using a mathematical modeling approach that allows differentiation between effects elicited at the receptor and postreceptor level, we studied uptake, receptor binding and effectuation kinetics after three consecutive digoxin doses (15, 30, and 45 microg) in the absence and presence of the reverse mode Na(+)/Ca(2+) exchange (NCX) inhibitor KB-R7943 (0.1 microM) in perfusate. LPS significantly depressed baseline contractility and the inotropic response to digoxin without affecting its uptake mechanism. Compared with the control group, the slope of the functional receptor occupancy (stimulus)-to-response relationship was reduced by 44% in the LPS group. Model analysis revealed a significant correlation between changes in digoxin action and LPS-induced febrile response: digoxin receptor affinity increased and the response/stimulus ratio decreased with rise in body temperature, respectively. In contrast, the diminished responsiveness to digoxin observed after NCX inhibition in the control group was not further attenuated in the LPS group. These results support the hypothesis that postreceptor events may be responsible for the diminished contractile response to digoxin during endotoxemia.

  4. Protective effect of Co-enzyme Q10 On doxorubicin-induced cardiomyopathy of rat hearts.

    Science.gov (United States)

    Chen, Pei-Yu; Hou, Chien-Wen; Shibu, Marthandam Asokan; Day, Cecilia Hsuan; Pai, Peiying; Liu, Zhao-Rong; Lin, Tze-Yi; Viswanadha, Vijaya Padma; Kuo, Chia-Hua; Huang, Chih-Yang

    2017-02-01

    Q10 is a powerful antioxidant often used in medical nutritional supplements for cancer treatment. This study determined whether Q10 could effectively prevent cardio-toxicity caused by doxorubicin treatment. Four week old SD rats were segregated into groups namely control, doxorubicin group (challenged with doxorubicin), Dox + Q10 group (with doxorubicin challenge and oral Q10 treatment), and Q10 group (with oral Q10 treatment). Doxorubicin groups received IP doxorubicin (2.5 mg/kg) every 3 days and Q10 groups received Q10 (10 mg/kg) every day. Three weeks of doxorubicin challenge caused significant reduction in heart weight, disarray in cardiomyocyte arrangement, elevation of collagen accumulation, enhancement of fibrosis and cell death associated proteins, and inhibition of survival proteins. However, Q10 effectively protected cardiomyocytes and ameliorated fibrosis and cell death induced by doxorubicin. Q10 is, therefore, evidently a potential drug to prevent heart damage caused by doxorubicin. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 679-689, 2017. © 2016 Wiley Periodicals, Inc.

  5. Differential hemodynamic effects of ethanol on rat heart: Beneficial vs. detrimental actions

    Energy Technology Data Exchange (ETDEWEB)

    Zou, L.Y.; Alture, B.T.; Wu, F.; Barbour, R.L.; Altura, B.M. (State Univ. of New York, Brooklyn (United States))

    1991-03-11

    Epidemiologic studies suggest that daily ingestion of small amounts of alcohol may protect the heart, whereas higher intake may be detrimental. The authors therefore studied cardiac performance of isolated working rat hearts during perfusion with Krebs-Nenseleit medium containing three different concentrations (conc) of ethanol (ET). ET produced a biphasic hemodynamic change depending upon conc. 45 mM ET was stimulatory; higher ET were depressive. 45 mM ET increased coronary flow (CF) by 45%, cardiac output (CO) 29%, stroke volume (SV) 30%, oxygen consumption (MVO{sub 2}) 29% at 25 min, respectively. However, higher conc of ET, e.g. 90 mM, depressed most parameters. CF was reduced by 62%, CO 56%, SV 57%, peak systolic pressure (PSP) 80%, and MVO{sub 2} 77%, respectively. Lactic acid (LA) fended to increase with decline of CF. 135 mM ET decreased all cardiac parameters and MVO{sub 2} rapidly and significantly from the first 5 min. LA, LDH and CPK levels tended to be elevated, and pH tended to be reduced. These data indicate that a low conc of ET is beneficial on cardiac performance; higher concentrations of ET are detrimental. High conc of ET decrease CF leading to hypoxia, metabolic acidosis of myocardium, and cell membrane damage.

  6. Influence of intracellular acidosis on contractile function in the working rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Jeffrey, F.M.H.; Malloy, C.R.; Radda, G.K. (Univ. of Oxford (England))

    1987-12-01

    The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. The authors developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O{sub 2} delivery. Intracellular pH and high-energy phosphates were monitored by {sup 31}P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH{sub 4}Cl. Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. It was concluded that (1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and (2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.

  7. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart

    Science.gov (United States)

    Limon-Miranda, Sarai; Salazar-Enriquez, Diana G.; Muñiz, Jesus; Ramirez-Archila, Mario V.; Sanchez-Pastor, Enrique A.; Andrade, Felipa; Soñanez-Organis, Jose G.; Moran-Palacio, Edgar F.; Virgen-Ortiz, Adolfo

    2014-01-01

    The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum. PMID:25147829

  8. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart

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    Sarai Limon-Miranda

    2014-01-01

    Full Text Available The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I and collagen III (Col III mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum.

  9. Immunomodulatory effects of bone marrow mesenchymal stem cells derived from homologous recipients in rats after heart transplantation

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    De-zhong LIU

    2012-03-01

    Full Text Available Objective To observe the immunomodulatory effects of homologous bone marrow mesenchymal stem cells (MSCs obtained from the bone marrow in rats after heart transplantation. Methods Twenty adult male Lewis rats were used as donors for the heart transplantation, whereas twenty adult male Wistar rats served as recipients. The recipients with cervical heart transplantation were randomly divided into two groups (10 each. Approximately 3ml 0.9% NaCl solution was injected through the tail vein 24h after heart transplantation in the control group (group A. About 2×106 MSCs (suspended in 3ml 0.9% NaCl solution were injected through the tail vein 24h after heart transplantation in the MSCs treatment group (group B. Four recipient rats from each group were randomly chosen one week after transplantation for determining proportion of CD4+ T, CD8+ T, CD4+CD25high T, and CD4+CD25highfoxp3+ T cells in the lymphocytes in the venous blood and grafts. Subsequently, the CD4+/CD8+ ratio was calculated. The survival time of the grafts were observed in the remaining six rats in each group. Results (1The survival time of the transplanted hearts was 7.2±1.3d in group A, and 14.8±2.9d in group B, showing a significant difference between the two groups (P 0.05. The ratios of CD4+CD25high T cells/total lymphocytes and CD4+CD25highFoxp3+ T cells/ total lymphocytes in the allografts were evidently higher in group B (2.74%±0.28%, 2.54%±0.31% than in group A (0.61%±0.06%, 0.53%±0.06%, showing a significant statistical difference (P < 0.01. Conclusion Intravenous infusion with MSCs from the bone marrow of the recipients can induce immune tolerance and prolong the survival time of transplanted heart in rats.

  10. Identifying Unique Neighborhood Characteristics to Guide Health Planning for Stroke and Heart Attack: Fuzzy Cluster and Discriminant Analyses Approaches

    Science.gov (United States)

    Pedigo, Ashley; Seaver, William; Odoi, Agricola

    2011-01-01

    Background Socioeconomic, demographic, and geographic factors are known determinants of stroke and myocardial infarction (MI) risk. Clustering of these factors in neighborhoods needs to be taken into consideration during planning, prioritization and implementation of health programs intended to reduce disparities. Given the complex and multidimensional nature of these factors, multivariate methods are needed to identify neighborhood clusters of these determinants so as to better understand the unique neighborhood profiles. This information is critical for evidence-based health planning and service provision. Therefore, this study used a robust multivariate approach to classify neighborhoods and identify their socio-demographic characteristics so as to provide information for evidence-based neighborhood health planning for stroke and MI. Methods and Findings The study was performed in East Tennessee Appalachia, an area with one of the highest stroke and MI risks in USA. Robust principal component analysis was performed on neighborhood (census tract) socioeconomic and demographic characteristics, obtained from the US Census, to reduce the dimensionality and influence of outliers in the data. Fuzzy cluster analysis was used to classify neighborhoods into Peer Neighborhoods (PNs) based on their socioeconomic and demographic characteristics. Nearest neighbor discriminant analysis and decision trees were used to validate PNs and determine the characteristics important for discrimination. Stroke and MI mortality risks were compared across PNs. Four distinct PNs were identified and their unique characteristics and potential health needs described. The highest risk of stroke and MI mortality tended to occur in less affluent PNs located in urban areas, while the suburban most affluent PNs had the lowest risk. Conclusions Implementation of this multivariate strategy provides health planners useful information to better understand and effectively plan for the unique

  11. Effects of Provinols on Cardiodynamics and Coronary Flow in Islodated Rat Hearts

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    Popovic Ana

    2016-06-01

    Full Text Available Provinols are an alcohol-free extract of red wine that contains a wide range of polyphenols. Polyphenols are a group of chemical compounds found in diverse plants. Polyphenols are considered to protect against cardiovascular disease. Although some older epidemiological studies have indicated that the positive effects of red wine on heart disease can be attributed to the alcohol content alone, there is now powerful evidence that polyphenols present in red wine are responsible for these positive effects. The hearts of male Wistar albino rats (n = 36, 12 in each experimental group, 10 weeks old, body mass 250 ± 30 g were excised and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure (40-120 cmH2O. Parameters of cardiac function (dp/dt max, dp/dt min, SLVP, DLVP, HR, CF were measured after perfusion with three different concentrations of provinols (5 μg/ml, 10 μg/ml and 50 μg/ml. Administration of the highest dose (50 μg/ml induced a significant increase in dp/dt max, dp/dt min, HR and CF compared with control conditions at CPP = 40 cmH2O, while an intermediate dose increased dp/dt max at the same CPP. Generally viewed, the results of the present study suggest that provinols may have a beneficial effect on the intact myocardium and coronary circulation. These findings could constitute an important step in further investigation of these polyphenols under different representative experimental conditions in the heart, as well as providing a good basis for potential clinical studies in this field.

  12. Rat Heterotopic Abdominal Heart/Single-lung Transplantation in a Volume-loaded Configuration.

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    Kearns, Mark J; Wang, Yingjin; Boyd, John H

    2015-05-29

    Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft involves anastomosis of donor inferior vena cava (IVC) to recipient IVC, and donor ascending aorta (Ao) to recipient abdominal Ao. The right upper and middle lung lobes are preserved and function as conduits for blood flow from right heart to left heart. There are several advantages to using this technique, and it lends itself to a broad range of applications. Because the graft is transplanted in a configuration that allows for dyamic volume-loading, cardiac function may be directly assessed in vivo. The use of pressure-volume conductance catheters permits characterization of load-dependent and load-independent hemodynamic parameters. The graft may be converted to a loaded configuration by applying a clamp to the recipient's infra-hepatic IVC. We describe modified surgical techniques for both donor and recipient operations, and an ideal myocardial protection strategy. Depending on the experimental aim, this model may be adapted for use in both acute and chronic studies of graft function, immunologic status, and variable ventricular loading conditions. The conducting airways to the transplanted lung are preserved, and allow for acute lung re-ventilation. This facilitates analysis of the effects of the mixed venous and arterial blood providing coronary perfusion to the graft. A limitation of this model is its technical complexity. There is a significant learning curve for new operators, who should ideally be mentored in the technique. A surgical training background is advantageous for those wishing to apply this model. Despite its complexity, we aim to present the model in a clear and easily applicable format. Because of the physiologic similarity of this model to orthotopic transplantation, and its broad range of study applications, the effort invested in learning the technique is likely to be worthwhile.

  13. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation.

    Science.gov (United States)

    Hirt, Marc N; Boeddinghaus, Jasper; Mitchell, Alice; Schaaf, Sebastian; Börnchen, Christian; Müller, Christian; Schulz, Herbert; Hubner, Norbert; Stenzig, Justus; Stoehr, Andrea; Neuber, Christiane; Eder, Alexandra; Luther, Pradeep K; Hansen, Arne; Eschenhagen, Thomas

    2014-09-01

    Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

  14. Perturbation of microRNAs in rat heart during chronic doxorubicin treatment.

    Directory of Open Access Journals (Sweden)

    Caterina Vacchi-Suzzi

    Full Text Available Anti-cancer therapy based on anthracyclines (DNA intercalating Topoisomerase II inhibitors is limited by adverse effects of these compounds on the cardiovascular system, ultimately causing heart failure. Despite extensive investigations into the effects of doxorubicin on the cardiovascular system, the molecular mechanisms of toxicity remain largely unknown. MicroRNAs are endogenously transcribed non-coding 22 nucleotide long RNAs that regulate gene expression by decreasing mRNA stability and translation and play key roles in cardiac physiology and pathologies. Increasing doses of doxorubicin, but not etoposide (a Topoisomerase II inhibitor devoid of cardiovascular toxicity, specifically induced the up-regulation of miR-208b, miR-216b, miR-215, miR-34c and miR-367 in rat hearts. Furthermore, the lowest dosing regime (1 mg/kg/week for 2 weeks led to a detectable increase of miR-216b in the absence of histopathological findings or alteration of classical cardiac stress biomarkers. In silico microRNA target predictions suggested that a number of doxorubicin-responsive microRNAs may regulate mRNAs involved in cardiac tissue remodeling. In particular miR-34c was able to mediate the DOX-induced changes of Sipa1 mRNA (a mitogen-induced Rap/Ran GTPase activating protein at the post-transcriptional level and in a seed sequence dependent manner. Our results show that integrated heart tissue microRNA and mRNA profiling can provide valuable early genomic biomarkers of drug-induced cardiac injury as well as novel mechanistic insight into the underlying molecular pathways.

  15. The Efficiency of Barley (Hordeum vulgare Bran in Ameliorating Blood and Treating Fatty Heart and Liver of Male Rats

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    Khalid O. Abulnaja

    2015-01-01

    Full Text Available The current study focused on testing the hypolipidemic activity of two doses of barley bran on hypercholesterolemic male rats. Twenty-four male albino rats weighing 180–200 gm were divided into four groups. The first group (G1 was the negative control, the second group (G2 was the positive control group fed 2% cholesterol in the diet, and rats of the third and the fourth groups were fed 2% cholesterol and were cosupplemented with 5% and 10% barley bran, respectively, for 8 weeks. The hypercholesterolemic rats of (G2 showed an increase in lipid profile, liver enzymes, lactate dehydrogenase, creatine kinase-MB, and lipid peroxide and a decrease in antioxidant enzymes, whereas kidney function, fasting blood sugar, glycated hemoglobin total protein, and total bilirubin were not significantly affected compared with the negative control group in G1. Moreover, histology of heart, liver, and kidney of G2 rats showed histopathological changes compared with the negative control. Administration of the two doses of barley bran in G3 and G4 to the hypercholesterolemic rats ameliorated the level of lipids, liver enzymes, lactate dehydrogenase, and creatine kinase-MB. In addition, the histology of heart, liver, and kidney tissues nearly restored the normal state as in G1.

  16. Autonomic control of heart rate and blood pressure in spontaneously hypertensive rats during aversive classical conditioning.

    Science.gov (United States)

    Hatton, D C; Buchholz, R A; Fitzgerald, R D

    1981-12-01

    An examination was made of the heart rate (HR) and blood pressure (BP) responses of 7-9-wk-old spontaneously hypertensive rats (SHR) and genetical control Wistar/Kyoto (WKY) rats during aversive classical conditioning. Subsequent to the development of conditioned responding (CRs), assessments were made of the effects of selective autonomic blockade by methyl atropine (10 mg/kg), phentolamine (2 mg/kg), and propranolol (2 mg/kg). The CR complex in the two strains consisted of pressor BP CRs in conjunction with vagally mediated decelerative HR CRs in the SHR strain and sympathetically mediated accelerative HR CRs in the WKY strain. The decelerative SHR HR CR did not appear to be secondary to baroreceptor reflex activity, although such activity did appear to be involved in the pressor BP and decelerative HR orienting response (OR) and unconditioned response (UR) complex of the SHRs on the initial application of the CS and the US, respectively. Augmented pressor BP ORs, CRs, and URs in the SHRs relative to the WKYs and differential drug effects on BP and HR baselines of the two strains suggested the presence of enhanced sympathetic activity in the SHRs that was not reflected in the SHR decelerative HR CR. Phentolamine unmasked evidence of reflex beta 2-vasodilation deficiency in the SHRs that could have contributed to the enhancement of their BP OR and CR.

  17. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

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    Stéphanie Rimbaud

    Full Text Available Heart failure (HF is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT. Resveratrol (18 mg/kg/day; HS-RSV was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition. Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001, and prevented the 25% reduction in body weight in HS-NT (P<0.001. Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  18. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    Science.gov (United States)

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  19. Nerve Growth Factor Decreases in Sympathetic and Sensory Nerves of Rats with Chronic Heart Failure

    Science.gov (United States)

    Lu, Jian

    2014-01-01

    Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6–20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185

  20. Effect of superoxide anion scavenger on rat hearts with chronic intermittent hypoxia.

    Science.gov (United States)

    Pai, Peiying; Lai, Ching Jung; Lin, Ching-Yuang; Liou, Yi-Fan; Huang, Chih-Yang; Lee, Shin-Da

    2016-04-15

    Only very limited information regarding the protective effects of the superoxide anion scavenger on chronic intermittent hypoxia-induced cardiac apoptosis is available. The purpose of this study is to evaluate the effects of the superoxide anion scavenger on cardiac apoptotic and prosurvival pathways in rats with sleep apnea. Forty-two Sprague-Dawley rats were divided into three groups, rats with normoxic exposure (Control, 21% O2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide anion scavenger and chronic intermittent hypoxia exposure (Hypoxia-O2 (-)-Scavenger, MnTMPyP pentachloride, 1 mg/kg ip per day; 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo) at 5-6 mo of age. After 1 mo, the protein levels and apoptotic cells of excised hearts from three groups were measured by Western blotting and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. The superoxide anion scavenger decreased hypoxia-induced myocardial architecture abnormalities, left ventricular hypertrophy, and TUNEL-positive apoptosis. The superoxide anion scavenger decreased hypoxia-induced Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathway) as well as Bad, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptotic pathway), endonuclease G (EndoG), apoptosis-inducing factor (AIF), and TUNEL-positive apoptosis. The superoxide anion scavenger increased IGF-1, IGF-1R, p-PI3k, p-Akt, p-Bad, Bcl-2, and Bcl-xL (survival pathway). Our findings imply that the superoxide anion scavenger might prevent cardiac Fas-mediated and mitochondrial-mediated apoptosis and enhance the IGF-1-related survival pathway in chronic intermittent hypoxia. The superoxide anion scavenger may prevent chronic sleep apnea-enhanced cardiac apoptotic pathways and enhances

  1. Inhalation of diluted diesel engine emission impacts heart rate variability and arrhythmia occurrence in a rat model of chronic ischemic heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Anselme, Frederic [Rouen University Hospital, Service de Cardiologie, Rouen (France); Loriot, Stephane; Henry, Jean-Paul; Thuillez, Christian; Morin, Jean-Paul [University of Rouen France, INSERM U644, School of Medicine-Pharmacy, Rouen, Cedex (France); Dionnet, Frederic [Centre d' Etudes et de Recherches Technologiques en Aerothermique et Moteurs, Saint Etienne du Rouvray (France); Napoleoni, Jean-Gerard [EMKA Technologies, Paris (France)

    2007-04-15

    Both increase in cardiac arrhythmia incidence and decrease in heart rate variability (HRV) have been described following human and experimental animal exposures to air pollutants. However, the potential causal relationship between these two factors remains unclear. Incidence of ventricular arrhythmia and HRV were evaluated during and after a 3 h period of Diesel engine exhaust exposure in ten healthy and ten chronic ischemic heart failure (CHF, 3 months after coronary ligation) Wistar rats using implantable ECG telemetry. Air pollutants were delivered to specifically designed whole body individual exposure chambers at particulate matter concentrations similar to those measured inside cabins of cars inserted in congested urban traffic. Recordings were obtained from unrestraint and unsedated vigil rats. Immediate decrease in RMSSD was observed in both healthy (6.64 {+-} 2.62 vs. 4.89 {+-} 1.67 ms, P < 0.05) and CHF rats (8.01 {+-} 0.89 vs. 6.6 {+-} 1.37 ms, P < 0.05) following exposure. An immediate 200-500% increase in ventricular premature beats was observed in CHF rats only. Whereas HRV progressively returned to baseline values within 2.5 h after exposure start, the proarrhythmic effect persisted as late as 5 h after exposure termination in CHF rats. Persistence of ventricular proarrhythmic effects after HRV normalization suggests that HRV reduction is not the mechanism of cardiac arrhythmias in this model. Our methodological approach, closely reflecting the real clinical situations, appeared to be a unique tool to provide further insight into the pathophysiological mechanisms of traffic related airborne pollution health impact. (orig.)

  2. Dietary red palm oil supplementation reduces myocardial infarct size in an isolated perfused rat heart model

    Directory of Open Access Journals (Sweden)

    Esterhuyse Adriaan J

    2010-06-01

    Full Text Available Abstract Background and Aims Recent studies have shown that dietary red palm oil (RPO supplementation improves functional recovery following ischaemia/reperfusion in isolated hearts. The main aim of this study was to investigate the effects of dietary RPO supplementation on myocardial infarct size after ischaemia/reperfusion injury. The effects of dietary RPO supplementation on matrix metalloproteinase-2 (MMP2 activation and PKB/Akt phosphorylation were also investigated. Materials and methods Male Wistar rats were divided into three groups and fed a standard rat chow diet (SRC, a SRC supplemented with RPO, or a SRC supplemented with sunflower oil (SFO, for a five week period, respectively. After the feeding period, hearts were excised and perfused on a Langendorff perfusion apparatus. Hearts were subjected to thirty minutes of normothermic global ischaemia and two hours of reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. Coronary effluent was collected for the first ten minutes of reperfusion in order to measure MMP2 activity by gelatin zymography. Results Dietary RPO-supplementation decreased myocardial infarct size significantly when compared to the SRC-group and the SFO-supplemented group (9.1 ± 1.0% versus 30.2 ± 3.9% and 27.1 ± 2.4% respectively. Both dietary RPO- and SFO-supplementation were able to decrease MMP2 activity when compared to the SRC fed group. PKB/Akt phosphorylation (Thr 308 was found to be significantly higher in the dietary RPO supplemented group when compared to the SFO supplemented group at 10 minutes into reperfusion. There was, however, no significant changes observed in ERK phosphorylation. Conclusions Dietary RPO-supplementation was found to be more effective than SFO-supplementation in reducing myocardial infarct size after ischaemia/reperfusion injury. Both dietary RPO and SFO were able to reduce MMP2 activity, which suggests that MMP2 activity does not play a major role in

  3. Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats.

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    Yoshitaka Fujimoto

    Full Text Available Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB-induced right heart failure model and investigated whether cardiac output (CO is responsible for the progression of hepatic fibrosis.Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01. Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01. Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-β1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2 were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05.Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats.

  4. Changes in perfusion and fatty acid metabolism of rat heart with autoimmune myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Tsujimura, Eiichiro; Kusuoka, Hideo; Fukuchi, Kazuki; Hasegawa, Shinji; Yutani, Kenji; Nishimura, Tsunehiko [Osaka Univ., Suita (Japan). Biomedical Research Center; Hori, Masatsugu; Hirono, Satoru; Izumi, Tohru

    2000-10-01

    To elucidate the change in perfusion and aerobic metabolism in myocarditis, tissue counting and dual tracer ex vivo autoradiography with Tl-201 and free fatty acid analog, I-123- or I-125-labeled (p-iodophenyl)-methyl-pentadecanoic acid (BMIPP), were performed in rats with myocarditis induced by immunization with cardiac myosin. Inflammatory damage was classified histologically. At the acute stage (2-4 weeks after the antigen-injection), total heart uptakes of Tl and BMIPP and the ratio (BMIPP/Tl) were significantly reduced in myocarditis rats (N=15) compared with the controls (N=12). Myocardial distribution of Tl and BMIPP was not homogeneous. Relative uptake of Tl and BMIPP (N=9, 128 regions) was gradually decreased with the extent of inflammation, and the regional BMIPP/Tl was smaller than the control. At the subacute stage (7 weeks after the antigen-injection), total Tl uptake in myocarditis rats (N=5) recovered to the control level (N=4), but that of BMIPP was still significantly lower than the control. BMIPP/Tl was still significantly lower in myocarditis. Myocardial distribution of Tl and BMIPP recovered to be more homogeneous. Relative uptake of Tl and BMIPP (N=6, 78 regions) still gradually but significantly decreased with the extent of inflammation. Regional BMIPP/Tl was still depressed in myocarditis. These results indicate that myocardial perfusion and aerobic metabolism were discrepant and heterogeneously suppressed with severe inflammation during the acute stages, but the difference decreases with time. Examination with Tl-201 and BMIPP may provide information about the severity of myocarditis. (author)

  5. Attenuated fatigue in slow twitch skeletal muscle during isotonic exercise in rats with chronic heart failure.

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    Morten Munkvik

    Full Text Available During isometric contractions, slow twitch soleus muscles (SOL from rats with chronic heart failure (chf are more fatigable than those of sham animals. However, a muscle normally shortens during activity and fatigue development is highly task dependent. Therefore, we examined the development of skeletal muscle fatigue during shortening (isotonic contractions in chf and sham-operated rats. Six weeks following coronary artery ligation, infarcted animals were classified as failing (chf if left ventricle end diastolic pressure was >15 mmHg. During isoflurane anaesthesia, SOL with intact blood supply was stimulated (1s on 1s off at 30 Hz for 15 min and allowed to shorten isotonically against a constant afterload. Muscle temperature was maintained at 37°C. In resting muscle, maximum isometric force (F(max and the concentrations of ATP and CrP were not different in the two groups. During stimulation, F(max and the concentrations declined in parallel sham and chf. Fatigue, which was evident as reduced shortening during stimulation, was also not different in the two groups. The isometric force decline was fitted to a bi-exponential decay equation. Both time constants increased transiently and returned to initial values after approximately 200 s of the fatigue protocol. This resulted in a transient rise in baseline tension between stimulations, although this effect which was less prominent in chf than sham. Myosin light chain 2s phosphorylation declined in both groups after 100 s of isotonic contractions, and remained at this level throughout 15 min of stimulation. In spite of higher energy demand during isotonic than isometric contractions, both shortening capacity and rate of isometric force decline were as well or better preserved in fatigued SOL from chf rats than in sham. This observation is in striking contrast to previous reports which have employed isometric contractions to induce fatigue.

  6. Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model.

    Science.gov (United States)

    Ahmad, Shafique; Panda, Bibhu Prasad; Kohli, Kanchan; Fahim, Mohammad; Dubey, Kiran

    2017-12-01

    The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats. This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats. Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2.5 mg/kg doxorubicin over a period of two weeks. The effect of 28 days of celecoxib (100 mg/kg/day) and its combination with folic acid (10 mg/kg/day) was studied on doxorubicin-induced cardiomyopathy according to serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), troponin-T (Tn-T), tumor necrosis factor alpha (TNF-α), cardiac thiobarbituric acid reactive substance (TBARS), and glutathione (GSH) levels as well as systolic blood pressure (SBP), heart rate (HR) and ultrastructural studies. Celecoxib cardiotoxicity was manifested by significant increases in the LDH, Tn-T, TNF-α, CK-MB, SBP, HR (p < 0.001) and TBARS (p < 0.01) levels and a significant decrease in the GSH (p < 0.05) level when used alone or administered with doxorubicin. However, the combination of folic acid with celecoxib caused a significant reversal of these parameters and reduced the cardiotoxicity of celecoxib that was aggravated by doxorubicin. The ultrastructural study also revealed myocardial protection with this combination. Folic acid protects against the cardiotoxic effects of celecoxib, which are aggravated in the presence of doxorubicin. Folic acid may act as a useful adjunct in patients who are taking celecoxib.

  7. Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Luana U. Pagan

    2015-04-01

    Full Text Available Background: Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF development and cardiac remodeling in aging spontaneously hypertensive rats (SHR. Methods: Sixteen month old SHR (n=50 and normotensive Wistar-Kyoto (WKY, n=35 rats were divided into sedentary (SED and exercised (EX groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. Statistical analyses: ANOVA and Tukey or Mann-Whitney, and Goodman test. Results: Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. Conclusion: Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

  8. The dissociation of heroin-seeking patterns induced by contextual, discriminative, or discrete conditioned cues in a model of relapse to heroin in rats

    Institute of Scientific and Technical Information of China (English)

    Wen-huaZHOU; Fu-qiangZHANG[; Shuai-enTANG; Hui-fenLIU; Guo-dongYANG

    2004-01-01

    AIM: To characterize the patterns of resumption of drug-seeking induced by drug-related cues and the extent to drug-seeking controlled by these cues in rats after withdrawal. METHODS: Nosepoke responding by male rats was reinforced with intravenous heroin (0.05 mg/kg per infusion, 4 h session daily) under a PR schedule of reinforcement for 14 d. A green light in active nosepoke served as discriminative cue (DS). Each earned heroin injection was also paired with 5 s red light and a house light, the

  9. Influence of renovascular hypertension on the distribution of vasoactive intestinal peptide in the stomach and heart of rats.

    Science.gov (United States)

    Kasacka, Irena; Piotrowska, Żaneta; Janiuk, Izabela

    2015-11-01

    Arterial hypertension is associated with serious dysfunction of the cardiovascular system and digestive system. Given the relevant role of vasoactive intestinal peptide (VIP) in the regulation of digestion process, control of blood pressure and heart rate as well as cardio- and gastro-protective character of the peptide, it appeared worthwhile to undertake the research aimed at immunohistochemical identification and evaluation of VIP-positive structures in the pylorus and heart of hypertensive rats. Up to now, this issue has not been investigated. The experimental model of hypertension in rats according to Goldblatt (two-kidney one clip model of hypertension) was used in the study. The experimental material (pylorus and heart) was collected in the sixth week of the study. VIP-containing structures were evaluated using immunohistochemical and morphometric methods. The analysis of the results showed a significant increase in the number of immunoreactive VIP structures and in the intensity of immunohistochemical staining in the stomach and in the heart of hypertensive rats. Our findings indicate that VIP is an important regulator of cardiovascular and digestive system in physiological and pathological conditions. However, to better understand the exact role of VIP in hypertension further studies need to be carried out.

  10. Leu-7 immunoreactivity in human and rat embryonic hearts, with special reference to the development of the conduction tissue.

    Science.gov (United States)

    Ikeda, T; Iwasaki, K; Shimokawa, I; Sakai, H; Ito, H; Matsuo, T

    1990-01-01

    The distribution pattern of Leu-7 (HNK-1) in developing human embryonic hearts and rat hearts was studied by immunohistochemistry. Human and rat embryos at Streeter's stages XIII approximately XX and fetus stage I were used. Leu-7, which is absent in the newborn rat heart, is expressed transiently in the embryo and fetus I stages. The earliest embryonic heart shows two incomplete circular structures with immunoreactivity in the myocardium along the primitive atrioventricular cushion and bulboventricular canal. These two structures become localized topographically in the definitive atrioventricular node and atrioventricular bundle after rearrangement and partial disappearance during embryonic development. At Streeter's stages XVIII approximately XX, Leu-7 immunoreactivity appears to localize topographically in almost all the pathways of the conduction system, although some discontinuities are observed in the atrioventricular junction and atrial internodal tracts. Thereafter, immunoreactivity decreases gradually and differentially by site and stage. The precise nature of Leu-7 immunoreactive cells, that is, whether or not they are neurogenic or myogenic, is not revealed by this study. The present observations are discussed in connection with the hypothesis that specialized ring tissue is the primordium of the conduction system.

  11. Effect of Noradrenergic Neurotoxin DSP-4 and Maprotiline on Heart Rate Spectral Components in Stressed and Resting Rats.

    Science.gov (United States)

    Kur'yanova, E V; Zhukova, Yu D; Teplyi, D L

    2017-07-01

    The effects of intraperitoneal DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a noradrenergic neurotoxin) and maprotiline (an inhibitor of norepinephrine reuptake in synapses) on spectral components of heart rhythm variability were examined in outbred male and female rats treated with these agents in daily doses of 10 mg/kg for 3 days. At rest, DSP-4 elevated LF and VLF spectral components in male and female rats. Maprotiline elevated LF and VLF components in males at rest, increased HR and reduced all spectral components in resting females. Stress against the background of DSP-4 treatment sharply increased heart rate and reduced the powers of all spectral components (especially LF and VLF components). In maprotiline-treated rats, stress increased the powers of LF and VLF components. Thus, the central noradrenergic system participates in the formation of LF and VLF spectral components of heart rate variability at rest and especially during stressful stimulation, which can determine the phasic character of changes in the heart rate variability observed in stressed organism.

  12. Short-term melatonin consumption protects the heart of obese rats independent of body weight change and visceral adiposity.

    Science.gov (United States)

    Nduhirabandi, Frederic; Huisamen, Barbara; Strijdom, Hans; Blackhurst, Dee; Lochner, Amanda

    2014-10-01

    Chronic melatonin treatment has been shown to prevent the harmful effects of diet-induced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI). However, the exact mechanism whereby it exerts its beneficial actions on the heart in obesity/insulin resistance remains unknown. Herein, we investigated the effects of relatively short-term melatonin treatment on the heart in a rat model of diet-induced obesity. Control and diet-induced obese Wistar rats (fed a high calorie diet for 20 wk) were each subdivided into three groups receiving drinking water with or without melatonin (4 mg/kg/day) for the last 6 or 3 wk of experimentation. A number of isolated hearts were perfused in the working mode, subjected to regional or global ischaemia-reperfusion; others were nonperfused. Metabolic parameters, myocardial infarct sizes (IFS), baseline and postischaemic activation of PKB/Akt, ERK42/44, GSK-3β and STAT-3 were determined. Diet-induced obesity caused increases in body weight gain, visceral adiposity, fasting blood glucose, serum insulin and triglyceride (TG) levels with a concomitant cardiac hypertrophy, large postischaemic myocardial IFSs and a reduced cardiac output. Melatonin treatment (3 and 6 wk) decreased serum insulin levels and the HOMA index (P melatonin administration to obese/insulin resistant rats reduced insulin resistance and protected the heart against ex vivo myocardial IRI independently of body weight change and visceral adiposity.

  13. β1 -Adrenoceptor, but not β2 -adrenoceptor, subtype regulates heart rate in type 2 diabetic rats in vivo.

    Science.gov (United States)

    Cook, Rosalind F; Bussey, Carol T; Mellor, Kimberley M; Cragg, Patricia A; Lamberts, Regis R

    2017-08-01

    What is the central question of the study? The sympathetic system regulates heart rate via β-adrenoceptors; this is impaired during diabetes. However, the specific β-adrenoceptor subtype contributions in heart rate regulation in diabetes in vivo are unknown. What is the main finding and its importance? Telemetric recordings in conscious non-diabetic and type 2 diabetic rats demonstrated that the β1 -adrenoceptor subtype, and not the β2 -adrenoceptor, regulated the lower resting heart rate and increased β-adrenoceptor responsiveness in diabetes in vivo. This provides new physiological insight into the dysregulation of heart rate in type 2 diabetes, which is important for improving therapeutic strategies targeting the diabetic chronotropic incompetence. β-Adrenoceptor blockers are widely used to reduce heart rate, the strongest predictor of mortality in cardiac patients, but are less effective in diabetic patients. This study aimed to determine the specific contributions of β1 - and β2 -adrenoceptor subtypes to chronotropic responses in type 2 diabetes in vivo, which are currently unknown. Type 2 diabetic and non-diabetic rats were implanted with radiotelemeters to measure arterial blood pressure and derive heart rate in conscious conditions. Vascular access ports were implanted to inject isoprenaline (β1 - and β2 -adrenoceptor agonist, 0.1-300 μg kg(-1) ) in the presence of atenolol (β1 -adrenoceptor antagonist, 2000 μg kg(-1) ) or nadolol (β1 - and β2 -adrenoceptor agonist, 4000 μg kg(-1) ) to determine the chronotropic contributions of the β-adrenoceptor subtypes. Resting heart rate was reduced in diabetic rats (388 ± 62 versus 290 ± 37 beats min(-1) non-diabetic versus diabetic, P heart rate at highest dose of isoprenaline: 135 ± 66 versus 205 ± 28 beats min(-1) , non-diabetic versus diabetic, P heart rate at highest dose of isoprenaline: 205 ± 37 versus 195 ± 22 beats min(-1) , non-diabetic versus diabetic, P heart

  14. Effects of altering motivation for food in rats trained with food reinforcement to discriminate between d-amphetamine and saline injections.

    Science.gov (United States)

    Lotfizadeh, Amin D; Redner, Ryan; Edwards, Timothy L; Quisenberry, Amanda J; Baker, Lisa E; Poling, Alan

    2012-12-01

    Previous studies have shown that altering motivation typically affects stimulus generalization in animals trained to discriminate exteroceptive stimuli, but few studies have evaluated the effects of manipulating motivation on drug stimuli. In the few published studies, motivation levels were manipulated by arranging different feeding conditions prior to stimulus generalization tests with rats trained to discriminate morphine from vehicle and in pigeons trained to discriminate phencyclidine or pentobarbital from vehicle. In the present study, rats maintained at 80% of free-feeding weights were trained to discriminate between injections of 1.0mg/kg d-amphetamine and saline in a two-lever food-reinforced operant procedure. Generalization tests were then conducted with a range of d-amphetamine doses (0, 0.03, 0.1, and 0.3, 1.0mg/kg) when the rats were not fed before experimental sessions (high motivation) and when they were pre-fed 1g of food (moderate motivation) or their daily ration of food (low motivation) 1h before test sessions. Changing the motivation level significantly affected response rate and latency to the first response in generalizations tests, but did not significantly affect mean percentage of drug-appropriate responding (a continuous measure) or percentage of animals that selected the drug-appropriate lever (a quantal measure). The present findings indicate that manipulating motivation for food minimally impacts d-amphetamine discrimination, however, the range of conditions used to examine the effects of motivating operations on stimulus control by d-amphetamine drugs and other drugs is limited and the topic may warrant further investigation.

  15. Could Cells from Your Nose Fix Your Heart? Transplantation of Olfactory Stem Cells in a Rat Model of Cardiac Infarction

    Directory of Open Access Journals (Sweden)

    Cameron McDonald

    2010-01-01

    Full Text Available This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiation in vitro and after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grown in vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.

  16. Modifications in nitric oxide and superoxide anion metabolism induced by fructose overload in rat heart are prevented by (-)-epicatechin.

    Science.gov (United States)

    Calabró, Valeria; Piotrkowski, Barbara; Fischerman, Laura; Vazquez Prieto, Marcela A; Galleano, Monica; Fraga, Cesar G

    2016-04-01

    Fructose overload promotes functional and metabolic derangements in humans and in animal experimental models. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate the development of metabolic diseases. In this work we investigated the effects of (-)-epicatechin on the modifications induced by fructose overload in the rat heart in terms of nitric oxide and superoxide metabolism. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8 weeks, with or without (-)-epicatechin (20 mg per kg body weight per day) in the rat chow diet. These conditions of fructose overload did not lead to overt manifestations of heart hypertrophy or tissue remodeling. However, biochemical and molecular changes were observed and could represent the onset of functional alterations. (-)-Epicatechin prevented a compromised NO bioavailability and the development of oxidative stress produced by fructose overload essentially acting on superoxide anion metabolism. In this line, the increase in superoxide anion production, the overexpression of NOX2 subunit p47phox and of NOX4, the decrease in superoxide dismutase activity, and the higher oxidized/reduced glutathione ratio installed by fructose overload were absent in the rats receiving (-)-epicatechin. These results support the hypothesis that diets rich in (-)-epicatechin could prevent the onset and progression of heart dysfunctions associated with metabolic alterations.

  17. A comparison of N,N-dimethyltryptamine, harmaline, and selected congeners in rats trained with LSD as a discriminative stimulus.

    Science.gov (United States)

    Helsley, S; Fiorella, D; Rabin, R A; Winter, J C

    1998-05-01

    1. A series of N-substituted tryptamines was compared with a series of beta-carbolines in rats trained to discriminate LSD (0.1 mg/kg) from saline. 2. Intermediate levels of substitution were elicited by MDMT (76.4%), DMT (77.9%), and DET (48.7%). 6-F-DET produced 41.3% LSD-appropriate responding at a dose of 6.0 mg/kg but only 4 of 8 subjects completed the test session thus precluding statistical analysis. Bufotenine (25.8%) also failed to substitute. Although none of the tryptamines substituted completely for LSD, the pattern of substitution is consonant with what is known of their activity in humans. MDMT, DMT, and DET are well established in the literature as hallucinogens but the same cannot be said for 6-F-DET and bufotenine. 3. Of the beta-carbolines tested, none substituted for LSD completely and only harmane elicited intermediate substitution (49.5%). No significant generalization of the LSD stimulus to 6-methoxyharmalan, harmaline, or THBC was observed. Thus, in contrast to the tryptamines, scant ability to substitute for LSD was observed in the beta-carbolines tested. 4. Taken together, the present data indicate that the representative tryptamines employed in the present study exhibit greater similarity to the LSD stimulus than do representative beta-carbolines. The receptor interactions responsible for these differences remain to be determined.

  18. Expression of genes participating in regulation of fatty acid and glucose utilization and energy metabolism in developing rat hearts.

    Science.gov (United States)

    Lavrentyev, Eduard N; He, Daifen; Cook, George A

    2004-11-01

    The heart is a unique organ that can use several fuels for energy production. During development, the heart undergoes changes in fuel supply, and it must be able to respond to these changes. We have examined changes in the expression of several genes that regulate fuel transport and metabolism in rat hearts during early development. At birth, there was increased expression of fatty acid transporters and enzymes of fatty acid metabolism that allow fatty acids to become the major source of energy for cardiac muscle during the first 2 wk of life. At the same time, expression of genes that control glucose transport and oxidation was downregulated. After 2 wk, expression of genes for glucose uptake and oxidation was increased, and expression of genes for fatty acid uptake and utilization was decreased. Expression of carnitine palmitoyltransferase I (CPT I) isoforms during development was different from published data obtained from rabbit hearts. CPT Ialpha and Ibeta isoforms were both highly expressed in hearts before birth, and both increased further at birth. Only after the second week did CPT Ialpha expression decrease appreciably below the level of CPT Ibeta expression. These results represent another example of different expression patterns of CPT I isoforms among various mammalian species. In rats, changes in gene expression followed nutrient availability during development and may render cardiac fatty acid oxidation less sensitive to factors that influence malonyl-CoA content (e.g., fluctuations in glucose concentration) and thereby favor fatty acid oxidation as an energy source for cardiomyocytes in early development.

  19. Cardioprotective effect of aqueous extract of Chichorium intybus on ischemia-reperfusion injury in isolated rat heart.

    Science.gov (United States)

    Sadeghi, Najmeh; Dianat, Mahin; Badavi, Mohammad; Malekzadeh, Ahad

    2015-01-01

    Several studies have shown that Chichorium intybus (C. intybus) which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract) of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV) and peak positive value of time derivate of LV pressure (+dp/dt), coronary flow (CF), and left ventricular systolic pressure (LVSP) in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. The results showed that heart rate (HR), coronary flow, and left ventricular developed pressure (LVDP) and rate of pressure product (RPP) significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml) improved significantly during reperfusion (p<0.001). It seems that flavonoid compounds of aqueous extract of C. intybus reduce ischemia - reperfusion injuries, suggesting its protective effect on heart function after ischemia.

  20. Pentaerythritol Tetranitrate Targeting Myocardial Reactive Oxygen Species Production Improves Left Ventricular Remodeling and Function in Rats With Ischemic Heart Failure.

    Science.gov (United States)

    Fraccarollo, Daniela; Galuppo, Paolo; Neuser, Jonas; Bauersachs, Johann; Widder, Julian D

    2015-11-01

    Reduced nitric oxide bioavailability contributes to progression of cardiac dysfunction and remodeling in ischemic heart failure. Clinical use of organic nitrates as nitric oxide donors is limited by development of nitrate tolerance and reactive oxygen species formation. We investigated the effects of long-term therapy with pentaerythritol tetranitrate (PETN), an organic nitrate devoid of tolerance, in rats with congestive heart failure after extensive myocardial infarction. Seven days after coronary artery ligation, rats were randomly allocated to treatment with PETN (80 mg/kg BID) or placebo for 9 weeks. Long-term PETN therapy prevented the progressive left ventricular dilatation and improved left ventricular contractile function and relaxation in rats with congestive heart failure. Mitochondrial superoxide anion production was markedly increased in the failing left ventricular myocardium and nearly normalized by PETN treatment. Gene set enrichment analysis revealed that PETN beneficially modulated the dysregulation of mitochondrial genes involved in energy metabolism, paralleled by prevention of uncoupling protein-3, thioredoxin-2, and superoxide dismutase-2 downregulation. Moreover, PETN provided a remarkable protective effect against reactive fibrosis in chronically failing hearts. Mechanistically, induction of heme oxygenase-1 by PETN prevented mitochondrial superoxide generation, NOX4 upregulation, and ensuing formation of extracellular matrix proteins in fibroblasts from failing hearts. In summary, PETN targeting reactive oxygen species generation prevented the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance. Therefore, PETN might be a promising therapeutic option in the treatment of ischemic heart diseases involving oxidative stress and impairment in nitric oxide bioactivity.

  1. Gene transfer of heat-shock protein 20 protects against ischemia/reperfusion injury in rat hearts

    Institute of Scientific and Technical Information of China (English)

    Yan-hui ZHU; Tie-min MA; Xian WANG

    2005-01-01

    Aim: To explore whether overexpression of HSP20 in the myocardium could protect against ischemia/reperfusion injury in rats. Methods: Rat hearts were injected with vector, recombinant adenovirus encoding green fluorescent protein (Ad. GFP) or recombinant adenovirus encoding wild-type HSP20 (Ad. HSP20) in the left ventricle. Four days later, hearts were removed and expression of HSP20was measured in the left ventricle. Subsets of animals in the vector-, Ad. GFP-, and Ad. HSP20-treated groups were subjected to 20-min ischemia and 120-min reperfusion. Myocardial injury was evaluated by infarct size and level of serum cardiac troponin T and creatine phosphokinase. Apoptosis of cardiomyocytes was determined by TUNEL staining. Cardiac function was evaluated by hemodynamic indexes. Results: Infarct size and serum cardiac troponin T and creatine phosphokinase levels were significantly reduced in Ad. HSP20-treated hearts compared with vector- and Ad. GFP-treated hearts. The ratio of TUNEL-positive cardiomyocytes to total number of cardiomyocytes in the Ad. HSP20 group was significantly reduced as compared with the vector and Ad. GFP groups. Left ventricular end systolic pressure, and maximal rate of pressure increase (+dp/dtmax)and decrease (-dp/dtmin) values were increased significantly, while left ventricular end diastolic pressure was decreased significantly in Ad.HSP20-treated hearts compared with vector- and Ad. GFP-treated hearts. Conclusion: These data indicate that the cardioprotective effects of HSP20 may contribute to the reduction of myocardial necrosis and apoptosis in ischemia/reperfusion injury in rats.

  2. Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

    Directory of Open Access Journals (Sweden)

    Noeman Saad A

    2011-08-01

    Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

  3. Rat's time estimation under conditional discrimination procedure / Estimação de tempo em ratos submetidos a um procedimento de discriminação condicional

    Directory of Open Access Journals (Sweden)

    José Lino Oliveira Bueno

    2007-01-01

    Full Text Available In a feature positive conditional discrimination procedure, a stimulus A is not followed by reinforcement when presented alone, but it is always followed by reinforcement when it is preceded by stimulus X. In the negative conditional discrimination procedure, a stimulus B is always followed by reinforcement when presented alone, but it is not followed by reinforcement when preceded by stimulus Y. This research examined if amodal information dealing with basic attributes, as duration, has the capability to acquire conditional properties in animals. Rats were submitted to positive or negative conditional discrimination procedures with stimulus X and Y, which were of the same physical modality, a light, but with different durations: X= 15 seg e Y= 5 seg (and A=5 seg, B=15 seg. The results showed that the animals discriminated excitatory and inhibitory properties related, respectively, to two different durations of the same stimulus, supporting the hypothesis that the duration, as an amodal stimulus component, can be associated to conditional properties, in rats.

  4. Triggering role of nitric oxide in the delayed protective effect of monophosphoryl lipid A in rat heart

    Science.gov (United States)

    György, Katalin; Muller, Bernard; Végh, Agnes; Kleschyov, Andrei L; Stoclet, Jean-Claud

    1999-01-01

    The main objective of the present study was to further evaluate the role of nitric oxide (NO) in delayed cardiac protection against ischaemia-reperfusion injury induced by monophosphoryl lipid A (MLA).For this purpose, rats were administered with either 0.5 or 2.5 mg kg−1 MLA (i.p.). Eight or 24 h later, in vivo NO production in the heart was analysed by electron paramagnetic resonance (EPR) spin trapping technique. In parallel experiments, hearts were removed and perfused according to Langendorff. Functional ventricular parameters and incidence of ventricular fibrillation (VF) were determined after 30 min global ischaemic insult (37°C) followed by 30 min reperfusion. Vascular reactivity of aortic rings was also assessed.Hearts from rats pretreated with 2.5 mg kg−1 MLA for 24 h (but not those from rats treated with 0.5 mg kg−1 MLA for 8 and 24 h, or with 2.5 mg kg−1 MLA for 8 h) exhibited preservation of ventricular function (LVDP, ±dP/dtmax) and a reduced incidence of VF (25% vs 87.5% in vehicle control) during reperfusion. At the cardioprotective dose of 2.5 mg kg−1 (for 8 or 24 h), MLA did not produce alterations of the contractile response of aortic rings to noradrenaline.An increased formation of NO was detected in hearts removed from rats pretreated with 2.5 mg kg−1 MLA for 8 h, but not in those from rats treated for 24 h (or with 0.5 mg kg−1 MLA).Pretreatment of the animals with the inhibitors of inducible NO-synthase, aminoguanidine (2×300 mg kg−1) or L-N6-(1-Iminoethyl)-lysine (L-NIL, 10 mg kg−1) abolished both MLA (2.5 mg kg−1)-induced rise of NO production (observed 8 h after MLA) and cardioprotection (observed 24 h after MLA). However MLA-induced cardioprotection was not attenuated when the hearts were perfused with aminoguanidine (150 μM) for 30 min before the ischaemic insult.Altogether, the present data suggest that NO acts as a trigger rather then a direct

  5. Behavioral determination of stimulus pair discrimination of auditory acoustic and electrical stimuli using a classical conditioning and heart-rate approach.

    Science.gov (United States)

    Morgan, Simeon J; Paolini, Antonio G

    2012-06-06

    Acute animal preparations have been used in research prospectively investigating electrode designs and stimulation techniques for integration into neural auditory prostheses, such as auditory brainstem implants and auditory midbrain implants. While acute experiments can give initial insight to the effectiveness of the implant, testing the chronically implanted and awake animals provides the advantage of examining the psychophysical properties of the sensations induced using implanted devices. Several techniques such as reward-based operant conditioning, conditioned avoidance, or classical fear conditioning have been used to provide behavioral confirmation of detection of a relevant stimulus attribute. Selection of a technique involves balancing aspects including time efficiency (often poor in reward-based approaches), the ability to test a plurality of stimulus attributes simultaneously (limited in conditioned avoidance), and measure reliability of repeated stimuli (a potential constraint when physiological measures are employed). Here, a classical fear conditioning behavioral method is presented which may be used to simultaneously test both detection of a stimulus, and discrimination between two stimuli. Heart-rate is used as a measure of fear response, which reduces or eliminates the requirement for time-consuming video coding for freeze behaviour or other such measures (although such measures could be included to provide convergent evidence). Animals were conditioned using these techniques in three 2-hour conditioning sessions, each providing 48 stimulus trials. Subsequent 48-trial testing sessions were then used to test for detection of each stimulus in presented pairs, and test discrimination between the member stimuli of each pair. This behavioral method is presented in the context of its utilisation in auditory prosthetic research. The implantation of electrocardiogram telemetry devices is shown. Subsequent implantation of brain electrodes into the Cochlear

  6. Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats.

    Science.gov (United States)

    Supakul, Luerat; Pintana, Hiranya; Apaijai, Nattayaporn; Chattipakorn, Siriporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Nipon

    2014-04-01

    Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. Male Wistar rats (180-200 g) were divided into two groups: normal-diet or high-fat-diet (n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups (n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.

  7. Interaction of signal transduction between angiotensin AT1 and AT2 receptor subtypes in rat senescent heart

    Institute of Scientific and Technical Information of China (English)

    SHI Shu-tian; LI Yan-fang

    2007-01-01

    Background Angiotensin Ⅱ (Ang Ⅱ) acting at angiotensin AT1 receptor (AT1R) has well documented effects on cardiovascular structure such as the promotion of cardiovascular hypertrophy and fibrosis, which are believed to be opposed by angiotensin AT2 receptor (AT2R) stimulation. The expressions of AT1R and AT2R are up-regulated in senescent hearts. The purpose of this study was to investigate the interaction of signal transduction between AT1R and AT2R, and to detect whether there is any difference in the interaction in rat hearts of different age.Methods In 3.5-, 12-, 18- and 24-month-old rats, the heart cell membrane activities of protein kinase C (PKC) andtyrosine kinase were measured when AT1R and AT2R were both activated by Ang Ⅱ or just the AT1R was activated by Ang Ⅱ and PD123319. The activities of cytosolic phospholipase A2 (cPLA2) and the levels of cGMP were investigated when AT1R and AT2R were both activated by Ang Ⅱ or just the AT2R was activated by Ang Ⅱ and Iosartan.Results When AT1R and AT2R were both activated compared to when the AT1R was activated, the activities of PKC were not different in hearts from 3.5- and 12-month-old rats, but decreased significantly in 18- and 24-month-old rats; the activities of tyrosine kinase were not different in 3.5-month-old rats but decreased significantly in 12-, 18- and 24-month-old rats. The activities of cPLA2 were all decreased significantly in rats of different age when AT1R and AT2R were both activated compared to when the AT2R was activated. Treatment with Ang Ⅱ alone compared to Ang Ⅱ and losartan decreased the levels of cGMP (fmol/mg) in rats of different age (102.7±12.7 versus 86.0±8.0 in 3.5-month-old rats, P<0.05; 81.0±9.4 versus 70.0±6.3 in 12-month-old rats, P<0.05; 69.8±5.6 versus 54.2±5.3 in 18-month-old rats,P<0.01; 57.7±8.0 versus 39.0±3.0 in 24-month-old rats, P<0.01).Conclusions The activation of AT1R inhibited the signal transduction of AT2R during the aging

  8. Effect of electro-acupuncture on gene expression in heart of rats with stress-induced pre-hypertension based on gene chip technology

    National Research Council Canada - National Science Library

    Guo Yan Xie Xiaojia Guo Changqing Wang Zhaoyang Liu Qingguo

    2015-01-01

    OBJECTIVE:To explore electro-acupuncture's(EA's)effect on gene expression in heart of rats with stress-induced pre-hypertension and try to reveal its biological mechanism based on gene chip...

  9. Pharmacological inhibition of I-K1 by PA-6 in isolated rat hearts affects ventricular repolarization and refractoriness

    DEFF Research Database (Denmark)

    Skarsfeldt, Mark A.; Carstensen, Helena; Skibsbye, Lasse

    2016-01-01

    The inwardly rectifying potassium current (IK1) conducted through Kir2.X channels contribute to repolarization of the cardiac action potential and to stabilization of the resting membrane potential in cardiomyocytes. Our aim was to investigate the effect of the recently discovered IK1 inhibitor PA......-6 on action potential repolarization and refractoriness in isolated rat hearts. Transiently transfected HEK-293 cells expressing IK1 were voltage-clamped with ramp protocols. Langendorff-perfused heart experiments were performed on male Sprague–Dawley rats, effective refractory period, Wenckebach...... experiments, PA-6 prolonged the ventricular action potential duration at 90% repolarization (from 41.8 6.5 msec to 72.6 21.1 msec, 74% compared to baseline, P

  10. No effect of aluminium upon the hydrolysis of ATP in the coronary circulation of the isolated working rat heart.

    Science.gov (United States)

    Korchazhkina, O; Wright, G; Exley, C

    1999-08-30

    Adenosine 5'-triphosphate (ATP) is now recognised as an important extracellular signalling molecule. Its action at a number of specific receptors is mediated by the activity of ectonucleotidases. We have optimised a high performance liquid chromatography (HPLC) method to allow the simultaneous determination of ATP, and the products of its hydrolysis, in the coronary effluent of an isolated working rat heart. The method is extremely sensitive allowing picomolar quantities of product to be determined. We have used this method to investigate the influence of aluminium on the hydrolysis of ATP by an ecto-ATPase located in the luminal surface of the coronary endothelium of the rat heart. Aluminium did not influence the hydrolysis of ATP by this enzyme.

  11. miRNA-146a induces vascular smooth muscle cell apoptosis in a rat model of coronary heart disease via NF-κB pathway.

    Science.gov (United States)

    Wu, Z W; Liu, Y F; Wang, S; Li, B

    2015-12-29

    The aim of this study was to investigate the role of miRNA-146a in modulating the function of vascular smooth muscle cells in a rat model of coronary heart disease. Vascular smooth muscle cells were isolated and cultured from the rat coronary heart disease model and normal rats (controls). miRNA-146a levels were measured in vascular smooth muscle cells obtained from rats with coronary heart disease and control rats. The proliferation, growth, apoptosis, and activation of the NF-κB pathway in the vascular smooth muscle cells were detected using the MTT assay and flow cytometry, respectively. The role of the NF-κB pathway in modulating the apoptosis of vascular smooth muscle cells was investigated by measuring the reactivity of the cells to an NF-κB pathway inhibitor (TPCA-1). Vascular smooth muscle cells from the disease model exhibited higher levels of miRNA-146a than that by the normal controls (P = 0.0024). The vascular smooth muscle cells obtained from rats with coronary heart disease showed decreased proliferation and growth and increased apoptosis. miRNA-146a overexpression elevated the rate of cell apoptosis. The NF-κB pathway was activated in vascular smooth muscle cells obtained from rats with coronary heart disease. Inhibition of the NF- κB pathway significantly decreased the rate of vascular smooth muscle cell apoptosis in coronary heart disease rats (P = 0.0038). In conclusion, miRNA- 146a was found to induce vascular smooth muscle cell apoptosis in rats with coronary heart disease via the activation of the NF-κB signal pathway.

  12. Assessment of Cardiovascular Apoptosis in the Isolated Rat Heart by Magnetic Resonance Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Hiller

    2006-04-01

    Full Text Available Apoptosis, an active process of cell self-destruction, is associated with myocardial ischemia. The redistribution of phosphatidylserine (PS from the inner to the outer leaflet of the cell membrane is an early event in apoptosis. Annexin V, a protein with high specificity and tight binding to PS, was used to identify and localize apoptosis in the ischemic heart. Fluorescein-labeled annexin V has been used routinely for the assessment of apoptosis in vitro. For the detection of apoptosis in vivo, positron emission tomography and single-photon emission computed tomography have been shown to be suitable tools. In view of the relatively low spatial resolution of nuclear imaging techniques, we developed a high-resolution contrast-enhanced magnetic resonance imaging (MRI method that allows rapid and noninvasive monitoring of apoptosis in intact organs. Instead of employing superparamagnetic iron oxide particles linked to annexin V, a new T1 contrast agent was used. To this effect, annexin V was linked to gadolinium diethylenetriamine pentaacetate (Gd-DTPA-coated liposomes. The left coronary artery of perfused isolated rat hearts was ligated for 30 min followed by reperfusion. T1 and T2* images were acquired by using an 11.7-T magnet before and after intracoronary injection of Gd-DTP-labeled annexin V to visualize apoptotic cells. A significant increase in signal intensity was visible in those regions containing cardiomyocytes in the early stage of apoptosis. Because labeling of early apoptotic cell death in intact organs by histological and immunohistochemical methods remains challenging, the use of Gd-DTPA-labeled annexin V in MRI is clearly an improvement in rapid targeting of apoptotic cells in the ischemic and reperfused myocardium.

  13. Global changes in the rat heart proteome induced by prolonged morphine treatment and withdrawal.

    Directory of Open Access Journals (Sweden)

    Zdenka Drastichova

    Full Text Available Morphine belongs among the most commonly used opioids in medical practice due to its strong analgesic effects. However, sustained administration of morphine leads to the development of tolerance and dependence and may cause long-lasting alterations in nervous tissue. Although proteomic approaches enabled to reveal changes in multiple gene expression in the brain as a consequence of morphine treatment, there is lack of information about the effect of this drug on heart tissue. Here we studied the effect of 10-day morphine exposure and subsequent drug withdrawal (3 or 6 days on the rat heart proteome. Using the iTRAQ technique, we identified 541 proteins in the cytosol, 595 proteins in the plasma membrane-enriched fraction and 538 proteins in the mitochondria-enriched fraction derived from the left ventricles. Altogether, the expression levels of 237 proteins were altered by morphine treatment or withdrawal. The majority of changes (58 proteins occurred in the cytosol after a 3-day abstinence period. Significant alterations were found in the expression of heat shock proteins (HSP27, α-B crystallin, HSP70, HSP10 and HSP60, whose levels were markedly up-regulated after morphine treatment or withdrawal. Besides that morphine exposure up-regulated MAPK p38 (isoform CRA_b which is a well-known up-stream mediator of phosphorylation and activation of HSP27 and α-B crystallin. Whereas there were no alterations in the levels of proteins involved in oxidative stress, several changes were determined in the levels of pro- and anti-apoptotic proteins. These data provide a complex view on quantitative changes in the cardiac proteome induced by morphine treatment or withdrawal and demonstrate great sensitivity of this organ to morphine.

  14. Global changes in the rat heart proteome induced by prolonged morphine treatment and withdrawal.

    Science.gov (United States)

    Drastichova, Zdenka; Skrabalova, Jitka; Jedelsky, Petr; Neckar, Jan; Kolar, Frantisek; Novotny, Jiri

    2012-01-01

    Morphine belongs among the most commonly used opioids in medical practice due to its strong analgesic effects. However, sustained administration of morphine leads to the development of tolerance and dependence and may cause long-lasting alterations in nervous tissue. Although proteomic approaches enabled to reveal changes in multiple gene expression in the brain as a consequence of morphine treatment, there is lack of information about the effect of this drug on heart tissue. Here we studied the effect of 10-day morphine exposure and subsequent drug withdrawal (3 or 6 days) on the rat heart proteome. Using the iTRAQ technique, we identified 541 proteins in the cytosol, 595 proteins in the plasma membrane-enriched fraction and 538 proteins in the mitochondria-enriched fraction derived from the left ventricles. Altogether, the expression levels of 237 proteins were altered by morphine treatment or withdrawal. The majority of changes (58 proteins) occurred in the cytosol after a 3-day abstinence period. Significant alterations were found in the expression of heat shock proteins (HSP27, α-B crystallin, HSP70, HSP10 and HSP60), whose levels were markedly up-regulated after morphine treatment or withdrawal. Besides that morphine exposure up-regulated MAPK p38 (isoform CRA_b) which is a well-known up-stream mediator of phosphorylation and activation of HSP27 and α-B crystallin. Whereas there were no alterations in the levels of proteins involved in oxidative stress, several changes were determined in the levels of pro- and anti-apoptotic proteins. These data provide a complex view on quantitative changes in the cardiac proteome induced by morphine treatment or withdrawal and demonstrate great sensitivity of this organ to morphine.

  15. Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration.

    Science.gov (United States)

    Solskov, Lasse; Løfgren, Bo; Kristiansen, Steen B; Jessen, Niels; Pold, Rasmus; Nielsen, Torsten T; Bøtker, Hans Erik; Schmitz, Ole; Lund, Sten

    2008-07-01

    The UK Prospective Diabetes Study demonstrated that the hypoglycaemic drug metformin is associated with a reduction in cardiovascular events in a group of obese type 2 diabetes patients. The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin. The aim of this study was to determine whether a single dose of metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of metformin results in an acute increase in myocardial AMPK activity. Wistar rats were given either a single oral dose of metformin (250 mg/kg body weight), or a single oral dose of saline. After 24 hr, the hearts were Langendorff-perfused and subjected to 45 min. of coronary artery occlusion. Infarct size was determined by staining with triphenyltetrazoliumchloride (TTC) and Evans Blue and expressed as a percentage of the risk zone (IS/AAR %). Isoform specific AMPK activity was measured 2 hr after administration of metformin or saline. Infarct size was significantly reduced in the metformin treated (I/R: 19.9 +/- 3.9%versus 36.7 +/- 3.6%, P < 0.01, n = 8-14) compared to the control group. A single oral dose of metformin resulted in an approximately ~2-fold increase in AMPK-alpha2 activity 2 hr after administration (P < 0.015, n = 10). In conclusion, a single dose of metformin results in an acute increase in myocardial AMPK activity measured 2 hr after administration and induces a significant reduction in myocardial infarct size 24 hr after metformin administration. Increased AMPK activity may be an important signal mediator involved in the mechanisms behind the cardioprotective effects afforded by metformin.

  16. Sex differences in heart rate variability during sleep following prenatal nicotine exposure in rat pups.

    Science.gov (United States)

    Boychuk, Carie R; Fuller, David D; Hayward, Linda F

    2011-05-16

    The influence of both prenatal nicotine exposure (PNE; 6 mg/kg/day) and sex on heart rate (HR) regulation during sleep versus wakefulness was evaluated in 13, 16 and 26 day old rat pups. Pups were chronically instrumented at least 24 h before testing. On postnatal day 13 (P13), PNE males spent significantly more time in NREM sleep and demonstrated a greater drop in HR when transitioning from quiet wake to sleep compared to age and sex matched controls (-14±5 bpm versus -1±3 bpm, respectively). Heart rate variability (HRV) analysis indicated that this state-dependent drop in HR was primarily associated with a greater reduction in sympathovagal balance (LF/HF ratio) in PNE males compared to controls. No parallel changes in indices of parasympathetic drive (HF power) were identified. In contrast, no significant effect of PNE on HR during sleep versus wakefulness was identified in P13 females. However, independent of state, a significant decrease in HF power was identified in P13 PNE females compared to controls. At P16, state-dependent differences in HR or HRV between PNE and sex-matched control pups were resolved. Additionally, at P26 no significant effect of PNE on state-dependent changes in HR or HRV was identified in either sex. Analysis of the hypothalamic peptide orexin identified that PNE induced approximately a 50% reduction in hypothalamic prepro-orexin mRNA and total mRNA was lowest in PNE males. These findings suggest that PNE induces sex dependent changes in sleep related autonomic regulation of HR during early postnatal development and these changes may be related to epigenetic alterations in the orexin system.

  17. Ischemic Postconditioning Does Not Provide Cardioprotection from Long Term Ischemic Injury in Isolated Male or Female Rat Hearts

    Science.gov (United States)

    Lee, Daniel S.; Steinbaugh, Gregory E.; Quarrie, Ricardo; Yang, Fuchun; Talukder, Hassan; Zweier, Jay L.; Crestanello, Juan A.

    2010-01-01

    Background Ischemic postconditioning(PoC) is a cardio-protective strategy in which initial reperfusion is interrupted by episodes of ischemia. It is unclear whether PoC can be achieved in the Langendorff perfused rat heart model. We investigated 1) whether postconditioning occurs in Langendorff perfused rat heart and 2) whether there is a gender specific response to PoC. Materials and methods Male/female rat hearts(n=8/group) were subjected to 30 minutes of equilibration, 30 minutes of ischemia, and 120 minutes of reperfusion (CONTROL). PoC was induced by 6 cycles(PoC 6c10s), 3 cycles(PoC 3c10s), or 2 cycles(PoC 2c10s) of 10 second reperfusion/10 second ischemia. Rate pressure product(RPP) and infarct size were measured. Male rats(n=7/group) were subjected in vivo to 30 minute left coronary ligation followed by 24 hours of reperfusion(CONTROL) or PoC 6c10s and 24 hours of reperfusion. Results Recovery of RPP was 18±4% in male CONTROL vs. 17±2% for 6c10s, 16±1% for 3c10s, and 15±3% for 2c10s. Female CONTROL hearts recovered 25±3% of their RPP vs. 21±2% for 6c10s. Infarct size was 25±3% for male CONTROL vs. 26±3% for 6c10s, 30±2% for 3c10s, 28±1% for 2c10s; and 30±2% for female CONTROL vs. 29±2% in 6c10s. In vivo Infarct size for CONTROL and PoC 6c10s was 44±3% and 28±5%, respectively (p<0.05). Conclusions In the Langendorff perfused rat hearts, none of the PoC protocols improved myocardial tolerance to ischemia reperfusion injury nor decreased infarct size; however, in vivo postconditioning did confer protection. The lack of protection in the isolated hearts was not gender specific. PMID:20934717

  18. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats.

    Science.gov (United States)

    Huisamen, Barbara; Genis, Amanda; Marais, Erna; Lochner, Amanda

    2011-02-01

    Cardiovascular risk is closely associated with insulin resistance and type 2 diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel approach to treat this disease. The aims of this study was therefore to use an animal model to determine whether (i) pre-treatment of obese, insulin resistant but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10 mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject hearts to ischaemia/reperfusion to determine infarct size, functional recovery and post-ischaemic activation of proteins associated with cardiac protection. Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity. Other assessments included body weight, intra-peritoneal fat weight, insulin and GLP-1 levels as well as histological evaluation of the pancreata. Results showed that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed animals. They presented with elevated plasma insulin levels and lower GLP-1 levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size development in hearts from DIO rats after ischaemia/reperfusion accompanied by activation of cardioprotective kinases. GLP-1 levels were elevated and plasma insulin levels lower after treatment. In addition, the beta-cell to alpha-cell ratio of the pancreas was improved. We conclude that treatment with PFK275-055 for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

  19. Transplantation tolerance in adult rats using total lymphoid irradiation: permanent survival of skin, heart, and marrow allografts

    Energy Technology Data Exchange (ETDEWEB)

    Slavin, S.; Reitz, B.; Bieber, C.P.; Kaplan, H.S.; Strober, S.

    1978-03-01

    Lewis rats given total lymphoid irradiation (TLI) accepted bone marrow allografts from AgB-incompatible donors. The chimeras showed no clinical signs of graft-versus-host disease. Skin allografts from the marrow donor strain survived for more than 150 days on the chimeras. However, third-party skin grafts were rejected promptly. Although heart allografts survived more than 300 days in Lewis recipients given TLI and bone marrow allografts, detectable levels of chimerism were not required for permanent survival.

  20. Time course and extent of alpha 1-adrenoceptor density changes in rat heart after beta-adrenoceptor blockade.

    OpenAIRE

    Steinkraus, V.; Nose, M.; Scholz, H; Thormählen, K.

    1989-01-01

    1. It has been suggested that impaired beta-adrenoceptor stimulation is a condition under which the functional role of cardiac alpha 1-adrenoceptors is enhanced. We therefore investigated the extent and time course of changes in alpha 1-adrenoceptor characteristics after chronic treatment with the beta-adrenoceptor blocker propranolol in rat heart. For comparison beta-adrenoceptors were also studied. The mechanism of the changes in adrenoceptor density was investigated with cycloheximide, an ...

  1. Effect of Stimulation of Neurotransmitter Systems on Heart Rate Variability and β-Adrenergic Responsiveness of Erythrocytes in Outbred Rats.

    Science.gov (United States)

    Kur'yanova, E V; Tryasuchev, A V; Stupin, V O; Teplyi, D L

    2017-05-01

    We studied heart rate variability and β-adrenergic responsiveness of erythrocytes and changes in these parameters in response to single administration of β-adrenoblocker propranolol (2 mg/kg) in outbred male rats against the background of activation of the noradrenergic, serotonergic, and dopaminergic neurotransmitter systems achieved by 4-fold injections maprotiline (10 mg/kg), 5-hydroxytryptophan (50 mg/kg) combined with fluoxetine (3 mg/kg), and L-DOPA (20 mg/kg) with amantadine (20 mg/kg), respectively. Stimulation of the noradrenergic system moderately enhanced the heart rhythm rigidity and β-adrenergic responsiveness of erythrocytes. In addition, it markedly augmented the moderating effect of subsequently administered propranolol on LF and VLF components in the heart rate variability and reversed the effect of propranolol on β-adrenergic responsiveness of erythrocytes. Stimulation of the serotonergic system dramatically decreased all components in the heart rate variability and pronouncedly enhanced β-adrenergic responsiveness of erythrocytes. Subsequent injection of propranolol slightly restored all components in the heart rate variability and decreased β-adrenergic responsiveness of erythrocytes to the control level. Stimulation of the dopaminergic system made the heart rate more rigid due to decrease of all components in the heart rate variability; in addition, it slightly but significantly enhanced β-adrenergic responsiveness of erythrocytes. Subsequent injection of propranolol produced no significant effects on all components in the heart rate variability and on β-adrenergic responsiveness of erythrocytes. Stimulation of noradrenergic, serotonergic, and dopaminergic neurotransmitter systems produced unidirectional and consorted effects on heart rate variability and β-adrenergic responsiveness of erythrocytes, although the magnitudes of these effects were different. Probably, the changes in the heart rate variability in rats with stimulated

  2. Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction

    Directory of Open Access Journals (Sweden)

    R. Aires

    Full Text Available Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days, sub-acute (7 days and chronic (28 days phases of myocardial infarction (MI in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV and heart rate variability (HRV. Pulsatile blood pressure (BP recordings (30 min were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old with MI (coronary ligature or sham operation (SO. Data are reported as means±SE. The high frequency (HF component (n.u. of HRV was significantly lower in MI-1- (P0.05. This reduction was mainly due to attenuation of the low frequency (LF band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%. The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance.

  3. Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction

    Science.gov (United States)

    Aires, R.; Pimentel, E.B.; Forechi, L.; Dantas, E.M.; Mill, J.G.

    2017-01-01

    Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance. PMID:28076450

  4. Effect of N-acetylcysteine in hearts of rats submitted to controlled hemorrhagic shock

    Directory of Open Access Journals (Sweden)

    Luiz Dantas de Oliveira Filho

    2015-04-01

    Full Text Available AbstractIntroduction:Pharmacological therapy is a strategy for the prevention of complications associated with ischemia and reperfusion injury that occurs after volume replacement in the treatment of hemorrhagic shock.Objective:The aim of this study was to evaluate the effect of N-acetylcysteine associated with fluid resuscitation in cardiac injury in a rat hemorrhagic shock model.Methods:Mice Wister male rats were randomly and subjected to controlled hemorrhagic shock for 60 min. and then, subjected to resuscitation with Ringer lactate. In a group of six animals, 150mg/kg of N-acetylcysteine were added to fluid volume replacement. The animals were observed for 120 min and after this period, were euthanized and cardiac tissue was collected for histopathological analysis and measurement of thiobarbituric acid reactive substances and pro-and anti-inflammatory interleukin.Results:Cardiac tissue of the group treated with N-acetylcysteine showed lower concentrations of thiobarbituric acid reactive substances (0.20±0.05 vs. 0.27±0.05, P=0.014 and reduced histopathological damage and edema when compared to the group whose volume replacement occurred only with Ringer lactate. There was no difference in the expression of cytokines interleukin 6 (2,138.29±316.89 vs. 1,870.16±303.68, P=0.091 and interleukin 10 (1.019,83±262,50 vs. 848.60±106.5, P=0.169 between the treated groups.Conclusion:The association of N-acetylcysteine on volume replacement attenuates oxidative stress in the heart, as well myocardial damage and edema, but does not modify the expression of inflammatory cytokines.

  5. Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

    Energy Technology Data Exchange (ETDEWEB)

    Coffeen, Paul R.; Efange, S.M.N.; Haidet, George C.; McKnite, Scott; Langason, Rosemary B.; Khare, A.B.; Pennington, Jennifer; Lurie, Keith G

    1996-10-01

    Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[{sup 125}I]iodobenzyl)trozamicol(+)-[{sup 125}I]MIBT), a novel radioligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[{sup 125}I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction-system elements. Marked similarities existed between (+)-[{sup 125}I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[{sup 125}I]MIBT uptake revealed significantly greater (+)-[{sup 125}I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 {+-} 0.37; His bundle: 2.16 {+-} 0.30; right bundle branch: 0.95 {+-} 0.13; right atrium: 0.68 {+-} 0.05; right ventricle: 0.57 {+-} 0.03; and left ventricle: 0.57 {+-} 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[{sup 125}I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[{sup 125}I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

  6. The increased susceptibility to hydrogen peroxide of the (post)-ischemic rat heart is associated with the magnitude of the low molecular weight iron pool

    NARCIS (Netherlands)

    A. Voogd (Arthur); W.J. Sluiter (Wim); J.F. Koster (Johan)

    1994-01-01

    textabstractRecently we have shown that intracellular low molecular weight (LMW) iron increases during ischemia. It is hypothesized that this increase in LMW iron during ischemia underlies the reported hydrogen peroxide toxicity toward ischemic hearts. To investigate this hypothesis, rat hearts were

  7. Activation of the elastin-laminin receptor (S-Gal) induces preconditioning in isolated rat heart submitted to ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    ArnaudROBINET; GeorgesBELLON; WilliamHORNEBECK; HerveMILLART

    2004-01-01

    AIM: Elastin-laminin receptor (S-Gal), was described to belong to G-protein-coupled receptors (GPCRs). Using an isolated nonworking rat heart model, we investigated whether S-Gal stimulation was able to mimic ischemic preconditioning as observed with some other GPCRs. METHODS: Hearts, after 6-hydroxydopamine pretreatment and a 20-min stabilization period,

  8. Relative contributions of Na+/H+ exchange and Na+/HCO3- cotransport to ischemic Na-i(+) overload in isolated rat hearts

    NARCIS (Netherlands)

    Ten Hove, M; Nederhoff, MGJ; Van Echteld, CJA

    2005-01-01

    The Na+/H+ exchanger (NHE) and/or the Na+/HCO3- cotransporter (NBC) were blocked during ischemia in isolated rat hearts. Intracellular Na+ concentration ([Na+](i)), intracellular pH (pH(i)), and energy-related phosphates were measured by using simultaneous Na-23 and P-31 NMR spectroscopy. Hearts wer

  9. Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart.

    Science.gov (United States)

    Penna, Claudia; Perrelli, Maria-Giulia; Tullio, Francesca; Angotti, Carmelina; Pagliaro, Pasquale

    2013-07-01

    Acidic perfusion (AP) performed at the onset of reperfusion (i.e., acid postconditioning) is cardioprotective. We investigated the effect of AP on postischemic cardiac function and on the activity of endogenous superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase. The role of exogenous CAT or SOD on AP cardioprotection was also investigated. Phosphorylation of redox-sensitive survival kinases (protein kinase C [PKC] ε and extracellular signal-regulated kinase [ERK] 1/2) was also checked. Isolated rat hearts underwent ischemia and reperfusion (I/R) for 30 and 120 min, respectively. AP was obtained by lowering [HCO3(-)] in the perfusion buffer. Infarct size and left ventricular pressure were measured. Protocols include I/R only, I/R plus acidic perfusion in early reperfusion (I/R + AP), and I/R plus AP and CAT (I/R + AP + CAT) or SOD (I/R + AP + SOD). I/R + SOD and I/R + CAT additional hearts served as controls. AP and/or antioxidants were given in the initial 3 min of reperfusion. Enzyme activities were studied in postischemic phase (seventh minute of reperfusion) in I/R or I/R + AP and Sham (buffer-perfused) hearts. AP with (I/R + AP + CAT or I/R + AP + SOD) or without (I/R + AP) antioxidant enzymes resulted in a larger reduction of infarct size compared with I/R, I/R + SOD, or I/R + CAT. Compared with I/R, the postischemic systolic and diastolic recoveries of the cardiac function were markedly improved by the addition of AP and a lesser extent by AP + SOD or AP + CAT. AP increased the postischemic activity of CAT and lowered that of SOD and glutathione peroxidase compared with I/R only. Also, the phosphorylation and activity of ERK1/2 and PKCε were increased by AP. Acid postconditioning affects the activity of endogenous antioxidant enzymes, activates ERK1/2-PKCε pathways, and protects against myocardial I/R injury. The combination of AP and exogenous SOD or CAT still provides cardioprotection. It is likely that intracellular (not

  10. METHYLENE BLUE IMPROVES MITOCHONDRIAL RESPIRATION AND DECREASES OXIDATIVE STRESS IN A SUBSTRATE-DEPENDENT MANNER IN DIABETIC RAT HEARTS.

    Science.gov (United States)

    Duicu, Oana M; Privistirescu, Andreea; Wolf, Adrian; Petrus, Alexandra; Dănilă, Maria D; Ratiu, Corina; Muntean, Danina M; Sturza, Adrian

    2017-07-24

    Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox-drug with reported protective effects mainly on brain mitochondria. The present study was purported to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H2O2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. Hydrogen peroxide production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μM) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H2O2 release in the presence of CI substrates (glutamate-malate), but had an opposite effect in mitochondria energized with CII substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and non-diabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

  11. Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts.

    Science.gov (United States)

    Chen, Na; Ko, Ming

    2010-01-01

    To investigate the involvement of reactive oxidant species (ROS), presumably arising from cytochrome P-450 (CYP)-catalyzed metabolism of schisandrin B (Sch B), in triggering glutathione antioxidant response, Sch B induced reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent and CYP-catalyzed reaction and associated ROS production were examined in rat heart microsomes. Sch B analogs were also studied for comparison. Using rat heart microsomes as a source of CYP, Sch B and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate (an intermediate compound derived from the synthesis of Sch C), were found to serve as co-substrate for the CYP-catalyzed NADPH oxidation reaction, with concomitant production of ROS. The stimulation of CYP-catalyzed NADPH oxidation reaction and/or ROS production by Sch B or Sch C correlated with the increase in mitochondrial reduced glutathione level and protection against ischemia/reperfusion (I/R) injury in rat hearts. The involvement of ROS in Sch B-induced cardioprotection was further confirmed by the suppressive effect produced by N-acetylcysteine or alpha-tocopherol pretreatment. Taken together, these results suggest that Sch B-induced glutathione antioxidant response and cardioprotection may be mediated by ROS arising from CYP-catalyzed reaction.

  12. The Effects Of L-Arginine And L-Name On Coronary Flow And Oxidative Stress In Isolated Rat Hearts

    Directory of Open Access Journals (Sweden)

    Sobot Tanja

    2015-12-01

    Full Text Available The aim of this experimental study was to assess the effects of the acute administration of L-arginine alone and in combination with L-NAME (a non-selective NO synthase inhibitor on the coronary flow and oxidative stress markers in isolated rat hearts. The experimental study was performed on hearts isolated from Wistar albino rats (n=12, male, 8 weeks old, body mass of 180-200 g. Retrograde perfusion of the isolated preparations was performed using a modified method according to the Langendorff technique with a gradual increase in the perfusion pressure (40–120 cmH2O. The following values were measured in the collected coronary effluents: coronary flow, released nitrites (NO production marker, superoxide anion radical and the index of lipid peroxidation (measured as thiobarbiturate reactive substances. The experimental protocol was performed under controlled conditions, followed by the administration of L-arginine alone (1 mmol and L-arginine (1 mmol + L-NAME (30 μmol. The results indicated that L-arginine did not significantly increase the coronary flow or the release of NO, TBARS and the superoxide anion radical. These effects were partially blocked by the joint administration of L-arginine + L-NAME, which indicated their competitive effect. Hence, the results of our study do not demonstrate significant effects of L-arginine administration on the coronary flow and oxidative stress markers in isolated rat hearts.

  13. Ozone protects rat heart against ischemia-reperfusion injury: A role for oxidative preconditioning in attenuating mitochondrial injury.

    Science.gov (United States)

    Meng, Weixin; Xu, Ying; Li, Dandan; Zhu, Erjun; Deng, Li; Liu, Zonghong; Zhang, Guowei; Liu, Hongyu

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a major cause of cardiac dysfunction during cardiovascular surgery, heart transplantation and cardiopulmonary bypass procedures. The purpose of the present study was to explore, firstly, whether ozone induces oxidative preconditioning by activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and, secondly, whether ozone oxidative preconditioning (OzoneOP) can protect the heart against IRI by attenuating mitochondrial damage. Rats were subjected to 30min of cardiac ischemia followed by 2h of reperfusion, with or without prior OzoneOP (100μg/kg/day) for 5 days. Antioxidant capacity, myocardial apoptosis and mitochondrial damage were evaluated and compared at the end of reperfusion. OzoneOP was found to increase antioxidant capacity and to protect the myocardium against IRI by attenuating mitochondrial damage and myocardial apoptosis. The study suggests a potential role for OzoneOP in protecting the heart against IRI during cardiovascular surgery, cardiopulmonary bypass procedures or transplantation.

  14. Effect of immobilization stress on gene expression of catecholamine biosynthetic enzymes in heart auricles of socially isolated rats

    Directory of Open Access Journals (Sweden)

    L. Gavrilovic

    2009-12-01

    Full Text Available Chronic stress is associated with the development of cardiovascular diseases. The sympathoneural system plays an important role in the regulation of cardiac function both in health and disease. In the present study, the changes in gene expression of the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH, dopamine-β-hydroxylase (DBH and phenylethanolamine N-methyltransferase (PNMT and protein levels in the right and left heart auricles of naive control and long-term (12 weeks socially isolated rats were investigated by Taqman RT-PCR and Western blot analysis. The response of these animals to additional immobilization stress (2 h was also examined. Long-term social isolation produced a decrease in TH mRNA level in left auricles (about 70% compared to the corresponding control. Expression of the DBH gene was markedly decreased both in the right (about 62% and left (about 81% auricles compared to the corresponding control, group-maintained rats, whereas PNMT mRNA levels remained unchanged. Exposure of group-housed rats to acute immobilization for 2 h led to a significant increase of mRNA levels of TH (about 267%, DBH (about 37% and PNMT (about 60% only in the right auricles. Additional 2-h immobilization of individually housed rats did not affect gene expression of these enzymes in either the right or left auricle. Protein levels of TH, DBH and PNMT in left and right heart auricles were unchanged either in both individually housed and immobilized rats. The unchanged mRNA levels of the enzymes examined after short-term immobilization suggest that the catecholaminergic system of the heart auricles of animals previously exposed to chronic psychosocial stress was adapted to maintain appropriate cardiovascular homeostasis.

  15. Cardioprotective effect of aqueous extract of Chichorium intybus L. on ischemia-reperfusion injury in isolated rat heart

    Directory of Open Access Journals (Sweden)

    Najmeh Sadeghi

    2015-10-01

    Full Text Available Objective: Several studies have shown that Chichorium intybus L. (C. intybus which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. Materials and Methods: The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV and peak positive value of time derivate of LV pressure (+dp/dt, coronary flow (CF, and left ventricular systolic pressure (LVSP in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. Results: The results showed that heart rate (HR, coronary flow, and left ventricular developed pressure (LVDP and rate of pressure product (RPP significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml improved significantly during reperfusion (p

  16. Estrogen Regulates Angiotensin II Receptor Expression Patterns and Protects the Heart from Ischemic Injury in Female Rats1

    Science.gov (United States)

    Xue, Qin; Xiao, Daliao; Zhang, Lubo

    2015-01-01

    Previous studies have shown that female offspring are resistant to fetal stress-induced programming of ischemic-sensitive phenotype in the heart; however, the mechanisms responsible remain unclear. The present study tested the hypothesis that estrogen plays a role in protecting females in fetal programming of increased heart vulnerability. Pregnant rats were divided into normoxic and hypoxic (10.5% O2 from Day 15 to 21 of gestation) groups. Ovariectomy (OVX) and estrogen (E2) replacement were performed in 8-wk-old female offspring. Hearts of 4-mo-old females were subjected to ischemia and reperfusion injury in a Langendorff preparation. OVX significantly decreased postischemic recovery of left ventricular function and increased myocardial infarction, and no difference was observed between normoxic and hypoxic groups. The effect of OVX was rescued by E2 replacement. OVX decreased the binding of glucocorticoid receptor (GR) to glucocorticoid response elements at angiotensin II type 1 (Agtr1) and type 2 (Agtr2) receptor promoters, resulting in a decrease in Agtr1 and an increase in Agtr2 in the heart. Additionally, OVX decreased estrogen receptor (ER) expression in the heart and inhibited ER/GR interaction in binding to glucocorticoid response elements at the promoters. Consistent with the changes in Agtrs, OVX significantly decreased Prkce abundance in the heart. These OVX-induced changes were abrogated by E2 replacement. The results indicate that estrogen is not directly responsible for the sex dimorphism in fetal programming of heart ischemic vulnerability but suggest a novel mechanism of estrogen in regulating cardiac Agtr1/Agtr2 expression patterns and protecting female hearts against ischemia and reperfusion injury. PMID:25972014

  17. Methylphenidate enhances the abuse-related behavioral effects of nicotine in rats: intravenous self-administration, drug discrimination, and locomotor cross-sensitization.

    Science.gov (United States)

    Wooters, Thomas E; Neugebauer, Nichole M; Rush, Craig R; Bardo, Michael T

    2008-04-01

    Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2-0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.

  18. Histological and physiological studies on rat heart following irradiation with single doses of X-rays

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    Yeung, T.K.; Hopewell, J.W.

    1986-01-01

    In the first 6 months after x-irradiation, most rats appeared normal, gaining weight after initial growth delay. Their general condition then declined, death occurring from about 230 days post-irradiation. Mean survival was dose-dependent, ranging from 550 +-12 days to 260 +- 13 days after 20 Gy and 50 Gy respectively. At post-mortem, 70% of irradiated animals had slight pleural effusions and 38% ascites. Early myocardial injury, indicated by T-wave abnormalities, were observed 2 months post-irradiation, consistent with observed degenerative changes seen in the myocardium, but the difference between cardiac output values measured in irradiated and control animals was very small. About 7 months after irradiation, ECG studies showed onset of arrhythmia. Histologically, in addition to chronic myocardial changes, lesions were observed in the larger vessel walls. Measurements of 'equivalent heart muscle wall thickness' showed a dose-dependent decline in irradiated animals after this. Histological and physiological changes were reflected by substantial reduction in cardiac output values in irradiated animals.

  19. Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

    Directory of Open Access Journals (Sweden)

    Vinoth Kumar Megraj Khandelwal

    2011-01-01

    Full Text Available Hemidesmus indicus (L. R. Br. (HI and Hibiscus rosa-sinensis L. (HRS are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R. Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure, reperfusion arrhythmias, and infarct size (TTC staining served as the endpoints. A transient increase in LVDP (32%–75% occurred at all concentrations of HI, while coronary flow (CF was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55% and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions.

  20. Kinetics of nucleotide transport in rat heart mitochondria studied by a rapid filtration technique

    Energy Technology Data Exchange (ETDEWEB)

    Brandolin, G.; Marty, I.; Vignais, P.V. (LBIO/Laboratoire de Biochimie, Grenoble (France))

    1990-10-01

    A rapid filtration technique has been used to measure at room temperature the kinetics of ADP and ATP transport in rat heart mitochondria in the millisecond time range. Transport was stopped by cessation of the nucleotide supply, without the use of a transport inhibitor, thus avoiding any quenching delay. The kinetics of ({sup 14}C)ADP transport in energized mitochondria were apparently monophasic. The rate of transport of ({sup 14}C)ATP in energized mitochondria was 5-10 times lower than that of ({sup 14}C)ADP. Upon uncoupling, the rate of ({sup 14}C)ATP uptake was enhanced, and that of ({sup 14}C)ADP uptake was decreased. However, the two rates did not equalize, indicating that transport was not exclusively electrogenic. Transport of ({sup 14}C)ADP and ({sup 14}C)ATP by resting mitochondria followed biphasic kinetics. Depletion of nucleotides in resting mitochondria resulted in a greater decrease in the extent of the slow phase than of the rapid one. In addition, about half of the nucleotides taken up at the end of the rapid phase were not discharged into the medium upon addition of carboxyatractyloside. This suggested that matricial nucleotides are compartmentalized in two pools which are exchangeable at different rates with external nucleotides.

  1. Evaluation of activity inotropic of a new steroid derivative using an isolated rat heart model.

    Science.gov (United States)

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Bety, Sarabia-Alcocer; Landy, Campos-Ramos

    2014-01-01

    There are studies which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, a new estradiol derivative was synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the estradiol derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; tamoxifen, prazosin, metoprolol, indomethacin and nifedipine. The results showed that the OTBDS-estradiol-hexanoic acid derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions. Additionally, other data indicate that OTBDS-estradiol-hexanoic acid derivative increase left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); nevertheless, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These data suggest that positive inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative is via activation of L-type calcium channel. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.

  2. Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model.

    Science.gov (United States)

    Figueroa-Valverde, L; Díaz-Cedillo, F; García-Cervera, E; Pool Gómez, E; López-Ramos, M; Rosas-Nexticapa, M; Martinez-Camacho, R

    2013-10-01

    Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 10(-4) mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1 × 10(-6) mmol. In conclusion, these data suggest that dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.

  3. Effects of moderate heart failure and functional overload on rat plantaris muscle

    Science.gov (United States)

    Spangenburg, Espen E.; Lees, Simon J.; Otis, Jeff S.; Musch, Timothy I.; Talmadge, Robert J.; Williams, Jay H.

    2002-01-01

    It is thought that changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca(2+) uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca(2+) uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca(2+) uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca(2+) handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.

  4. Effects of halothane, isoflurane and enflurane on isolated rat heart muscle.

    Science.gov (United States)

    Miralles, F S; Carceles, M D; Laorden, M L; Hernandez, J

    1989-05-01

    Since the effects in the intact organism are complicated by central as well as peripheral effects, we compared the direct cardiac effects of three commonly used inhalational anaesthetics--halothane, isoflurane and enflurane--on isolated heart muscle. Concentration-response curves for inotropic, chronotropic and ventricular automaticity effects of halothane, isoflurane and enflurane (0.1-2% v/v) on electrically stimulated left atria, right atria and right ventricles of the rat were obtained. All three inhalational anaesthetics significantly decreased contractile force; the inhibitory concentration 50 (IC50) of enflurane was 0.55 +/- 0.06% v/v, significantly lower than halothane (0.96 +/- 0.08% v/v) and isoflurane (0.67 +/- 0.05% v/v). Similar results were obtained on atrial nomotopic rate. Halothane, isoflurane and enflurane produced negative chronotropic effects in this preparation. On the other hand, halothane and isoflurane significantly reduced the ventricular ectopic automaticity. However enflurane (0.3, 0.5, 1% v/v) increased ventricular rate. There were statistically significant differences between the IC50 values of atrial and ventricular rate for halothane and isoflurane. These results indicate: (a) direct negative inotropic and chronotropic effects for the three inhalational anaesthetics tested; (b) anti-dysrhythmic actions for halothane and isoflurane; and (c) dysrhythmogenic effects of enflurane.

  5. Gene expression of ANP, BNP and ET-1 in the heart of rats during pulmonary embolism.

    Directory of Open Access Journals (Sweden)

    Henrik Gutte

    Full Text Available AIMS: Atrial natriuretic petide (ANP, brain natriuretic peptide (BNP and endothelin-1 (ET-1 may reflect the severity of right ventricular dysfunction (RVD in patients with pulmonary embolism (PE. The exact nature and source of BNP, ANP and ET-1 expression and secretion following PE has not previously been studied. METHODS AND RESULTS: Polystyrene microparticles were injected to induce PE in rats. Gene expression of BNP, ANP and ET-1 were determined in the 4 cardiac chambers by quantitative real time polymerase chain reaction (QPCR. Plasma levels of ANP, BNP, ET-1 and cardiac troponin I (TNI were measured in plasma. PE dose-dependently increased gene expression of ANP and BNP in the right ventricle (RV and increased gene expression of ANP in the right atrium (RA. In contrast PE dose-dependently decreased BNP gene expression in both the left ventricle (LV and the left atrium (LA. Plasma levels of BNP, TNI and ET-1 levels dose-dependently increased with the degree of PE. CONCLUSION: We found a close correlation between PE degree and gene-expression of ANP, and BNP in the cardiac chambers with a selective increase in the right chambers of the heart. The present data supports the idea of natriuretic peptides as valuable biomarkers of RVD in PE.

  6. Tricarboxylic acid cycle metabolites during ischemia in isolated perfused rat heart.

    Science.gov (United States)

    Peuhkurinen, K J; Takala, T E; Nuutinen, E M; Hassinen, I E

    1983-02-01

    Isolated rat hearts were, after a retrograde perfusion by the Langendorff procedure, rendered ischemic by lowering the aortic pressure to zero. The rate of proteolysis and temporal patterns of the changes in the concentrations of the metabolites of the tricarboxylic acid cycle, related amino acids, ammonia, and breakdown products of the adenine nucleotides were determined. The most significant change in the amino acid metabolism was a decrease of the proteolysis to one-tenth and a large accumulation of alanine, which was almost stoichiometric to the degradation of aspartate plus asparagine. The accumulation of malate and succinate was small compared with the metabolic net fluxes of aspartate and alanine. The metabolic balance sheet suggests that aspartate was converted to alanine. A prerequisite for this would be a feed in of carbon of aspartate to the tricarboxylic acid cycle as oxalacetate, reversal of the malate dehydrogenase, and production of pyruvate by the malic enzyme reaction. Alanine accumulating during ischemia is not glycolytic in origin but occurs through a concerted operation of anaplerotic reactions and tricarboxylic acid cycle metabolite disposal. The data also suggest that the potentially energy-yielding reduction of fumarate to succinate is not significant in the ischemic myocardium.

  7. Effects of an acidic phospholipase A2 purified from Ophiophagus hannah (king cobra) venom on rat heart.

    Science.gov (United States)

    Huang, M Z; Wang, Q C; Liu, G F

    1993-05-01

    An acidic phospholipase A2 (OHV A-PLA2) purified from Ophiophagus hannah venom had a cardiotoxic action on rat heart. In rats OHV A-PLA2 (2-4 mg/kg) caused ECG abnormalities including decreased heart rate, prolonged P-R interval, widened QRS complex and complete A-V block. When tested on isolated rat right atria, OHV A-PLA2 (10-20 micrograms/ml) produced a positive chronotropic effect. When tested on isolated rat left atria or papillary muscle preparations, OHV A-PLA2 (2.5-20 micrograms/ml) caused positive inotropic effect, followed by contracture. The positive inotropic effects could be abolished by high Ca2+ and enhanced by low Ca2+; both treatments accelerated contracture. The contracture could be inhibited in Mn2+ (5 mM)-containing medium and abolished by Ca(2+)-free bath solution containing 1 mM EDTA. The cardiotoxic action of OHV A-PLA2 was not influenced by verapamil, tetrodotoxin, propranolol, phentolamine, atropine or indomethacin. It is suggested that the cardiotoxic effects of OHV A-PLA2 may result from increasing intracellular levels of Ca2+.

  8. Inhibition of the membrane attack complex of complement for induction of accommodation in the hamster-to-rat heart transplant model.

    Science.gov (United States)

    Suhr, Benjamin D; Black, Sylvester M; Guzman-Paz, Manuel; Matas, Arthur J; Dalmasso, Agustin P

    2007-11-01

    To induce accommodation in the hamster-to-rat cardiac transplantation model, in addition to cyclosporin A (CSA) to inhibit T-cell-mediated graft rejection, cobra venom factor (CVF) is often used to prevent complement-mediated graft rejection. Although it is generally assumed that CVF makes accommodation possible because it inactivates the complement membrane attack complex (MAC), it is not known which complement components must be inactivated and whether complement activation products generated by CVF are also involved in the induction of accommodation. Therefore, to investigate mechanisms by which CVF contributes to accommodation, we studied induction of accommodation of hamster hearts grafted into rats with complement deficiencies of C6; these rats cannot assemble the MAC but, in contrast to CVF, retain in their native state all complement proteins that precede the MAC. Golden Syrian hamster hearts were transplanted heterotopically into the abdomen of normocomplementemic and C6-deficient (C6D) PVG rats. Graft rejection was determined by cessation of palpable cardiac contractions. CSA, 10 mg/kg, was administered daily to all rats. Graft survival was compared in rats given CVF (60 U/kg 1-day pre-transplant and 20 U/kg/day for the next 9 days), C6D rats given no CVF, normocomplementemic rats given anti-C6 IgG or non-immune IgG but no CVF, and C6D rats reconstituted with normocomplementemic rat serum. Total complement and C6 serum levels were measured using hemolytic assays in rat peripheral blood. We found that hamster hearts transplanted into C6D rats receiving CSA but no CVF survived long-term, with histology typical of an accommodated heart. The accommodated hamster heart did not reconstitute C6 levels of the C6D recipient rats. Moreover, in normocomplementemic rats given anti-C6 antibodies (abs) to induce partial C6 deficiency, accommodation also developed without administration of CVF. Accommodation of the hamster heart failed to develop in C6D rats whose

  9. Effects of wire-bottom caging on heart rate, activity and body temperature in telemetry-implanted rats.

    Science.gov (United States)

    Giral, Marta; García-Olmo, Dolores C; Kramer, Klaas

    2011-10-01

    Some experimental procedures are associated with placement of animals in wire-bottom cages. The goal of this study was to evaluate stress-related physiological parameters (heart rate [HR], body temperature [BT], locomotor activity [LA], body weight [BW] and food consumption) in rats under two housing conditions, namely in wire-bottom cages and in bedding-bottom cages. Telemetry devices were surgically implanted in male Sprague-Dawley rats. HR, BT and LA were recorded at 5 min intervals. Analysis under each housing condition was performed from 16:00 to 08:00 h of the following day (4 h light, 12 h dark). During almost all of the light phase, the HR of rats housed in wire-bottom cages remained high (371 ± 35 bpm; mean ± SD; n = 6) and was significantly different from that of rats housed in bedding-bottom cages (340 ± 29 bpm; n = 6; P wire-bottom cages, BT tended to fluctuate more widely during the dark phase. LA decreased when animals were housed in wire-bottom cages, in particular during the dark phase. Moreover, there was a significant difference with respect to the gain in BW: BW of rats housed in bedding-bottom cages increased 12 ± 2 g, whereas that of rats in wire-bottom cages decreased by 2 ± 3 g (P wire-bottom cages overnight leads to immediate alterations of HR, BW and LA, which might be related to a stress response.

  10. Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Y. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China); Liu, B. [Department of Pathology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei (China); Wang, H.P. [Department of Histology and Embryology, Hebei North University, Zhangjiakou, Hebei (China); Zhang, L. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China)

    2016-05-31

    The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats.

  11. Effects of long-term exposure to 900 megahertz electromagnetic field on heart morphology and biochemistry of male adolescent rats.

    Science.gov (United States)

    Kerimoğlu, G; Mercantepe, T; Erol, H S; Turgut, A; Kaya, H; Çolakoğlu, S; Odacı, E

    2016-08-11

    The pathological effects of exposure to an electromagnetic field (EMF) during adolescence may be greater than those in adulthood. We investigated the effects of exposure to 900 MHz EMF during adolescence on male adult rats. Twenty-four 21-day-old male rats were divided into three equal groups: control (Cont-Gr), sham (Shm-Gr) and EMF-exposed (EMF-Gr). EMF-Gr rats were placed in an EMF exposure cage (Plexiglas cage) for 1 h/day between postnatal days 21 and 59 and exposed to 900 MHz EMF. Shm-Gr rats were placed inside the Plexiglas cage under the same conditions and for the same duration, but were not exposed to EMF. All animals were sacrificed on postnatal day 60 and the hearts were extracted for microscopic and biochemical analyses. Biochemical analysis showed increased levels of malondialdehyde and superoxide dismutase, and reduced glutathione and catalase levels in EMF-Gr compared to Cont-Gr animals. Hematoxylin and eosin stained sections from EMF-Gr animals exhibited structural changes and capillary congestion in the myocardium. The percentage of apoptotic myocardial cells in EMF-Gr was higher than in either Shm-Gr or Cont-Gr animals. Transmission electron microscopy of myocardial cells of EMF-Gr animals showed altered structure of Z bands, decreased myofilaments and pronounced vacuolization. We found that exposure of male rats to 900 MHz EMF for 1 h/day during adolescence caused oxidative stress, which caused structural alteration of male adolescent rat heart tissue.

  12. Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    SUN Hai-yan; XUE Fu-shan; XU Ya-chao; LI Cheng-wen; XIONG Jun; LIAO Xu; ZHANG Yan-ming

    2009-01-01

    Background There are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.Methods The hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n=10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 μg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 μg/ml) and L-NAME (100 μmol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment.The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.Results The cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1

  13. Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

    Science.gov (United States)

    Brooks, W W; Bing, O H; Litwin, S E; Conrad, C H; Morgan, J P

    1994-09-01

    We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30 degrees C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O2/5% CO2) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca2+]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca2+]o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca2+]i and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca2+]i, peak systolic pressure, and +/- dP/dt fell in SHR-F hearts. Peak systolic pressure decreased in the SHR-NF group at rates above 2.4 Hz but did not decline in the WKY group. Peak [Ca2+]i increased in the WKY and SHR-NF groups with increasing heart rates. Peak systolic pressure did not fall significantly in the WKY group at any heart rate. Elevation of diastolic [Ca2+]i and/or calcium transient and pressure alternans were present in 8 of 13 SHR-F hearts at the highest stimulation rate, findings that were absent in both the WKY and SHR-NF hearts. We conclude the following: (1) Under baseline conditions, depressed contractile function of

  14. MCT1 and MCT4 Expression During Myocardial Ischemic-Reperfusion Injury in the Isolated Rat Heart

    Directory of Open Access Journals (Sweden)

    Yi Zhu

    2013-09-01

    Full Text Available Background/Aims: Myocardium ischemia-reperfusion (I/R injury can be caused by imbalances in cellular metabolism. Lactate, transported by monocarboxylate transporters (MCTs, has been implicated as a mechanism in this process. The present study was designed to investigate the expression and functional role of MCTs in rat hearts during ischemia and reperfusion. Methods: Langendorff-perfused rat hearts were subjected to 20 minutes stabilization, 30 minutes of global ischemia and 60 minutes reperfusion. Hearts were collected serially for detecting expression changes in MCT1, MCT4 during myocardial I/R injury and lactate concentration was measured. Post-ischemic left ventricular function and infract size were determined at end-point, followed by the pretreatment of D-lactate, a competitive inhibitor of MCTs. Results: MCT4 was significantly increased following global ischemia and MCT1 expression was increased during the early stages of reperfusion in isolated rat hearts, while the expression of the ancillary protein CD147 was increased during I/R injury. We determined increases in AMPK phosphorylation status, which was significantly elevated following ischemia and early reperfusion. Blocking monocarboxylate transport by competitive inhibition with D-lactate caused decreased left ventricular performance and increased infarct size. Conclusion: Increased MCT4 expression facilitates lactate extrusion during the ischemic period, while increased MCT1 may facilitate lactate transport into and out of cells simultaneously during early reperfusion, with increases in AMPK phosphorylation status during the myocardial I/R period. Lactate transport by MCTs has a profound protective effect during myocardial ischemia reperfusion injury.

  15. Evaluation of right ventricle by speckle tracking and conventional echocardiography in rats with right ventricular heart failure.

    Science.gov (United States)

    Kimura, Koichi; Daimon, Masao; Morita, Hiroyuki; Kawata, Takayuki; Nakao, Tomoko; Okano, Tomoko; Lee, Seitetsu L; Takenaka, Katsu; Nagai, Ryozo; Yatomi, Yutaka; Komuro, Issei

    2015-05-13

    Speckle tracking echocardiography (STE) has been reported to be a promising technique for evaluating right ventricular (RV) function in the clinical setting. On the other hand, the usefulness of STE for RV evaluation in small animal models has not been clarified, although the rat model is among the most commonly used animal models to develop novel effective treatments against pulmonary hypertension and RV heart failure (HF).We validated the use of STE and conventional echocardiographic variables for evaluating RV functions in a rat model by comparing the echocardiographic values of RVHF rats (n = 12) induced by monocrotaline injection with those of control rats (n = 12).Most conventional echocardiographic variables demonstrated that RVHF rats have significant RV dysfunction. The area under the curve (AUC) values to distinguish RV dysfunction in RVHF rats from normal RV funct