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Sample records for rat isolated heart

  1. Communication: Effect of diperoxovandate on isolated rat heart ...

    African Journals Online (AJOL)

    Diperoxovanadate (DPV), a product of vanadate is gaining importance as a biologically active vanadium compound. The aim of the present study was to evaluate the chronotropic and inotropic activity of DPV using isolated rat heart and to determine the concentration at which it is toxic to the heart. The study was carried out ...

  2. Complete inhibition of creatine kinase in isolated perfused rat hearts

    International Nuclear Information System (INIS)

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. 31 P-NMR of the heart was carried out

  3. Ciprofloxacin, an antibiotic with cardiac actions on isolated rat hearts

    Directory of Open Access Journals (Sweden)

    Loipa Galán-Martínez

    2018-04-01

    Full Text Available Context: Ciprofloxacin is the most commonly used fluoroquinolone and is prescribed as the antibiotic of choice in the treatment of several microbial infections. Some clinical reports have suggested that ciprofloxacin may induce QT-interval prolongation and Torsades de Pointes arrhythmias. This drug is a weak inhibitor of a rapid component of the cardiac delayed rectifier potassium current IKr, but there are few electrophysiological data available to assess whether ciprofloxacin has the potency to provoke QT prolongation and subsequent Torsades de Pointes arrhythmias. Aims: To evaluate the effect of ciprofloxacin on the contractile and electrical activity of isolated rat hearts. Methods: The Langendorff technique was performed in rat hearts, and the effects of ciprofloxacin (0.001 – 100 μM were measured on the cardiac force of contraction and on the RR, QRS and QTc intervals. The arrhythmogenic potential and the ventricular fibrillation threshold were evaluated with ciprofloxacin. Results: Ciprofloxacin decreased the force of contraction of all hearts studied, in a concentration-dependent manner. The estimated IC50 for the inotropic negative effect was 0.15 ± 0.04 μM. Ciprofloxacin significantly prolonged the QRS complex, QTc and RR interval. Significant arrhythmic effects with ciprofloxacin were shown and the ventricular fibrillation threshold was decreased. Conclusions: These results suggest that ciprofloxacin exerted effects on cardiac Na+, K+ and Ca2+ channels. The actions of ciprofloxacin require further studies at the cellular level. These conclusions may account for clinical data that have been reported previously.

  4. Metabolic variations of fatty acid in isolated rat heart reperfused after a transient global ischemia

    International Nuclear Information System (INIS)

    Huang Gang; Michel Comet; Zhao Huiyang; Zhu Cuiying; Yuan Jimin

    1998-01-01

    Purpose: The fatty acid metabolism and the effect of glucose on it were studied in isolated and reperfused rat heat. Methods: 32 isolated working rat hearts were perfused in Langengdorff device with modified Krebs and were divided into normal and ischemia-reperfused group. Each group was also classified into two subgroups, modified krebs with or without glucose subgroup. 131 I-HA was injected into aorta of isolated working rat heart and then the radio-residue curves were acquired. Results: When the isolated rat hearts were perfused with krebs plus glucose, the catabolism of fatty acid was significantly decreased in normal group, but a remarkable increase of fatty acid catabolism was found in ischemia-reperfused group. While the isolated rat hearts were perfused with krebs without glucose, the catabolism of fatty acid in ischemia-reperfused isolated rat hearts were perfused with krebs without glucose, the catabolism of fatty acid in ischemia-reperfused isolated rat heart was less than that in normal group. Conclusions: Transient ischemia damages the catabolism of myocardial fatty acid in mitochondria in some degree. In normal isolated working rat heart, the principal energy source is glucose. However, the major energy source is switched to catabolism of fatty acid in ischemia-reperfused isolated rat heart. This phenomenon may be related to compensative increase of fatty acid catabolism for replenishing the loss of energy during ischemia

  5. Transcapillary transport of metaiodobenzylguanidine (MIBG) in isolated rat heart

    International Nuclear Information System (INIS)

    DeGrado, Timothy R.; Wang Shuyan

    1998-01-01

    A better understanding of transcapillary transport for tracer metaiodobenzylguanidine (MIBG) is desirable for development of tracer kinetic models that yield meaningful estimates of neuronal uptake function from tissue radioactivity time courses. This study utilized a multiple-indicator approach in Langendorff-perfused rat hearts to define transport mechanisms and determine the capillary permeability-surface area (PSc) over a broad range of flow (F). Multiple injections within the same heart at different flows allowed characterization of the PSc/F relationship within the same heart. The coefficient of variation of E for multiple injections within the same hearts at constant flow was 6±2% (3 to 6 injections in 9 hearts). In 10 hearts (4 to 6 injections per heart), flow was varied between 2.0-16.5 mL/min. PSc was found to be nearly proportional to flow in each heart (r=0.88±0.14; slope = 0.23±0.10; intercept = 11±7 mL/min/g dry). Tissue hypoxia at low flows, as evidenced by enhanced lactate production, did not appear to influence the PSc/F relationship. Pharmacologic blockade of uptake-1 and uptake-2 had negligible affect on E or PSc as compared with flow-matched controls, although tissue retention was markedly reduced. The results show PSc of MIBG to be nearly proportional to flow but independent of specific neuronal and extraneuronal transport mechanisms and tissue hypoxia. The results are consistent with a passive diffusion process across the capillary endothelial barrier. The increase in PSc with increasing flow could reflect capillary recruitment and/or enhanced capillary permeability

  6. In vitro assessment of cardiac performance after irradiation using an isolated working rat heart preparation

    International Nuclear Information System (INIS)

    Wondergem, J.; Laarse, A. van der; Ravels, F.J.M. van; Wermeskerken, A.-M. van; Verhoeve, H.R.; Graaf, B.W. de; Leer, J.W.H.

    1991-01-01

    The effect of irradiation on cardiac function was assessed using an isolated working rat heart preparation. The animals were given single doses of X-rays in the range 15-30 Gy to their hearts. Cardiac output (CO = aortic flow + coronary flow), heart weight and body weight were followed for a period of 10 months after treatment. Irradiation led to a decrease in cardiac function. This reduction was dose-dependent and progressive with time after treatment. The shape of the Frank-Starling curves constructed for irradiated hearts suggests a loss of contractile function of the myocardium. Coronary flow rates measured in 'working' hearts and in 'Langendorff' hearts were not significantly changed by the irradiation treatment. The isolated working rat heart preparation proved to be a simple and suitable animal model for the investigation of irradiation-induced cardiotoxicity. (author)

  7. Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

    OpenAIRE

    Haleh Vaez; Mehrban Samadzadeh; Fahimeh Zahednezhad; Moslem Najafi

    2012-01-01

    Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibra...

  8. Kinetics of the norepinephrine analog [76Br]-meta-bromobenzylguanidine in isolated working rat heart

    International Nuclear Information System (INIS)

    Raffel, David; Loc'h, Christian; Mardon, Karine; Maziere, Bernard; Syrota, Andre

    1998-01-01

    A related set of kinetic studies of the norepinephrine analog [ 76 Br]-meta-bromobenzylguanidine (MBBG) were performed with an isolated working rat heart preparation. A series of constant infusion studies over a wide range of MBBG concentrations allowed estimation of the Michaelis-Menten constants for transport by the neuronal norepinephrine transporter (uptake 1 ) and the extraneuronal uptake system (uptake 2 ). Pharmacological blocking studies with inhibitors of uptake 1 , uptake 2 and vesicular uptake were performed to delineate the relative importance of these norepinephrine handling mechanisms on the kinetics of MBBG in the rat heart. Bolus injection studies were done to assess the ability of compartmental modeling techniques to characterize the kinetics of MBBG. These studies demonstrate that MBBG shares many of the same uptake mechanisms as norepinephrine in the rat heart. PET imaging studies with MBBG would be useful for assessing sympathetic nerve status in the living human heart

  9. Heterogeneous response of isolated adult rat heart cells to insulin

    International Nuclear Information System (INIS)

    Haworth, R.A.; Hunter, D.R.; Berkoff, H.A.

    1984-01-01

    3-O-Methylglucose uptake by Ca2+-resistant adult rat heart cells in suspension was measured, free of artifactual inhibitor-insensitive uptake, and with an accuracy of +/- 1.9% pellet water. (Ca2+-resistant cells are cells which retain their original rod-shaped morphology in the presence of physiological levels of Ca2+.) High levels of insulin (10(-6) M) stimulated the rate of 3-O-methylglucose uptake approximately 10-fold. In the presence of low levels of insulin (3 X 10(-11) M, 10(-10) M) uptake was biphasic; it could not be described by a single exponential function within experimental error, but required the sum of two exponentials. Deviation from a single exponential function was not so great with high levels of insulin (10(-6) M) or no insulin. Cell sugar uptake was also investigated using autoradiography of cells which had accumulated [2-14C]deoxyglucose under similar conditions. This showed considerable heterogeneity of 2-deoxyglucose uptake by cells treated with low levels of insulin, but significantly less heterogeneity of 2-deoxyglucose uptake by cells treated with high levels of insulin. It is concluded that the deviation of 3-O-methylglucose uptake from a single exponential observed at low insulin levels can be accounted for in terms of a heterogeneous response of cells to insulin

  10. Plasma protein concentration and control of coronary vascular resistance in isolated rat heart

    NARCIS (Netherlands)

    Avolio, A. P.; Spaan, J. A.; Laird, J. D.

    1980-01-01

    Isolated externally paced (300 beats/min) rat hearts were perfused at constant pressure (70 mmHg) using a modified Krebs-Henseleit solution with (n = 52) and without (n = 15) washed bovine red cells. Albumin concentration varied from 1 to 10 g/dl. With increasing albumin concentration in

  11. Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

    International Nuclear Information System (INIS)

    Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

    2010-01-01

    The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 μM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt max of 105 ± 8 mN/s in control hearts vs. 49 ± 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 ± 0.2 in control hearts vs. 2.2 ± 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 ± 1 μM cytochrome c/min/mg in control hearts vs. 14 ± 3 μM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

  12. 31P nuclear magnetic resonance surface coil study of ischemic preconditioned isolated perfused rat heart

    International Nuclear Information System (INIS)

    Yan Yongbin; Luo Xuechun; Zhang Riqing; Wang Xiaoyin; Zuo Lin; Liu Wei

    2000-01-01

    ischemic preconditioning (IPC) will protect the heart from the damage caused by a subsequent long ischemia period. 31 P spectra of isolated perfused rat heart measured by the nuclear magnetic resonance (NMR) surface coil technique can be used to continually, dynamically and noninvasively obtain metabolism information. This paper explores the IPC mechanisms by NMR. This study shows that IPC has no effect on enhancing the ATP and PCr levels during reperfusion but makes significantly slows and smooths the changes of intracellular pH and ATP during ischemia periods. The ATP and PCr recovery rate of the IPC group after ischemia is significantly higher than that of the control group. In conclusion, the above results support that IPC can protect the rat heart by reducing damage during the ischemia period

  13. Calcium uptake by sarcoplasmic reticulum isolated from hearts of septic rats

    International Nuclear Information System (INIS)

    McDonough, K.H.

    1988-01-01

    Myocardial sarcoplasmic reticulum (SR) plays a critical role in the regulation of the cytosolic calcium fluctuations that occur during the cardiac cycle. One function of the SR is to lower the calcium concentration so that myocardial relaxation and thus ventricular filling can occur. The aim of the present study was to determine if hyperdynamic sepsis induced a decrease in the capacity of SR to take up calcium. This defect would result in decreased ventricular filling and thus decreased cardiac output, as has previously been shown in isolated perfused working hearts removed from septic rats. Therefore, rats were anesthetized with ether, and sepsis was induced by the injection of an aliquot of a fecal homogenate into the peritoneal cavity. Control animals either underwent surgery and received an aliquot of sterilized fecal inoculum (sham) or were untreated (no surgery). On day 2 after surgery, animals were anesthetized with pentobarbital, and hearts were removed, weighted, and SR isolated. The rate of uptake of 45 Ca 2+ by SR from septic rats was not depressed compared to controls but in fact was elevated. Maximum 45 Ca 2+ accumulated by the SR and Ca 2+ -stimulated ATPase activity were similar in SR from control and septic hearts. These results suggest that the contractile dysfunction noted in the myocardium in early sepsis is probably not due to inadequate SR removal of Ca 2+ during diastole

  14. Development of an Assay Based on the Effects of PGBx on the Isolated Perfused Rat Heart and Rat Skeletal Muscle.

    Science.gov (United States)

    1980-09-01

    had no effect on discphe- nol induced alterations in spontaneous heart rate, but did appear to prevent the increase in coronary flow caused by...Phosphorylase a i -24 activity was also the same in each of the groups examined (Table 2-4). DISCUSSION The ability of PGBx to prevent 2,4-dinitrophenol-induced...euthyroid and hyperthyroid rats. Eur. J. Pharmac. 19, 12-17. Aronson, C. E. and Serlick, E. R. (1977a) Effects of chlorpromazine on the isolated

  15. 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

    -specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......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...... 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak [University of Ljubljana, Department of Biology, Biotechnical Faculty (Slovenia); Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd, E-mail: gorazd.drevensek@mf.uni-lj.si [University of Ljubljana, Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine (Slovenia)

    2016-10-15

    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.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

    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 [ 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 2+ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K + currents

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Myocardial 99mTc-sestamibi extraction and washout in hypertensive heart failure using an isolated rat heart

    International Nuclear Information System (INIS)

    Fukushima, Kenji; Momose, Mitsuru; Kondo, Chisato; Higuchi, Takahiro; Kusakabe, Kiyoko; Hagiwara, Nobuhisa

    2010-01-01

    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 99m Tc-sestamibi [( 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 1 (ml/min) and washout rate, k 2 (min -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 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 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 washout was increased in the transitional state

  20. 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

  1. Functional response of white rats isolated heart to the stimulation of adrenergic receptors after gamma-irradiation in low doses

    International Nuclear Information System (INIS)

    Antonenko, A.N.; Lobanok, L.M.

    1999-01-01

    It was investigated the effects of acute gamma-irradiation on bio mechanical activity of rats heart isolated by Langendorf's method in early and delayed terms after exposure to gamma-rays. Intra ventricle pressure and the rate of its growth, volumetric rate of coronal flow, frequency of heart contraction were registered. Stimulation of alpha-adrenergic receptors was conducted by means of specific agonist mesatone and stimulation of beta-adrenergic receptors was made by means of isoprenaline. The study has shown that acute irradiation of rats caused the decrease of both contractile ability and relaxation of myocardium in a 10 days after exposure. In delayed period bio mechanical activity of isolated heart was restored. Functional response of heart to the stimulation of alpha- and beta-adrenergic receptors was decreased in all terms of investigation

  2. 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.

  3. The influence of Poly-Vinyl-Chloride tubing on the isolated perfused rat´s heart.

    NARCIS (Netherlands)

    Meijler, F.L.; Durrer, D.

    1950-01-01

    There are types of poly-vinyl-chloride tubing sold and used for medical and biological purposes which deteriorate heart action in a few minutes. A simple method for testing P.V.C. tubing can be found in the isolated rat's he art perfused according to Langendorff.

  4. Measurement of the efficacy of 2% lipid in reversing bupivacaine- induced asystole in isolated rat hearts

    Science.gov (United States)

    2014-01-01

    Background The reversal efficacy of 2% lipid emulsion in cardiac asystole induced by different concentrations of bupivacaine is poorly defined and needs to be determined. Methods Forty-two male Sprague–Dawley rats were randomly divided into seven groups: B40, B60, B80, B100, B120, B140 and B160, n = 6. The Langendorff isolated heart perfusion model was used, which consisted of a balanced perfusion with Krebs-Henseleit solution for 25 minutes and a continuous infusion of 100 μmol/L bupivacaine until asystole had been induced for 3 minutes. The hearts in the seven groups were perfused with Krebs-Henseleit solution containing a 2% lipid emulsion, and 40, 60, 80, 100, 120, 140 or 160 μmol/L bupivacaine, respectively. Cardiac recovery was defined as a spontaneous and regular rhythm with a rate-pressure product > 10% of the baseline value for more than 1 minute. Our primary outcome was the rate-pressure product 25 minutes after cardiac recovery. Other cardiac function parameters were also recorded. Results All groups demonstrated cardiac recovery. During the recovery phase, heart rate, rate-pressure product, the maximum left ventricular pressure rise and decline in heart rate in the B120-B160 groups was significantly lower than those in the B40-B80 groups (P bupivacaine and the reversal effects of a 2% lipid emulsion showed a typical transoid S-shaped curve, R2 = 0.9983, IC50 value was 102.5 μmol/L (95% CI: 92.44 - 113.6). Conclusions There is a concentration-response relationship between the concentrations of bupivacaine and the reversal effects of 2% lipid emulsion. PMID:25089118

  5. beta-Methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart.

    Science.gov (United States)

    DeGrado, T R; Holden, J E; Ng, C K; Raffel, D M; Gatley, S J

    1989-01-01

    The use of 15-p-iodophenyl-beta-methyl-pentadecanoic acid (beta Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both beta Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, beta Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond beta Me-IPPA-CoA in the oxidative pathway.

  6. β-methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

    International Nuclear Information System (INIS)

    DeGrado, T.R.; Holden, J.E.; Ng, C.K.; Raffel, D.M.; Gatley, S.J.

    1989-01-01

    The use of 15-p-iodophenyl-β-methyl-pentadecanoic acid (βMe-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both βMe-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). In contrast, βMe-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond βMe-IPPA-CoA in the oxidative pathway. (orig.)

  7. beta. -methyl-15-p-iodophenylpentadecanoic acid metabolism and kinetics in the isolated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    DeGrado, T.R.; Holden, J.E.; Ng, C.K.; Raffel, D.M.; Gatley, S.J.

    1989-02-01

    The use of 15-p-iodophenyl-..beta..-methyl-pentadecanoic acid (..beta..Me-IPPA) as an indicator of long chain fatty acid (LCFA) utilization in nuclear medicine studies was evaluated in the isolated, perfused, working rat heart. Time courses of radioactivity (residue curves) were obtained following bolus injections of both ..beta..Me-IPPA and its straight chain counterpart 15-p-iodophenyl-pentadecanoic acid (IPPA). IPPA kinetics clearly indicated flow independent impairment of fatty acid oxidation caused by the carnitine palmitoyltransferase I inhibitor 2(5(4-chlorophenyl)pentyl)oxirane-2-carboxylate (POCA). In contrast, ..beta..Me-IPPA kinetics were insensitive to changes in fatty acid oxidation rate and net utilization of long chain fatty acid. Analysis of radiolabeled species in coronary effluent and heart homogenates showed the methylated fatty acid to be readily incorporated into complex lipids but a poor substrate for oxidation. POCA did not significantly alter metabolism of the tracer, suggesting that the tracer is poorly metabolized beyond ..beta..Me-IPPA-CoA in the oxidative pathway.

  8. Effects of ketamine and its isomers on ischemic preconditioning in the isolated rat heart

    NARCIS (Netherlands)

    Molojavyi, A.; Preckel, B.; Comfère, T.; Müllenheim, J.; Thämer, V.; Schlack, W.

    2001-01-01

    BACKGROUND: Ischemic preconditioning protects the heart against subsequent ischemia. Opening of the adenosine triphosphate-sensitive potassium (KATP) channel is a key mechanism of preconditioning. Ketamine blocks KATP channels of isolated cardiomyocytes. The authors investigated the effects of

  9. 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

  10. 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.

  11. Assessment of Cardiovascular Apoptosis in the Isolated Rat Heart by Magnetic Resonance Molecular Imaging

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    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.

  12. Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

    Science.gov (United States)

    Vaez, Haleh; Samadzadeh, Mehrban; Zahednezhad, Fahimeh; Najafi, Moslem

    2012-01-01

    Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H) solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2%) for 15 min and was resumed until the end of 120 min with normal K/H solution. Results: In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (Phoney. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2%) markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (Phoney in global ischemia showed protective effects against ischemia/reperfusion (I/R) injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects. PMID:24312792

  13. Enhanced preservation of the isolated rat heart after hypothermic storage by pinacidil pretreatment and storage in lazaroid U74500A

    International Nuclear Information System (INIS)

    Hicks, M.; Du, Z.Y.; Spratt, P.; Macdonald, P.

    1998-01-01

    The aim of the present study was to compare 3 protocols incorporating these approaches on the preservation of haemodynamic function in the isolated working rat heart after hypothermic storage. These protocols were: 1) pretreatment of the heart with 200 μM pinacidil, an ATP-sensitive potassium channel opener; 2) storage in cardioplegic solution containing the lipid soluble lazaroid antioxidant U74500A (30 μM); 3) A combination of protocols 1 and 2. Methods: Hearts from Wistar rats (250 to 330g body weight) were perfused on a Langendorff apparatus. Each heart was ligated to an aortic cannula and perfused retrogradely, with oxygenated Krebs solution at a hydrostatic pressure of 100 cm H 2 O. The system was then converted to 'working mode' by switching the perfusate from aorta to a left atrial cannula (filling pressure 15 cm H 2 O). After stabilisation, the following pre-arrest indices of cardiac function were recorded: heart rate (HR), coronary flow (CF), aortic flow (AF) and cardiac output (CO). Hearts were then randomised to protocols 1-3, untreated controls or vehicle treated controls (n=6 animals/ group). Hearts were stored in an extracellular-based preservation solution for 12 hours at 2-3degC, remounted on the perfusion apparatus and stabilised as before. Haemodynamic measurements were then repeated. Conclusions: Combined pharmacological activation of ATP-sensitive potassium channels before cardioplegia and the addition of U74500A to the preservation solution is associated with a significantly enhanced haemodynamic function in the rat heart after 12 hours of hypothermic storage. These data suggest a novel use for these agents in the transplantation context

  14. Enhanced preservation of the isolated rat heart after hypothermic storage by pinacidil pretreatment and storage in lazaroid U74500A

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, M. [St Vincent`s Hospital, Darlinghurst, NSW (Australia). Division of Clinical Pharmacology and Toxicology; Du, Z.Y.; Spratt, P.; Macdonald, P. [St Vincent`s Hospital, Darlinghurst, NSW (Australia). Cardiopulmonary Transplant Unit

    1998-12-31

    The aim of the present study was to compare 3 protocols incorporating these approaches on the preservation of haemodynamic function in the isolated working rat heart after hypothermic storage. These protocols were: 1) pretreatment of the heart with 200 {mu}M pinacidil, an ATP-sensitive potassium channel opener; 2) storage in cardioplegic solution containing the lipid soluble lazaroid antioxidant U74500A (30 {mu}M); 3) A combination of protocols 1 and 2. Methods: Hearts from Wistar rats (250 to 330g body weight) were perfused on a Langendorff apparatus. Each heart was ligated to an aortic cannula and perfused retrogradely, with oxygenated Krebs solution at a hydrostatic pressure of 100 cm H{sub 2}O. The system was then converted to `working mode` by switching the perfusate from aorta to a left atrial cannula (filling pressure 15 cm H{sub 2}O). After stabilisation, the following pre-arrest indices of cardiac function were recorded: heart rate (HR), coronary flow (CF), aortic flow (AF) and cardiac output (CO). Hearts were then randomised to protocols 1-3, untreated controls or vehicle treated controls (n=6 animals/ group). Hearts were stored in an extracellular-based preservation solution for 12 hours at 2-3degC, remounted on the perfusion apparatus and stabilised as before. Haemodynamic measurements were then repeated. Conclusions: Combined pharmacological activation of ATP-sensitive potassium channels before cardioplegia and the addition of U74500A to the preservation solution is associated with a significantly enhanced haemodynamic function in the rat heart after 12 hours of hypothermic storage. These data suggest a novel use for these agents in the transplantation context Truncated abstract. 1 tab.

  15. The role of K –ATP channel in the preconditioning effect of magnesium in the rat isolated heart

    Directory of Open Access Journals (Sweden)

    Bazargan M.

    2007-05-01

    Full Text Available There is growing interest for beneficial effect of Mg in the cardiovascular disorders. A number of cardiovascular disorders including myocardial infarction, arrhythmias and congestive heart failure have been associated with low extracellular or intracellular concentrations of Mg. The aim of present study was to investigate the preconditioning effects of magnesium (Mg on cardiac function and infarct size in the globally ischemic-reperfusion in isolated rat heart. Rat hearts were Langendorff-perfused, subjected to 30 minutes of global ischemia and 90 minutes of reperfusion, and assigned to one of the following treatment groups with 7 hearts in each group: (1 control, (2 ischemic- reperfusion, (IR, (3 ischemic preconditioning, (IPC of 5 minutes of global ischemia - reperfusion before lethal ischemia; or pretreatment with (4 30 µmol/L of Diazoxide (Dia, (5 8 mmol/L magnesium, (6 10 µmol/L glibenclamid (Gli, (7 magnesium and Dia and (8 magnesium and Gli. Infarct size was measured by the triphenyltetrazolium chloride method. Left ventricular function was assessed by left ventricular developed pressure (LVDP, heart rate and coronary flow (CF. Mg limited infarct size (9.76 % vs 44.47% in IR, P< 0.001 as did Dia (10.2 % vs 44.4 % in IR P< 0.001 and IPC (8.69 % vs 44.47% in IR, P< 0.001. The protective effect of magnesium was abolished by Gli. Administration of Mg had an anti-infarct effect in ischemic-reperfusion isolated rat hearts and improved cardiac function. Blockade of K-ATP channel abolished the protective effects of magnesium and suggest that K-ATP channel has an important role in this effects.

  16. Correlation between Amitriptyline-Induced Cardiotoxic Effects and Cardiac S100b Protein in Isolated Rat Hearts

    Directory of Open Access Journals (Sweden)

    Nil Hocaoğlu

    2016-12-01

    Full Text Available Background: Amitriptyline is an important cause of mortality due to its cardiovascular toxicity. Aims: To investigate the changes in levels of cardiac S100b protein on amitriptyline-induced cardiotoxicity and also to examine the correlation between amitriptyline-induced cardiotoxic effects and cardiac S100b protein in an isolated rat heart model. Study Design: Animal experimentation, isolated heart model. Methods: After a stabilization period, isolated hearts were randomized to two groups (n=5 and n=7. In the control group, isolated hearts were subjected to an infusion of 5% dextrose for 60 minutes. In the amitriptyline group, 5.5×10-5 M amitriptyline was infused for 60 minutes to achieve amitriptyline toxicity. After the infusion period, heart tissues were removed for histological examination. Results: In comparison to control treatment, amitriptyline infusion decreased left ventricular developed pressure (LVDP, dp/dtmax and heart rate (HR and significantly prolonged QRS duration (p<0.05. The semiquantitative scores for S100b protein levels in amitriptyline-infused hearts were higher than in the control group (p<0.01. At the end of the experiment, in the amitriptyline-infused group, significant correlations were found between LVDP and S100b protein scores (r=-0.807, p=0.003 and between QRS duration and S100b protein scores (r=0.859, p=0.001. Conclusion: Our results indicate that the S100b protein may be a helpful indicator or biomarker in studying the cardiotoxic effects of amitriptyline.

  17. Hydroxyl radicals' production and ECG parameters during ischemia and reperfusion in rat, guinea pig and rabbit isolated heart.

    Science.gov (United States)

    Paulova, Hana; Stracina, Tibor; Jarkovsky, Jiri; Novakova, Marie; Taborska, Eva

    2013-06-01

    Ischemic and reperfusion injury is a serious condition related to numerous biochemical and electrical abnormalities of the myocardium. It has been repeatedly studied in various animal models. In this study, the production of hydroxyl radicals and electrophysiological parameters were compared in three species. Rat, guinea pig and rabbit isolated hearts were perfused according to Langendorff under strictly identical conditions. The heart rate and arrhythmia were monitored during ischemia and reperfusion periods at defined time intervals; the production of hydroxyl radical was determined by HPLC as 2.5-dihydroxybenzoic acid (2.5-DHBA) formed by salicylic acid hydroxylation. Relationship between arrhythmias and production of 2.5-DHBA was studied. The inter-species differences were observed in timing of arrhythmias onset and their severity, and in the production of 2.5-DHBA in both ischemia and reperfusion. The most considerable changes were observed in rats, where arrhythmias appeared early and with highest severity during ischemia on one side and the regular rhythm was restored early and completely during reperfusion. The corresponding changes in the production of 2.5-DHBA were observed. It can be concluded that rat isolated heart is the most suitable model for evaluation of ischemia/reperfusion injury under given experimental conditions.

  18. Metabolism in the isolated rat heart: comparison of 125I-BMIPP with 125I-IPPA

    International Nuclear Information System (INIS)

    Chen Shaoliang; Cheng Aiping; Xu Lanwen; Qiao Weiwei

    2008-01-01

    Objective: The fatty acid metabolism in myocardium is recently one of the most interesting subjects in nuclear cardiology. The purpose of this study was to clarify the metabolic fate of 125 I-labeled 15-(p-iodophenyl)-3-(R, S)-methyl-pentadecanoic acid ( 125 I-BMIPP) and 15-(p-[ 125 I] iodophenyl) pentadecanoic acid ( 125 I-IPPA) by means of isolated rat hearts. Methods: Ten isolated rat hearts were prepared and perfused with 125 I-BMIPP (5 rats) or 125 I-IPPA (5 rats) for 3 h following a basic perfusion of 30 min. After perfusion, the radioactivity in the recirculated buffer was measured. The metabolites in the buffer were then extracted and analyzed using high performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). Results: At the beginning (5 rain) of 125 I-BMIPP perfusion, the main radioactive peak appeared on HPLC at 37 min, which remained after 3 h perfusion. Several small peaks eluting were found before the parent peak at 30, 26, 21, 16, 12 and 9 min, respectively. At the beginning (5 min) of 125 I-IPPA perfusion, the main peak appeared on HPLC at 33 min, which disappeared after 3 h. Conclusions: 125 I-BMIPP strongly inhibited beta-oxidation, therefore appeared suitable for myocardial metabolic imaging. 125 I-IPPA was metabolized rapidly. (authors)

  19. Protectant activity of defibrotide in cardioplegia followed by ischemia/reperfusion injury in the isolated rat heart.

    Science.gov (United States)

    Rossoni, G; Pompilio, G; Biglioli, P; Alamanni, F; Tartara, P; Rona, P; Porqueddu, M; Berti, F

    1999-01-01

    Previous studies have shown that defibrotide, a polydeoxyribonucleotide obtained by depolymerization of DNA from porcine tissues, has important protective effects on myocardial ischemia, which may be associated with a prostacyclin-related mechanism. The purpose of this study was to investigate the direct effects of defibrotide (given in cardioplegia or after ischemia) on a model of rat heart recovery after cardioplegia followed by ischemia/reperfusion injury. Isolated rat hearts, undergoing 5 minutes of warm cardioplegic arrest followed by 20 minutes of global ischemia and 30 minutes of reperfusion, were studied using the modified Langendorff model. The cardioplegia consisted of St. Thomas' Hospital solution augmented with defibrotide (50, 100, and 200 microg/mL) or without defibrotide (controls). Left ventricular mechanical function and the levels of creatine kinase, lactate dehydrogenase, and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha; the stable metabolite of prostacyclin) were measured during preischemic and reperfusion periods. After global ischemia, hearts receiving defibrotide in the cardioplegic solution (n = 8) manifested in a concentration-dependent fashion lower left ventricular end-diastolic pressure (p defibrotide in the cardioplegic solution also had, in a dose-dependent way, lower levels of creatine-kinase (p defibrotide was given alone to the hearts at the beginning of reperfusion (n = 7), the recovery of postischemic left ventricular function was inferior (p defibrotide was given in cardioplegia. Defibrotide confers to conventional crystalloid cardioplegia a potent concentration-dependent protective effect on the recovery of isolated rat heart undergoing ischemia/reperfusion injury. The low cost and the absence of contraindications (cardiac toxicity and hemodynamic effects) make defibrotide a promising augmentation to cardioplegia.

  20. Effect of immobilization stress on gene expression of catecholamine biosynthetic enzymes in heart auricles of socially isolated rats

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    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.

  1. Influence of fasting on the myocardial metabolsim of [123I] 16-iodohexadecenoic acid (IHA): a study on isolated rat heart

    International Nuclear Information System (INIS)

    Ghezzi, C.; Bontemps, L.; Demaison, L.; Dubois, F.; Comet, M.; Cuchet, P.

    1986-01-01

    IHA has been proposed for the study of myocardial metabolism by external detection. This requires numerical data on the iodinated fatty acid metabolism of the myocardium which can be derived from an analysis of the time activity curve. We developed a mathematical 4-compartment model for this purpose with compartments 0, 1, 2 and 3 representing vascular IHA, intracellular IHA, esterified forms and iodide, respectively. To validate this model it was applied to the study of the effect of fasting on rat myocardial metabolism. Two groups of rats were used, one fed ad lib. and the other fasted for 36 hours. After a bolus injection of IHA into the perfused rat coronaries myocardial time activity curves were recorded for 30 minutes and the activity distribution in the 4 compartments was simulated. Then intracellular activity in perfused rat heart homogenates was determined at different intervals p.i.. Measured and computed values were found to agree well in all compartments. A 36-hour fast was associated with increased uptake and accelerated β-oxidation, while esterification was unchanged. In conclusion, the proposed mathematical model helps to demonstrate even discrete changes of myocardial fatty acid metabolism in the isolated rat heart. Our results, once again, document the excellent suitability of IHA for assessing myocardial metabolism. (Author)

  2. Differential uptake of FDG and DG during post-ischaemic reperfusion in the isolated, perfused rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Garlick, P.B.; Medina, R.A.; Southworth, R.; Marsden, P.K. [Department of Radiological Sciences, Guy' s, King' s and St. Thomas' School of Medicine, London (United Kingdom)

    1999-10-01

    Fluorine-18 2-fluoro-2-deoxyglucose (FDG) and 2-deoxyglucose (DG) are widely used as tracers of glucose uptake in the myocardium. Although there is agreement that the two analogues behave similarly to glucose under control conditions, there is growing evidence that some interventions (e.g. insulin stimulation or ischaemia/reperfusion) cause differential changes in their behaviour. The addition of a two-surface coil nuclear magnetic resonance (NMR) probe and a dual-perfusion cannula to our recently developed PET and NMR dual-acquisition (PANDA) system allows us to collect PET (FDG) images and phosphorus-31 NMR (2-deoxyglucose-6-phosphate) spectra simultaneously from each independently perfused coronary bed of the heart. We have used this technique to study the effect of regional ischaemia/reperfusion on FDG and DG uptake in the isolated, perfused rat heart. During control perfusion, FDG uptake was almost identical in both coronary beds. When one coronary bed was made ischaemic, FDG uptake ceased on that side but continued on the control side. Reperfusion failed to restore FDG uptake. In contrast, NMR spectra showed that, during reperfusion, the uptake and phosphorylation of DG did not differ between the two coronary beds. The results thus demonstrate that regional myocardial ischaemia/reperfusion has different effects on the uptake of FDG and DG in the isolated, perfused rat heart. (orig.)

  3. Differential uptake of FDG and DG during post-ischaemic reperfusion in the isolated, perfused rat heart

    International Nuclear Information System (INIS)

    Garlick, P.B.; Medina, R.A.; Southworth, R.; Marsden, P.K.

    1999-01-01

    Fluorine-18 2-fluoro-2-deoxyglucose (FDG) and 2-deoxyglucose (DG) are widely used as tracers of glucose uptake in the myocardium. Although there is agreement that the two analogues behave similarly to glucose under control conditions, there is growing evidence that some interventions (e.g. insulin stimulation or ischaemia/reperfusion) cause differential changes in their behaviour. The addition of a two-surface coil nuclear magnetic resonance (NMR) probe and a dual-perfusion cannula to our recently developed PET and NMR dual-acquisition (PANDA) system allows us to collect PET (FDG) images and phosphorus-31 NMR (2-deoxyglucose-6-phosphate) spectra simultaneously from each independently perfused coronary bed of the heart. We have used this technique to study the effect of regional ischaemia/reperfusion on FDG and DG uptake in the isolated, perfused rat heart. During control perfusion, FDG uptake was almost identical in both coronary beds. When one coronary bed was made ischaemic, FDG uptake ceased on that side but continued on the control side. Reperfusion failed to restore FDG uptake. In contrast, NMR spectra showed that, during reperfusion, the uptake and phosphorylation of DG did not differ between the two coronary beds. The results thus demonstrate that regional myocardial ischaemia/reperfusion has different effects on the uptake of FDG and DG in the isolated, perfused rat heart. (orig.)

  4. NMR study of damage on isolated perfused rat heart exposed to ischemia and hypoxia

    International Nuclear Information System (INIS)

    Luo Xuechun; Yan Yongbin; Zhang Riqing; Fan Lili

    2001-01-01

    Myocardial ischemia is the most common and primary cause of myocardium damage. Numerous conventional techniques and methods have been developed for ischemia and reperfusion studies. However, because of damage to the heart sample, most of these techniques can not be used to continuously monitor the full dynamic course of the myocardial metabolic pathway. The nuclear magnetic resonance (NMR) surface coil technique, which overcomes the limitations of conventional instrumentation, can be used to quantitatively study every stage of the perfused heart (especially after perfusion stoppage) continuously, dynamically, and without damage under normal or designed physiological conditions at the molecular level. In this paper, 31 P-NMR was used to study the effects of ischemia and hypoxia on isolated perfused hearts. The results show that complete hypoxia caused more severe functional damage to the myocardial cells than complete ischemia

  5. Effects of Scirpusin B, a polyphenol in passion fruit seeds, on the coronary circulation of the isolated perfused rat heart

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    Yutaka Matsumoto, Nozomi Gotoh, Shoko Sano, Kenkichi Sugiyama, Tatsuhiko Ito, Yohei Abe, Yumi Katano, Akira Ishihata

    2014-07-01

    Full Text Available Objective: Piceatannol, a polyphenol which is contained in passion fruits seed, is a derivative of resveratrol and is known to have antioxidant, anti-inflammatory and vasorelaxing activities. Passion fruits seed also contains a dimer of Piceatannol, Scirpusin B. The aim of this study was to investigate the effect of Scirpusin B on the coronary circulation of the isolated rat heart. Methods: Hearts were isolated from male Fischer 344 rats (5 – 6 months old, and perfused with modified Krebs-Henseleit solution aerated with 95% O2 and 5% CO2 (37 °C at constant pressure (75 cmH2O by Langendorff’s method. Piceatannol or Scirpusin B (10, 30 and 100 μM was injected as a bolus into the aortic cannula and coronary flow (CF was continuously measured by the electromagnetic flow meter. In some experiments, rat hearts were pretreated with L-NAME (an inhibitor of nitric oxide synthase or Diclofenac (an inhibitor of cyclooxygenase to reveal the possible involvement of nitric oxide (NO and vasodilating prostanoids in the effect of Scirpusin B. Results: Scirpusin B increased CF up to 108.2 % of the initial value, while Piceatannol did not increase CF. In addition; Scirpusin B increased CF concentration-dependently. Pretreatment with L-NAME or Diclofenac significantly attenuated the Scirpusin B-induced coronary vasodilatation. Scirpusin B did not change the heart rate either left ventricular pressure. Conclusion: This study shows that Scirpusin B could increase CF via production of NO and vasodilating prostanoids.

  6. Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

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    Haleh Vaez

    2012-08-01

    Full Text Available Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13. The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2% for 15 min and was resumed until the end of 120 min with normal K/H solution. Results: In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (P<0.001, 138±48 (P<0.01, 142±37 (P<0.001 and 157±40 (P<0.01, respectively. Number and duration of VT and time spent in reversible VF were also reduced by honey. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2% markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (P<0.001, respectively. Conclusion: Postischemic administration of natural honey in global ischemia showed protective effects against ischemia/reperfusion (I/R injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects.

  7. Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

    Science.gov (United States)

    Liao, Z; Feng, Z; Long, C

    2014-07-01

    Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

  8. Cardiovascular Activity of Labdane Diterpenes from Andrographis paniculata in Isolated Rat Hearts

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    Khalijah Awang

    2012-01-01

    Full Text Available The dichloromethane (DCM extract of Andrographis paniculata Nees was tested for cardiovascular activity. The extract significantly reduced coronary perfusion pressure by up to 24.5±3.0 mm Hg at a 3 mg dose and also reduced heart rate by up to 49.5±11.4 beats/minute at this dose. Five labdane diterpenes, 14-deoxy-12-hydroxyandrographolide (1, 14-deoxy-11,12-didehydroandrographolide (2, 14-deoxyandrographolide (3, andrographolide (4, and neoandrographolide (5, were isolated from the aerial parts of this medicinal plant. Bioassay-guided studies using animal model showed that compounds, (2 and (3 were responsible for the coronary vasodilatation. This study also showed that andrographolide (4, the major labdane diterpene in this plant, has minimal effects on the heart.

  9. Cardiovascular Activity of Labdane Diterpenes from Andrographis paniculata in Isolated Rat Hearts

    Science.gov (United States)

    Awang, Khalijah; Abdullah, Nor Hayati; Hadi, A. Hamid A.; Su Fong, Yew

    2012-01-01

    The dichloromethane (DCM) extract of Andrographis paniculata Nees was tested for cardiovascular activity. The extract significantly reduced coronary perfusion pressure by up to 24.5 ± 3.0 mm Hg at a 3 mg dose and also reduced heart rate by up to 49.5 ± 11.4 beats/minute at this dose. Five labdane diterpenes, 14-deoxy-12-hydroxyandrographolide (1), 14-deoxy-11,12-didehydroandrographolide (2), 14-deoxyandrographolide (3), andrographolide (4), and neoandrographolide (5), were isolated from the aerial parts of this medicinal plant. Bioassay-guided studies using animal model showed that compounds, (2) and (3) were responsible for the coronary vasodilatation. This study also showed that andrographolide (4), the major labdane diterpene in this plant, has minimal effects on the heart. PMID:22536026

  10. MCT1 and MCT4 Expression During Myocardial Ischemic-Reperfusion Injury in the Isolated Rat Heart

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    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.

  11. Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

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    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.

  12. Extraction of long-chain fatty acids in isolated rat heart during acute low-flow ischemia.

    Science.gov (United States)

    Richter, W S; Fischer, S; Ernst, N; Munz, D L

    2001-07-01

    Although beta-oxidation of fatty acids is suppressed rapidly during ischemia, the behavior of fatty acid extraction at different flow rates is incompletely understood. This study assessed the relationship between flow and extraction of (123)I-iodophenylpentadecanoic acid (IPPA) in the isolated heart model, especially at low flow. Isolated hearts from male Wistar rats (n = 15) were subjected to retrograde perfusion with constant flow (Krebs Henseleit solution containing 10 mmol/L glucose). A latex balloon in the left ventricle allowed isovolumetric contractions and ventricular pressure measurements. The extraction of (123)I-IPPA was assessed with the indicator dilution technique and (99m)Tc-albumin as the intravascular reference. The flow was either increased from the control flow (8 mL/min) until 300% or reduced until 10%. (123)I-IPPA extraction was measured three times before and 10 min after flow alteration. The tracer uptake was estimated from the product of net extraction and flow. The mean (123)I-IPPA extraction at the control flow (third measurement) was 51.6% +/- 2.8%. Between flow rates of approximately 25% and 300%, (123)I-IPPA extraction increased exponentially at decreasing flow rates. At flow rates < or =25% of the control flow, (123)I-IPPA extraction was exponentially higher than predicted. (123)I-IPPA uptake and flow changed largely in parallel. During low flow, the rate-pressure product showed the expected decline (perfusion-contraction matching). The extraction of (123)I-IPPA is preserved and slightly increased (relative to flow) during acute low-flow ischemia.

  13. The cardioprotective and inotropic components of the postconditioning effects of GLP-1 and GLP-1(9-36)a in an isolated rat heart

    DEFF Research Database (Denmark)

    Ossum, Alvilde; van Deurs, Ulla; Engstrøm, Thomas

    2009-01-01

    GLP-1 and its metabolite GLP-1(9-36)a have been shown to exert cardiotropic effects, and were demonstrated to be cardioprotective agents in isolated, postischemic rat or mouse hearts. An agent's total effect on myocardial performance in a postconditioning paradigm is a sum of its myocyte-preservi......GLP-1 and its metabolite GLP-1(9-36)a have been shown to exert cardiotropic effects, and were demonstrated to be cardioprotective agents in isolated, postischemic rat or mouse hearts. An agent's total effect on myocardial performance in a postconditioning paradigm is a sum of its myocyte...... protocol, as exemplified by use of GLP-1 and GLP-1(9-36)a following a global ischemia in isolated rat hearts. Peptides were administered during the first 15min of 120min reperfusion. GLP-1 0.3nM reduced infarct size from 23.2+/-2.4% to 14.1+/-2.3% of area-at-risk (n=15, P=0.0223), an effect abolished......, rather than any true inotropic effect. In contrast, GLP-1(9-36)a did not reduce infarct size significantly, but acted as a strong negative inotrope in postischemic hearts, causing a contractility deficit (LVDP 58.8%, P=0.0004; RPP 58.2%, P=0.0007; dP/dt(max)=58.2%, P=0.0012), quantifiable by an analysis...

  14. Intermittent losartan administration triggers cardiac post-conditioning in isolated rat hearts: role of BK2 receptors.

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    Luca Sgarra

    Full Text Available The angiotensin (Ang and bradykinin (BK tissue-system plays a pivotal role in post-conditioning, but the efficacy of angiotensin type 1 receptor (AT1R blockers (ARBs in post-ischemic strategies is still under investigation. We evaluated functional and morphological outcomes, together with activation of cytosolic RISK pathway kinases, in rat hearts subjected to losartan (LOS or irbesartan (IRB post-ischemic administration.Isolated rat hearts underwent 30 min ischemia and 120 min reperfusion. Post-conditioning was obtained by intermittent (10 s/each or continuous drug infusion during the first 3 min of reperfusion. Left ventricular end-diastolic pressure (LVEDP, left ventricular developed pressure (dLVP, coronary flow (CF, and left ventricular infarct mass (IM were measured together with the activation status of RISK kinases Akt, p42/44 MAPK and GSK3β.When compared to hearts subjected to ischemia/reperfusion (iI/R alone, continuous IRB or LOS administration did not significantly reduce total infarct mass (cIRB or cLOS vs. iI/R, p = 0.2. Similarly, intermittent IRB (iIRB was not able to enhance cardioprotection. Conversely, intermittent LOS administration (iLOS significantly ameliorated cardiac recovery (iLOS vs iI/R, p<0.01. Differences between iLOS and iIRB persisted under continuous blockade of AT2R (iLOS+cPD vs. iIRB+cPD, p<0.05. Interestingly, iLOS cardioprotection was lost when BK2R was simultaneously blocked (iLOS+cHOE vs. iI/R, p = 0.6, whereas concurrent administration of iBK and iIRB replicated iLOS effects (iIRB+iBK vs. iLOS, p = 0.7. At the molecular level, iIRB treatment did not significantly activate RISK kinases, whereas both iLOS and iBK treatments were associated with activation of the Akt/GSK3β branch of the RISK pathways (p<0.05 vs. iI/R, for both.Our results suggest that intermittent losartan is effective in mediating post-conditioning cardioprotection, whereas irbesartan is not. The infarct mass reduction by intermittent

  15. Direct comparison of cardioprotective effects of necroptosis inhibitors against global ischemia-reperfusion in the isolated rat heart

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    Yu. V. Dmitriev

    2017-01-01

    Full Text Available The study was aimed at comparative assessment of cardioprotective properties of various necroptosis inhibitors in the isolated perfused rat heart subjected to global ischemia-reperfusion.Materials and Methods. The study was performed on 38 male Wistar rats weighting 250–300 g. The following necroptosis inhibitors were tested: necrostatin-1 (Nec-1, necrostatin-5 (Nec-5, necrostatin-1s (Nec1s, and necrosulfonamide (NSA. All tested substances were administered intraperitoneally (i.p. 1 hour prior to heart perfusion. Control animals were treated either with the vehicle (dimethyl sulfoxide, DMSO or with 0,9% sodium chloride solution (Controls. The dose of necroptosis inhibitors was calculated on the basis of effective concentration (EC50 data. One hour after i.p. injection, the animals were anesthetized, the hearts were rapidly excised, the aorta was cannulated and retrogradely perfused according to Langendorff. After stabilization, the perfusion was stopped for 35 minutes, which was followed by 2 hours of reperfusion. Prior to stabilization, fluid-filled polyethylene balloon was placed into the left ventricle for left ventricular pressure registration. Coronary flow was measured at baseline and during reperfusion by means of perfusate collection. The volume of necrotic myocardium was expressed as a percentage of triphenyltetrazolium chloride-negative tissue relative to the entire heart volume.Results. The volume of myocardial necrosis and functional heart parameters were not different between Controls and DMSO group. All tested necroptosis inhibitors demonstrated infarct-limiting effect. However, there were no differences between the groups. The volume of necrotic myocardium was (50,5 ± 7,82%, (29,9 ± 3,42%, (27,7 ± 3,42%, (30,6 ± 3,82%, and (34,7 ± 5,82% in DMSO, Nec-1, Nec-5, Nec-1s, and NSA groups, respectively (p < 0,01 vs. DMSO group.Nec-1s and NSA were shown to improve functional recovery of the heart after ischemia. In particular, left

  16. The effect of streptomycin on stretch-induced electrophysiological changes of isolated acute myocardial infarcted hearts in rats.

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    Fu, Lu; Cao, Jun-xian; Xie, Rong-sheng; Li, Jia; Han, Ying; Zhu, Li-qun; Dai, Ying-nan

    2007-08-01

    To explore whether the stretch of ischaemic myocardium could modulate the electrophysiological characteristics, especially repolarization via mechanoelectric feedback (MEF), as well as the effect of streptomycin (SM) on these changes. Methods Thirty-six wistar rats were randomly divided into four groups: control group (n = 9), SM group (n = 9), myocardial infarction (MI) group (n = 9), and MI + SM group (n = 9). After perfused on Langendorff, the isolated hearts were stretched for 5s by a ballon inflation of 0.2mL. After being stretched, the effect of the stretch was observed for 30s, including the 20, 20-70, 70, and 90% monophasic action potential duration (MAPD), i.e. MAPD(20), MAPD(20-70), MAPD(70), and MAPD(90), respectively, premature ventricular beats (PVB), and ventricular tachycardia (VT). Results The stretch caused a decrease in MAPD(20-70) (both P 0.05, except MAPD(20-70) between the control and SM groups, P maintenance of malignant arrhythmias. SM could significantly inhibit the occurrence of arrhythmias, which may correlate with the effect on blocking stretch-activated ion channels.

  17. Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart

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    Tamaki Sato

    2014-01-01

    Full Text Available Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins received 0.5 U/L insulin during the reperfusion period only. The control group (Control was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max was recorded continuously. Measurements of TNF-α and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-α levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-α suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.

  18. Role of glycolysis in maintenance of the action potential duration and contractile activity in isolated perfused rat heart.

    Science.gov (United States)

    Opie, L H; Tuschmidt, R; Bricknell, O; Girardier, L

    1980-01-01

    1. Changing substrates from glucose to pyruvate in paced isolated rat hearts, perfused by the Langendorff technique at 65 cm H2O with a Krebs-Henseleit bicarbonate buffer, produced effects which are opposite to those of ouabain treatment: negative inotropy, decreased work efficiency, hyperpolarization, increased maximum rate of rise and amplitude of the action potential, increased conduction velocity. 2. All the effects resulting from perfusion with pyruvate can be reversed by adding ouabain at a concentration of 100 microM. 3. The correlation between various tissue metabolises and change in contractile force (delta F), rate of tension development [maximum + (dF/dt)] and rate of relaxation [maximum -(dF/dt)] was studied by multiple linear regression. No significant correlation was found with either glycogen content and tissue lactate or with cAMP and cGMP. A weak negative correlation was found with ATP and phosphocreatine. The strongest correlation was found 76 to 807 nM/g in passing from glucose- to pyruvate-containing perfusion solution. 4. In vitro tests performed with a solution containing high energy phosphates and magnesium at concentrations equal to their calculated values in the cytosol (pH 7.0) showed that a significant negative correlation exists between citrate concentration (range: 1 and 1500 M) and free calcium concentration in the micromole range. 5. It is concluded that the effects of pyruvate (non glucose substrate) perfusion could be mediated by a decrease in cytosolic-free calcium resulting from an increase in intracellular citrate. The observation that all these effects can be reversed by ouabain is taken as a circumstantial evidence of a common mechanism.

  19. Influence of β-adrenoceptor stimulation on the metabolism of C 18 unsaturated fatty acids in isolated heart of rat

    International Nuclear Information System (INIS)

    Makdissi, Samar

    1993-02-01

    The influence of stimulating β receptors on the metabolism of 18:1 n-9, 18:2 n-6 and 18:3 n-3 acids in an isolated perfused heart of a rat was studied. Experiments were carried out in two stages. In the first stage, each fatty acid was entered solely in Krebs liquid labelled with C 14 and complexed with albumin. In the second stage, isoproterenol (10 -4 M) was added to the previous mixture in order to stimulate the cardiac β-receptors. It appeared that the heart extracts each of 18:1 and 18:3 in a rate that exceeds the rate of extracting 18:2 and that the oxidation rate of 18:1 was the highest among the three studied acids which were alike in their esterification so they were all entered mainly in the triglycerid group (65-66%) and to less extend in the phospholipids (16-18%). While, the diglycerid and the free fatty acids did only form secondary compounds that would soon convert to the other groups that are more stable the reactions of double bond breakage for the 18:1 acid that converts to triple bond derivatives and 18:3 that converts to tetra, penta and hexa derivatives in the triglycerid were noticed. The 18:3 acid was the least influenced by the stimulation of β. The uptake rate of 18:2 acid was increased slightly while the 18:1 was decreased would indicate a competition between this acid ant the stored one in the cell. Also, the oxidation rate of 18:1 acid as well as the rate of entering it in the triglycerid and the phospholipids increased. In the same way, the oxidation rate of 18:2 acid increased, but its esterification turned in a way that the rate of entering it among the phospholipids increased, while the rate of entering it in the triglycerid decreased. According to what has been mentioned above, it can be said that the 18:1 plays an essential role in the production of direct power besides its role as a component of phospholipids that are deposited in the cellular membranes, while the metabolism of 18:2 acid turns-largely towards the phospholipids

  20. Hydrogen sulfide postconditioning protects isolated rat hearts against ischemia and reperfusion injury mediated by the JAK2/STAT3 survival pathway

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    Heng-Fei Luan

    2012-10-01

    Full Text Available The JAK2/STAT3 signal pathway is an important component of survivor activating factor enhancement (SAFE pathway. The objective of the present study was to determine whether the JAK2/STAT3 signaling pathway participates in hydrogen sulfide (H2S postconditioning, protecting isolated rat hearts from ischemic-reperfusion injury. Male Sprague-Dawley rats (230-270 g were divided into 6 groups (N = 14 per group: time-matched perfusion (Sham group, ischemia/reperfusion (I/R group, NaHS postconditioning group, NaHS with AG-490 group, AG-490 (5 µM group, and dimethyl sulfoxide (DMSO; <0.2% group. Langendorff-perfused rat hearts, with the exception of the Sham group, were subjected to 30 min of ischemia followed by 90 min of reperfusion after 20 min of equilibrium. Heart rate, left ventricular developed pressure (LVDP, left ventricular end-diastolic pressure (LVEDP, and the maximum rate of increase or decrease of left ventricular pressure (± dp/dt max were recorded. Infarct size was determined using triphenyltetrazolium chloride (TTC staining. Myocardial TUNEL staining was used as the in situ cell death detection method and the percentage of TUNEL-positive nuclei to all nuclei counted was used as the apoptotic index. The expression of STAT3, bcl-2 and bax was determined by Western blotting. After reperfusion, compared to the I/R group, H2S significantly improved functional recovery and decreased infarct size (23.3 ± 3.8 vs 41.2 ± 4.7%, P < 0.05 and apoptotic index (22.1 ± 3.6 vs 43.0 ± 4.8%, P < 0.05. However, H2S-mediated protection was abolished by AG-490, the JAK2 inhibitor. In conclusion, H2S postconditioning effectively protects isolated I/R rat hearts via activation of the JAK2/STAT3 signaling pathway.

  1. Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System

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    Kamran Rakhshan

    2015-10-01

    Full Text Available Exposure to stress leads to physiological changes called “stress response” which are the result ofthe changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA and sympatheticnervous system (SNS activity. In the present study, the effects of chronic physical and psychological stressand also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R injuries have beenstudied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 minreperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was donechemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes inheart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP and rate productpressure (RPP in both physical and psychological stress groups decreased significantly compared to those incontrol group (Pgroups. Infarct size significantly increased in both physical and psychological stress groups and control group(Pas compared with stress groups (Ppsychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seemsthat increased sympathetic activity in response to stress is responsible for these adverse effects of stress onischemic/reperfused heart.

  2. Attenuation of ischemia-reperfusion injury by sevoflurane postconditioning involves protein kinase B and glycogen synthase kinase 3 beta activation in isolated rat hearts.

    Science.gov (United States)

    Fang, Neng-Xin; Yao, Yun-Tai; Shi, Chun-Xia; Li, Li-Huan

    2010-12-01

    Volatile anesthetic ischemic postconditioning reduces infarct size following ischemia/reperfusion. Whether phosphorylation of protein kinase B (PKB/Akt) and glycogen synthase kinase 3 beta (GSK3β) is causal for cardioprotection by postconditioning is controversial. We therefore investigated the impact of PKB/Akt and GSK3β in isolated perfused rat hearts subjected to 40 min of ischemia followed by 1 h of reperfusion. 2.0% sevoflurane (1.0 minimum alveolar concentration) was administered at the onset of reperfusion in 15 min as postconditioning. Western blot analysis was used to determine phosphorylation of PKB/Akt and its downstream target GSK3β after 1 h of reperfusion. Mitochondrial and cytosolic content of cytochrome C checked by western blot served as a marker for mitochondrial permeability transition pore opening. Sevoflurane postconditioning significantly improved functional cardiac recovery and decreased infarct size in isolated rat hearts. Compared with unprotected hearts, sevoflurane postconditioning-induced phosphorylation of PKB/Akt and GSK3β were significantly increased. Increase of cytochrome C in mitochondria and decrease of it in cytosol is significant when compared with unprotected ones which have reversal effects on cytochrome C. The current study presents evidence that sevoflurane-induced cardioprotection at the onset of reperfusion are partly through activation of PKB/Akt and GSK3β.

  3. The cardioprotective effect of thymoquinone on ischemia-reperfusion injury in isolated rat heart via regulation of apoptosis and autophagy.

    Science.gov (United States)

    Xiao, Junhui; Ke, Zun-Ping; Shi, Yan; Zeng, Qiutang; Cao, Zhe

    2018-06-22

    Thymoquinone (TQ), as the active constituents of black cumin (Nigella sativa) seed oil, has been reported to have potential protective effects on the cardiovascular system. This study aimed to investigate the effects and the underlying mechanisms of TQ on myocardial ischemia-reperfusion (I/R) injury in Langendorff-perfused rat hearts. Wister rat hearts were subjected to I/R and the experimental group were pretreated with TQ prior to I/R. Hemodynamic parameters, myocardial infarct size, cardiac marker enzymes, superoxide dismutase (SOD), malondialdehyde (MDA) content, and cardiomyocyte apoptosis were assayed. Compared with the untreated group, TQ preconditioning significantly improved cardiac function, reduced infarct size, decreased cardiac lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) levels, suppressed enedoxidative stress, and apoptosis. In addition, TQ treatment promoted autophagy, which was partially reversed by chloroquine (CQ), a kind of autophagy blocker. Our study suggests that TQ can protect heart against I/R injury, which is associated with anti-oxidative and anti-apoptotic effects through activation of autophagy. © 2018 Wiley Periodicals, Inc.

  4. Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

    Science.gov (United States)

    Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

    2017-07-01

    Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

  5. The cardioprotective effect of vanillic acid on hemodynamic parameters, malondialdehyde, and infarct size in ischemia-reperfusion isolated rat heart exposed to PM10

    Directory of Open Access Journals (Sweden)

    Esmat Radmanesh

    2017-07-01

    Full Text Available Objective(s: Particulate matter (PM exposure can promote cardiac ischemia and myocardial damage. The effects of PM10 on hemodynamic parameters, lipid peroxidation, and infarct size induced by ischemia-reperfusion injury and the protective effects of vanillic acid (VA in isolated rat heart were investigated. Materials and Methods: Eighty male Wistar rats (250–300 g were divided into 8 groups (n=10: Control, Sham, VAc, VA, PMa (0.5 mg/kg PM, intratracheal instillation, PMb (2.5 mg/kg PM, intratracheal instillation, PMc (5 mg/kg PM, intratracheal instillation, and PMc + VA (5 mg/kg PM, intratracheal instillation; and 10 mg/kg vanillic acid, gavage for 10 days. PM10 was instilled into the trachea in two stages, within 48 hr. After isolating the hearts and transfer to a Langendorff apparatus, hearts were subjected to 30 min ischemia and 60 min reperfusion. Hemodynamic parameters (±dp/dt, LVSP, LVDP, and RPP, production of lipid peroxidation (MDA, and infarct size were assessed. Results: A significant decrease in ±dp/dt, LVSP, LVDP and RPP occurred in PM groups. A significant increase in MDA and myocardial infarct size occurred in PM groups. A significant increase in LVDP, LVSP, ±dp/dt, RPP and decrease in infarct size, MDA, and myocardial dysfunction was observed in groups that received vanillic acid after ischemia–reperfusion. Conclusion: It was demonstrated that PM10 increases MDA, as well as the percentage of cardiac infarct size, and has negative effects on hemodynamic parameters. This study suggests that vanillic acid may serve as an adjunctive treatment in delaying the progression of ischemic heart disease.

  6. Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

    Directory of Open Access Journals (Sweden)

    H. Rodriguez-Angulo

    2013-01-01

    Full Text Available Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

  7. Hypercholesterolemia downregulates autophagy in the rat heart.

    Science.gov (United States)

    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

  8. Amino acid transamination is crucial for ischaemic cardioprotection in normal and preconditioned isolated rat hearts--focus on L-glutamate

    DEFF Research Database (Denmark)

    Løfgren, Bo; Povlsen, Jonas Agerlund; Rasmussen, Lars Ege

    2010-01-01

    We have found that cardioprotection by l-glutamate mimics protection by classical ischaemic preconditioning (IPC). We investigated whether the effect of IPC involves amino acid transamination and whether IPC modulates myocardial glutamate metabolism. In a glucose-perfused, isolated rat heart model...... subjected to 40 min global no-flow ischaemia and 120 min reperfusion, the effects of IPC (2 cycles of 5 min ischaemia and 5 min reperfusion) and continuous glutamate (20 mm) administration during reperfusion on infarct size and haemodynamic recovery were studied. The effect of inhibiting amino acid...... transamination was evaluated by adding the amino acid transaminase inhibitor amino-oxyacetate (AOA; 0.025 mm) during reperfusion. Changes in coronary effluent, interstitial (microdialysis) and intracellular glutamate ([GLUT](i)) concentrations were measured. Ischaemic preconditioning and postischaemic glutamate...

  9. Inotropic and chronotropic effects of crude extract and its butanol fraction of dry fruit of aegle marmelos linn. in isolated working rat heart

    International Nuclear Information System (INIS)

    Rahman, A.U.

    2016-01-01

    The fruit of Aegle marmelos Linn. is a most edible part of the tree, ripe, unripe and dry fruit is recommended for wide variety of disorders. Lack of pharmacological evaluation limits the use to nutritional value. Dry and ripe fruit of A. marmelos was investigated as crude extract and its butanol fraction in isolated working male Wistar rat heart. Aortic out flow, coronary effluent, cardiac output, dP/dt(max), dP/dt(min), systolic and diastolic pressure, heart rate, and aortic pressure were measured. Preload and after load was kept constant. These parameters are relevant to cardiac physiology and pathological conditions. All the concentrations of crude extract caused concentration-dependent effects. The crude extract decreased coronary effluent at 100.0 and 300.0 mg/mL, increased the dP/dt(max) at 300.0 mg/mL, systolic pressure and aortic pressure were observed maximum at 100.0 mg/mL. Whereas, aortic out flow, dP/dt(min) diastolic pressure and cardiac output and heart rate remained unaffected. The butanol fraction increased the aortic outflow, dP/dt(max), aortic pressure at 10.0 and 30.0 mg/mL maximally. Whereas, dP/dt(min), diastolic pressure and cardiac output remained unaffected. Coronary effluent at 1.0, 10.0, and 30.0 mg/mL and heart rate at 10.0 and 30.0 mg/mL were decreased maximally. It seems that the bioactive compound got concentrated in butanol fraction according to polarity of the solvent. The crude extract and butanol fraction were found to be positive inotropic whereas, butanol fraction showed negative chronotropic effect as well. (author)

  10. Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

    Science.gov (United States)

    Delgado, Nathalie T. B.; Rouver, Wender do N.; Freitas-Lima, Leandro C.; de Paula, Tiago D.-C.; Duarte, Andressa; Silva, Josiane F.; Lemos, Virgínia S.; Santos, Alexandre M. C.; Mauad, Helder; Santos, Roger L.; Moysés, Margareth R.

    2017-01-01

    Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser1177, p-eNOS Thr495, total eNOS, p-AKT Ser473, total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser1177), total eNOS, p-AKT (Ser473) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr495) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment

  11. Effects of Gallic Acid and Cyclosporine A on Antioxidant Capacity and Cardiac Markers of Rat Isolated Heart After Ischemia/Reperfusion

    Science.gov (United States)

    Badavi, Mohammad; Sadeghi, Najmeh; Dianat, Mahin; Samarbafzadeh, Alireza

    2014-01-01

    Background: Myocardial infarction is one of the important causes of death during old ages. Gallic acid as an antioxidant or cyclosporine A (CsA) as inhibitor of mitochondrial permeability transition pore (mPTP) alone could prevent these complications to some extent, but their combination effect has not been investigated. Objectives: The aim of this study was to determine the combined effect of gallic acid and CsA on antioxidant capacity of isolated heart tissues during ischemia reperfusion. Materials and Methods: Eighty male Wistar rats were randomly assigned to different groups: sham, control (Ca, received saline, 1 mL/kg); 3 groups were pretreated with gallic acid (G1a: 7.5, G2a: 15, G3a: 30 mg/kg) for 10 days, and the other 3 groups were pretreated with gallic acid and received CsA (0.2 µM) for 10 minutes before induction of ischemia and during the first 10 minutes of reperfusion (G1b, G2b and G3b) and the last group received CsA alone (Cb). After 10 days of pretreatment, the heart was isolated and transferred to the Langendorff apparatus and exposed to 30 minutes ischemia followed by 60 minutes of reperfusion. After that cardiac markers and antioxidant enzymes were assessed in cardiac tissues. Results: Lactate dehydrogenase (LDH), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activity increased and malondialdehyde (MDA) decreased in animals pretreated with gallic acid significantly. However, pretreatment with gallic acid followed by CsA during reperfusion improved the antioxidant capacity and cardiac marker enzymes and restored the lipid peroxidation more effective than gallic acid or CsA alone. Nevertheless, CsA did not change the cardiac marker enzymes significantly. Conclusions: Gallic acid and CsA combination improved antioxidant capacity and cell membrane integrity more than each one alone. Therefore, it can be a therapeutic approach to reduce the I/R injury. PMID:25068044

  12. Characterizing potential heart agents with an isolated perfused heart system

    International Nuclear Information System (INIS)

    Pendleton, D.B.; Sands, H.; Gallagher, B.M.; Camin, L.L.

    1984-01-01

    The authors have used an isolated perfused heart system for characterizing potential myocardial perfusion radiopharamaceuticals. Rabbit or guinea pig (GP) hearts are removed and perfused through the aorta with a blood-free buffer. Heart rate and ventricular pressure are monitored as indices of viability. Tc-99m-MAA is 96-100% retained in these hearts, and Tc-99m human serum albumin shows less than 5% extraction. Tl-201 is 30-40% extracted. It is known that in-vivo, Tc-99m(dmpe)/sub 2/Cl/sub 2//sup +/ is taken up by rabbit heart but not by GP or human heart. Analogous results are obtained with the isolated perfused heart model, where the complex is extracted well by the isolated rabbit heart (24%) but not by the GP heart (<5%). Values are unchanged if human, rabbit or GP blood is mixed and co-injected with the complex. Tc-99m)dmpe)/sub 3//sup +/ is also taken up by rabbit but not by GP hearts in-vivo. However, isolated perfused hearts of both species extract this complex well (45-52%). Heart uptake is diminished to <7% if the complex is pre-equilibrated with human blood. GP blood produces a moderate inhibition (in GP hearts only) and rabbit blood has no effect. This suggests that a human or GP blood factor may have a significant effect on heart uptake of this complex. Tc-99m(CN-t-butyl)/sub 6//sup +/ is taken up well by both rabbit and GP hearts in-vivo, and is extracted 100% by both isolated perfused hearts. Heart retention remains high (73-75%) in the presence of human blood

  13. Deficiency of sex hormones does not affect 17-ß-estradiol-induced coronary vasodilation in the isolated rat heart.

    Science.gov (United States)

    Santos, R L; Lima, J T; Rouver, W N; Moysés, M R

    2016-01-01

    The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9-12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.

  14. [Effects of synthetic antioxidant ionol on bioelectric activity of cardiomyocytes and arrhythmia in global ischemia and reperfusion of the isolated rat heart].

    Science.gov (United States)

    Belkina, L M; Vovk, V I; Meerson, F Z

    1992-04-01

    Isolated rat hearts were subjected to global ischemia (15 min) and reperfusion (20 min). Transmembrane potentials were recorded on the epicardial surface and contractile force was measured. Ischemia reduced the resting potential, the action potential (AP) amplitude and the AP duration (APD) in control animals. Pretreatment with synthetic antioxidant ionol (BHT, 50 mg/kg, per os) didn't influence the time course of changes in the resting potential and AP amplitude during ischemia, but significantly increased APD. In the pretreated group, 5 min after the aorta clamping, the APD at 50% and 90% levels of repolarization was 36% (p less than 0.05) and 13% (p less than 0.1) higher in comparison to the preischemic level and 10 min after clamping by 27% (p less than 0.1) and 29% (p less than 0.05), respectively. By the end of ischemia in the pretreated group, APD re-decreased almost to basal level, but in control group, it remained decreased. During reperfusion BHT improved the recovery of bioelectrical activity and the contractile function. The BHT 10-fold reduced the malignant arrhythmias duration and 2.5-fold the incidence of ventricular tachycardia and fibrillation during reperfusion. These results indicate that the induced by BHT increase in APD can contribute to the mechanism of BHT antiarrhythmic action.

  15. Mechanisms for altered carnitine content in hypertrophied rat hearts

    International Nuclear Information System (INIS)

    Reibel, D.K.; O'Rourke, B.; Foster, K.A.

    1987-01-01

    Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-[ 14 C]carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by ∼20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels

  16. Altered carnitine transport in pressure-overload hypertrophied rat hearts

    International Nuclear Information System (INIS)

    O'Rourke, B.; Foster, K.; Reibel, D.K.

    1986-01-01

    The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L- 14 C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 μM carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 μM carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart

  17. The efficiency coefficient of the rat heart and muscular system after physical training and hypokinesia

    Science.gov (United States)

    Alyukhin, Y. S.; Davydov, A. F.

    1982-01-01

    The efficiency of an isolated heart did not change after prolonged physical training of rats for an extreme load. The increase in oxygen consumption by the entire organism in 'uphill' running as compared to the resting level in the trained rats was 14% lower than in the control animals. Prolonged hypokinesia of the rats did not elicit a change in the efficiency of the isolated heart.

  18. Radiation-induced damage of the Wistar Rat heart

    International Nuclear Information System (INIS)

    Cilliers, G.D.; Lochner, A.

    1993-01-01

    A time sequence study was performed on Wistar rats to investigate the early effects of radiation on the mechanical function and energy metabolism of the heart. Two series of rats were exposed to 20 Gy electron irradiation to a field including the heart and approximately a third of the lungs. The hearts were excised at varying time intervals (8-180 days) post irradiation. In one series of hearts the mechanical function was measured using the isolated perfused working rat heart model. At the end of the perfusion the hearts were freeze-clamped for analysis of the high energy phosphate contents (ATP, ADP, AMP and creatine phosphate). In the second series, mitochondria were isolated and the oxidative phosphorylation function measured polarographically (substrate: glutamate). Maximal depression of mechanical function was observed at 60 days post irradiation. Thereafter the work performance of these hearts improved significantly, almost reaching control levels after 180 days. The mitochondrial oxidative phosphorylation function (as measured on the total mitochondrial population) was significantly depressed 30-120 days post irradiation. As in the case of the mechanical changes, the depression was transient and after 180 days post irradiation, values similar to those of controls were obtained. Myocardial high energy phosphates remained unaltered throughout the experiment. (author)

  19. Isolation of rat adrenocortical mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Solinas, Paola [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Fujioka, Hisashi [Electron Microscopy Facility, Department of Pharmacology, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Tandler, Bernard [Department of Biological Sciences, School of Dental Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Hoppel, Charles L., E-mail: charles.hoppel@case.edu [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  20. Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart

    International Nuclear Information System (INIS)

    DeGrado, T.R.; Ng, C.K.; Raffel, D.M.; Holden, J.E.

    1988-01-01

    Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two 125 I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examined by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue: Albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled (catabolite(s)) and were therefore more sensitive to the oxidation rate of long chain fatty acids. (orig.)

  1. Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    DeGrado, T.R.; Ng, C.K.; Raffel, D.M.; Holden, J.E.

    1988-12-01

    Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two /sup 125/I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examined by pretreatment of animals with 2(5(4-chlorophenyl)pentyl)oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue: Albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled (catabolite(s)) and were therefore more sensitive to the oxidation rate of long chain fatty acids.

  2. Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart.

    Science.gov (United States)

    DeGrado, T R; Holden, J E; Ng, C K; Raffel, D M; Gatley, S J

    1988-01-01

    Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two 125I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue:albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.

  3. Isolating Lysosomes from Rat Liver.

    Science.gov (United States)

    Pryor, Paul R

    2016-04-01

    This protocol describes the generation of a fraction enriched in lysosomes from rat liver. The lysosomes are rapidly isolated using density-gradient centrifugation with gradient media that retain the osmolarity of the lysosomes such that they are functional and can be used in in vitro assays. © 2016 Cold Spring Harbor Laboratory Press.

  4. Total excitation of the isolated human heart

    NARCIS (Netherlands)

    Durrer, D.; Dam, R.Th. van; Freud, G.E.; Janse, M.J.; Meijler, F.L.; Arzbaecher, R.C.

    To obtain information conceming the time course and instantaneous distribution of the excitatory process of the normal human healt, studies were made on isolated human hearts from seven individuals who died from various cerebral conditions, but who had no history of cardiac disease. Measurements

  5. Phosphorus nuclear magnetic resonance studies of the energetic state and of the intracellular pH of the isolated rat heart in the course of ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, A [Grenoble-1 Univ., 38 (France); Martin, J; de Leiris, J [CEA Centre d' Etudes Nucleaires de Grenoble, 38 (France). Lab. de Chimie Organique Physique

    1981-01-01

    Continuous measurements of high energy phosphate compounds and intracellular pH in perfused, beating rat hearts, were performed by /sup 31/P nuclear magnetic resonance (NMR). Hearts were placed in a 15 mm NMR tube and perfused at 28/sup 0/C by conventional methods with a phosphate-free solution. Phosphorus NMR spectra were recorded at 101,3 MHz in a Brucker WP 250 spectrometer. Global mild ischemia was achieved by reducing the coronary flow to 1/10 of its initial value. Changes in creatine phosphate (CP) and inorganic phosphate (Pi) levels and intracellular pH (pHi) were monitored in the course of a 50 min ischemia and during the post-ischemic phase. When the breakdown of CP was less than 30%, the decrease in pHi was about 0.1 to 0.2 pH unit; for a greater CP decrease, the fall in pHi was about 1 pH unit.

  6. Identification, purification, and localization of tissue kallikrein in rat heart.

    OpenAIRE

    Xiong, W; Chen, L M; Woodley-Miller, C; Simson, J A; Chao, J

    1990-01-01

    A tissue kallikrein has been isolated from rat heart extracts by DEAE-Sepharose and aprotinin-affinity column chromatography. The purified cardiac enzyme has both N-tosyl-L-arginine methyl ester esterolytic and kinin-releasing activities, and displays parallelism with standard curves in a kallikrein radioimmunoassay, indicating it to have immunological identity with tissue kallikrein. The enzyme is inhibited by aprotinin, antipain, leupeptin and by high concentrations of soybean trypsin inhib...

  7. Effects of thyroid state on respiration of perfused rat and guinea pig hearts

    International Nuclear Information System (INIS)

    Read, L.C.; Wallace, P.G.; Berry, M.N.

    1987-01-01

    The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. Hypothyroidism was caused by injecting animals with Na 131 I. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses

  8. Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, C. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Institute of Neuroscience, Soochow University, Suzhou (China); Hu, S.M. [Institute of Neuroscience, Soochow University, Suzhou (China); Xie, H.; Qiao, S.G. [Department of Anesthesiology and Critical Care, The Second Affiliate Hospital, Soochow University, Suzhou (China); Liu, H. [Department of Anesthesiology and Pain Medicine, University of California Davis Health System, Davis, CA (United States); Liu, C.F. [Institute of Neuroscience, Soochow University, Suzhou (China)

    2015-03-27

    This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoK{sub ATP}) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoK{sub ATP} channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoK{sub ATP} channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

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

    Directory of Open Access Journals (Sweden)

    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

  10. Cerveau isolé and pretrigeminal rats.

    Science.gov (United States)

    Zernicki, B; Gandolfo, G; Glin, L; Gottesmann, C

    1984-01-01

    Cortical and hippocampal EEG activity was analysed in 14 cerveau isole and 8 pretrigerninal rats. In the acute stage, waking EEG patterns were absent in the cerveau isole, whereas sleep EEG patterns were absent in the pretrigeminal preparations. However, already on the second day the EEG waking-sleep cycle recovered in the majority of rats. Paradoxically, stimuli directed to the caudal part of preparations evoked stronger cortical and hippocampal EEG arousal than olfactory and visual stimuli. The behavior of the caudal part was observed in 25 preparations. Although in abortive form, the rats did show some locomotor and grooming behavior, and could be fed orally. The peripheral events of paradoxical sleep appeared only on the fourth or fifth day of survival of the cerveau isole rats. It is concluded that the activity of the isolated cerebrum of the rat is similar to that of cat preparations, but that functions of the caudal neuraxis are superior in rats.

  11. Control of ribosome formation in rat heart

    International Nuclear Information System (INIS)

    Russo, L.A.

    1987-01-01

    Diabetes of 9 days duration produced a 17% diminution in the rate of total protein synthesis in rat hearts perfused as Langendorff preparations supplied with glucose, plasma levels of amino acids, and 400 μU/ml insulin. This reduction was attributable to a decrease in efficiency of protein synthesis and total RNA content. Total messenger RNA content decreased in diabetic hearts in proportion to the reduction in total RNA. Diabetes also resulted in diminished ribosome content as reflected by the induction in total RNA. Ribosome production was investigated by monitoring incorporation of [ 3 H]phenylalanine into the proteins of cytoplasmic ribosomes. Rates of ribosome formation in diabetic hearts were as fast as control rates in the presence of insulin, and were faster than control rates in the absence of the hormone. These results indicated that ribosome content fell in diabetic hearts despite unchanged or faster rates of ribosome formation

  12. Reirradiation tolerance of the rat heart

    International Nuclear Information System (INIS)

    Wondergem, Jan; Ravels, Frank J.M. van; Reijnart, Ivonne W.C.; Strootman, Erwin G.

    1996-01-01

    Purpose: To investigate the influence of reirradiation on the tolerance of the heart after a previous irradiation treatment. Methods and Materials: Female Wistar rats were locally irradiated to the thorax. Development of cardiac function loss was studied with the ex vivo working rat heart preparation. To compare the retreatment experiments, initial, and reirradiation doses were expressed as the percentage of the extrapolated tolerance dose (ETD). Results: Local heart irradiation with a single dose led to a dose-dependent and progressive decrease in cardiac function. The progressive nature of irradiation-induced heart disease is shown to affect the outcome of the retreatment, depending on both the time interval between subsequent doses and the size of the initial dose. The present data demonstrate that hearts are capable of repairing a large part of the initial dose of 10 Gy within the first 24 h. However, once biological damage as a result of the first treatment is fixed, the heart does not show any long-term recovery. At intervals up to 6 months between an initial treatment with 10 Gy and subsequent reirradiation, the reirradiation tolerance dose slightly decreased from 74% of the ETD ref (at 24-h interval) to 68% of the ETD ref (at 6-month interval). Between 6 and 9 months, reirradiation tolerance dose dropped more even to 43% of the ETD ref . Treatment of the heart with an initial dose of 17.5 Gy, instead of 10 Gy, 6 months prior to reirradiation, also led to a further decrease of the reirradiation tolerance dose ( ref ). Conclusions: The outcome of the present study shows a decreased tolerance of the heart to reirradiation at long time intervals (interval > 6 months). This has clinical implications for the estimation of reirradiation tolerance in patients whose mediastinum has to be reirradiated a long time after a first irradiation course

  13. Zero Flow Global Ischemia-Induced Injuries in Rat Heart Are Attenuated by Natural Honey

    OpenAIRE

    Najafi, Moslem; Zahednezhad, Fahimeh; Samadzadeh, Mehrban; Vaez, Haleh

    2012-01-01

    Purpose: In the present study, effects of preischemic administration of natural honey on cardiac arrhythmias and myocardial infarction size during zero flow global ischemia were investigated in isolated rat heart. Methods: The isolated hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion then perfused by a modified drug free Krebs-Henseleit solution throughout the experiment (control) or the solution containing 0.25, 0.5, 1 and 2% of natural honey...

  14. Efeitos da N-acetilcisteína no precondicionamento isquêmico: estudo em corações isolados de ratos Effects of n-acetylcysteine on ischemic preconditioning: study in isolated rat hearts

    Directory of Open Access Journals (Sweden)

    Denoel Marcelino de Oliveira

    2009-03-01

    Full Text Available OBJETIVO: Avaliar se a N-Acetilcisteína (NAC altera o Precondicionamento Isquêmico (PC em corações isolados de ratos usando apenas um ciclo de PC. MÉTODOS: Freqüência Cardíaca (FC, Fluxo Coronariano (FLC e Contratilidade Miocárdica (dP/dt foram registradas em 30 corações de ratos Wistar. Após anestesia, os corações foram perfundidos em sistema de Langendorff com solução de Krebs-Hensleit (K-H, equilibrada (95% de O2 e 5% de CO2. GI: Controle (n=6; GII: 20 min. isquemia (n=6; GIII: PC (n=6; GIV 50 µg/ml/min NAC antes do PC (n =6; GV: 100 µg/ml/min NAC antes do PC (n=6. Todos os parâmetros foram mensurados após 15 minutos de estabilização (T0 e T3, T5, T10, T15, T20, T25 e T30 minutos de reperfusão. Significância estatística foi considerada quando P0,05. dP/dt foi maior no GV comparado com GIV, mas com diferença estatisticamente significativa somente em T30. CONCLUSÃO: Os corações precondicionados tiveram melhor dP/dt, sendo alteradas pelo uso de NAC no GIV e não alteradas no GV.OBJECTIVE: The aim of this study is to assess if N-Acetylcysteine (NAC changes the Ischemic Preconditioning (IP in isolated rat hearts using only one cycle of IP. METHODS: Heart Rate (HR, Coronary Flow (CF and Myocardial Contractility (dP/dt were registered in 30 Wistar rat's hearts. After anesthesia the hearts were removed and perfused with Krebes-Hensleit equilibrated solution with 95% of O2 and 5% of CO2 according Langendorff's method. GI: Control (n=6; GII: 20 min. ischemia (n=6; GIII: IP (n=6; GIV 50 µg/ml/min NAC before IP (n =6; GV: 100 µg/ ml/min NAC before IP (n=6. Parameters were measured after 15 min. of stabilization (T 0 and T3, T5, T10, T15, T20, T25 and T30 min. after reperfusion. Statistical significance was considered when P0.05. dP/dt was higher in GV than GIV but with statistically significant difference only at T30. CONCLUSION: dP/dt was better in preconditioned hearts and was changed if using NAC in GIV. The use of NAC

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

    International Nuclear Information System (INIS)

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-01

    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

  16. The Effects of Cisplatin and Its PT(II Analogue on Oxidative Stress of Isolated Rat Heart/ Efekti Cisplatine I PT(II Analoga Cisplatine Na Oksidacioni Stres Izolovanog Srca Pacova

    Directory of Open Access Journals (Sweden)

    Stojic Isidora

    2016-03-01

    Full Text Available To date, numerous platinum (II complexes have been successfully used in the treatment of different types of cancer. Therapeutic platinum complexes are different in terms of their structure, chemical reactivity, solubility, pharmacokinetics and toxicity. The aim of our research was the evaluation of cardiotoxicity of dichloro-(ethylendiamine platinum (II in a model of isolated rat heart using the Langedorff technique. Oxidative stress was assessed by determination of superoxide anion radical, hydrogen peroxide, Thiobarbituric Acid Reactive Substances and nitric oxide levels from coronary venous effluent. All reagents were perfused at increasing concentrations from 10-8 to 10-4 M for 30 minutes. In this paper, we report that substances administered at higher doses did not induce dose-dependent effects on oxidative stress markers. The results of this research may be of great interest for future studies in this area. There are many novel platinum compounds that had previously demonstrated antitumour activity, and these types of experiments in our study can assist in the examination of their cardiotoxicity. These results could be helpful for understanding dose-dependent side effects of existing and novel platinum compounds

  17. 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.

  18. Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β

    Science.gov (United States)

    Zhou, Mingjie; Ren, Huanhuan; Wang, Wenjuan; Zheng, Qiusheng; Wang, Dong

    2015-01-01

    Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats. Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dt max) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β (GSK-3β), phospho-GSK-3β (P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis. Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and ±dp/dt max, as well as increased the levels of SOD and P-GSK-3β and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α. Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3β activity in rats with I/R. PMID:26265983

  19. Isolated heart models: cardiovascular system studies and technological advances.

    Science.gov (United States)

    Olejnickova, Veronika; Novakova, Marie; Provaznik, Ivo

    2015-07-01

    Isolated heart model is a relevant tool for cardiovascular system studies. It represents a highly reproducible model for studying broad spectrum of biochemical, physiological, morphological, and pharmaceutical parameters, including analysis of intrinsic heart mechanics, metabolism, and coronary vascular response. Results obtained in this model are under no influence of other organ systems, plasma concentration of hormones or ions and influence of autonomic nervous system. The review describes various isolated heart models, the modes of heart perfusion, and advantages and limitations of various experimental setups. It reports the improvements of perfusion setup according to Langendorff introduced by the authors.

  20. Hyperoxic preconditioning fails to confer additional protection against ischemia-reperfusion injury in acute diabetic rat heart.

    Science.gov (United States)

    Pourkhalili, Khalil; Hajizadeh, Sohrab; Akbari, Zahra; Dehaj, Mansour Esmaili; Akbarzadeh, Samad; Alizadeh, Alimohammad

    2012-01-01

    Experimental studies show that detrimental effects of ischemia-reperfusion (I/R) injury can be attenuated by hyperoxic preconditioning in normal hearts, however, there are few studies about hyperoxia effects in diseased myocardium. The present study was designed to assess the cardioprotective effects of hyperoxia pretreatment (≥ 95 % O2) in acute diabetic rat hearts. Normal and one week acute diabetic rats were either exposed to 60 (H60) and 180 (H180) min of hyperoxia or exposed to normal atmospheric air (21 % O2). Then hearts were isolated immediately and subjected to 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size, cardiomyocyte apoptosis, enzymes release and ischemia induced arrhythmias were determined. Heart of diabetic control rats had less infarct size and decreased LDH and CK-MB release compared to normal hearts. 60 and 180 min of hyperoxia reduced myocardial infarct size and enzymes release in normal hearts. 180 min of hyperoxia also decreased cardiomyocytes apoptosis in normal state. On the other hand, protective values of hyperoxia were not significantly different in diabetic hearts. Moreover, hyperoxia reduced severity of ventricular arrhythmias in normal rat hearts whereas; it did not confer any additional antiarrhythmic protection in diabetic hearts. These findings suggest that diabetic hearts are less susceptible to ischemia-induced arrhythmias and infarction. Hyperoxia greatly protects rat hearts against I/R injury in normal hearts, however, it could not provide added cardioprotective effects in acute phase of diabetes.

  1. Isomyosin expression patterns during rat heart morphogenesis: an immunohistochemical study

    NARCIS (Netherlands)

    de Groot, I. J.; Lamers, W. H.; Moorman, A. F.

    1989-01-01

    An immunohistochemical study of cardiac alpha and beta myosin heavy chain (MHC) expression during rat heart morphogenesis was performed. In tubular hearts (embryonic days, ED10-11) coexpression of both cardiac alpha and beta MHC was found throughout the heart, except for the left free wall of the

  2. Hyperthyroidism results in increased glycolytic capacity in the rat heart. A 31P-NMR study.

    Science.gov (United States)

    Seymour, A M; Eldar, H; Radda, G K

    1990-11-12

    We have investigated the metabolic adaptations that occur in the thyroxine-treated rat heart. Rats were made hyperthyroid by daily intra-peritoneal injections of thyroxine (35 micrograms/100 g body weight) over seven days. 31P-NMR investigations of isolated glucose-perfused isometric hearts showed that thyroxine treatment caused an increase in Pi (from 4.9 mumols.(g dry wt.)-1 in control hearts to 11.7 mumols.(g dry wt.)-1 in hyperthyroid hearts), a decrease in phosphocreatine (from 36.5 mumols.(g dry wt.)-1 to 21.8 mumols.(g dry wt.)-1) with no change in ATP or ADP concentrations under the same conditions of cardiac work. The unidirectional exchange flux Pi----ATP was measured by saturation transfer NMR in hyperthyroid rat hearts. This exchange (which has been shown to contain a significant glycolytic component) increased by 2.2-fold in thyroxine-treated hearts in comparison to control hearts (to 3.6 mumols.(g dry wt.)-1.s-1, from 1.6 mumols.(g dry wt.)-1.s-1). In parallel experiments, NMR analysis of extracts from hyperthyroid rat hearts showed significantly elevated levels of glucose 6-phosphate, and fructose 6-phosphate. Measurements of enzyme activities isolated from hyperthyroid and control tissue showed a 40% increase in phosphofructokinase activity. These data together with the increased concentration of Pi show that both glycolytic and glycogenolytic fluxes are increased in the hyperthyroid rat heart. This metabolic adaptation may be necessary to cope with the increased number and activity of Na+/K(+)-ATPase pumps that occur in response to thyroxine treatment.

  3. 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

  4. Metabolic fate of rat heart endothelial lipoprotein lipase

    International Nuclear Information System (INIS)

    Chajek-Shaul, T.; Bengtsson-Olivecrona, G.; Peterson, J.; Olivecrona, T.

    1988-01-01

    When isolated rat hearts were perfused with medium containing 125I-labeled bovine lipoprotein lipase (LPL), they bound both lipase activity and radioactivity. More than 80% of the bound lipase could be rapidly released by heparin. Low concentrations of bovine LPL displaced 50-60% of the endogeneous, endothelial-bound LPL. Higher concentrations caused additional binding. Both binding and exchange were rapid processes. The hearts continuously released endogenous LPL into the medium. An antiserum that inhibited bovine but not rat LPL was used to differentiate endogeneous and exogeneous LPL activity. When the pool of endothelial LPL was labeled with bovine 125I-labeled LPL and then chased with unlabeled bovine LPL, approximately 50% of the labeled lipase was rapidly displaced. During chase perfusion with medium only, catalytically active bovine LPL appeared in the perfusate. The rate of release was similar to that observed for endogeneous LPL activity and amounted to 10-13% of the heparin-releasable fraction in the first 5 min of perfusion. There was little or no degradation of bovine 125I-labeled LPL to fragments or acid-soluble products. These results indicate that endothelial LPL is accessible for exchange with exogeneous LPL and that detachment rather than degradation may be the pathway for catabolism of endothelial LPL

  5. Using a Phototransduction System to Monitor the Isolated Frog Heart

    Science.gov (United States)

    Stephens, Philip J.

    2015-01-01

    A simple and inexpensive method of monitoring the movement of an isolated frog heart provides comparable results to those obtained with a force transducer. A commercially available photoresistor is integrated into a Wheatstone bridge circuit, and the output signal is interfaced directly with a recording device. An excised, beating frog heart is…

  6. DNA isolation from rat tail or ear

    NARCIS (Netherlands)

    Cuppen, E.

    2010-01-01

    This protocol describes a rapid procedure for isolating DNA from rat tail or ear punches. The simplest version of the protocol can be scaled for use in 96-well (deep-well) plates. The quality of the DNA is sufficient for any polymerase chain reaction (PCR)-based genotyping approach.

  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...

  8. Contractility of isolated hearts from myxedematous rats

    NARCIS (Netherlands)

    Meijler, F.L.

    1963-01-01

    HYPOTHYROIDISM is often complicated by coronary sclerosis and cardiac failure. It is generally believed that the coronary sclerosis is mainly caused by the disturbed lipoid metabolism. The cardiac failure, however, is less well understood. Our findings demonstrate that current concepts about

  9. Heart dysfunction and fibrosis in rat treated with myocardial ...

    African Journals Online (AJOL)

    Because cardiovascular disease remains a serious problem in modern human society, the aim of this study was to establish the rat model animal and to compare the heart dysfunction and fibrosis with SD and LE rats when treated with myocardial ischemia and reperfusion operation. A 20-minute thoracotomy was performed ...

  10. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

    Directory of Open Access Journals (Sweden)

    Boyd R Rorabaugh

    Full Text Available We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury.Adult male and female rats received daily injections of methamphetamine (5 mg/kg or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining.Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine.Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  11. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    Science.gov (United States)

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  12. Fatty acid utilization in pressure-overload hypertrophied rat hearts

    International Nuclear Information System (INIS)

    Reibel, D.K.; O'Rourke, B.

    1986-01-01

    The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H 2 O left atrial filling pressure with a ventricular afterload of 80 cm of H 2 O with buffer containing 1.2 mM 14 C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. 14 CO 2 production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by 14 CO 2 production during this time was 0.728 +/- 0.06 μmoles/min/g dry in control hearts and 0.710 +/- 0.02 μmoles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O 2 consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 μmoles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine

  13. Perceived Social Isolation and Outcomes in Patients With Heart Failure.

    Science.gov (United States)

    Manemann, Sheila M; Chamberlain, Alanna M; Roger, Véronique L; Griffin, Joan M; Boyd, Cynthia M; Cudjoe, Thomas K M; Jensen, Daniel; Weston, Susan A; Fabbri, Matteo; Jiang, Ruoxiang; Finney Rutten, Lila J

    2018-05-23

    Perceived social isolation has been shown to have a negative impact on health outcomes, particularly among older adults. However, these relationships have not been fully examined among patients with heart failure. Residents from 11 southeast Minnesota counties with a first-ever International Classification of Diseases, Ninth Revision ( ICD-9 ) code 428 for heart failure between January 1, 2013, and March 31, 2015 (N=3867), were prospectively surveyed to measure perceived social isolation. A total of 2003 patients returned the survey (response rate, 52%); 1681 patients completed all questions and were retained for analysis. Among these patients (53% men; mean age, 73 years), ≈19% (n=312) had moderate perceived social isolation and 6% (n=108) had high perceived social isolation. After adjustment, patients reporting moderate perceived social isolation did not have an increased risk of death, hospitalizations, or emergency department visits compared with patients reporting low perceived social isolation; however, patients reporting high perceived social isolation had >3.5 times increased risk of death (hazard ratio, 3.74; 95% confidence interval [CI], 1.82-7.70), 68% increased risk of hospitalization (hazard ratio, 1.68; 95% CI, 1.18-2.39), and 57% increased risk of emergency department visits (hazard ratio, 1.57; 95% CI, 1.09-2.27). Compared with patients who self-reported low perceived social isolation, patients reporting moderate perceived social isolation had a 16% increased risk of outpatient visits (rate ratio, 1.16; 95% CI, 1.03-1.31), whereas those reporting high perceived social isolation had a 26% increased risk (rate ratio, 1.26; 95% CI, 1.04-1.53). In patients with heart failure, greater perceived social isolation is associated with an increased risk of death and healthcare use. Assessing perceived social isolation during the clinical encounter with a brief screening tool may help identify patients with heart failure at greater risk of poor outcomes.

  14. Polarographic measurement of ascorbate washout in isolated perfused rabbit hearts

    International Nuclear Information System (INIS)

    Arts, T.; Kuikka, J.T.; Reneman, R.S.; Bassingthwaighte, J.B.

    1985-01-01

    To study the myocardial washout of ascorbate, the applicability of polarographic detection of ascorbate ions by a platinum electrode (sensitive area 0.03 mm2) was investigated, in both a calibration setup (sampling flow along the electrode: 100 microliter X s-1) and isolated, retrogradely perfused rabbit hearts. In the calibration setup at pH 7.4, the sensitivity of the electrode was 70 microA/mol. This sensitivity increased moderately with increasing pH (13%/unit pH) and increasing sampling flow rate (14% at an increase from 100 to 150 microliter X s-1). In the isolated hearts, ascorbate infused into the aorta was detected in a right ventricular drain by the electrode as well as by the use of 14 C-labeled ascorbate. Both recorded time courses were similar except for a scaling factor dependent on flow velocity. During continuous infusion the arteriovenous difference of ascorbate was 2 +/- 2% (SD), indicating a relatively low consumption of ascorbate by the isolated heart. The authors conclude that polarographic measurement of ascorbate in the coronary effluent of an isolated rabbit heart can be performed on-line and relatively easily

  15. EFFECT OF ETHANOL ON HEPATOBILIARY TRANSPORT OF CATIONIC DRUGS - A STUDY IN THE ISOLATED-PERFUSED RAT-LIVER, RAT HEPATOCYTES AND RAT MITOCHONDRIA

    NARCIS (Netherlands)

    STEEN, H; MEIJER, DKF; Merema, M.T.

    The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation

  16. Physiologic consequences of local heart irradiation in rats

    International Nuclear Information System (INIS)

    Geist, B.J.; Lauk, S.; Bornhausen, M.; Trott, K.R.

    1990-01-01

    Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions

  17. 1H nuclear magnetic resonance studies of sarcoplasmic oxygenation in the red cell-perfused rat heart

    OpenAIRE

    Jelicks, L.A.; Wittenberg, B.A.

    1995-01-01

    The proximal histidine N delta H proton of deoxymyoglobin experiences a large hyperfine shift resulting in its 1H nuclear magnetic resonance (NMR) signal appearing at approximately 76 ppm (at 35 degrees C), downfield of the diamagnetic spectral region. 1H NMR of this proton is used to monitor sarcoplasmic oxygen pressure in isolated perfused rat heart. This method monitors intracellular oxygenation in the whole heart and does not reflect oxygenation in a limited region. The deoxymyoglobin res...

  18. 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.

  19. Protection of Ischemic and Reperfused Rat Heart by Aqueous Extract of Urtica Dioica

    Directory of Open Access Journals (Sweden)

    D Shackebaei

    2010-09-01

    Full Text Available Background: Urtica dioica (U.D has widely been used in traditional medicine for its hypotensive and vasodilatory effects. The objective of this study was to clarify the effects of aqueous extract of Urtica dioica on isolated ischemia- reperfused heart.Methods: The heart of male wistar rats were isolated and perfused according to langendorff method. In the control group (n = 13 the hearts were subjected to three steps of stabilization (30 min, normothermic global ischemia (40 min and reperfusion (45 min. In addition, before and after ischemia, the aqueous extract of U.D (200 mg/ml was added to perfusion solution in the test group (n=14. Different cardiac variables including left ventricular pressure, heart rate and coronary flow were measured and rate pressure product was calculated.Results: Results showed that left ventricular pressure (59.11±4.7 and rate pressure product (13680±1136 in 45th minute of reperfusion in the test group were significantly (P=0.0187 and 0.0321 respectively greater than the control group (39.1±6.0, 9480±1480 respectively. These findings indicated decreased cardiac damage following ischemia in the test group, compared with that of control group.Conclusion: Results of the present study showed that the aqueous extract of U.D, increased the tolerance of isolated rat hearts against ischemic damage. This effect can be explained by potent antioxidant activity of the U.D extract, suggesting its clinical use in ischemic heart disease.

  20. Effect of desferrioxamine on reperfusion damage of rat heart ...

    African Journals Online (AJOL)

    1990-09-01

    Sep 1, 1990 ... ... deferrioxamine on rat heart mitochondrial oxidative phosphorylation after normothermic ischemic cardiac arrest and of reperfusion. Res Commun Chem Pathol Pharmacol 1988;. 62: 419-434. IL Sordahl LA, Johnson C, Blailock ZR. Schwartz A. The mitochondrion. Mechods Phannacol1971; 1: 247-286.

  1. Photochemical (PUVA) treatment of isolated rat islets

    International Nuclear Information System (INIS)

    Schmidt, S.; Wilke, B.; Kloeting, I.

    1984-01-01

    Isolated rat islets were irradiated with long-wave ultraviolet light alone or in combination with the photosensitizer 8-methoxypsoralen. The influence on specific beta cell functions was determined with the aim to find out experimental conditions which allow the use of such islets for transplantation. Short-term effects: Ultraviolet light affected [ 3 H]leucine incorporation into (pro)insulin (5 J/cm 2 : 53.8 %, 10 J/cm 2 : 41.0 % of the controls) and insulin release was slightly reduced. 8-methoxypsoralen enhanced the irradiation effect. Long-term effects: A restoration of irradiation-affected beta cell function was detected after 5 days of culture unless the dose exceeded 2 J/cm 2 (0.1 μM 8-methoxypsoralen) or 1 J/cm 2 (1 μM 8-methoxypsoralen). After functional restoration islets were used for transplantation experiments. (author)

  2. Photochemical (PUVA) treatment of isolated rat islets

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, S; Wilke, B; Kloeting, I [Zentralinstitut fuer Diabetes, Karlsburg (German Democratic Republic)

    1984-05-01

    Isolated rat islets were irradiated with long-wave ultraviolet light alone or in combination with the photosensitizer 8-methoxypsoralen. The influence on specific beta cell functions was determined with the aim to find out experimental conditions which allow the use of such islets for transplantation. Short-term effects: Ultraviolet light affected (/sup 3/H)leucine incorporation into (pro)insulin (5 J/cm/sup 2/ : 53.8 %, 10 J/cm/sup 2/ : 41.0 % of the controls) and insulin release was slightly reduced. 8-methoxypsoralen enhanced the irradiation effect. Long-term effects: A restoration of irradiation-affected beta cell function was detected after 5 days of culture unless the dose exceeded 2 J/cm/sup 2/ (0.1 ..mu..M 8-methoxypsoralen) or 1 J/cm/sup 2/ (1 ..mu..M 8-methoxypsoralen). After functional restoration islets were used for transplantation experiments.

  3. A comparative study of myosin and its subunits in adult and neonatal-rat hearts and in rat heart cells from young and old cultures.

    OpenAIRE

    Ghanbari, H A; McCarl, R L

    1980-01-01

    A possible explanation for the decrease in myosin Ca2+-dependent ATPase activity as rat heart cells age in culture is presented. The subunit structure and enzyme kinetics of myosin from adult and neonatal rat hearts and from rat heart cells of young and old cultures are compared. These studies indicate that the loss in Ca-ATPase activity of myosin from older cultures was an intrinsic property of the myosin itself. Myofibrillar fractions from the indicated four sources showed no qualitative or...

  4. Protective effects of hydroalcoholic extract from rhizomes of Cynodon dactylon (L.) Pers. on compensated right heart failure in rats.

    Science.gov (United States)

    Garjani, Alireza; Afrooziyan, Arash; Nazemiyeh, Hossein; Najafi, Moslem; Kharazmkia, Ali; Maleki-Dizaji, Nasrin

    2009-08-05

    The rhizomes of Cynodon dactylon are used for the treatment of heart failure in folk medicine. In the present study, we investigated the effects of hydroalcoholic extract of C. dactylon rhizomes on cardiac contractility in normal hearts and on cardiac functions in right-heart failure in rats. Right-heart failure was induced by intraperitoneal injection of monocrotaline (50 mg/kg). Two weeks later, the animals were treated orally with different doses of the extract for fifteen days. At the end of the experiments cardiac functions and markers of myocardial hypertrophy were measured. The treated rats showed very less signs of fatigue, peripheral cyanosis and dyspnea. The survival rate was high in the extract treated groups (90%). Administration of C. dactylon in monocrotaline-injected rats led to profound improvement in cardiac functions as demonstrated by decreased right ventricular end diastolic pressure (RVEDP) and elevated mean arterial pressure. RVdP/dtmax, and RVdP/dt/P as indices of myocardial contractility were also markedly (p < 0.001; using one way ANOVA) increased by the extract. The extract reduced heart and lung congestion by decreasing tissue wet/dry and wet/body weight ratios (p < 0.01). In the isolated rat hearts, the extract produced a remarkable (P < 0.001) positive inotropic effect concomitant with a parallel decrease in LVEDP. The results of this study indicated that C. dactylon exerted a strong protective effect on right heart failure, in part by positive inotropic action and improving cardiac functions.

  5. [Effects of flunarizine and vitamin C on hemodynamics in rat heart subjected to ischemia-reperfusion].

    Science.gov (United States)

    Xian, Y; Lan, T; Wang, Y

    1998-09-01

    Langendorff perfusion isolated rat heart was subjected to total global ischemia (coronary flow rate is equal to zero) for 10 minutes and reperfusion for 15 minutes. The heart rate (HR), left ventricular developed pressure (LVDP), coronary flow rate (CFR), electrocardiogram (ECG) and the effects of calcium antagonist-flunarizine (FNZ) and/or oxygen free radical scavenger--vitamine C on the above parameters were observed. The results showed that FNZ dilated coronary vessel (P Vitamine C did not affect HR, LVP and CFR. The recovery of the product of HR and LVDP-Rate Pressure Product (RPP) in the FNZ + Vit. C group, Vit. C group and FNZ group was significantly higher than that in the control group (P C may improve the recovery of heart function after reperfusion.

  6. Heart Rate Changes in Electroacupuncture Treated Polycystic Ovary in Rats.

    Science.gov (United States)

    Ramadoss, Mukilan; Ramanathan, Gunasekaran; Subbiah, Angelie Jessica; Natrajan, Chidambaranathan

    2016-03-01

    Polycystic Ovary Syndrome (PCOS) is a common metabolic disorder, it affects both humans and animals. It may induce coronary heart disease, obesity and hyperandrogenism. Previous studies show that Low frequency Electroacupuncture (EA) have an effect on PCOS, however the exact pathway is unclear. To find the effect of EA on autonomic activity of the heart in Estradiol Valerate (EV) induced PCOS rats. Heart rate variability (HRV) was assessed in 3 groups: 1) Control; 2) PCOS rats; and 3) PCOS rats after EA treatment (n=8 in each group). From the time domain analysis and frequency domain analysis (linear measures) HRV analysis was done. EA stimulation was given at low frequency of 2Hz for 15 min on alternate days for 4-5 weeks. Collected data were statistically analysed using One-Way Analysis of Variance with the application of multiple comparisons of Tukey test. EA treatment group shows significant reduction in Heart Rate (HR) and low frequency, high frequency ratio (LF/HF); and increase in RR interval, Total Power (TP) when compared to PCOS group. The study concludes that EA treatment has a significant effect on reducing sympathetic tone and decreasing HR in PCOS.

  7. 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.

  8. Hyperthyroidism presenting as isolated tricuspid regurgitation and right heart failure.

    Science.gov (United States)

    Whitner, Tanya E; Hudson, Christopher J; Smith, Timothy D; Littmann, Laszlo

    2005-01-01

    Although hyperthyroidism has many signs and symptoms, right heart failure can occasionally be the main presenting symptom. We describe the case of a previously healthy 42-year-old woman whose chief complaint was progressive bilateral lower extremity edema. The echocardiogram revealed right atrial dilatation and moderate-to-severe tricuspid regurgitation. Results of laboratory studies were consistent with hyperthyroidism. Thyroid ablation resulted in permanent resolution of symptoms and resolution of tricuspid incompetence on echocardiography. In a case of isolated, unexplained tricuspid regurgitation, it is important to consider indolent hyperthyroidism in the differential diagnosis.

  9. Cerveau isolé and pretrigeminal rat preparations.

    Science.gov (United States)

    Zernicki, B; Gandolfo, G; Glin, L; Gottesmann, C

    1985-01-01

    Cortical and hippocampal EEG activity was analysed in cerveau isolé and and pretrigeminal rats. In the acute stage, waking EEG patterns were absent in the cerveau isolé, whereas sleep EGG patterns were absent in the preparations. However, already on the second day the EEG waking sleep cycle recovered in the majority of rats. Paradoxically, stimuli directed to the caudal part of the preparations evoked stronger cortical and hippocampal EEG arousal than olfactory and visual stimuli. The rats exhibited some locomotor and grooming behaviour and could be fed orally. It is concluded that the activity of the isolated cerebrum of the rat is similar to that of cat preparations, but that functions of the caudal neuraxis are superior in rats.

  10. 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.

  11. Insulin internalization in isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Galan, J.; Trankina, M.; Noel, R.; Ward, W.

    1990-01-01

    This project was designed to determine whether neomycin, an aminoglycoside antibiotic, has a significant effect upon the pathways of ligand endocytosis in isolated rat hepatocytes. The pathways studied include receptor-mediated endocytosis and fluid-phase endocytosis. Neomycin causes a dose-dependent acceleration of 125 I-insulin internalization. Since fluid-phase endocytosis can also be a significant factor in 125 I-insulin internalization, lucifer yellow (LY), a marker for fluid-phase endocytosis, was incorporated into an assay similar to the 125 I-insulin internalization procedure. In the presence of 5 mM neomycin, a significant increase in LY uptake was evident at 0.2 and 0.4 mg/ml of LY. At 0.8 mg/ml, a decrease in LY uptake was observed. The increased rate of 125 I-insulin internalization in the presence of neomycin was intriguing. Since one action of neomycin is to inhibit phosphoinositidase C, it suggests that the phosphotidylinositol cycle may be involved in ligand internalization by hepatocytes. At low insulin concentrations, receptor-mediated uptake predominates. Fluid-phase uptake can become an important uptake route as insulin concentrations are increased. Since neomycin stimulates fluid-phase endocytosis, it must also be taken into account when measuring ligand internalization

  12. 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.

  13. Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart.

    Science.gov (United States)

    Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

    2008-05-01

    The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts. The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry. SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities. NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.

  14. Isolation and identification of two galangin metabolites from rat urine ...

    African Journals Online (AJOL)

    Isolation and identification of two galangin metabolites from rat urine and determination of their in vitro hypolipidemic activity. Xuguang Zhang, Shouqian Cheng, Hailong Li, Xiaopo Zhang, Feng Chen, Youbin Li, Junqing Zhang, Yinfeng Tan ...

  15. Chronic heat improves mechanical and metabolic response of trained rat heart on ischemia and reperfusion.

    Science.gov (United States)

    Levy, E; Hasin, Y; Navon, G; Horowitz, M

    1997-05-01

    Cardiac mechanics and metabolic performance were studied in isolated perfused hearts of rats subjected to a combined chronic stress of heat acclimation and swimming training (EXAC) or swimming training alone (EX). Diastolic (DP) and systolic pressures (SP), coronary flow (CF), and oxygen consumption were measured during normoperfusion (80 mmHg), and the appearance of ischemic contracture (IC), DP, and SP were measured during progressive graded ischemia, total ischemia (TI), and reperfusion insults. ATP, phosphocreatine, and intracellular pH were measured during TI and reperfusion with 31P nuclear magnetic resonance spectroscopy. During normoperfusion, SP and cardiac efficiency (derived from rate-pressure product-oxygen consumption relationships) were the highest in the 2-mo EXAC hearts (P pool and there was a delayed decline in intracellular pH. On reperfusion, these hearts also displayed improved ATP and phosphocreatine recovery, the 2-mo EXAC heart demonstrating significantly faster high-energy phosphate salvage, improved diastolic function, and pulse pressure recovery. The data attest to the beneficial effects of heat acclimation on cardiac mechanics of trained rats during normoperfusion and cardiac protection on ischemia and reperfusion. Possibly, energy sparing, lesser acidosis, and shorter duration of IC on ischemia and improved energy salvage on reperfusion contribute synergistically to this potent beneficial effect.

  16. NDM 1 Gene Carrying Gram negative Bacteria Isolated from Rats ...

    African Journals Online (AJOL)

    In this study, we screened 56 Gram negative bacteria comprising: 3 isolates of Enterobacter ludwigii, 30 Pseudomonas aeruginosa, 22 Proteus mirabilis, and 1 Aeromonas caviae isolated from oral cavity and rectum of rats captured from commercial poultry houses in Ibadan, Oyo State, Nigeria that were resistant to at least ...

  17. Angiotensinergic and noradrenergic neurons in the rat and human heart.

    Science.gov (United States)

    Patil, Jaspal; Stucki, Silvan; Nussberger, Juerg; Schaffner, Thomas; Gygax, Susanne; Bohlender, Juergen; Imboden, Hans

    2011-02-25

    Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT₂ (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine-β-hydroxylase (DβH) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or DβH. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor DβH, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with DβH in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Cellular location of rat muscle ferritins and their preferential loss during cell isolation.

    Science.gov (United States)

    Linder, M C; Roboz, M; McKown, M J; Pardridge, W M; Zak, R

    1984-04-10

    Heart and other muscles of the rat contain two forms of ferritin separable in polyacrylamide gel electrophoresis. The cellular location of the fast- and slow-migrating ferritins was investigated using primary cultures of hindlimb skeletal muscle, and isolated myocardial cell populations. Muscle and non-muscle cells were isolated in good yield from hearts of adult rats pretreated with large doses of iron to increase their ferritin content. In virtually all cases, the isolated muscle cells contained traces only of the fast-migrating species and the non-muscle cells contained small amounts of the slow-migrating ferritin. During cell isolation, 90-100% of both ferritins was lost and could be recovered in the perfusates and solutions employed, while one third of the total tissue protein, and a larger percentage of creatine phosphokinase, was recovered in the isolated cells. Primary cultures of thigh muscle from adult rats which had differentiated into multi-nucleated myotubes, were incubated for 1-3 days with chelated iron. These cells contained substantial amounts of the electrophoretically fast migrating ferritin, with its characteristic larger Stokes' radius (determined by quantitative polyacrylamide gel electrophoresis). None of the slow-migrating ferritin species was detected, although hindlimb muscle from iron-treated rats contained both forms. It is concluded that the fast-migrating ferritin of muscle, which is much larger and more asymmetric than other ferritins, is confined to the muscle cell population, while the other form is predominantly or exclusively in the non-muscle cells. Both ferritins are lost preferentially over other proteins during procedures which injure muscle tissue.

  19. Reiki improves heart rate homeostasis in laboratory rats.

    Science.gov (United States)

    Baldwin, Ann Linda; Wagers, Christina; Schwartz, Gary E

    2008-05-01

    To determine whether application of Reiki to noise-stressed rats can reduce their heart rates (HRs) and blood pressures. In a previous study, we showed that exposure of rats to 90 dB white noise for 15 minutes caused their HRs and blood pressures to significantly increase. Reiki has been shown to significantly decrease HR and blood pressure in a small group of healthy human subjects. However, use of humans in such studies has the disadvantage that experimental interpretations are encumbered by the variable of belief or skepticism regarding Reiki. For that reason, noise-stressed rats were used as an animal model to test the efficacy of Reiki in reducing elevated HR and blood pressure. Three unrestrained, male Sprague-Dawley rats implanted with radiotelemetric transducers were exposed daily for 8 days to a 15-minute white noise regimen (90 dB). For the last 5 days, the rats received 15 minutes of Reiki immediately before the noise and during the noise period. The experiment was repeated on the same animals but using sham Reiki. The animals were housed in a quiet room in University of Arizona Animal Facility. Mean HRs and blood pressure were determined before Reiki/sham Reiki, during Reiki/sham Reiki, and during the noise in each case. Reiki, but not sham Reiki, significantly reduced HR compared to initial values. With Reiki, there was a high correlation between change in HR and initial HR, suggesting a homeostatic effect. Reiki, but not sham Reiki, significantly reduced the rise in HR produced by exposure of the rats to loud noise. Neither Reiki nor sham Reiki significantly affected blood pressure. Reiki is effective in modulating HR in stressed and unstressed rats, supporting its use as a stress-reducer in humans.

  20. Heart resistance to oxidative stress in rats of different genetic strains.

    Science.gov (United States)

    Belkina, L M; Lakomkin, V L; Zhukova, A G; Kirillina, T N; Saltykova, V A; Sazontova, T G; Kapel'ko, V I

    2004-09-01

    In August rats reperfusion after regional myocardial ischemia in situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity.

  1. Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts Efeitos benéficos da perfusão hiperosmótica no miocárdio após lesão isquemia/reperfusão em corações isolados de ratos

    Directory of Open Access Journals (Sweden)

    Yong Cao

    2013-03-01

    Full Text Available OBJECTIVE: A simple method to reduce the ischemia/reperfusion injury that can accompany cardiac surgery would have great clinical value. This study was to investigate the effect of hyperosmotic perfusion on ischemia/reperfusion injury in isolated perfused rat hearts. METHOD: Forty male Sprague-Dawley rats were randomly divided either to have their isolated hearts perfused with normal osmotic buffer or buffer made hyperosmotic by addition of glucose. Hearts were then subjected to 30 min ischemia followed by 30 min reperfusion. Coronary flow, time to ischemic arrest, reperfusion arrhythmia, and ventricular function were recorded. Creatine phosphokinase leakage into the coronary artery, and myocardial content and activity of superoxide dismutase and catalase were also examined. RESULTS: Rat hearts with hyperosmotic perfusion showed higher coronary flow, a prolonged time to ischemic arrest (10.60 vs. 5.63 min, POBJETIVO: Um método simples para reduzir a lesão de isquemia/reperfusão que pode acompanhar a cirurgia cardíaca teria grande valor clínico. O objetivo deste estudo foi investigar o efeito da perfusão hiperosmótica na isquemia/reperfusão em corações isolados de ratos perfundidos. MÉTODOS: Quarenta ratos machos Sprague-Dawley foram divididos aleatoriamente e tiveram os seus corações isolados perfundidos com tampão osmótico normal ou tampão hiperosmótico com a adição de glucose. Os corações foram então submetidos a 30 minutos de isquemia, seguida de 30 min de reperfusão. O fluxo coronariano, tempo de parada isquêmica, arritmia de reperfusão e da função ventricular foram registrados. Vazamento creatinofosfoquinase na artéria coronária, o miocárdio e atividade de superóxido dismutase e catalase foram também examinados. RESULTADOS: Crações de ratos com perfusão hiperosmótica apresentaram maior fluxo coronariano, tempo prolongado de parada isquêmica (10,60 vs. 5,63 min, P<0,005, menor pontuação de reperfus

  2. 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 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.

  3. Effect of oxygen deprivation on metabolism of arachidonic acid by cultures of rat heart cells

    International Nuclear Information System (INIS)

    Freyss-Beguin, M.; Millanvoye-van Brussel, E.; Duval, D.

    1989-01-01

    To investigate the mechanisms responsible for the impairment of phospholipid metabolism observed in ischemic cells, we have studied the effect of conditions simulating ischemia on the metabolism of arachidonic acid (AA) by muscle (M-) and nonmuscle (F-) cells isolated from newborn rat hearts and cultured separately. In muscle cells, oxygen deprivation induces a significant stimulation of the release of [ 14 C]AA from prelabeled cells associated with a preferential redistribution of [ 14 C]AA into cell triglycerides but not formation of radioactive prostaglandins. Moreover, the fatty acid content of phospholipids, as measured by capillary gas chromatography, appears markedly reduced in ischemic myocardial cells. This fact may be related to phospholipase stimulation during ischemia as suggested by the antagonistic effect of mepacrine or p-bromophenacyl bromide. In contrast, oxygen deprivation failed to induce any significant alteration of AA metabolism in fibroblast-like heart cells. Our results indicate that these cultures of newborn rat heart cells, which exhibit many of the features observed in intact organ during ischemia, may represent a useful experimental model to investigate the pharmacological control of the membrane phospholipid turnover

  4. Zero Flow Global Ischemia-Induced Injuries in Rat Heart Are Attenuated by Natural Honey

    Directory of Open Access Journals (Sweden)

    Moslem Najafi

    2012-06-01

    Full Text Available Purpose: In the present study, effects of preischemic administration of natural honey on cardiac arrhythmias and myocardial infarction size during zero flow global ischemia were investigated in isolated rat heart. Methods:The isolated hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion then perfused by a modified drug free Krebs-Henseleit solution throughout the experiment (control or the solution containing 0.25, 0.5, 1 and 2% of natural honey for 15 min before induction of global ischemia (treated groups, respectively. Cardiac arrhythmias were determined based on the Lambeth conventions and the infarct size was measured by computerized planimetry. Results: Myocardial infarction size was 55.8±7.8% in the control group, while preischemic perfusion of honey (0.25, 0.5, 1 and 2% reduced it to 39.3±11, 30.6±5.5 (P<0.01, 17.9±5.6 (P<0.001 and 8.7±1.1% (P<0.001, respectively. A direct linear correlation between honey concentrations and infarction size reduction was observed (R2=0.9948. In addition, total number of ventricular ectopic beats were significantly decreased by all used concentrations of honey (P<0.05 during reperfusion time. Honey (0.25, 0.5 and 1 % also lowered incidence of irreversible ventricular fibrillation (P<0.05. Moreover, number and duration of ventricular tachycardia were reduced in all honey treated groups. Conclusion: Preischemic administration of natural honey before zero flow global ischemia can protect isolated rat heart against ischemia/reperfusion injuries as reduction of infarction size and arrhythmias. Maybe, antioxidant and free radical scavenging activities of honey, reduction of necrotized tissue and providing energy sources may involve in these cardioprotective effects of honey.

  5. Zero Flow Global Ischemia-Induced Injuries in Rat Heart Are Attenuated by Natural Honey

    Science.gov (United States)

    Najafi, Moslem; Zahednezhad, Fahimeh; Samadzadeh, Mehrban; Vaez, Haleh

    2012-01-01

    Purpose: In the present study, effects of preischemic administration of natural honey on cardiac arrhythmias and myocardial infarction size during zero flow global ischemia were investigated in isolated rat heart. Methods: The isolated hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion then perfused by a modified drug free Krebs-Henseleit solution throughout the experiment (control) or the solution containing 0.25, 0.5, 1 and 2% of natural honey for 15 min before induction of global ischemia (treated groups), respectively. Cardiac arrhythmias were determined based on the Lambeth conventions and the infarct size was measured by computerized planimetry. Results: Myocardial infarction size was 55.8±7.8% in the control group, while preischemic perfusion of honey (0.25, 0.5, 1 and 2%) reduced it to 39.3±11, 30.6±5.5 (Phoney concentrations and infarction size reduction was observed (R2=0.9948). In addition, total number of ventricular ectopic beats were significantly decreased by all used concentrations of honey (PHoney (0.25, 0.5 and 1 %) also lowered incidence of irreversible ventricular fibrillation (Phoney treated groups. Conclusion: Preischemic administration of natural honey before zero flow global ischemia can protect isolated rat heart against ischemia/reperfusion injuries as reduction of infarction size and arrhythmias. Maybe, antioxidant and free radical scavenging activities of honey, reduction of necrotized tissue and providing energy sources may involve in these cardioprotective effects of honey. PMID:24312788

  6. Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

    Directory of Open Access Journals (Sweden)

    Singh Manjeet

    2011-07-01

    Full Text Available Abstract Background Nitric oxide (NO has been noted to produce ischemic preconditioning (IPC-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM. The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat. Methods Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, i.p, and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H. Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC staining, and release of lactate dehydrogenase (LDH and creatin kinase-MB (CK-MB in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent. Results IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ a caveolin inhibitor (0.2 mg/Kg/s.c, for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L, a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD, a mito KATP channel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination. Conclusions Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in

  7. 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)

  8. Myocardial myostatin in spontaneously hypertensive rats with heart failure.

    Science.gov (United States)

    Damatto, R L; Lima, A R R; Martinez, P F; Cezar, M D M; Okoshi, K; Okoshi, M P

    2016-07-15

    Myostatin has been shown to regulate skeletal and cardiac muscle growth. However, its status on long-term hypertrophied myocardium has not been addressed. The purpose of this study was to evaluate the expression of myocardial myostatin and its antagonist follistatin in spontaneously hypertensive rats (SHR) with heart failure. Eighteen-month-old SHR were evaluated to identify clinical features of heart failure such as tachypnea/labored respiration and weight loss. After heart failure was detected, rats were subjected to echocardiogram and euthanized. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Myostatin and follistatin protein expression was assessed by Western blotting. Statistical analysis was performed by Student's t test. All SHR (n=8) presented right ventricular hypertrophy and five had lung congestion. SHR had left chambers hypertrophy and dilation (left atrial diameter: WKY 5.73±0.59; SHR 7.28±1.17mm; p=0.004; left ventricular (LV) diastolic diameter/body weight ratio: WKY 19.6±3.1; SHR 27.7±4.7mm/kg; p=0.001), and LV systolic dysfunction (midwall fractional shortening: WKY 34.9±3.31; SHR 24.8±3.20%; p=0.003). Myocyte diameter (WKY 23.1±1.50, SHR 25.5±1.33μm; p=0.004) and myocardial interstitial collagen fraction (WKY 4.86±0.01; SHR 8.36±0.02%; pMyostatin (WKY 1.00±0.16; SHR 0.77±0.23 arbitrary units; p=0.035) and follistatin (WKY 1.00±0.35; SHR 0.49±0.18 arbitrary units; p=0.002) expression was lower in SHR. Myostatin and follistatin expression negatively correlated with LV diastolic diameter-to-body weight ratio and LV systolic diameter, and positively correlated with midwall fractional shortening. Myostatin and follistatin protein expression is reduced in the long-term hypertrophied myocardium from spontaneously hypertensive rats with heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Contribution of social isolation, restraint, and hindlimb unloading to changes in hemodynamic parameters and motion activity in rats.

    Directory of Open Access Journals (Sweden)

    Darya Tsvirkun

    Full Text Available The most accepted animal model for simulation of the physiological and morphological consequences of microgravity on the cardiovascular system is one of head-down hindlimb unloading. Experimental conditions surrounding this model include not only head-down tilting of rats, but also social and restraint stresses that have their own influences on cardiovascular system function. Here, we studied levels of spontaneous locomotor activity, blood pressure, and heart rate during 14 days under the following experimental conditions: cage control, social isolation in standard rat housing, social isolation in special cages for hindlimb unloading, horizontal attachment (restraint, and head-down hindlimb unloading. General activity and hemodynamic parameters were continuously monitored in conscious rats by telemetry. Heart rate and blood pressure were both evaluated during treadmill running to reveal cardiovascular deconditioning development as a result of unloading. The main findings of our work are that: social isolation and restraint induced persistent physical inactivity, while unloading in rats resulted in initial inactivity followed by normalization and increased locomotion after one week. Moreover, 14 days of hindlimb unloading showed significant elevation of blood pressure and slight elevation of heart rate. Hemodynamic changes in isolated and restrained rats largely reproduced the trends observed during unloading. Finally, we detected no augmentation of tachycardia during moderate exercise in rats after 14 days of unloading. Thus, we concluded that both social isolation and restraint, as an integral part of the model conditions, contribute essentially to cardiovascular reactions during head-down hindlimb unloading, compared to the little changes in the hydrostatic gradient.

  10. 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...

  11. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

    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 (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

  12. Proteção da recuperação funcional do miocárdio pelo omeprazol após isquemia-reperfusão em corações isolados de ratos Myocardium functional recovery protection by omeprazole after ischemia-reperfusion in isolated rat hearts

    Directory of Open Access Journals (Sweden)

    Otoni Moreira Gomes

    2010-09-01

    Full Text Available OBJETIVO: Analisar efeitos do omeprazol na proteção da recuperação funcional de corações isolados de ratos submetidos à lesão de isquemia-reperfusão. MÉTODOS: Foram estudados 12 ratos Wistar, peso corpóreo médio de 280g. Após anestesia com injeção intra-abdominal de 10mg de cetamina e 2mg de xilazina, os corações foram removidos e mantidos em perfusão com solução Krebs-Henseleit (95%O2 e 5% CO2, 37ºC, 110-120mmHg de pressão de perfusão e pressão diastólica de 8 mmHg em sistema Langendorff, modificado, descartável, modelo FCSFA-ServCor (Comex Ltda.. Os seis corações do Grupo I (GI e os seis do Grupo II (GII foram submetidos a 20 minutos de isquemia e 30 minutos de reperfusão. Nos corações do Grupo II, imediatamente antes da isquemia, foram administrados via perfusão coronária 200mcg de omeprazol. Foram controlados frequência cardíaca (FC, fluxo coronário (FCo, pressão sistólica (PS, +dP/dt e -dP/dt, após estabilização (t0 e no final da reperfusão (t30. Empregou-se método não paramétrico de Kruskal-Wallis (P0,05 entre os valores de FCo e FC nos dois grupos. No final do período de reperfusão (t30, foram significantes (POBJECTIVE: To evaluate the myocardium contractility alterations of isolated hearts of rats, submitted to ischemia and reperfusion with and without administration of the omeprazole. METHODS: Twelve Wistar breed rats with 270g mean body weight was studied. After anesthesia by intraperitoneal injection of ketamine 10mg and xylazine 2mg, their hearts were removed and perfused with Krebs-Henseleit solution (95% of O2 and 5% of CO2, 37ºC, 110-120 mmHg perfusion pressure, 8 mmHg ventricular diastolic pressure in the São Francisco de Assis disposable Langendorff system model Comex Ltda, MG. The six hearts of Group I (GI and of the Group II (GII were submitted to 20 min ischemia and 30 min reperfusion. In GII hearts, intracoronary injection of omeprazole 200 mcg was done immediately before the

  13. Fatty Acid Oxidation Is Preserved Regardless of Impaired Uptake in the Chronically Failing Rat Heart

    OpenAIRE

    TACHIKAWA, Hitoshi

    2004-01-01

    Fatty acid is used as a major fuel in the fasting heart, but the precise metabolism in the failing heart remains unknown. We assessed the hypothesis that the fatty acid metabolism might be impaired or delayed during heart failure. We examined in vivo kinetics of an isotope-labeled fatty acid analogue and its substrates as well as hemodynamic parameters and histopathological findings in a rat model of postmyocarditic dilated cardiomyopathy. Rat experimental autoimmune myocarditis (EAM) was ind...

  14. 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.

  15. Expression of cardiac neural crest and heart genes isolated by modified differential display.

    Science.gov (United States)

    Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

    2003-08-01

    The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

  16. Structure and composition of synaptonemal complexes, isolated from rat spermatocytes

    NARCIS (Netherlands)

    Heyting, C.; Dietrich, A. J.; Redeker, E. J.; Vink, A. C.

    1985-01-01

    Synaptonemal complexes (SCs) (structures involved in chromosome pairing during meiosis) were isolated and purified from rat spermatocytes for the purpose of biochemical and morphological analysis. Spermatocytes were lysed in a medium, containing Triton X-100, EDTA and DTT; the resulting swollen

  17. desensitisation and calcium-sensitivity in the isolated perfused rat ...

    African Journals Online (AJOL)

    Dr Olaleye

    -induced desensitisation to noradrenaline were studied in the isolated perfused rat tail artery. Responses to the activators noradrenaline (NA). (3μM) and potassium chloride (KCl) (100mM) were obtained in Ca2+-buffered saline. Activators ...

  18. The structurally novel Ca2+ channel blocker Ro 40-5967, which binds to the [3H] desmethoxyverapamil receptor, is devoid of the negative inotropic effects of verapamil in normal and failing rat hearts

    International Nuclear Information System (INIS)

    Clozel, J.P.; Veniant, M.; Osterrieder, W.

    1990-01-01

    Ro 40-5967 is a structurally novel Ca 2+ channel blocker that binds to the verapamil-type receptor of cardiac membranes but that has been shown in isolated guinea-pig hearts to be about ten times less potent a negative inotropic agent than verapamil. The goals of the present study were to confirm these findings in vitro in isolated perfused rat hearts as well as in vivo in conscious rats and to compare Ro 40-5967 to verapamil. The effects of Ro 40-5967 and verapamil were tested not only in normal rats, but also in rats with heart failure induced by chronic myocardial infarction. In isolated Langendorff hearts (without heart failure), no decrease of contractility was observed with Ro 40-5967 up to complete AV block. In contrast, verapamil decreased contractility with an IC50 of 100 nM. In isolated, electrically stimulated rat papillary muscles, the IC50 values for the decrease of contractile force were 15,000 and 440 nM for Ro 40-5967 and verapamil, respectively. In vivo, Ro 40-5967 did not decrease left ventricular contractility (as assessed by changes of dP/dt max +) in rats without and with heart failure. In contrast, verapamil was markedly negative inotropic in both conditions

  19. 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; Petruş, Alexandra; Dănilă, Maria D; Raţiu, Corina D; Muntean, Danina M; Sturza, Adrian

    2017-11-01

    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 purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H 2 O 2 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. H 2 O 2 production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μmol·L -1 ) 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 H 2 O 2 release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II 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 nondiabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

  20. [Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats].

    Science.gov (United States)

    Kong, Ling-Heng; Gu, Xiao-Ming; Su, Xing-Li; Sun, Na; Wei, Ming; Zhu, Juan-Xia; Chang, Pan; Zhou, Jing-Jun

    2016-05-01

    To investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms. Thirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c. Compared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (Pparadox, and markedly down-regulated the levels of LVEDP and LDH (Pparadox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.

  1. on Isolated Smooth Muscle Preparation in Rats

    African Journals Online (AJOL)

    Samuel Olaleye

    ABSTRACT. This study investigated the receptor effects of methanolic root extract of ... Phytochemical Analysis: Photochemistry of the methanolic extract was ... mounted with resting tension 0.5g in an organ bath containing .... Effects of extra cellular free Ca2+ and 0.5mM ... isolated smooth muscle by high K+ on the other.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Effects of adriamycin and irradiation on beating of rat heart muscle cells in culture

    International Nuclear Information System (INIS)

    Petrovic, D.; Brown, S.M.; Yatvin, M.B.

    1977-01-01

    In an attempt to elucidate the mechanisms involved in Adriamycin (ADM) induced cardiotoxicity as well as determining the possible potentiating effect that irradiation has when it is combined with the drug, heart cells from newborn rats were isolated, cultured and treated with Adriamycin. The actions of these two agents separately or in combination on the survival of beating activity and beating frequency are measured. Beating activity could be decreased temporarily either by exposing the cells to 50 krad of γ-irradiation or 0.1 μg of Adriamycin. Following 100 krad of γ-radiation or 1.0 μg Adriamycin, an irreversible cessation of beating occurred. In the case of Adriamycin, cessation was preceded by a temporary sharp increase in beating frequency. Doses of radiation up to 10 krad in combination with Adriamycin were not potentiating. The results indicate that Adriamycin produces its cardiotoxic effects, at least in part, by a direct action on heart muscle cells. It is less likely, however, that damage which occurs in the heart following therapeutic doses of irradiation is the result of such direct action

  4. Influence of intracellular acidosis on contractile function in the working rat heart

    International Nuclear Information System (INIS)

    Jeffrey, F.M.H.; Malloy, C.R.; Radda, G.K.

    1987-01-01

    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 2 delivery. Intracellular pH and high-energy phosphates were monitored by 31 P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH 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

  5. Isolated working heart: description of models relevant to radioisotopic and pharmacological assessments

    International Nuclear Information System (INIS)

    Depre, Christophe

    1998-01-01

    Isolated heart preparations are used to study physiological and metabolic parameters of the heart independently of its environment. Several preparations of isolated perfused heart are currently used, mainly the retrograde perfusion system and the working heart model. Both models allow investigations of the metabolic regulation of the heart in various physiological conditions (changes in workload, hormonal influences, substrate competition). These systems may also reproduce different pathological conditions, such as ischemia, reperfusion and hypoxia. Quantitation of metabolic activity can be performed with specific radioactive tracers. Finally, the effects of various drugs on cardiac performance and resistance to ischemia can be studied as well. Heart perfusion also revealed efficient methods to determine the tracer/tracee relation for radioisotopic analogues used with Positron Emission Tomography

  6. Reversible Pulmonary Hypertension and Isolated Right-sided Heart Failure Associated with Hyperthyroidism

    OpenAIRE

    Ismail, Hassan M.

    2007-01-01

    Hyperthyroidism may present with signs and symptoms related to dysfunction of a variety of organs. Cardiovascular pathology in hyperthyroidism is common. A few case reports describe isolated right heart failure, tricuspid regurgitation, and pulmonary hypertension as the prominent cardiovascular manifestations of hyperthyroidism. Although most textbooks do not mention hyperthyroidism as a cause of pulmonary hypertension and isolated right heart failure, the literature suggests that some hypert...

  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. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

    International Nuclear Information System (INIS)

    Benderitter, M.; Assem, M.; Maupoil, V.

    1995-01-01

    During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab

  9. Fetal and neonatal mortality in patients with isolated congenital heart diseases and heart conditions associated with extracardiac abnormalities.

    Science.gov (United States)

    Marantz, Pablo; Sáenz Tejeira, M Mercedes; Peña, Gabriela; Segovia, Alejandra; Fustiñana, Carlos

    2013-10-01

    Congenital malformations are a known cause of intrauterine death; of them, congenital heart diseases (CHDs) are accountable for the highest fetal and neonatal mortality rates. They are strongly associated with other extracardiac malformations and an early fetal mortality. Two hundred and twenty fves cases of CHDs are presented. Of them, 155 were isolated CHDs (group A) and 70 were associated with extracardiac malformations, chromosomal disorders, or genetic syndromes (group B). The overall mortality in group B was higher than that observed in group A (p Heart diseases associated with extracardiac abnormalities had a higher mortality rate than isolated congenital heart diseases in the period up to 60 weeks of postmenstrual age (140 days post-term). No differences were observed between both groups of patients in terms of prenatal mortality.

  10. [Crabtree effect caused by ketoses in isolated rat hepatocytes].

    Science.gov (United States)

    Martínez, P; Carrascosa, J M; Núñez de Castro, I

    1982-01-01

    Oxygen uptake and glycolytic activity were studied in hepatocytes isolated from fed rats. The addition of fructose or tagatose resulted in a 38% and 31% inhibition of cellular respiration respectively. The addition of 10 mM D-glyceraldehyde caused a slight Crabtree effect. Glucose, L-sorbose, or glycerol failed to modify oxygen consumption. Only incubation in the presence of fructose showed a high aerobic glycolysis measured by lactate production.

  11. Efeitos do propofol na resposta contrátil do miocárdio à dopamina e dobutamina: estudo experimental em corações isolados de ratos Effects of the propofol in the myocardial contractile response to dopamine and dobutamine in isolated rat's heart

    Directory of Open Access Journals (Sweden)

    José Carlos Dorsa Pontes

    1996-12-01

    Full Text Available OBJETIVO: Estudo experimental das ações farmacodinâmicas do propofol e sua interação com a dopamina e dobutamina em corações isolados de ratos. MÉTODO: Foram estudadas as variações da contratilidade miocárdica (dT/dt, em 30 corações isolados de ratos. Em todos os animais, após anestesia por inalação de éter, os corações foram excisados e perfundidos em sistema de Langendorff com solução de Krebs - Hensleit enriquecida com 95% O2 e 5% CO2, (pressão de 90 cm de H2O, temperatura constante de 37,0ºC ± 0,5ºC. Foram estudados 30 animais divididos em: Grupo I (controle - 10 corações perfundidos durante 11 minutos com solução de Krebs - Hensleit; Grupo II (dopamina-propofol-dopamina -10 corações onde foram administrados dopamina (50 mcg/ml e analisados os resultados nos 1º, 3º e 5º minutos e, posteriormente, propofol, (25 mcg/ml infundindo-se 1 minuto após, dopamina (50 mcg/ml e analisando-se os 1º, 3º e 5º minutos. Grupo III (dobutamina-propofol-dobutamina - diferiu do Grupo II pela substituição da dopamina por dobutamina (50 mcg/ml. RESULTADOS: No Grupo I observou-se que a dT/dt variou de 39,57 ± 3,97 (g.seg-1 a 39,37 ± 3,44 (g.seg-1 (p>0,05 no período estudado. No Grupo II observou-se que, após a administração de propofol e dopamina, a dT/dt em (g.seg-1 apresentou queda de 17,61% (p0,05 no 1º minuto; 3,62% (p>0,05 no 3º minuto e 3,08% (p>0,05 no 5º minuto, comparado à injeção isolada da dobutamina. CONCLUSÃO: O propofol (25 mcg/ml não alterou a resposta contrátil do miocárdio à dobutamina (50 mcg/ml; no entanto, inibiu a resposta esperada pela ação da dopamina (50 mcg/ml na contratilidade miocárdica.PURPOSE: Experimental investigation of the pharmacodynamic effects of propofol with and without simultaneous injections of dopamine or dobutamine in isolated hearts of rats. METHODS: In all animals under anaesthesia the hearts were removed and irrigated by a Krebs-Hensleit solution containing O2

  12. Cardioprotective effect of hyperthyroidism on the stunned rat heart during ischaemia-reperfusion: energetics and role of mitochondria.

    Science.gov (United States)

    Ragone, María Inés; Bonazzola, Patricia; Colareda, Germán A; Consolini, Alicia E

    2015-06-01

    What is the central question of this study? Hyperthyroidism is a cardiac risk factor, but thyroid therapy is used on myocardial stunning. What is the consequence of hyperthyroidism for mitochondrial metabolism and Ca(2+) handling of the postischaemic stunned heart? What is the main finding and its importance? Hyperthyroidism reduced stunning and improved muscle economy of the postischaemic rat heart. The activities of the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channel in hyperthyroid rat hearts were different from those in the euthyroid rat hearts. These findings contribute to the understanding of mitochondrial bioenergetics in pathology and support thyroid therapy in the stunning induced by ischaemia. Transient ischaemia and hyperthyroidism are cardiovascular risk factors. Nevertheless, 3,5,3'-triiodothyronine/thyroxine therapy has been used to revert myocardial stunning. We studied the influence of hyperthyroidism on the role played by mitochondria in myocardial stunning consequent to ischaemia-reperfusion. Rats were injected s.c. daily with 20 μg kg(-1) triiodothyronine for 15 days (HpT group). Isolated ventricles from either HpT or euthyroid (EuT) rats were perfused in a calorimeter, and left intraventricular pressure (in millimetres of mercury) and heat release (Ht; in milliwatts per gram) were measured. Stunning was evoked by 20 min of no-flow ischaemia and 45 min reperfusion. The HpT hearts developed higher postischaemic contractile recovery (PICR) and improved total muscle economy (P/Ht) with lower diastolic contracture (ΔLVEDP) than EuT hearts. Release of Ca(2+) from the sarcoplasmic reticulum during reperfusion with 10 mm caffeine in low-[Na(+) ] Krebs solution evoked a higher contracture in EuT than in HpT hearts. Blockade of the mitochondrial sodium-calcium exchanger with clonazepam increased ΔLVEDP and reduced P/Ht and PICR in HpT but not in EuT hearts. The clonazepam-induced dysfunction in HpT hearts was reduced by

  13. Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart

    International Nuclear Information System (INIS)

    Bar, R.S.; Clemmons, D.R.; Boes, M.; Busby, W.H.; Booth, B.A.; Dake, B.L.; Sandra, A.

    1990-01-01

    Insulin-like growth factor (IGF) binding proteins (IGFBP) were purified from conditioned media of cultured bovine endothelial cells (ECBP) and from human amniotic fluid (IGFBP-1), and then labeled by radioiodination. 125I-ECBP and 125I-IGFBP-1 were perfused through isolated beating rat hearts for 1 and 5 min, and the hearts fixed and analyzed for 125I-BP content and distribution. One to 4% of the perfused 125I-ECBP and 125I-IGFBP-1 crossed the capillary boundary. The ECBPs predominantly localized as intact 125I-BP in connective tissue elements of the heart with less 125I-BP in cardiac muscle. The ratio of 125I-ECBP in connective tissue: muscle (normalized to percent vol of these compartments) was greater than or equal to 10:1. In contrast, the IGFBP-1 had a greater affinity for cardiac muscle with ratios of 125I-IGFBP-1 in connective tissue:muscle of approximately 1:2. When 125I-IGF-I, in the absence of any BPs, was perfused through the hearts approximately 3-5% left the microcirculation and was found in subendothelial tissues. 125I-IGF-I localized primarily to cardiac muscle with a distribution of connective tissue:cardiac muscle of about 1:3. The findings in the isolated perfused heart were confirmed in intact animals. After 125I-IGFBP-1 was injected into anesthetized rats and allowed to circulate for 5 min, substantial radioactivity was associated with the heart. As in the isolated heart, the IGFBP-1 preferentially localized to cardiac muscle with a connective tissue:cardiac muscle ratio of 1:3. We conclude that IGFBPs produced by endothelial cells and the IGFBP-1 contained in amniotic fluid can cross the capillary boundaries of the rat heart, and that the ECBPs preferentially localize in connective tissue elements of the myocardium, whereas IGFBP-1 predominantly localizes in cardiac muscle

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Isolation, culture and intraportal transplantation of rat marrow stromal cell

    International Nuclear Information System (INIS)

    Wang Ping; Wang Jianhua; Yan Zhiping; Li Wentao; Lin Genlai; Hu Meiyu; Wang Yanhong

    2004-01-01

    Objective: To observe the tracing and evolution of marrow stromal cell (MSC) after intraportal transplantation into the liver of homogenous rats, and to provide experimental data for MSC differentiation to hepatocyte in vivo. Methods: The MSC was isolated from the leg bone marrow of adult SD rats, and purified by culture-expanded in vitro. Before transplantation, MSC was labeled with DAPI. Then 10 5 MSC were intraportally transplanted into the homogenous rat liver. Rats were killed at 2 hours and 1, 2, 3 and 4 weeks after transplantation. The cryosection samples of liver and lung were observed under fluorescence microscopy. Results: MSC in vitro culture had high ability of proliferation. Except 4 rats were dead because of abdominal bleeding or infection, other recipients were healthy until sacrificed. The implantation cells were detected by identifying the DAPI labeled MSC in the host livers, but not in the host lungs. Conclusion: Intraportal transplanted MSC could immigrate and survive in the host livers at least for 4 weeks. They could immigrate from the small branches of portal veins to hepatic parenchyma

  16. Effects of perfusion pressure and insulin on (3H) cytochalasin B (CB) binding to control and diabetic rat hearts

    International Nuclear Information System (INIS)

    Pleta, M.; Chan, T.

    1987-01-01

    Using ( 3 H) CB, they attempted to quantitate the changes in the amount of glucose transporters in the plasma membrane (PM) and intracellular membranes (HSP) prepared from rat hearts perfused with insulin, under low and high pressure. Membranes isolated from non-perfused hearts showed a PM/HSP ratio of (0.593). Hearts perfused with low pressure showed a lower ratio of (0.474). Perfusion with insulin increased the ratio to (1.8), almost a 3-4 fold increase from low perfusion pressure. These data correlate with insulin effects in glucose transport and CB binding in the fat cells. High pressure perfusion increased the PM/HSP ratio by 1-2 fold. ( 3 H) 2-DG transport indicates a comparable increase in glucose uptake with high pressure, but with insulin only a 1.5 fold increase was observed. Initial data obtained from streptozotocin (STZ) injected diabetic rats indicate low CB binding in the PM fraction. Only insulin, but not high perfusion pressure increased PM/HSP ratio in the STZ-diabetic hearts. Their data imply that while both caused apparent translocation of glucose transporters, influences on cardiac glucose metabolism by work load are different. Furthermore, STZ induced diabetes affected only the high perfusion pressure-induced and not the insulin-stimulated change in CB binding

  17. Beta Adrenergic Regulation of Intrapulmonary Arteriovenous Anastomoses in Intact Rat and Isolated Rat Lungs

    Directory of Open Access Journals (Sweden)

    Melissa L. Bates

    2017-04-01

    Full Text Available Intrapulmonary arteriovenous anastomoses (IPAVA allow large diameter particles of venous origin to bypass the pulmonary capillary bed and embolize the systemic arterial circulation. IPAVA have been routinely observed in healthy humans with exercise, hypoxia, and catecholamine infusion, but the mechanism by which they are recruited is not well-defined. We hypothesized that beta-adrenergic receptor stimulation recruits IPAVA and that receptor blockade would limit hypoxia-induced IPAVA recruitment. To test our hypothesis, we evaluated the transpulmonary passage of microspheres in intact rats and isolated rats lung infused with the beta-adrenergic receptor agonist isoproterenol. We also evaluated IPAVA recruitment in intact rats with hypoxia and the beta-adrenergic receptor blocker propranolol. We found that IPAVA are recruited in the intact rat by isoproterenol and their recruitment by hypoxia can be minimized by propranolol, suggesting a role for the adrenergic system in the recruitment of IPAVA by hypoxia. IPAVA recruitment is completely abolished by ventilation with 100% oxygen. Isoproterenol also recruits IPAVA in isolated rat lungs. The fact that isoproterenol can recruit IPAVA in isolated lungs, without increased pulmonary flow, suggests that elevated cardiac output is not required for IPAVA recruitment.

  18. Use of microdialysis for monitoring sympathetic and parasympathetic innervation of heart in conscious rats

    NARCIS (Netherlands)

    Cremers, T.I.F.H.; Teisman, A.C H; van Gilst, W.H; Westerink, B.H.C.

    1997-01-01

    A microdialysis method was developed to sample norepinephrine and acetylcholine from the heart of freely moving rats. A flexible dialysis fiber (length 14 mm), with a copper wire inserted inside, was implanted into the heart. Extracellular norepinephrine was detectable for at least 72 h after

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

    NARCIS (Netherlands)

    W. Chai (Wenxia); I.M. Garrelds (Ingrid); U. Arulmani (Udayasankar); R.G. Schoemaker (Regien); J.M.J. Lamers (Jos); A.H.J. Danser (Jan)

    2005-01-01

    textabstract1. 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.

  20. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

    International Nuclear Information System (INIS)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-01-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. - Highlights: • Arsenic exposure has been associated with a number of adverse health effects. • The molecular mechanisms involved in arsenic-induced cardiotoxicity remain unclear. • Differential proteins were identified in arsenic-exposed rat heart by proteomics. • Arsenic induces heart toxicity through the Akt/p38 MAPK signaling pathway. - Label-free quantitative proteomic analysis of rat heart reveals putative mechanisms and biomarkers for arsenic-induced cardiotoxicity.

  1. Differential expression of parvalbumin interneurons in neonatal phencyclidine treated rats and socially isolated rats

    DEFF Research Database (Denmark)

    Kaalund, Sanne Simone; Riise, Jesper; Broberg, Brian

    2013-01-01

    of parvalbumin-positive interneurons (PV(+) interneurons). In this study we examined PV(+) expression in two rat models of cognitive dysfunction in schizophrenia, the environmental social isolation (SI) and pharmacological neonatal phencyclidine (neoPCP) models. Using a stereological method, the optical...

  2. Increased dopaminergic activity in socially isolated rats: an electrophysiological study

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Fink-Jensen, Anders

    2010-01-01

    The development of animal models mimicking symptoms associated with schizophrenia has been a critical step in understanding the neurobiological mechanisms underlying the disease. Long-term social isolation from weaning in rodents, a model based on the neurodevelopmental hypothesis of schizophrenia......, has been suggested to mimic some of the deficits seen in schizophrenic patients. We confirm in the present study that socially isolated rats display an increase in both spontaneous and d-amphetamine-induced locomotor activity, as well as deficits in sensorimotor gating as assessed in a pre......, and a change of firing activity towards a more irregular and bursting firing pattern. Taken together, our findings suggest that the behavioral phenotype induced by social isolation may be driven by an overactive dopamine system....

  3. Electromechanical effects of bepridil on rabbit isolated hearts.

    OpenAIRE

    Anno, T.; Furuta, T.; Itoh, M.; Kodama, I.; Toyama, J.; Yamada, K.

    1984-01-01

    Electromechanical effects of a new antianginal agent, bepridil, on Langendorff-perfused rabbit hearts were compared with those of verapamil and lidocaine. Bepridil at concentrations above 2 X 10(-7)M caused a dose-related decrease in heart rate (HR), a prolongation of the atrio-His bundle conduction time (A-H interval) and a prolongation of the functional refractory period (FRP) of the atrioventricular (A-V) node. Similar changes in HR, A-H interval and the FRP of the A-V node were observed w...

  4. Comparative effect of lidocaine and bupivacaine on glucose uptake and lactate production in the perfused working rat heart

    International Nuclear Information System (INIS)

    Cronau, L.H. Jr.; Merin, R.G.; Aboulish, E.; Steenberg, M.L.; Maljorda, A.

    1986-01-01

    It has been suggested that at equivalent therapeutic concentrations, lidocaine and bupivacaine may have different cardiotoxic potency. In the isolated working rat heart preparation, the effect of a range of lidocaine and bupivacaine concentrations on glucose uptake and lactate production (LP) were observed. Insulin was added, 10 μ/L, to Ringer's solution containing 3 H-labeled glucose to measure the glycolytic flux (GF). The effect of the local anesthetics on LP at the indicated concentrations were similar. Lidocaine appears to depress the glycolytic flux from exogenous glucose to a lesser degree. Bupivacaine, 10 mg/L, depresses VO 2 to a greater degree than does lidocaine, 40 mg/L

  5. Investigation of the behaviour of some elements in heart of thymectomised rats

    International Nuclear Information System (INIS)

    Kinova, L.

    1985-01-01

    By means of instrumental neutron activation annalysis the elements K, Mn, Ca and Zn in heart of normal (intact) and thymectomised Wistar rats. Thymectomy was performed at the age of 3 months. Analysed were the hearths of intact animals at the age 3, 6, 9 and 12 months and the hearts of thymectomised animals at 15 days, 3, 6, and 9 months after thymectomy. Collection, cleaning, storage of the samples, as well as the irradiation, cooling and measuring mode and analytical isotopes used were described. It was established that the changes in the concentrations of the elements K, Mn, and Zn decrease in comparision with intact rats, and Ca concentration in heart increases

  6. 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.

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

    International Nuclear Information System (INIS)

    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.

    2016-01-01

    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

  8. Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Iga, C.; Lau, H.; Hardy, M.A.

    1985-01-01

    The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators

  9. Protein phosphorylation in isolated hepatocytes of septic and endotoxemic rats

    International Nuclear Information System (INIS)

    Deaciuc, I.V.; Spitzer, J.A.

    1989-01-01

    The purpose of this study was to investigate possible alterations induced by sepsis and endotoxicosis in the late phase of Ca2+-dependent signaling in rat liver. Hepatocytes isolated from septic or chronically endotoxin (ET)-treated rats were labeled with [32P]H3PO4 and stimulated with various agents. Proteins were resolved by one-dimensional polyacrylamide gel electrophoresis and autoradiographed. Vasopressin (VP)- and phenylephrine (PE)-induced responses were attenuated in both septic and ET-treated rats for cytosolic and membrane proteins compared with their respective controls. Glucagon and 12-O-myristate phorbol-13-acetate (TPA) affected only the phosphorylation of membrane proteins. Glucagon-induced changes in the phosphorylation of membrane proteins were affected by both sepsis and endotoxicosis, whereas TPA-stimulated phosphorylation was lowered only in endotoxicosis. Response to the Ca2+ ionophore A23187 was depressed in septic rats for cytosolic proteins. The phosphorylation of two cytosolic proteins, i.e., 93 and 61 kDa (previously identified as glycogen phosphorylase and pyruvate kinase, respectively), in response to VP, PE, and A23187 was severely impaired by endotoxicosis and sepsis. TPA did not affect the phosphorylation state of these two proteins. The results show that sepsis and endotoxicosis produce perturbations of the phosphorylation step in Ca2+ transmembrane signaling. Such changes can explain alterations of glycogenolysis and gluconeogenesis associated with sepsis and endotoxicosis

  10. Increased ANF secretion after volume expansion is preserved in rats with heart failure

    International Nuclear Information System (INIS)

    Chien, Young Wei; Barbee, R.W.; MacPhee, A.L.; Frohlich, E.D.; Trippodo, N.C.

    1988-01-01

    To examine whether the failing heart has reached a maximal capacity to increase plasma atrial natriuretic factor (ANF) concentration, the change in plasma immunoreactive ANF, measured by radioimmunoassay level due to acute blood volume expansion was determined in conscious rats with chronic heart failure. Varying degrees of myocardial infarction and thus heart failure were induced by coronary artery ligation 3 wk before study. Compared with controls, infarcted rats had decreases in mean arterial pressure cardiac index, renal blood flow, and peak left ventricle-developed pressure after aortic occlusion, and increases in central venous pressure, left ventricular end-diastolic pressure, total peripheral resistance, plasma ANF level. Plasma ANF was correlated with infarct size, cardiac filling pressures, and left ventricle pressure-generating ability. At 5 min after 25% blood volume expansion, plasma ANF in rats with heart failure increased by 2,281 ± 345 pg/ml; the magnitude of the changes in circulating ANF and hemodynamic measurements was similar in controls. The results suggest that plasma ANF level can be used as a reliable index of the severity of heart failure, and that the capacity to increase plasma ANF concentration after acute volume expansion is preserved in rats with heart failure. There was no evidence of a relative deficiency of circulating ANF in this model of heart failure

  11. 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

  12. Coronary blood flow and thallium 201 uptake in rejecting rat heart transplantations

    International Nuclear Information System (INIS)

    Bergsland, J.; Hwang, K.; Driscoll, R.; Carr, E.A.; Wright, J.R.; Curran-Everett, D.C.; Carroll, M.; Krasney, E.; Krasney, J.A.

    1989-01-01

    The effects of rejection on coronary flow (CAF) in heart allografts are unclear, although previous evidence with cardiac imaging agents indicates impaired flow during advanced rejection. The purpose of this study was to measure CAF in heterotopically placed heart grafts. Lewis rats (LEW) received grafts from either syngeneic Lewis rats (LEW/LEW group) or allogeneic ACI rats (ACI/LEW group). CAF was measured in both the transplanted and native hearts with radiolabeled microspheres. Rejection was measured histologically (grades 0 [absent] to 4+ [severe]). In addition systemic blood pressure and cardiac outputs of the native hearts were determined with microspheres. Different animals were studied during relatively early (4 days) and late (6 days) rejection. Among the 4-day animals a cyclosporine-treated group was included (ACI/LEW CyA). In 6-day rats CAF in allografts was lower (0.56 +/- .06 ml/gm/min) compared with syngeneic grafts (1.72 +/- 0.4 ml/gm/min) (p less than 0.05). The CAF in the native hearts did not differ significantly but was higher than in the grafts in both groups. Heart rates were reduced in allografts (p less than 0.05). It is interesting that arterial pressure and cardiac output were significantly lower in animals bearing allogeneic than syngeneic grafts. In rats studied at 4 days graft CAF was lower than in the native heart in both the LEW/LEW and ACI/LEW groups, but there was no significant difference in behavior between groups. The same was true for a cyclosporine-treated group. Graft heart rates were similar in all 4-day rats

  13. Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

    Science.gov (United States)

    Honda, Nobuhiro; Hirooka, Yoshitaka; Ito, Koji; Matsukawa, Ryuichi; Shinohara, Keisuke; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

    2013-11-01

    Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved. As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction. Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

  14. Hyperthyroidism: Presenting as Isolated Tricuspid Regurgitation and Right Heart Failure

    OpenAIRE

    Whitner, Tanya E.; Hudson, Christopher J.; Smith, Timothy D.; Littmann, Laszlo

    2005-01-01

    Although hyperthyroidism has many signs and symptoms, right heart failure can occasionally be the main presenting symptom. We describe the case of a previously healthy 42-year-old woman whose chief complaint was progressive bilateral lower extremity edema. The echocardiogram revealed right atrial dilatation and moderate-to-severe tricuspid regurgitation. Results of laboratory studies were consistent with hyperthyroidism. Thyroid ablation resulted in permanent resolution of symptoms and resolu...

  15. Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

    Science.gov (United States)

    Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

    2015-02-01

    Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart

    DEFF Research Database (Denmark)

    Osadchii, Oleg E; Bentzen, Bo Hjorth; Olesen, Søren-Peter

    2009-01-01

    of hypokalaemic perfusion (2.5 mm K(+) for 30 min) were assessed in isolated guinea-pig heart preparations using simultaneous recordings of volume-conducted electrocardiogram and monophasic action potentials from six ventricular epicardial sites. Effective refractory periods, ventricular fibrillation thresholds...... for re-entrant tachyarrhythmias. Taken together, these findings suggest that proarrhythmic effects of hypokalaemia are mostly attributed to increased LV arrhythmogenicity in the guinea-pig heart....

  17. 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.

  18. L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

    Science.gov (United States)

    Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

    2009-02-01

    The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

  19. Reactivity of the isolated perfused rat tail vascular bed

    Directory of Open Access Journals (Sweden)

    A.S. França

    1997-07-01

    Full Text Available Isolated segments of the perfused rat tail artery display a high basal tone when compared to other isolated arteries such as the mesenteric and are suitable for the assay of vasopressor agents. However, the perfusion of this artery in the entire tail has not yet been used for functional studies. The main purpose of the present study was to identify some aspects of the vascular reactivity of the rat tail vascular bed and validate this method to measure vascular reactivity. The tail severed from the body was perfused with Krebs solution containing different Ca2+ concentrations at different flow rates. Rats were anesthetized with sodium pentobarbital (65 mg/kg and heparinized (500 U. The tail artery was dissected near the tail insertion, cannulated and perfused with Krebs solution plus 30 µM EDTA at 36oC and 2.5 ml/min and the procedures were started after equilibration of the perfusion pressure. In the first group a dose-response curve to phenylephrine (PE (0.5, 1, 2 and 5 µg, bolus injection was obtained at different flow rates (1.5, 2.5 and 3.5 ml/min. The mean perfusion pressure increased with flow as well as PE vasopressor responses. In a second group the flow was changed (1.5, 2, 2.5, 3 and 3.5 ml/min at different Ca2+ concentrations (0.62, 1.25, 2.5 and 3.75 mM in the Krebs solution. Increasing Ca2+ concentrations did not alter the flow-pressure relationship. In the third group a similar protocol was performed but the rat tail vascular bed was perfused with Krebs solution containing PE (0.1 µg/ml. There was an enhancement of the effect of PE with increasing external Ca2+ and flow. PE vasopressor responses increased after endothelial damage with air and CHAPS, suggesting an endothelial modulation of the tone of the rat tail vascular bed. These experiments validate the perfusion of the rat tail vascular bed as a method to investigate vascular reactivity

  20. Standardization of an isolated pig heart preparation with parabiotic circulation: methodological considerations

    Directory of Open Access Journals (Sweden)

    Petrucci Júnior O.

    2003-01-01

    Full Text Available In the present study we standardized an experimental model of parabiotic circulation of isolated pig heart. The isolated heart was perfused with arterial blood from a second animal as support and submitted to regional ischemia for 30 min, followed by total ischemia for 90 min and reperfusion for 90 min. Parameters for measurement of ventricular performance using different indices measured directly or indirectly from intraventricular pressure were defined as: maximum peak pressure, final diastolic pressure, pressure developed, first derivative of maximum pressure (dP/dt max, first derivative of minimum pressure (dP/dt min, systolic stress of the left ventricle (sigmas, and maximum elastance of the left ventricle. Isolated hearts subjected to regional and global ischemia presented significant worsening of all measured parameters. Less discriminative parameters were dP/dt max and dP/dt min. Elastance was the most sensitive parameter during the reperfusion period, demonstrating an early loss of ventricular function during reperfusion. The model proved to be stable and reproducible and permitted the study of several variables in the isolated heart, such as ischemia and reperfusion phenomena, the effects of different drugs, surgical interventions, etc. The model introduces an advantage over the classical models which use crystalloid solutions as perfusate, because parabiotic circulation mimics heart surgery with extracorporeal circulation.

  1. Myocardial energy metabolism during global ischemia and reperfusion in SHR hypertrophic rat heart assessed by 31P-NMR

    International Nuclear Information System (INIS)

    Shirotani, Hitoshi; Oka, Hiroshi; Katayama, Osamu; Nishioka, Takazumi; Oku, Hidetaka

    1983-01-01

    An experiment regarding myocardial ischemia and reperfusion was performed under various conditions in SHR hypertrophic and WKY non-hypertrophic rat hearts. An effect of cardioplegia was evaluated in the following 4 conditions, that is, Group 1: hypothermia only, Group 2: hypothermia with intermittent infusion of GIK solution, Group 3: hypothermia with intermittent infusion of cold blood cardioplegia, Group 4: hypothermia with intermittent infusion of cold blood cardioplegia and administration of coenzyme Q 10 prior to isolation of the heart. 1) In WKY heart, ATP contents after 90 minutes myocardial ischemia at 15 0 C decreased to 25% in Group 1,42% in Group 2,52% in Group 3 and 62% in Group 4, and the contents after 30 minutes reperfusion increased to 42, 50, 60 and 75%, respectively. On the other hand, in SHR heart, ATP contents decreased to 22, 38, 40 and 41% but no trend of recovery was present. 2) Creatine phosphate content in SHR heart was 50% of that in WKY heart during isolated perfusion. Creatine phosphate decreased to zero after 30 minutes myocardial ischemia. In WKY heart, the content was recovered to over 100% by 30 minutes reperfusion after 90 minutes myocardial ischemia in all groups. On the contrary, in SHR heart, the contents increased to only 10, 15, 22 and 41%, in 4 groups, respectively. 3) In WKY heart, pH fell to 6.2, 6.7, 6.8 and 6.8, in 4 groups, respectively, a fter 90 minutes myocardial ischemia, and returned to the preischemic value of 7.2 after 30 minutes reperfusion in all groups. In SHR heart, pH fell to 6.1 in group 1, 6.3 in group 2, 6.4 in group 3 and 6.7 in group 4 after 90 minutes myocardial ischemia and the values returned to 6.5, 6.6, 6.7 and 6.8, respectively, after 30 minutes reperfusion. The latter values were lower than preischemic value of 7.0. (J.P.N.)

  2. Myocardial energy metabolism during global ischemia and reperfusion in SHR hypertrophic rat heart assessed by /sup 31/P-NMR

    Energy Technology Data Exchange (ETDEWEB)

    Shirotani, Hitoshi; Oka, Hiroshi; Katayama, Osamu; Nishioka, Takazumi; Oku, Hidetaka [Kinki Univ., Higashi-Osaka, Osaka (Japan)

    1983-12-01

    An experiment regarding myocardial ischemia and reperfusion was performed under various conditions in SHR hypertrophic and WKY non-hypertrophic rat hearts. An effect of cardioplegia was evaluated in the following 4 conditions, that is, Group 1: hypothermia only, Group 2: hypothermia with intermittent infusion of GIK solution, Group 3: hypothermia with intermittent infusion of cold blood cardioplegia, Group 4: hypothermia with intermittent infusion of cold blood cardioplegia and administration of coenzyme Q/sub 10/ prior to isolation of the heart. 1) In WKY heart, ATP contents after 90 minutes myocardial ischemia at 15/sup 0/ C decreased to 25% in Group 1,42% in Group 2,52% in Group 3 and 62% in Group 4, and the contents after 30 minutes reperfusion increased to 42, 50, 60 and 75%, respectively. On the other hand, in SHR heart, ATP contents decreased to 22, 38, 40 and 41% but no trend of recovery was present. 2) Creatine phosphate content in SHR heart was 50% of that in WKY heart during isolated perfusion. Creatine phosphate decreased to zero after 30 minutes myocardial ischemia. In WKY heart, the content was recovered to over 100% by 30 minutes reperfusion after 90 minutes myocardial ischemia in all groups. On the contrary, in SHR heart, the contents increased to only 10, 15, 22 and 41%, in 4 groups, respectively. 3) In WKY heart, pH fell to 6.2, 6.7, 6.8 and 6.8, in 4 groups, respectively, a fter 90 minutes myocardial ischemia, and returned to the preischemic value of 7.2 after 30 minutes reperfusion in all groups. In SHR heart, pH fell to 6.1 in group 1, 6.3 in group 2, 6.4 in group 3 and 6.7 in group 4 after 90 minutes myocardial ischemia and the values returned to 6.5, 6.6, 6.7 and 6.8, respectively, after 30 minutes reperfusion. The latter values were lower than preischemic value of 7.0.

  3. Prevention of reperfusion lung injury by lidocaine in isolated rat lung ventilated with higher oxygen levels.

    Directory of Open Access Journals (Sweden)

    Das K

    2003-01-01

    Full Text Available BACKGROUND: Lidocaine, an antiarrhythmic drug has been shown to be effective against post-ischaemic reperfusion injury in heart. However, its effect on pulmonary reperfusion injury has not been investigated. AIMS: We investigated the effects of lidocaine on a postischaemic reperfused rat lung model. MATERIALS AND METHODS: Lungs were isolated and perfused at constant flow with Krebs-Henseilet buffer containing 4% bovine serum albumin, and ventilated with 95% oxygen mixed with 5% CO2. Lungs were subjected to ischaemia by stopping perfusion for 60 minutes followed by reperfusion for 10 minutes. Ischaemia was induced in normothermic conditions. RESULTS: Postischaemic reperfusion caused significant (p < 0.0001 higher wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure compared to control lungs. Lidocaine, at a dose of 5mg/Kg b.w. was found to significantly (p < 0.0001 attenuate the increase in the wet-to-dry lung weight ratio, pulmonary arterial pressure and peak airway pressure observed in post-ischaemic lungs. CONCLUSION: Lidocaine is effective in preventing post-ischaemic reperfusion injury in isolated, perfused rat lung.

  4. Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

    Science.gov (United States)

    da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

    2015-07-15

    We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. Copyright © 2015 the American Physiological Society.

  5. Protective Effect of Antenatal Antioxidant on Nicotine-Induced Heart Ischemia-Sensitive Phenotype in Rat Offspring.

    Directory of Open Access Journals (Sweden)

    DaLiao Xiao

    Full Text Available Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.

  6. The Effect of Chlorpyrifos on Isolated Thoracic Aorta in Rats

    Directory of Open Access Journals (Sweden)

    Ebru Yıldırım

    2013-01-01

    Full Text Available This study investigated the effect of chlorpyrifos on thoracic aorta and on the level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups with 15 rats each: control group 1 received distilled water, control group 2 was given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in corn oil every other day for 8 weeks orally. Chlorpyrifos (10−10 M–10−5 M showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased, while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group compared to control groups. Plasma NO level was increased in chlorpyrifos group compared to control groups. iNOS expression was present in all groups in the cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to semiquantitative histomorphological analysis, iNOS immunopositive reactions were seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups. eNOS immunopositive reactions were observed in the endothelial cell cytoplasm, rarely in the subintimal layer, and the smooth muscle cells of aorta. There were no differences among the groups in terms of eNOS immunostaining. In conclusion, chlorpyrifos induced NO production in aorta following an increase in NOS expression.

  7. The Effect of Chlorpyrifos on Isolated Thoracic Aorta in Rats

    Science.gov (United States)

    Yıldırım, Ebru; Baydan, Emine; Kanbur, Murat; Kul, Oğuz; Çınar, Miyase; Ekici, Hüsamettin; Atmaca, Nurgül

    2013-01-01

    This study investigated the effect of chlorpyrifos on thoracic aorta and on the level of NO in plasma and aorta. The effect of chlorpyrifos on thoracic aorta in organ bath was determined in 10 rats. Another 45 rats were assigned to 3 groups with 15 rats each: control group 1 received distilled water, control group 2 was given corn oil, and the last group was given 13.5 mg/kg chlorpyrifos dissolved in corn oil every other day for 8 weeks orally. Chlorpyrifos (10−10 M–10−5 M) showed no effect on isolated thoracic aorta. Plasma AChE activity was decreased, while LDH, ALT, GGT, and AST activities were increased in chlorpyrifos group compared to control groups. Plasma NO level was increased in chlorpyrifos group compared to control groups. iNOS expression was present in all groups in the cytoplasm of the endothelia and in the smooth muscle cells of aorta. According to semiquantitative histomorphological analysis, iNOS immunopositive reactions were seen in the decreasing order in chlorpyrifos, control 2, and control 1 groups. eNOS immunopositive reactions were observed in the endothelial cell cytoplasm, rarely in the subintimal layer, and the smooth muscle cells of aorta. There were no differences among the groups in terms of eNOS immunostaining. In conclusion, chlorpyrifos induced NO production in aorta following an increase in NOS expression. PMID:23878805

  8. Isolation and purification of rat liver morphine UDP-glucuronosyltransferase

    International Nuclear Information System (INIS)

    Puig, J.F.; Tephly, T.R.

    1986-01-01

    The enhancement of rat liver microsomal morphine (M) and 4-hydroxybiphenyl (4-HBP) UDP-glucuronyltransferase (UDPGT) activities by phenobarbital treatment has been proposed to represent increased activity of a single enzyme form, GT-2. They have separated M and 4-HBP UDPGT activities from Emulgen 911-solubilized microsomes obtained from livers of phenobarbital-treated Wistar rats. A sensitive assay procedure was developed to quantify M-UDPGT and 4-HBP-UDPGT activities using 14 C-UDP-glucuronic acid (UDPGA) and reversed phase C-18 minicolumns whereby the radioactive glucuronides were differentially eluted from labeled UDPGA. Trisacryl DEAE, and chromatofocusing procedures were employed to separate M-UDPGT and 4-HBP-UDPGT in the presence of exogenous phosphatidylcholine (PC). The PC is necessary to stabilize UDPGT activities. M-UDPGT was isolated to apparent homogeneity and displayed a monomeric molecular weight of 56,000 daltons on SDS-PAGE. It reacted with M but not with 4-HBP, bilirubin, p-nitrophenol, testosterone, androsterone, estrone, 4-aminobiphenyl or α-naphthylamine. 4-HBP-UDPGT did not react with M. Therefore, M and 4-HBP glucuronidations are catalyzed by separate enzymes in rat liver microsomes

  9. Notch1 Mediates Preconditioning Protection Induced by GPER in Normotensive and Hypertensive Female Rat Hearts

    Directory of Open Access Journals (Sweden)

    Carmine Rocca

    2018-05-01

    Full Text Available G protein-coupled estrogen receptor (GPER is an estrogen receptor expressed in the cardiovascular system. G1, a selective GPER ligand, exerts cardiovascular effects through activation of the PI3K-Akt pathway and Notch signaling in normotensive animals. Here, we investigated whether the G1/GPER interaction is involved in the limitation of infarct size, and improvement of post-ischemic contractile function in female spontaneous hypertensive rat (SHR hearts. In this model, we also studied Notch signaling and key components of survival pathway, namely PI3K-Akt, nitric oxide synthase (NOS and mitochondrial K+-ATP (MitoKATP channels. Rat hearts isolated from female SHR underwent 30 min of global, normothermic ischemia and 120 min of reperfusion. G1 (10 nM alone or specific inhibitors of GPER, PI3K/NOS and MitoKATP channels co-infused with G1, just before I/R, were studied. The involvement of Notch1 was studied by Western blotting. Infarct size and left ventricular pressure were measured. To confirm endothelial-independent G1-induced protection by Notch signaling, H9c2 cells were studied with specific inhibitor, N-[N-(3,5 difluorophenacetyl-L-alanyl]-S-phenylglycine t-butyl ester (DAPT, 5 μM, of this signaling. Using DAPT, we confirmed the involvement of G1/Notch signaling in limiting infarct size in heart of normotensive animals. In the hypertensive model, G1-induced reduction in infarct size and improvement of cardiac function were prevented by the inhibition of GPER, PI3K/NOS, and MitoKATP channels. The involvement of Notch was confirmed by western blot in the hypertensive model and by the specific inhibitor in the normotensive model and cardiac cell line. Our results suggest that GPERs play a pivotal role in mediating preconditioning cardioprotection in normotensive and hypertensive conditions. The G1-induced protection involves Notch1 and is able to activate the survival pathway in the presence of comorbidity. Several pathological conditions

  10. PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

    Science.gov (United States)

    Kurtz, Melisa; Capobianco, Evangelina; Martinez, Nora; Roberti, Sabrina Lorena; Arany, Edith; Jawerbaum, Alicia

    2014-10-01

    In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands. © 2014 Society for Endocrinology.

  11. The Actions of Lyophilized Apple Peel on the Electrical Activity and Organization of the Ventricular Syncytium of the Hearts of Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Elideth Martínez-Ladrón de Guevara

    2016-01-01

    Full Text Available This study was designed to examine the effects of lyophilized red delicious apple peel (RDP on the action potentials (APs and the input resistance-threshold current relationship. The experiments were performed on isolated papillary heart muscles from healthy male rats, healthy male rats treated with RDP, diabetic male rats, and diabetic male rats treated with RDP. The preparation was superfused with oxygenated Tyrode’s solution at 37°C. The stimulation and the recording of the APs, the input resistance, and the threshold current were made using conventional electrophysiological methods. The RDP presented no significant effect in normal rats. Equivalent doses in diabetic rats reduced the APD and ARP. The relationship between input resistance and threshold current established an inverse correlation. The results indicate the following: (1 The functional structure of the cardiac ventricular syncytium in healthy rats is heterogeneous, in terms of input resistance and threshold current. Diabetes further accentuates the heterogeneity. (2 As a consequence, conduction block occurs and increases the possibility of reentrant arrhythmias. (3 These modifications in the ventricular syncytium, coupled with the increase in the ARP, are the adequate substrate so that, with diabetes, the heart becomes more arrhythmogenic. (4 RDP decreases the APD, the ARP, and most syncytium irregularity caused by diabetes.

  12. Hesperidin produces cardioprotective activity via PPAR-γ pathway in ischemic heart disease model in diabetic rats.

    Directory of Open Access Journals (Sweden)

    Yogeeta O Agrawal

    Full Text Available The present study investigated the effect of hesperidin, a natural flavonoid, in cardiac ischemia and reperfusion (I/R injury in diabetic rats. Male Wistar rats with diabetes were divided into five groups and were orally administered saline once daily (IR-sham and IR-control, Hesperidin (100 mg/kg/day; IR-Hesperidin, GW9962 (PPAR-γ receptor antagonist, or combination of both for 14 days. On the 15th day, in the IR-control and IR-treatment groups, rats were subjected to left anterior descending (LAD coronary artery occlusion for 45 minutes followed by a one-hour reperfusion. Haemodynamic parameters were recorded and rats were sacrificed; hearts were isolated for biochemical, histopathological, ultrastructural and immunohistochemistry. In the IR-control group, significant ventricular dysfunctions were observed along with enhanced expression of pro-apoptotic protein Bax. A decline in cardiac injury markers lactate dehydrogenase activity, CK-MB and increased content of thiobarbituric acid reactive substances, a marker of lipid peroxidation, and TNF-α were observed. Hesperidin pretreatment significantly improved mean arterial pressure, reduced left ventricular end-diastolic pressure, and improved both inotropic and lusitropic function of the heart (+LVdP/dt and -LVdP/dt as compared to IR-control. Furthermore, hesperidin treatment significantly decreased the level of thiobarbituric acid reactive substances and reversed the activity of lactate dehydrogenase towards normal value. Hesperidin showed anti-apoptotic effects by upregulating Bcl-2 protein and decreasing Bax protein expression. Additionally, histopathological and ultrastructural studies reconfirmed the protective action of hesperidin. On the other hand, GW9662, selective PPAR-γ receptor antagonist, produced opposite effects and attenuated the hesperidin induced improvements. The study for the first time evidence the involvement of PPAR-γ pathway in the cardioprotective activity of

  13. Isolating the delay component of impulsive choice in adolescent rats

    Directory of Open Access Journals (Sweden)

    Jesse eMcClure

    2014-01-01

    Full Text Available Impulsive choice — the preference for small immediate rewards over larger delayed rewards — has been linked to various psychological conditions ranging from behavioral disorders to addiction. These links highlight the critical need to dissect the various components of this multifaceted behavioral trait. Delay discounting tasks allow researchers to study an important factor of this behavior: how the subjective value of a rewards changes over a delay period. However, existing methods of delay discounting include a confound of modifying reward sizes during the procedure. Here we present a new approach of using a single constant reward size to assess delay discounting. A complementary approach could hold delay constant and assess the utility of changing quantities of a reward. Isolating these behavioral components can advance our ability to explore the behavioral complexity of impulsive choice. We present the methods for isolating delay in detail, and further capitalize on this method by pairing it with a standard peak interval task to test whether individual variation in delay discounting can be explained by differences in perception of time in male and female adolescent rats. We find that rats that were more precise in discriminating time intervals were also less impulsive in their choice. Our data suggest that differences in timing and delay discounting are not causally related, but instead are more likely influenced by a common factor. Further, the mean-level change in our measure between postnatal day 28 and 42 suggests this test may be capturing a developmental change in this factor. In summary, this new method of isolating individual components of impulsive choice (delay or quantity can be efficiently applied in either adolescent or adult animal models and may help elucidate the mechanisms underlying impulsivity and its links to psychological disorders.

  14. Water and nonelectrolyte permeability of isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Alpini, G.; Garrick, R.A.; Jones, M.J.; Nunes, R.; Tavoloni, N.

    1986-01-01

    We have measured the diffusive permeability coefficients of isolated rat hepatocytes to 3 H 2 O, [ 14 C]urea, [ 14 C]erythritol, [ 14 C]mannitol, [ 3 H]sucrose, and [ 3 H]inulin, employing a technique previously developed for erythrocytes (Redwood et al., J. Gen. Physiol 64:706-729, 1974). Diffusion coefficients for the tracer molecules were measured in packed hepatocytes, supernatant fluid, and intracellular medium (lysed hepatocytes) and were calculated assuming one-dimensional semi-infinite diffusion through a homogeneous medium. By applying the series-parallel pathway model, the following permeability coefficients (10(-5) cm/sec) for the hepatocyte plasma membrane were obtained. 3 H 2 O, 98.6 +/- 18.4; [ 14 C]urea, 18.2 +/- 5.3; [ 14 C]erythritol, 4.8 +/- 1.6; [ 14 C]mannitol, 3.1 +/- 1.4; [ 3 H]sucrose, 0; [ 3 H]inulin, 0. These results indicate that isolated rat hepatocytes are highly permeable to water and polar nonelectrolytes, when compared with other transporting epithelia. This relatively high cellular permeability is consistent with a model in which nonelectrolyte permeation is via an aqueous pathway of equivalent pore diameter of 8-12 A. The finding that [ 14 C]erythritol and [ 14 C]mannitol cross the hepatocyte plasma membrane indicates that these molecules enter the bile canaliculus through the transcellular route. Conversely, the failure of [ 3 H]sucrose and [ 3 H]inulin to permeate the hepatocyte in the isolated condition supports the concept that biliary entry of these large carbohydrates, at least that fraction which cannot be accounted for by a vesicular mechanism, must occur via the transjunctional shunt pathway

  15. Uptake, incorporation and metabolism of (3H)triolein in the isolated perfused rabbit heart

    International Nuclear Information System (INIS)

    Weis, M.T.; Palazzo, A.J.; Williams, J.L. Jr.; Malik, K.U.

    1990-01-01

    The purpose of these experiments was to study the uptake and metabolism of exogenous triglyceride in the isolated perfused rabbit heart. When infused into the rabbit heart, [9,10-3H(N)]triolein was retained and incorporated into a lipid fraction that had the chromatographic mobility of authentic triolein. Incorporation of labeled triolein was not likely to be the result of a lipoprotein lipase-mediated lipolysis/resynthesis cycle, since: (i) The distribution of radioactivity following administration of [3H]oleic acid was markedly different from the distribution of radioactivity following the administration of [3H]triolein; (ii) heparin was administered to the rabbits at the time of sacrifice; and (iii) the hearts were perfused with a protein-free buffer for 20 min prior to the labelling period. When isoproterenol was administered to hearts labelled with [3H]triolein, there was an increased output of total radioactivity, composed of labelled free fatty acids, diacylglycerol and monoacylglycerol. In these same hearts, there was an increased output of glycerol in response to isoproterenol. However, following the administration of bradykinin or angiotensin II, neither the radioactivity nor the glycerol content of the perfusate was changed. These data suggest that [3H]triolein is selectively incorporated into the triglyceride pool of the isolated perfused rabbit heart. Furthermore, this [3H]triolein is available to hormonally-activated lipolytic enzymes

  16. Delayed Repolarization Underlies Ventricular Arrhythmias in Rats With Heart Failure and Preserved Ejection Fraction.

    Science.gov (United States)

    Cho, Jae Hyung; Zhang, Rui; Kilfoil, Peter J; Gallet, Romain; de Couto, Geoffrey; Bresee, Catherine; Goldhaber, Joshua I; Marbán, Eduardo; Cingolani, Eugenio

    2017-11-21

    Heart failure with preserved ejection fraction (HFpEF) represents approximately half of heart failure, and its incidence continues to increase. The leading cause of mortality in HFpEF is sudden death, but little is known about the underlying mechanisms. Dahl salt-sensitive rats were fed a high-salt diet (8% NaCl) from 7 weeks of age to induce HFpEF (n=38). Rats fed a normal-salt diet (0.3% NaCl) served as controls (n=13). Echocardiograms were performed to assess systolic and diastolic function from 14 weeks of age. HFpEF-verified and control rats underwent programmed electrical stimulation. Corrected QT interval was measured by surface ECG. The mechanisms of ventricular arrhythmias (VA) were probed by optical mapping, whole-cell patch clamp to measure action potential duration and ionic currents, and quantitative polymerase chain reaction and Western blotting to investigate changes in ion channel expression. After 7 weeks of a high-salt diet, 31 of 38 rats showed diastolic dysfunction and preserved ejection fraction along with signs of heart failure and hence were diagnosed with HFpEF. Programmed electric stimulation demonstrated increased susceptibility to VA in HFpEF rats ( P hearts demonstrated prolonged action potentials ( P hearts. Susceptibility to VA was markedly increased in rats with HFpEF. Underlying abnormalities include QT prolongation, delayed repolarization from downregulation of potassium currents, and multiple reentry circuits during VA. Our findings are consistent with the hypothesis that potassium current downregulation leads to abnormal repolarization in HFpEF, which in turn predisposes to VA and sudden cardiac death. © 2017 American Heart Association, Inc.

  17. Effect of increased left ventricle mass on ischemia assessment in electrocardiographic signals: rabbit isolated heart study

    Czech Academy of Sciences Publication Activity Database

    Ronzhina, M.; Olejníčková, Veronika; Stračina, T.; Nováková, M.; Janoušek, O.; Hejč, J.; Kolářová, J.; Hlaváčová, M.; Paulová, H.

    2017-01-01

    Roč. 17, Aug 4 (2017), č. článku 216. ISSN 1471-2261 Institutional support: RVO:67985823 Keywords : myocardial ischemia detection * increased left ventricular mass * electrogram * ROC analysis * isolated heart * rabbit Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Physiology (including cytology) Impact factor: 1.832, year: 2016

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

    International Nuclear Information System (INIS)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar

    2015-01-01

    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 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 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

  19. 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.

  20. 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.

  1. Uptake of 67Ga in the heart of rats treated with isoproterenol

    International Nuclear Information System (INIS)

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

    1982-01-01

    Gallium-67 citrate ( 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 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 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 67 Ga accumulation during the repair of rat heart with infarct-like lesions, in accord with our previous results on CCl 4 -damaged rat liver. (orig.)

  2. Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

    Directory of Open Access Journals (Sweden)

    Matthew S Barnabei

    Full Text Available Duchenne muscular dystrophy (DMD is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α(2 mutant mice, but not in dysferlin-null mice, suggesting that increased whole-organ compliance in mdx mice is a specific effect of disrupted cell-extracellular matrix contacts and not a general consequence of cardiomyopathy via membrane defect processes. Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.

  3. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, van den G.J.; de Goeij, J.J.M.; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendriks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (<1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  4. Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

    NARCIS (Netherlands)

    Berg, G.J. van den; Goeij, J.J.M. de; Bock, I.; Gijbels, M.J.J.; Brouwer, A.; Lei, K.Y.; Hendruiks, H.F.J.

    1991-01-01

    Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (< 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver,

  5. Importance of Pulmonary Vein Preferential Fibrosis for Atrial Fibrillation Promotion in Hypertensive Rat Hearts.

    Science.gov (United States)

    Iwasaki, Yu-Ki; Yamashita, Takeshi; Sekiguchi, Akiko; Hayami, Noriyuki; Shimizu, Wataru

    2016-06-01

    Hypertension is one of the independent risk factors for atrial fibrillation (AF). Pulmonary veins (PVs) play an important role as the substrate for AF and triggers of AF. The purpose of this study was to determine the structural remodelling of the PVs and its effect on promoting AF in hypertensive (HT) rat hearts. Eighteen-week-old Dahl salt-sensitive HT rats and their controls were used for histological and immunohistological analyses, and electrophysiological studies were performed in Langendorff perfused hearts. Masson-trichrome staining revealed that hypertension significantly increased the fibrosis in the PVs, particularly in subendocardial and perivascular areas, compared with that in control rats, however, at this early stage of hypertension, left atrial fibrosis was not prominent. In the HT rat hearts with PVs, electrical stimulation significantly increased the number of repetitive atrial firing and atrial tachycardia inducibility, which significantly diminished after the excision of the PVs. An immunofluorescent analysis revealed that HT rats had PV specific endocardial smooth muscle actin (αSMA)-positive cells with remarkable proliferation of platelet-derived growth factor (PDGF)-C and vascular endothelial growth factor (VEGF), which was lacking in the left atrial structures of the control and the HT rats. Pretreatment with imatinib, a PDGF receptor activity blocker, in HT rats reduced the αSMA-positive cell proliferation and fibrosis in the PVs and also induced a significant reduction in VEGF expression. Also, the drug pretreatment effectively prevented repetitive atrial firing promotion without affecting the blood pressure. PV preferential fibrosis might play an important role in the arrhythmogenic substrate of AF in HT rat hearts. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  6. Effect of Housing Rats in Dim Light or Long Nights on Heart Rate

    OpenAIRE

    Azar, Toni A; Sharp, Jody L; Lawson, David M

    2008-01-01

    Housing laboratory animals under lighting conditions that more closely mimic the natural environment may improve their wellbeing. This study examined the effects of dim light or a long-night photocycle on resting heart rate (HR) of rats and their HR responses to acute procedures. Male and female Sprague–Dawley (SD) and spontaneously hypertensive (SHR) rats, instrumented with radiotelemetry transmitters and housed individually under a 12:12-h light:dark photocycle with 10 lx illumination (dim ...

  7. Effect of venlafaxine hydrochloride in different preparations of isolated guinea-pig and rat organ tissues.

    Science.gov (United States)

    Velasco, A; Arruza, A; Maroto, M; Carvajal, A; Fernández del Busto, E; García del Pozo, J

    1999-04-01

    A study was undertaken to know better the effects of venlafaxine hydrochloride on the responses of isolated rat vas deferens to noradrenaline and dopamine, those of isolated rat uterus to serotonin and histamine, and those of isolated guinea-pig ileum to acetylcholine and histamine. Venlafaxine hydrochloride increased the response of rat vas deferens to noradrenaline but not to dopamine. Venlafaxine did not alter the response of rat isolated uterus to serotonin. In rat uterus, venlafaxine did not modify the response to histamine but was able to increase it in guinea-pig ileum. An anticholinergic effect was observed with the lowest concentration tested. Although venlafaxine is a selective serotonine reuptake inhibitor in the central nervous system, serotonin uptake was not seen in the rat uterus. The anticholinergic effects observed in the present study might be consistent with some of the side-effects associated with venlafaxine.

  8. Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

    Directory of Open Access Journals (Sweden)

    Casper G. Schalkwijk

    2013-07-01

    Full Text Available Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE Nε-(1-carboxymethyllysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.

  9. Substrate specific effects of calcium on metabolism of rat heart mitochondria.

    Science.gov (United States)

    Panov, A V; Scaduto, R C

    1996-04-01

    Oxidative metabolism in the heart is tightly coupled to mechanical work. Because this coupling process is believed to involve Ca2+, the roles of mitochondrial Ca2+ in the regulation of oxidative phosphorylation was studied in isolated rat heart mitochondria. The electrical component of the mitochondrial membrane potential (delta psi) and the redox state of the pyridine nucleotides were determined during the oxidation of various substrates under different metabolic states. In the absence of added adenine nucleotides, the NADP+ redox couple was almost completely reduced, regardless of the specific substrate and the presence of Ca2+, whereas NAD+ couple redox state was highly dependent on the substrate type and the presence of Ca2+. Titration of respiration with ADP, in the presence of excess hexokinase and glucose, showed that both respiration and NAD(P)+ reduction were very sensitive to ADP. The maximal enzyme reaction rate of ADP-stimulated respiration Michaelis constants (Km) for ADP were dependent on the particular substrate employed. delta psi was much less sensitive to ADP. With either alpha-ketoglutarate or glutamate as substrate, Ca2+ significantly increased reduction of NAD(P)+.Ca2+ did not influence NAD(P)+ reduction with either acetylcarnitine or pyruvate as substrate. In the presence of ADP, delta psi was increased by Ca2+ at all metabolic states with glutamate plus malate, 0.5 mM alpha-ketoglutarate plus malate, or pyruvate plus malate as substrates. The data presented support the hypothesis that cardiac respiration is controlled by the availability of both Ca2+ and ADP to mitochondria. The data indicate that an increase in substrate supply to mitochondria can increase mitochondrial respiration at given level of ADP. This effect can be produced by Ca2+ with substrates such as glutamate, which utilize alpha-ketoglutarate dehydrogenase activity for oxidation. Increases in respiration by Ca2+ may mitigate an increase in ADP during periods of increased

  10. Overexpression of cyclic adenosine monophosphate effluent protein MRP4 induces an altered response to β-adrenergic stimulation in the senescent rat heart.

    Science.gov (United States)

    Carillion, Aude; Feldman, Sarah; Jiang, Cheng; Atassi, Fabrice; Na, Na; Mougenot, Nathalie; Besse, Sophie; Hulot, Jean-Sébastien; Riou, Bruno; Amour, Julien

    2015-02-01

    In the senescent heart, the positive inotropic response to β-adrenoceptor stimulation is reduced, partly by dysregulation of β1- and β3-adrenoceptors. The multidrug resistance protein 4 (MRP4) takes part in the control of intracellular cyclic adenosine monophosphate concentration by controlling its efflux but the role of MRP4 in the β-adrenergic dysfunction of the senescent heart remains unknown. The β-adrenergic responses to isoproterenol were investigated in vivo (stress echocardiography) and in vitro (isolated cardiomyocyte by Ionoptix with sarcomere shortening and calcium transient) in young (3 months old) and senescent (24 months old) rats pretreated or not with MK571, a specific MRP4 inhibitor. MRP4 was quantified in left ventricular homogenates by Western blotting. Data are mean ± SD expressed as percent of baseline value. The positive inotropic effect of isoproterenol was reduced in senescent rats in vivo (left ventricular shortening fraction 120 ± 16% vs. 158 ± 20%, P < 0.001, n = 16 rats) and in vitro (sarcomere shortening 129 ± 37% vs. 148 ± 35%, P = 0.004, n = 41 or 43 cells) as compared to young rats. MRP4 expression increased 3.6-fold in senescent compared to young rat myocardium (P = 0.012, n = 8 rats per group). In senescent rats, inhibition of MRP4 by MK571 restored the positive inotropic effect of isoproterenol in vivo (143 ± 11%, n = 8 rats). In vitro in senescent cardiomyocytes pretreated with MK571, both sarcomere shortening (161 ± 45% vs. 129 ± 37%, P = 0.007, n = 41 cells per group) and calcium transient amplitude (132 ± 25% vs. 113 ± 27%, P = 0.007) increased significantly. MRP4 overexpression contributes to the reduction of the positive inotropic response to β-adrenoceptor stimulation in the senescent heart.

  11. Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats.

    Science.gov (United States)

    Dronjak, S; Gavrilovic, L

    2006-06-01

    Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days) and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4 degrees C, 2 h), were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(3H-methyl)-methionine was used. The O-methylated derivatives were oxidized to 3H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18%) and hippocampal dopamine (about 20%) stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39%) in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20%) as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

  12. Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats

    Directory of Open Access Journals (Sweden)

    Dronjak S.

    2006-01-01

    Full Text Available Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4ºC, 2 h, were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(³H-methyl-methionine was used. The O-methylated derivatives were oxidized to ³H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18% and hippocampal dopamine (about 20% stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39% in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20% as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

  13. Isolation of plasma membrane-associated membranes from rat liver.

    Science.gov (United States)

    Suski, Jan M; Lebiedzinska, Magdalena; Wojtala, Aleksandra; Duszynski, Jerzy; Giorgi, Carlotta; Pinton, Paolo; Wieckowski, Mariusz R

    2014-02-01

    Dynamic interplay between intracellular organelles requires a particular functional apposition of membrane structures. The organelles involved come into close contact, but do not fuse, thereby giving rise to notable microdomains; these microdomains allow rapid communication between the organelles. Plasma membrane-associated membranes (PAMs), which are microdomains of the plasma membrane (PM) interacting with the endoplasmic reticulum (ER) and mitochondria, are dynamic structures that mediate transport of proteins, lipids, ions and metabolites. These structures have gained much interest lately owing to their roles in many crucial cellular processes. Here we provide an optimized protocol for the isolation of PAM, PM and ER fractions from rat liver that is based on a series of differential centrifugations, followed by the fractionation of crude PM on a discontinuous sucrose gradient. The procedure requires ∼8-10 h, and it can be easily modified and adapted to other tissues and cell types.

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

    Science.gov (United States)

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-07-06

    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, 3×10 6 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.

  15. Stabilization of glucocorticoid receptors in isolated rat hepatocytes by radioprotectants

    International Nuclear Information System (INIS)

    Karle, J.M.; Ridder, W.E.; Wright, N.; Olmeda, R.; Nielsen, C.J.

    1986-01-01

    Previous work has shown that glucocorticoid receptors in rat liver homogenate can be stabilized by the addition of MoO 4 plus the sulfhydryl-containing compounds dithiothreitol and WR 1065. The latter is the dephosphorylated, principal metabolite of the radioprotectant WR 2721 (or S-2-(3-aminopropylamino)ethanesphosphorothioic acid). The current work results from applying this knowledge to intact rat hepatocytes. Cells were isolated by collagenase perfusion and incubated in supplemented minimum essential medium at 37 0 C with various concentrations of WR 2721, WR 1065, or vehicle. Samples of these cell suspensions were analyzed at various times for steroid binding capacity by incubating homogenates (27,000 x g supernates) with 50 nM 3 H-triamcinolone acetonide in the presence or absence of excess unlabelled dexamethasone. Concentrations of 10 mM WR 2721 provided marked preservation of the binding capacity (>85% of the initial value at 5 hours) compared to control at 60% of the binding capacity. WR 1065 at 10 mM provided no such protection. This is consistent with the observation that WR 1065 does not pass cell membranes. The authors propose that supplying reducing equivalents to intracellular components such as the glucocorticoid receptor may be one mechanism of the radioprotection afforded by WR 2721

  16. Agmatine Modulation of Noradrenergic Neurotransmission in Isolated Rat Blood Vessels.

    Science.gov (United States)

    Török, Jozef; Zemančíková, Anna

    2016-06-30

    Agmatine, a vasoactive metabolite of L-arginine, is widely distributed in mammalian tissues including blood vessels. Agmatine binding to imidazoline and α₂-adrenoceptors induces a variety of physiological and pharmacological effects. We investigated the effect of agmatine on contractile responses of the rat pulmonary artery and portal vein induced by electrical stimulation of perivascular nerves and by exogenous adrenergic substances. Experiments were performed on isolated segments of rat main pulmonary artery and its extralobular branches, and portal vein suspended in organ bath containing modified Krebs bicarbonate solution and connected to a force-displacement transducer for isometric tension recording. Electrical field stimulation (EFS) produced tetrodotoxin-sensitive contractile responses of pulmonary artery and portal vein. Besides the well known vasorelaxant actions, we found that agmatine also produced a concentration-dependent inhibition of neurogenic contractions induced by EFS in pulmonary arteries; however, the agmatine treatment did not influence the responses to exogenous noradrenaline. The inhibitory effect on EFS-induced contractions was not abolished by the α₂-adrenoceptor antagonist rauwolscine. In portal vein, in contrast, agmatine increased spontaneous mechanical contractions and enhanced the contractions induced by EFS. The results suggest that agmatine can significantly influence vascular function of pulmonary arteries and portal veins by modulating sympathetically mediated vascular contractions by pre- and postsynaptic mechanisms.

  17. Heart malformation induced by ionizing irradiation in rat embryo

    International Nuclear Information System (INIS)

    Higo, Hiromi; Satow, Yukio; Lee, Juing-Yi; Higo, Ken-ichi

    1986-01-01

    Proteins were extracted from morphologically abnormal heart induced by gamma-irradiation, and fractionated into the soluble and the insoluble (''muscle structural proteins'') fractions. Protein compositions of these fractions were examined by O'Farrell's two-dimensional polyacrylamide gel electrophoresis, and also by non-equilibrium pH gradient electrophoresis. The protein patterns thus obtained were then compared with those of the normal heart. Among about 450 major protein species observed, no significant difference was detected between normal and abnormal hearts as to the intensity and the location of the protein spots. Several minor protein species were found varying among the samples examined, but their relevance to the heart malformation are not clear at present. (author)

  18. Short-Term Thyroid Hormone Excess Affects the Heart but Does not Affect Adrenal Activity in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Szkudlarek, Ariani Cavazzani, E-mail: arianiinaira@yahoo.com.br; Aldenucci, Bruno; Miyagui, Nelson Itiro; Silva, Ilana Kassouf [Universidade Federal do Paraná, Curitiba, PR (Brazil); Moraes, Rosana Nogueira [Pontifícia Universidade Federal do Paraná, Curitiba, PR (Brazil); Ramos, Helton Estrela [Universidade Federal da Bahia, Salvador, BA (Brazil); Fogaça, Rosalva Tadeu Hochmuller [Universidade Federal do Paraná, Curitiba, PR (Brazil)

    2014-03-15

    Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis. Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats. Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5{sup th} and 10{sup th} days of T3 treatment. In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels. Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity.

  19. Short-Term Thyroid Hormone Excess Affects the Heart but Does not Affect Adrenal Activity in Rats

    Science.gov (United States)

    Szkudlarek, Ariani Cavazzani; Aldenucci, Bruno; Miyagui, Nelson Itiro; Silva, Ilana Kassouf; Moraes, Rosana Nogueira; Ramos, Helton Estrela; Fogaça, Rosalva Tadeu Hochmuller

    2014-01-01

    Background Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis. Objective Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats. Methods Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5th and 10th days of T3 treatment. Results In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels. Conclusions Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity. PMID:24676225

  20. Short-Term Thyroid Hormone Excess Affects the Heart but Does not Affect Adrenal Activity in Rats

    International Nuclear Information System (INIS)

    Szkudlarek, Ariani Cavazzani; Aldenucci, Bruno; Miyagui, Nelson Itiro; Silva, Ilana Kassouf; Moraes, Rosana Nogueira; Ramos, Helton Estrela; Fogaça, Rosalva Tadeu Hochmuller

    2014-01-01

    Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis. Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats. Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5 th and 10 th days of T3 treatment. In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels. Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity

  1. Characterizing Spatial Dynamics of Bifurcation to Alternans in Isolated Whole Rabbit Hearts Based on Alternate Pacing

    Directory of Open Access Journals (Sweden)

    Kanchan Kulkarni

    2015-01-01

    Full Text Available Sudden cardiac death instigated by ventricular fibrillation (VF is the largest cause of natural death in the USA. Alternans, a beat-to-beat alternation in the action potential duration, has been implicated as being proarrhythmic. The onset of alternans is mediated via a bifurcation, which may occur through either a smooth or a border-collision mechanism. The objective of this study was to characterize the mechanism of bifurcation to alternans based on experiments in isolated whole rabbit hearts. High resolution optical mapping was performed and the electrical activity was recorded from the left ventricle (LV epicardial surface of the heart. Each heart was paced using an “alternate pacing protocol,” where the basic cycle length (BCL was alternatively perturbed by ±δ. Local onset of alternans in the heart, BCLstart, was measured in the absence of perturbations (δ=0 and was defined as the BCL at which 10% of LV exhibited alternans. The influences of perturbation size were investigated at two BCLs: one prior to BCLstart (BCLprior=BCLstart+20 ms and one preceding BCLprior (BCLfar=BCLstart+40 ms. Our results demonstrate significant spatial correlation of the region exhibiting alternans with smooth bifurcation characteristics, indicating that transition to alternans in isolated rabbit hearts occurs predominantly through smooth bifurcation.

  2. Stereological brain volume changes in post-weaned socially isolated rats

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn

    2010-01-01

    Rearing rats in isolation after weaning is an environmental manipulation that leads to behavioural and neurochemical alterations that resemble what is seen in schizophrenia. The model is neurodevelopmental in origin and has been used as an animal model of schizophrenia. However, only a few studies...... Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...... than controls. However, this was not seen in female rats. Isolated males had a significant smaller hippocampus, dentate gyrus and CA2/3 where isolated females had a significant smaller CA1 compared to controls. Thus, our results indicate that long-term isolation of male rats leads to neuroanatomical...

  3. Global Changes in the Rat Heart Proteome Induced by Prolonged Morphine Treatment and Withdrawal

    Czech Academy of Sciences Publication Activity Database

    Drastichová, Z.; Škrabalová, J.; Jedelský, P.; Neckář, Jan; Kolář, František; Novotný, J.

    2012-01-01

    Roč. 7, č. 10 (2012), e47167 E-ISSN 1932-6203 R&D Projects: GA AV ČR(CZ) IAA501110901 Institutional support: RVO:67985823 Keywords : morphine * rat * heart * proteome Subject RIV: ED - Physiology Impact factor: 3.730, year: 2012

  4. The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

    Czech Academy of Sciences Publication Activity Database

    Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

    2016-01-01

    Roč. 2016, č. 2016 (2016), s. 9814038 ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.593, year: 2016

  5. Characterization of spinal afferent neurons projecting to different chambers of the rat heart.

    Science.gov (United States)

    Guić, Maja Marinović; Kosta, Vana; Aljinović, Jure; Sapunar, Damir; Grković, Ivica

    2010-01-29

    The pattern of distribution of spinal afferent neurons (among dorsal root ganglia-DRGs) that project to anatomically and functionally different chambers of the rat heart, as well as their morphological and neurochemical characteristics were investigated. Retrograde tracing using a patch loaded with Fast blue (FB) was applied to all four chambers of the rat heart and labeled cardiac spinal afferents were characterized by using three neurochemical markers. The majority of cardiac projecting neurons were found from T1 to T4 DRGs, whereas the peak was at T2 DRG. There was no difference in the total number of FB-labeled neurons located in ipsilateral and contralateral DRGs regardless of the chambers marked with the patch. However, significantly more FB-labeled neurons projected to the ventricles compared to the atria (859 vs. 715). The proportion of isolectin B(4) binding in FB-labeled neurons was equal among all neurons projecting to different heart chambers (2.4%). Neurofilament 200 positivity was found in greater proportions in DRG neurons projecting to the left side of the heart, whereas calretinin-immunoreactivity was mostly represented in neurons projecting to the left atrium. Spinal afferent neurons projecting to different chambers of the rat heart exhibit a variety of neurochemical phenotypes depending on binding capacity for isolectin B(4) and immunoreactivity for neurofilament 200 and calretinin, and thus represent important baseline data for future studies. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  6. Beneficial effects of exercise training in heart failure are lost in male diabetic rats.

    Science.gov (United States)

    Boudia, Dalila; Domergue, Valérie; Mateo, Philippe; Fazal, Loubina; Prud'homme, Mathilde; Prigent, Héloïse; Delcayre, Claude; Cohen-Solal, Alain; Garnier, Anne; Ventura-Clapier, Renée; Samuel, Jane-Lise

    2017-12-01

    Exercise training has been demonstrated to have beneficial effects in patients with heart failure (HF) or diabetes. However, it is unknown whether diabetic patients with HF will benefit from exercise training. Male Wistar rats were fed either a standard (Sham, n = 53) or high-fat, high-sucrose diet ( n = 66) for 6 mo. After 2 mo of diet, the rats were already diabetic. Rats were then randomly subjected to either myocardial infarction by coronary artery ligation (MI) or sham operation. Two months later, heart failure was documented by echocardiography and animals were randomly subjected to exercise training with treadmill for an additional 8 wk or remained sedentary. At the end, rats were euthanized and tissues were assayed by RT-PCR, immunoblotting, spectrophotometry, and immunohistology. MI induced a similar decrease in ejection fraction in diabetic and lean animals but a higher premature mortality in the diabetic group. Exercise for 8 wk resulted in a higher working power developed by MI animals with diabetes and improved glycaemia but not ejection fraction or pathological phenotype. In contrast, exercise improved the ejection fraction and increased adaptive hypertrophy after MI in the lean group. Trained diabetic rats with MI were nevertheless able to develop cardiomyocyte hypertrophy but without angiogenic responses. Exercise improved stress markers and cardiac energy metabolism in lean but not diabetic-MI rats. Hence, following HF, the benefits of exercise training on cardiac function are blunted in diabetic animals. In conclusion, exercise training only improved the myocardial profile of infarcted lean rats fed the standard diet. NEW & NOTEWORTHY Exercise training is beneficial in patients with heart failure (HF) or diabetes. However, less is known of the possible benefit of exercise training for HF patients with diabetes. Using a rat model where both diabetes and MI had been induced, we showed that 2 mo after MI, 8 wk of exercise training failed to improve

  7. Platelet deposition in rat heart allografts and the effect of a thromboxane receptor antagonist

    International Nuclear Information System (INIS)

    Foegh, M.L.; Khirabadi, B.S.; Ramwell, P.W.

    1986-01-01

    The effect of a thromboxane antagonist, L640,035 on platelet deposition in heart allografts was studied. Twenty Lewis rats received heterotopic allografts from Lewis x Brown-Norway F1 hybrid. All recipients received azathioprine (5 mg/kg/day). The rats were divided into three groups. Groups II and III were also treated daily with either the vehicle for L640,035 or L640,035 respectively. Syngeneic indium-111-labeled platelet deposition was determined in the allograft and the native heart at 6, 9, and 13 days after transplantation; group III was studied on the sixth and ninth day only. A rapidly increasing platelet deposition was seen in allografts from rats given azathioprine; whereas the thromboxane antagonist prevented the increase in platelet deposition on the ninth day

  8. Curcumin mediated attenuation of carbofuran induced toxicity in the heart of Wistar rats.

    Science.gov (United States)

    Jaiswal, S K; Gupta, V K; Siddiqi, N J; Sharma, B

    2017-07-31

    Carbofuran is used to improve the agricultural productivity as well as to protect the house hold and industrial products, but due to accumulation in the biological system, it causes serious side effects in many non-targets mammalian systems. The aim of present study is to evaluate the carbofuran induced oxidative stress in rat heart and its attenuation by using herbal product curcumin. Rats were divided into four groups; one group received 20 % LD50 of carbofuran another group of rats received same doses of carbofuran was  pretreated with curcumin (100 mg kg-1 body weight) and remaining two other groups served as control and curcumin treated animals. The activity of lactate dehydrogenase (LDH) in the heart tissues and serum was evaluated and the activity of enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) was estimated in the heart tissues. The level of malondialdehyde (MDA) in heart tissues was also measured. The Total cholesterol (TC) and high density lipoprotein (HDL) was measured in the serum of the entire animals group. The results of present study showed that the activity of LDH in heart tissues were decreased and in serum was elevated. The MDA level was significantly elevated due to exposure of carbofuran. The enzymatic antioxidants, SOD and CAT activities were also inhibited. The ratio of pro-oxidant (P)/antioxidant (A) was also found to be sharply increased in the rat heart tissues of carbofuran exposed animals. The alterations in all the parameter were recovered by the pretreatment of curcumin (100 mg kg-1 body weight).

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

    International Nuclear Information System (INIS)

    Cilliers, G.D.; Lochner, A.

    1989-01-01

    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

  10. Congenital heart defects in newborns with apparently isolated single gastrointestinal malformation: A retrospective study.

    Science.gov (United States)

    Schierz, Ingrid Anne Mandy; Pinello, Giuseppa; Giuffrè, Mario; La Placa, Simona; Piro, Ettore; Corsello, Giovanni

    2016-12-01

    Congenital gastrointestinal system malformations/abdominal wall defects (GISM) may appear as isolated defects (single or complex), or in association with multiple malformations. The high incidence of association of GISM and congenital heart defects (CHD) in patients with syndromes and malformative sequences is known, but less expected is the association of apparently isolated single GISM and CHD. The aim of this study was to investigate the frequency of CHD in newborns with isolated GISM, and the possibility to modify the diagnostic-therapeutic approach just before the onset of cardiac symptoms or complications. Anamnestic, clinical, and imaging data of newborns requiring abdominal surgery for GISM, between 2009 and 2014, were compared with a control group of healthy newborns. Distribution of GISM and cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes were identified. Seventy-one newborns with isolated GISM were included in this study. More frequent GISM were intestinal rotation and fixation disorders. CHD were observed in 15.5% of patients, augmenting their risk for morbidity. Risk factors for morbidity related to sepsis were identified in central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover, 28.2% of newborns presented only functional cardiac disorders but an unexpectedly higher mortality. The high incidence of congenital heart disease in infants with apparently isolated GISM confirms the need to perform an echocardiographic study before surgery to improve perioperative management and prevent complications such as sepsis and endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Cardiac endothelial cells isolated from mouse heart - a novel model for radiobiology

    International Nuclear Information System (INIS)

    Jelonek, K.; Walaszczyk, A.; Gabrys, D.; Pietrowska, M.; Widlak, P.; Kanthou, Ch.

    2011-01-01

    Cardiovascular disease is recognized as an important clinical problem in radiotherapy and radiation protection. However, only few radiobiological models relevant for assessment of cardiotoxic effects of ionizing radiation are available. Here we describe the isolation of mouse primary cardiac endothelial cells, a possible target for cardiotoxic effects of radiation. Cells isolated from hearts of juvenile mice were cultured and irradiated in vitro. In addition, cells isolated from hearts of locally irradiated adult animals (up to 6 days after irradiation) were tested. A dose-dependent formation of histone γH 2 A.X foci was observed after in vitro irradiation of cultured cells. However, such cells were resistant to radiation-induced apoptosis. Increased levels of actin stress fibres were observed in the cytoplasm of cardiac endothelial cells irradiated in vitro or isolated from irradiated animals. A high dose of 16 Gy did not increase permeability to Dextran in monolayers formed by endothelial cells. Up-regulated expression of Vcam1, Sele and Hsp70i genes was detected after irradiation in vitro and in cells isolated few days after irradiation in vivo. The increased level of actin stress fibres and enhanced expression of stress-response genes in irradiated endothelial cells are potentially involved in cardiotoxic effects of ionizing radiation. (authors)

  12. Flow heterogeneity following global no-flow ischemia in isolated rabbit heart

    International Nuclear Information System (INIS)

    Marshall, Robert C.; Powers-Risius, Patricia; Reutter, Bryan W.; Schustz, Amy M.; Kuo, Chaincy; Huesman, Michelle K.; Huesman, Ronald H.

    2002-01-01

    The purpose of this study was to evaluate flow heterogeneity and impaired reflow during reperfusion following 60 min global no-flow ischemia in the isolated rabbit heart. Radiolabeled microspheres were used to measure relative flow in small left ventricular (LV) segments in five ischemia + reperfused hearts and in five non-ischemic controls. Although variable in the post-ischemic hearts, flow heterogeneity was increased relative to pre-ischemia for the whole LV (0.92 plus or minus 0.41 vs. 0.37 plus or minus 0.07, P < 0.05) as well as the subendocardium (Endo) and subepicardium (Epi) considered separately (endo: 1.28 plus or minus 0.74 vs. 0.30 plus or minus 0.09; epi: 0.69 plus or minus 0.22 vs. 0.38 plus or minus 0.08; P < 0.05 for both comparisons) during early reperfusion. There were also segments with abnormally reduced reflow. The number of segments with abnormally reduced reflow increased as flow heterogeneity increased. Abnormally reduced reflow indicates that regional ischemia can persist despite restoration of normal global flow. In addition, the relationship between regional and global flow is altered and venous outflow is derived from regions with continued perfusion and not the whole LV. These observations emphasize the need to quantify regional reflow during reperfusion following sustained no-flow ischemia in the isolated rabbit heart

  13. Flow heterogeneity following global no-flow ischemia in isolated rabbit heart

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, Robert C.; Powers-Risius, Patricia; Reutter, Bryan W.; Schustz, Amy M.; Kuo, Chaincy; Huesman, Michelle K.; Huesman, Ronald H.

    2003-02-01

    The purpose of this study was to evaluate flow heterogeneity and impaired reflow during reperfusion following 60 min global no-flow ischemia in the isolated rabbit heart. Radiolabeled microspheres were used to measure relative flow in small left ventricular (LV) segments in five ischemia + reperfused hearts and in five non-ischemic controls. Although variable in the post-ischemic hearts, flow heterogeneity was increased relative to pre-ischemia for the whole LV (0.92 plus or minus 0.41 vs. 0.37 plus or minus 0.07, P < 0.05) as well as the subendocardium (Endo) and subepicardium (Epi) considered separately (endo: 1.28 plus or minus 0.74 vs. 0.30 plus or minus 0.09; epi: 0.69 plus or minus 0.22 vs. 0.38 plus or minus 0.08; P < 0.05 for both comparisons) during early reperfusion. There were also segments with abnormally reduced reflow. The number of segments with abnormally reduced reflow increased as flow heterogeneity increased. Abnormally reduced reflow indicates that regional ischemia can persist despite restoration of normal global flow. In addition, the relationship between regional and global flow is altered and venous outflow is derived from regions with continued perfusion and not the whole LV. These observations emphasize the need to quantify regional reflow during reperfusion following sustained no-flow ischemia in the isolated rabbit heart.

  14. Compartment analysis of 125I-labelled albumin washout from coronary vessels of isolated perfused hearts

    International Nuclear Information System (INIS)

    Cheng Eap Ng; Seh-Hoon Song

    1978-01-01

    Albumin labelled with 125 I was used as a tracer to investigate the washout kinetics of plasma from the coronary circulation of isolated perfused feline hearts. Compartmentalization with experimental results showed at least two compartments. The model was compared with a three-compartment model found previously for red blood cells. The results indicate that there is a separation of plasma and RBC in the coronary microcirculation. (author)

  15. A method for isolating identifying and culturing of rat trachea-bronchia epithelial cells

    International Nuclear Information System (INIS)

    Cui Fengmei; Su Shibiao; Nie Jihua; Li Bingyan; Tong Jian

    2005-01-01

    Objective: To explore a method for isolating identifying and culturing the rat trachea-bronchia epithelial cells. Methods: The rat trachea-bronchia epithelial cells were isolated by digestion with pronase and brushing with cell brush, identified using confocul and cultured in entire F12 media with no serum. Results: With this method, cells in high purity and high viability could be obtained, and about 10 6 cells per rat. The cells grow well in entire F12 media with no serum. Conclusion: The method is useful for isolating rate trachea-bronchia epithelial cells and the entire F12 media with no serum is effective for culturing. (authors)

  16. Reduced density and altered regulation of rat atrial L-type Ca2+ current in heart failure.

    Science.gov (United States)

    Bond, Richard C; Bryant, Simon M; Watson, Judy J; Hancox, Jules C; Orchard, Clive H; James, Andrew F

    2017-03-01

    Constitutive regulation by PKA has recently been shown to contribute to L-type Ca 2+ current ( I CaL ) at the ventricular t-tubule in heart failure. Conversely, reduction in constitutive regulation by PKA has been proposed to underlie the downregulation of atrial I CaL in heart failure. The hypothesis that downregulation of atrial I CaL in heart failure involves reduced channel phosphorylation was examined. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N =10) or equivalent sham-operation (Sham, N =12). Left atrial myocytes were isolated ~18 wk postsurgery and whole cell currents recorded (holding potential=-80 mV). I CaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted. CAL cell capacitances were ~1.67-fold greater than Sham ( P ≤ 0.0001). Maximal I CaL conductance ( G max ) was downregulated more than 2-fold in CAL vs. Sham myocytes ( P 50% more effectively in CAL than in Sham so that differences in I CaL density were abolished. Differences between CAL and Sham G max were not abolished by calyculin A (100 nmol/l), suggesting that increased protein dephosphorylation did not account for I CaL downregulation. Treatment with either H-89 (10 μmol/l) or AIP (5 μmol/l) had no effect on basal currents in Sham or CAL myocytes, indicating that, in contrast to ventricular myocytes, neither PKA nor CaMKII regulated basal I CaL Expression of the L-type α 1C -subunit, protein phosphatases 1 and 2A, and inhibitor-1 proteins was unchanged. In conclusion, reduction in PKA-dependent regulation did not contribute to downregulation of atrial I CaL in heart failure. NEW & NOTEWORTHY Whole cell recording of L-type Ca 2+ currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit

  17. Neonatal rat hearts cannot be protected by ischemic postconditioning

    Czech Academy of Sciences Publication Activity Database

    Doul, J.; Charvátová, Z.; Ošťádalová, Ivana; Kohutiar, M.; Maxová, H.; Ošťádal, Bohuslav

    2015-01-01

    Roč. 64, č. 6 (2015), s. 789-794 ISSN 0862-8408 Institutional support: RVO:67985823 Keywords : neonatal rats * ischemic postconditioning * tolerance to ischemia * contractile function * lactate dehydrogenase Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.643, year: 2015

  18. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

    DEFF Research Database (Denmark)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen

    2017-01-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative...... proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33...... proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb...

  19. Comparative effect of lidocaine and bupivacaine on glucose uptake and lactate production in the perfused working rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Cronau, L.H. Jr.; Merin, R.G.; Aboulish, E.; Steenberg, M.L.; Maljorda, A.

    1986-03-01

    It has been suggested that at equivalent therapeutic concentrations, lidocaine and bupivacaine may have different cardiotoxic potency. In the isolated working rat heart preparation, the effect of a range of lidocaine and bupivacaine concentrations on glucose uptake and lactate production (LP) were observed. Insulin was added, 10 ..mu../L, to Ringer's solution containing /sup 3/H-labeled glucose to measure the glycolytic flux (GF). The effect of the local anesthetics on LP at the indicated concentrations were similar. Lidocaine appears to depress the glycolytic flux from exogenous glucose to a lesser degree. Bupivacaine, 10 mg/L, depresses VO/sub 2/ to a greater degree than does lidocaine, 40 mg/L.

  20. Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure.

    Science.gov (United States)

    Xu, Bo; Zheng, Hong; Patel, Kaushik P

    2012-04-15

    Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 ± 0.6 vs. 2.6 ± 0.3 spikes/s, P neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 ± 7% vs. +184 ± 61%) or an increase in MAP (-42 ± 8% vs. -71 ± 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 ± 15% vs. 92 ± 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to baroreceptor and osmotic challenges observed during CHF.

  1. Neonatal hyperthyroidism on rat heart: interrelation with nitric oxide and sex.

    Science.gov (United States)

    Rodríguez, L; Detomaso, F; Braga, P; Prendes, M; Perosi, F; Cernadas, G; Balaszczuk, A; Fellet, A

    2015-06-01

    To clarify the mechanism mediating the effect of hyperthyroidism on cardiac function during the second month of life in rats. Male and female Sprague-Dawley rats were assigned to a control or to a triiodothyronine (T3)-treated group. Treatment of each group was started on the third day after birth. Control rats (Eut) received 0.9 NaCl [0.1 ml/100 g body weight (BW)] every second day during 60 days and T3-treated rats (Hyper) received subcutaneous (SC) T3 injections every second day during 60 days. Hyperthyroidism decreased left ventricle volume only in male rats. Female euthyroid rats presented higher atrial nitric oxide synthase (NOS) activity than male rats and hormonal treatment decreased this enzyme's activity in both sexes. Euthyroid male and female rats had similar atrial NOS protein levels, but females had higher caveolin (cav) 3 protein levels. T3 treatment increased this protein only in males. Female rats had lower ventricular NOS activity than male rats; hyperthyroidism increased NOS activity in both sexes but this effect was associated with lower cav 3 protein levels. Hyperthyroidism did not change cav 1 protein levels in both male and female rats. The results of this study demonstrating clinically relevant sex-related differences in the pathophysiology of the hyperthyroid heart have raised new questions regarding the mechanisms responsible for the observed differences. This study suggests that sex-related intrinsic factors such as nitric oxide may modulate the response to hyperthyroidism that leads to cardiovascular dysfunction.

  2. 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.

  3. Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats.

    Science.gov (United States)

    Durak, Aysegul; Olgar, Yusuf; Tuncay, Erkan; Karaomerlioglu, Irem; Kayki Mutlu, Gizem; Arioglu Inan, Ebru; Altan, Vecdi Melih; Turan, Belma

    2017-11-01

    Mechanical activity of the heart is adversely affected in metabolic syndrome (MetS) characterized by increased body mass and marked insulin resistance. Herein, we examined the effects of high carbohydrate intake on cardiac function abnormalities by evaluating in situ heart work, heart rate, and electrocardiograms (ECGs) in rats. MetS was induced in male Wistar rats by adding 32% sucrose to drinking water for 22-24 weeks and was confirmed by insulin resistance, increased body weight, increased blood glucose and serum insulin, and increased systolic and diastolic blood pressures in addition to significant loss of left ventricular integrity and increased connective tissue around myofibrils. Analysis of in situ ECG recordings showed a markedly shortened QT interval and decreased QRS amplitude with increased heart rate. We also observed increased oxidative stress and decreased antioxidant defense characterized by decreases in serum total thiol level and attenuated paraoxonase and arylesterase activities. Our data indicate that increased heart rate and a shortened QT interval concomitant with higher left ventricular developed pressure in response to β-adrenoreceptor stimulation as a result of less cyclic AMP release could be regarded as a natural compensation mechanism in overweight rats with MetS. In addition to the persistent insulin resistance and obesity associated with MetS, one should consider the decreased heart work, increased heart rate, and shortened QT interval associated with high carbohydrate intake, which may have more deleterious effects on the mammalian heart.

  4. Phosphorus nuclear magnetic resonance in isolated perfused rat pancreas

    International Nuclear Information System (INIS)

    Matsumoto, Takehisa; Kanno, Tomio; Seo, Yoshiteru; Murakami, Masataka; Watari, Hiroshi

    1988-01-01

    Phosphorus nuclear magnetic resonance spectroscopy was applied to measure phosphorus energy metabolites in isolated perfused rat pancreas. The gland was perfused with a modified Krebs-Henseleit solution at room temperature (25 degree C). 31 P resonances of creatine phosphate (PCr), ATP, ADP, inorganic phosphate (P i ) and phosphomonoesters (PMEs) were observed in all the preparations of pancreas. In different individual preparations, the resonance of PCr varied, but those of ATP were almost the same. The initial levels of PCr and ATP in individual preparations, however, remained almost unchanged during perfusion with the standard solution for 2 h. When the perfusion was stopped, the levels of ATP and PCr decreased, while the levels of PME and P i increased. At that time, the P i resonance shfted to a higher magnetic field, indicating that the tissue pH decreased. On reperfusion, the tissue levels of phosphorus compounds and the tissue pH were restored to their initial resting levels. Continuous infusion of 0.1 μM acetylcholine caused marked and sustained increases in the flow of pancreatic juice and protein output. During the stimulation the tissue levels of phosphorus compounds remained unchanged, while the tissue pH was decreased slightly

  5. Anabolic regulation of gluconeogenesis by insulin in isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Mohan, C.; Bessman, S.P.

    1985-01-01

    The role of substrate availability in the regulation of gluconeogenesis in isolated rat hepatocytes was studied using [U- 14 C]alanine as a tracer in the presence of different concentrations of L-alanine in the incubation medium. At low alanine concentrations (0.5 mM) insulin decreased the 14 C incorporation into the glucose pool and increased the incorporation of tracer carbons into the protein and lipid pools and into CO 2 . The net radioactivity lost from the glucose pool was only a small percentage of the total increase in the activity of the protein, lipid, CO 2 , or glycogen pools, supporting the notion that the effect of insulin in diminishing gluconeogenesis is secondary to its effects on pathways using pyruvate. At higher concentrations of alanine (2.5, 5.0, and 10.0 mM) in the incubation medium insulin increased the movement of alanine carbons into protein and glucose. These results were further confirmed by using [U- 14 C]lactate. The increases in observed specific activity of glucose following insulin administration would not be possible if insulin acted by affecting the activity of any enzyme directly involved in the formation or utilization of pyruvate, most of which have been proposed as sites of insulin action. Data presented show that insulin inhibits gluconeogenesis by affecting a change in substrate availability

  6. Stimulation of glucose phosphorylation by fructose in isolated rat hepatocytes.

    Science.gov (United States)

    Van Schaftingen, E; Vandercammen, A

    1989-01-15

    The phosphorylation of glucose was measured by the formation of [3H]H2O from [2-3H]glucose in suspensions of freshly isolated rat hepatocytes. Fructose (0.2 mM) stimulated 2-4-fold the rate of phosphorylation of 5 mM glucose although not of 40 mM glucose, thus increasing the apparent affinity of the glucose phosphorylating system. A half-maximal stimulatory effect was observed at about 50 microM fructose. Stimulation was maximal 5 min after addition of the ketose and was stable for at least 40 min, during which period 60% of the fructose was consumed. The effect of fructose was reversible upon removal of the ketose. Sorbitol and tagatose were as potent as fructose in stimulating the phosphorylation of 5 mM glucose. D-Glyceraldehyde also had a stimulatory effect but at tenfold higher concentrations. In contrast, dihydroxyacetone had no significant effect and glycerol inhibited the detritiation of glucose. Oleate did not affect the phosphorylation of glucose, even in the presence of fructose, although it stimulated the formation of ketone bodies severalfold, indicating that it was converted to its acyl-CoA derivative. These results allow the conclusion that fructose stimulates glucokinase in the intact hepatocyte. They also suggest that this effect is mediated through the formation of fructose 1-phosphate, which presumably interacts with a competitive inhibitor of glucokinase other than long-chain acyl-CoAs.

  7. Concentration of (+/-)-propranolol in isolated, perfused lungs of rat.

    Science.gov (United States)

    Dollery, C T; Junod, A F

    1976-01-01

    1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation. PMID:1276542

  8. Effect of heavy water on isolated rat liver mitochondria

    International Nuclear Information System (INIS)

    Huebner, G.

    1981-01-01

    The rate of O 2 consumption by isolated rat liver mitochondria was determined polarographically with a Clark electrode at 25 0 C in the active (state 3), strongly coupled (state 4) and decoupled state of the mitochondria in media containing H 2 16 O, D 2 16 O or H 2 18 O. The results confirm the value of the D 2 O isotope effect in the form on an O 2 -consumption inhibition. In H 2 18 O no isotope effect has been detected in the state of controlled respiration. In contrast, a strongly marked inverse isotope effect has been found in the active state after ADP addition and in the decoupled state after DNP addition. This inverse isotope effect occurs in reactions involving a preceding equilibrium. According to the chemiosmotic hypothesis of oxidative phosphorylation the formation of hydronium ions is part of this reaction. The equilibrium constant k 2 = 0.9774 for the hydronium ion in H 2 16 O and H 2 18 O implies that the formation of the hydronium ion in H 2 18 O is preferred to that in H 2 16 O. The high inverse H 2 18 O isotope effect respiration shows that the formation of H 3 O + contributes to the vectorial proton transport, probably as a preceding equilibrium, and that in the active state of the respiratory chain this reaction may be the rate-determining step. (author)

  9. Immunohistochemical characteristics of neurons in nodose ganglia projecting to the different chambers of the rat heart.

    Science.gov (United States)

    Kosta, Vana; Guić, Maja Marinović; Aljinović, Jure; Sapunar, Damir; Grković, Ivica

    2010-06-24

    Despite the contribution of nodose ganglia neurons to the innervation of the heart being the subject of several studies, specific neuronal subpopulations innervating the four different chambers of the heart have not been distinguished. In our study, the application of Fast Blue-loaded patch to the epicardial surface of different chambers of the rat heart (the right or left atrium or the right or left ventricle) resulted in labeling of discrete populations of immunohistochemically diverse neurons. About one half (55%) of these neurons showed immunoreactivity for the 200-kDa neurofilament protein (marker of myelinated neurons), with a higher proportion of positive staining among neurons projecting to the left than to the right ventricle. Isolectin B4 immunoreactivity (characteristic for a subset of nonmyelinated non-peptidergic neurons) was more abundant among neurons projecting to the right side of the heart (right atria and right ventricles) compared to the left side (23% vs. 16%). Calretinin immunoreactivity (possible marker of mechanosensitive neurons) was significantly higher among neurons projecting to the ventricles than among those projecting to atria (36% vs. 11%). These findings reveal that chambers of the rat heart are innervated with immunohistochemically different subpopulations of neurons from the nodose ganglia.

  10. Effects of dietary magnesium on sodium-potassium pump action in the heart of rats

    International Nuclear Information System (INIS)

    Fischer, P.W.; Giroux, A.

    1987-01-01

    Sprague-Dawley rats were fed a basal AIN-76 diet containing 80, 200, 350, 500 or 650 mg of magnesium per kilogram of diet for 6 wk. Ventricular slices, as well as microsomal fractions, were prepared from the hearts and were used to determine sodium-potassium pump activity. Sodium-potassium pump activity was assessed in the microsomal membranes by determining the ouabain-inhibitable Na+, K+-ATPase activity and [ 3 H]ouabain binding, and in the ventricular slices, by determining ouabain-sensitive 86 Rb uptake under K+-free conditions. The ATPase activity increased with increasing dietary magnesium, so that in the hearts of those animals that were fed 500 and 650 mg of magnesium/kg diet, it was significantly greater than the activity in the hearts of the animals fed 80 and 200 mg/kg diet. Similarly, 86 Rb uptake by heart slices from rats fed 500 and 650 mg of magnesium/kg diet was significantly greater than the uptake by heart slices from animals fed 80 and 200 mg/kg diet. [ 3 H]Ouabain binding did not change with increasing dietary magnesium. Thus, magnesium deficiency appears to have no effect on the number of sodium-potassium pump sites, but does decrease the activity of the pump. It is suggested that this leads to an increase in intracellular Na+, resulting in a change in the membrane potential, and may contribute to the arrhythmias associated with magnesium deficiency

  11. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

    Science.gov (United States)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-10-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. 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

  13. Treadmill exercise ameliorates social isolation-induced depression through neuronal generation in rat pups.

    Science.gov (United States)

    Cho, Jung-Wan; Jung, Sun-Young; Lee, Sang-Won; Lee, Sam-Jun; Seo, Tae-Beom; Kim, Young-Pyo; Kim, Dae-Young

    2017-12-01

    Social isolation is known to induce emotional and behavioral changes in animals and humans. The effect of treadmill exercise on depression was investigated using social isolated rat pups. The rat pups in the social isolation groups were housed individually. The rat pups in the exercise groups were forced to run on treadmill for 30 min once a day from postnatal day 21 to postnatal day 34. In order to evaluate depression state of rat pups, forced swimming test was performed. Newly generated cells in the hippocampal dentate gyrus were determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry. We examined the expression of 5-hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe using immunofluorescence. The expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was detected by Western blot analysis. The present results demonstrated that social isolation increased resting time and decreased mobility time. Expression of 5-HT and TPH in the dorsal raphe and expression of BDNF and TrkB in the hippocampus were decreased by social isolation. The number of BrdU-positive cells in the hippocampal dentate gyrus was suppressed by social isolation. Treadmill exercise decreased resting time and increased mobility in the social isolated rat pups. Expression of 5-HT, TPH, BDNF, and TrkB was increased by treadmill exercise. The present results suggested that treadmill exercise may ameliorates social isolation-induced depression through increasing neuronal generation.

  14. A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.

    Science.gov (United States)

    Silva, Fábio Henrique; Veiga, Frederico José Reis; Mora, Aline Gonçalves; Heck, Rodrigo Sader; De Oliveira, Caroline Candida; Gambero, Alessandra; Franco-Penteado, Carla Fernanda; Antunes, Edson; Gardner, Jason D; Priviero, Fernanda Bruschi Marinho; Claudino, Mário Angelo

    2017-01-01

    Patients with heart failure (HF) display erectile dysfunction (ED). However, the pathophysiology of ED during HF remains poorly investigated. This study aimed to characterize the aortocaval fistula (ACF) rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO) pathway, autonomic nervous system and oxidative stress in the penis. Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine) and relaxant agents (sodium nitroprusside; SNP), as well as to electrical field stimulation (EFS), were obtained in the cavernosal smooth muscle (CSM) strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox) and superoxide dismutase (SOD) mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs) were also performed in plasma. HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats. ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF.

  15. Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats.

    Science.gov (United States)

    Boero, Giorgia; Pisu, Maria Giuseppina; Biggio, Francesca; Muredda, Laura; Carta, Gianfranca; Banni, Sebastiano; Paci, Elena; Follesa, Paolo; Concas, Alessandra; Porcu, Patrizia; Serra, Mariangela

    2018-05-01

    We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Arterio-venous anastomoses in isolated, perfused rat lungs.

    Science.gov (United States)

    Conhaim, Robert L; Segal, Gilad S; Watson, Kal E

    2016-11-01

    Several studies have suggested that large-diameter (>25 μm) arterio-venous shunt pathways exist in the lungs of rats, dogs, and humans. We investigated the nature of these pathways by infusing specific-diameter fluorescent latex particles (4, 7, 15, 30, or 50 μm) into isolated, ventilated rat lungs perfused at constant pressure. All lungs received the same mass of latex (5 mg), which resulted in infused particle numbers that ranged from 1.7 × 10 7 4 μm particles to 7.5 × 10 4 50 μm particles. Particles were infused over 2 min. We used a flow cytometer to count particle appearances in venous effluent samples collected every 0.5 min for 12 min from the start of particle infusion. Cumulative percentages of infused particles that appeared in the samples averaged 3.17 ± 2.46% for 4 μm diameter particles, but ranged from 0.01% to 0.17% for larger particles. Appearances of 4 μm particles followed a rapid upslope beginning at 30 sec followed by a more gradual downslope that lasted for up to 12 min. All other particle diameters also began to appear at 30 sec, but followed highly irregular time courses. Infusion of 7 and 15 μm particles caused transient but significant perfusate flow reductions, while infusion of all other diameters caused insignificant reductions in flow. We conclude that small numbers of bypass vessels exist that can accommodate particle diameters of 7-to-50 μm. We further conclude that our 4 μm particle data are consistent with a well-developed network of serial and parallel perfusion pathways at the acinar level. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  17. Stereological brain volume changes in post-weaned socially isolated rats

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn

    2010-01-01

    Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...... have evaluated the neuroanatomical changes in this animal model in comparison to changes seen in schizophrenia. In this study, we applied stereological volume estimates to evaluate the total brain, the ventricular system, and the pyramidal and granular cell layers of the hippocampus in male and female...... than controls. However, this was not seen in female rats. Isolated males had a significant smaller hippocampus, dentate gyrus and CA2/3 where isolated females had a significant smaller CA1 compared to controls. Thus, our results indicate that long-term isolation of male rats leads to neuroanatomical...

  18. [ATP-synthetase activity, respiration and cytochromes of rat heart mitochondria in aging and hyperthyroidism].

    Science.gov (United States)

    Lemeshko, V V; Kaliman, P A; Belostotskaia, L I; Uchitel', A A

    1982-04-01

    The ATP-synthetase activity, the rate of oxygen uptake under different metabolic conditions, the tightness of coupling of respiration to oxidative phosphorylation and the cytochrome contents in heart mitochondria of rats from different age groups were studied under normal conditions and in hyperthyroidism. It was found that heart mitochondria of aged animals did not practically differ in terms of their functional activity from those of the young animals. Administration of thyroxin to the animals from all age groups produced no significant effects on the state of mitochondria, increasing the rate of ATP synthesis on alpha-glycerophosphate, which was especially well-pronounced in aged animals, and the cytochrome content in 1-month-old rats.

  19. Ontogenetic changes of lipofuscin-like pigments in the rat heart

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, Jiří; Ošťádalová, Ivana

    2012-01-01

    Roč. 61, Suppl.1 (2012), S173-S179 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP303/11/0298 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat heart * ontogenetic development * lipofuscin-like pigments (LFP) * reactive oxygen species (ROS) * gender difference * right/left ventricle ratio Subject RIV: ED - Physiology Impact factor: 1.531, year: 2012

  20. Generation of hydrogen peroxide in the developing rat heart: the role of elastin metabolism

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, J.; Ošťádalová, Ivana; Vytášek, R.; Vajner, L.

    2011-01-01

    Roč. 358, 1-2 (2011), s. 215-220 ISSN 0300-8177 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:GA ČR(CZ) GAP303/11/0298 Program:GA Institutional research plan: CEZ:AV0Z50110509 Keywords : rat heart * ontogenetic development * hydrogen peroxide * elastin * fluorescence Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.057, year: 2011

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

    Directory of Open Access Journals (Sweden)

    Antti Siltanen

    2011-04-01

    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

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

    Directory of Open Access Journals (Sweden)

    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

  3. Pulmonary hypertension and isolated right heart failure complicating amiodarone induced hyperthyroidism.

    Science.gov (United States)

    Wong, Sean-Man; Tse, Hung-Fat; Siu, Chung-Wah

    2012-03-01

    Hyperthyroidism is a common side effect encountered in patients prescribed long-term amiodarone therapy for cardiac arrhythmias. We previously studied 354 patients prescribed amiodarone in whom the occurrence of hyperthyroidism was associated with major adverse cardiovascular events including heart failure, myocardial infarction, ventricular arrhythmias, stroke and even death [1]. We now present a case of amiodarone-induced hyperthyroidism complicated by isolated right heart failure and pulmonary hypertension that resolved with treatment of hyperthyroidism. Detailed quantitative echocardiography enables improved understanding of the haemodynamic mechanisms underlying the condition. Copyright © 2011 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  4. Patient perceptions of experience with cardiac rehabilitation after isolated heart valve surgery

    DEFF Research Database (Denmark)

    Hansen, Tina B; Berg, Selina K; Sibilitz, Kirstine L

    2018-01-01

    in a cardiac rehabilitation programme, and none have analysed their experiences with it. AIMS: The purpose of this qualitative analysis was to gain insight into patients' experiences in cardiac rehabilitation, the CopenHeartVR trial. This trial specifically assesses patients undergoing isolated heart valve...... to take active personal responsibility for their health. Despite these benefits, participants experienced existential and psychological challenges and musculoskeletal problems. Participants also sought additional advice from healthcare professionals both inside and outside the healthcare system....... CONCLUSIONS: Even though the cardiac rehabilitation programme reduced insecurity and helped participants take active personal responsibility for their health, they experienced existential, psychological and physical challenges during recovery. The cardiac rehabilitation programme had several limitations...

  5. Efficacy of wheat germ oil in modulating radiation-induced heart damage in rats

    International Nuclear Information System (INIS)

    Said, U.Z.; Azab, Kh.Sh.

    2006-01-01

    Wheat Germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. This study was designed to investigate the cardio-protective efficacy of wheat germ oil, on radiation-induced oxidative damage in rat's heart. Wheat germ oil was supplemented by gavage to rats at a dose of 81 mg/ kg body wt for 10 successive days pre- and 7 successive days post-exposure to 7 Gy (single dose) of whole body gamma irradiation. The dose of wheat germ oil is equivalent to daily human nutritional supplementation quantity. The results revealed that whole body ?-irradiation of rats produced significant alterations in blood cells picture. The erythrocyte, leucocyte, platelet counts and hemoglobin levels decreased after irradiation. Also, radiation-induced biochemical disorders manifested by significant elevation in xanthine oxidase activity (XO) and thiobarbituric acid reactive substances (TBARS) level, with decrease in reduced glutathione (GSH) content in heart tissues, indicating depression in the antioxidant status. Serum lipid profile as total cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and triglycerides levels (TG) were significantly higher than normal control rats. Radiation exposure produced a significant rise in the activities of serum markers for heart damage as creatine phosphokinase (CPK), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH) indicating acute cardiac toxicity. Moreover, the obtained results revealed abnormal electrophoretic pattern of LDH isoenzymes in the 7th day after exposure to gamma rays. Three bands only appear on the agarose film comparing with 4 bands in normal control rats. The rats that received wheat germ oil supplement showed significantly less severe damage and remarkable improvement in all of the measured parameters when compared to

  6. Comparison of carbon dioxide and argon euthanasia: effects on behavior, heart rate, and respiratory lesions in rats.

    Science.gov (United States)

    Burkholder, Tanya H; Niel, Lee; Weed, James L; Brinster, Lauren R; Bacher, John D; Foltz, Charmaine J

    2010-07-01

    In this study we compared rat (n = 16) responses to euthanasia with either gradual-fill CO(2) or rapid induction argon gas by evaluating the animals' heart rate via radiotelemetry, behavior, and vocalizations. We also evaluated the histologic effects of the gases. Rats were placed in an open test chamber 24 h before the start of the experiment. During baseline tests, rats were exposed to oxygen to evaluate the effects of the noise and movement of gas entering the chamber; 1 wk later, rats were euthanized by gas displacement with either 10%/min CO(2) or 50%/min argon gas. Rats tended to have higher heart rats and were more active during the baseline test, but these parameters were normal before the euthanasia experiment, suggesting that the rats had acclimated to the equipment. Heart rate, behavior, and ultrasonic vocalizations were recorded for 2 min after gas introduction in both groups. All rats appeared conscious throughout the test interval. The heart rates of rats exposed to argon did not change, whereas those of rats exposed to CO(2) declined significantly. Unlike those exposed to CO(2), rats euthanized with argon gas gasped and demonstrated seizure-like activity. There were no differences in the pulmonary lesions resulting from death by either gas. Our results suggest that argon as a sole euthanasia agent is aversive to rats. CO(2) using a 10%/min displacement may be less aversive than more rapid displacements. Future research investigating methods of euthanasia should allow sufficient time for the rats to acclimate to the test apparatus.

  7. K+ transport and membrane potentials in isolated rat parotid acini

    International Nuclear Information System (INIS)

    Nauntofte, B.; Dissing, S.

    1988-01-01

    42K+ transport properties of isolated rat parotid acini were characterized concomitant with measurements of membrane potentials (Em) by means of the fluorescent dye diSC3-(5). In unstimulated acini suspended in a 5 mM K+ buffer, Em was governed by the K+ and Cl- gradients and amounted to about -59 mV, a value that remained unaffected on cholinergic stimulation. In unstimulated acini, 42K+ influx was largely mediated by the Na+-K+ pump, and the residual influxes were mediated by a bumetanide-sensitive component (cotransport system) and by K+ channels. Efflux of 42K+ was largely mediated by a bumetanide-sensitive component and by K+ channels. In the unstimulated state, the cotransport system was mediating K+-K+ exchange without contributing to the net uptake of K+. Within 10 s after stimulation, a approximately 10-fold increase in the acinar K+ conductance (gK) occurred, resulting in a rapid net efflux of K+ that amounted to approximately 3.8 mmol.l cells-1.s-1. Measurements of 42K+ fluxes as a function of the external K+ concentration revealed that in the stimulated state gK increases when external K+ is raised from 0.7 to 10 mM, consistent with an activation of acinar gK by the binding of external K+ to the channel. 42K+ flux ratios as well as the effect of the K+ channel inhibitor from scorpion venom (LQV) suggest that approximately 90% of K+ transport in the stimulated state is mediated by ''maxi'' K+ channels

  8. Transport of cysteate by synaptosomes isolated from rat brain

    International Nuclear Information System (INIS)

    Wilson, D.F.; Pastuszko, A.

    1986-01-01

    Synaptosomes isolated from rat brain were observed to take up cysteic acid by a high affinity transport system (K/sub M = 12.3 +/- 2.1 μM; V/sub m/ = 2.5 n mole/mg protein/minute). This uptake was competitively inhibited by aspartate (K/sub i/ = 13.3 +/- 1.8 μM) and cysteine sulfinate (K/sub i/ = 13.3 +/- 3.3 μM). Addition of extrasynaptosomal cysteate, aspartate or cysteine sulfinate to synaptosomes loaded with [ 35 S] cysteate induced rapid efflux of the cysteate. This efflux was via stoichiometric exchange of amino acids with half maximal rates at 5.0 +/- 1.1 μM aspartate or 8.0 +/- 1.3 μM cysteine sulfinate. Conversely, added extrasynaptosomal cysteate exchanged for endogenous aspartate and glutamate with half maximal rates at 5.0 +/- 0.4 μM cysteate. In the steady state after maximal accumulation of cysteate, the intrasynaptosomal cysteate concentrations exceeded the extrasynaptosomal concentrations by up to 10,000 fold. The measured concentration ratios were the same, within experimental error, as those for aspartate and glutamate. Depolarization, with either high K + or veratridine, of the plasma membrane of synaptosomes loaded with cysteate caused parallel release of cysteate, aspartate and glutamate. It is concluded that neurons transport cysteate, cysteine sulfinate, aspartate and glutamate with the same transport system. This transport system catalyzes homoexchange and heteroexchange as well as net uptake and release of all these amino acids

  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.

    2011-01-01

    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 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. PMID:21460193

  10. Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

    Science.gov (United States)

    Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

    1984-04-01

    Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

  11. The Effect of Methanolic Soy Extract on Heart Tissue Changes in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nasirzadeh

    2012-04-01

    Full Text Available Background & Objectives: Following to estrogen depletion in postmenopausal womens, its cardioprotective effect decreases. Stroke usually occurs in women during the menopause years. Estrogen hormone therapy is still controversial. Epidemiological data suggest that phytoestrogens have a preventive effect on various estrogen-related diseases/symptoms such as menopausal symptoms, cardiovascular diseases. Some studies suggest that genistein as an important component of soy have cardioprotection effects but its role on inflammation and cardiomyocte injury remained to be elucidated. So, this study was goaled to investigate the cardioprotective effect of methanolic soy extract on heart tissue injures.   Method: In this study 40 female rats were randomly allocated into 4 groups: 1 Control (intact animals, 2 sham surgery (without ovarictomy, 3 ovariectomized (ovx, and 4 treatment (ovx and soy gavage group that received 60mg/kg per day soy extract in drinking water for 28days (4 weeks. At the end of experiments, the rat heart tissue was processed histologically and the sections were stained with hematoxylin and eosin to examine under light microscope. Statistical analysis was performed using the wilcoxon test.   Results: The results showed that ovariectomy significantly increased inflammation and cardiomyocte injury and soy extract significantly promoted heart tissue recovery (p<0.05.   Conclosions: This study indicated that oral administration of soy extract has a positive effect on attenuation of inflammation and myocyte injury in ovariectomized rat.

  12. The Toxicity Mechanisms of Action of Aβ25–35 in Isolated Rat Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Beiru Zhang

    2014-08-01

    Full Text Available β-Amyloid (Aβ is deposited in neurons and vascular cells of the brain and is characterized as a pathologic feature of Alzheimer’s disease (AD. Recently studies have reported that there is an association between cardiovascular risk factors and AD, however the mechanism of this association is still uncertain. In this study we observed Aβ had an effect on cardiovascular cells. We represent as a major discovery that Aβ25–35 had toxicity on isolated rat cardiac myocytes by impacting the cytoskeleton assembly and causing ER stress, ultimately contributing to the apoptosis of the myocytes. Importantly, the activation of ER stress and subsequent cellular dysfunction and apoptosis by Aβ25–35 was regulated by the MAPK pathway, which could be prevented by inhibition of p38 via pharmacological inhibitors. It was noteworthy that Aβ25–35 played a critical role in cardiac myocytes, suggesting that Alzheimer’s disease (AD had a relation with the heart and understanding of these associations in future will help search for effective treatment strategies.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Early Treatment of radiation-Induced Heart Damage in Rats by Caffeic acid phenethyl Ester

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Mansour, H. H.

    2012-12-01

    The study designed to determine the therapeutic effect of caffeic acid phenethyl ester (CAPE) in minimising radiation-induced injuries in rats. Rats were exposed to 7 Gy γ-rays, 30 minutes later; rats were injected with CAPE (10μmol/ kg body, i.p.) for 7 consecutive days. Rats were sacrificed at 8 and 15 days after starting the experiment. Gamma-irradiation induced significant increase in malonaldehyde (MDA) level and xanthine oxidase (XO) and adenosine deaminase (ADA) activities, and significant decrease in total nitrate/nitrate (NO (x)) level and glutathione peroxidise (Gpx), superoxide dismutase (SOD)and catalase (CAT) activities in heart tissue and augmented activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate transaminase (AST) in serum. Irradiated rats early treated with CAPE showed significant decrease in MDA, XO and ADA and significant increase in group. Cardiac enzymes were restored. Conclusion, CAPE could exhibits curable effect on gamma irradiation-induced cardiac-oxidative impairment in rats. (Author)

  16. Saw palmetto is an indirectly acting sympathomimetic in the rat-isolated prostate gland.

    Science.gov (United States)

    Cao, Nga; Haynes, John M; Ventura, Sabatino

    2006-02-01

    To investigate whether saw palmetto that inhibits alpha1-adrenoceptor binding in vitro affects contractility of the rat prostate gland. The effects of a commercially available saw palmetto extract were examined on the contractility of rat-isolated prostate glands. The extract was tested in the presence and absence of phentolamine, prazosin, yohimbine, propranolol, hexamethonium, cocaine, desipramine, nifedipine, guanethidine, atropine, and alpha,beta-methylene ATP to evaluate the mechanism of action. Isolated preparations of rat vas deferens and bladder were used for comparison. Unexpectedly, saw palmetto extract caused contractions of the rat prostate gland that could be attenuated by prazosin, phentolamine, nifedipine, guanethidine, cocaine, and desipramine but not by any of the other pharmacological tools. Similar contractile effects were observed in rat-isolated vas deferens preparations but not in rat-isolated bladder preparations. In the rat prostate gland, saw palmetto extract causes indirect alpha1-adrenoceptor-mediated contractions via the release of noradrenaline from sympathetic neurons. Copyright 2005 Wiley-Liss, Inc.

  17. Draft genome of the emerging pathogen, Kocuria marina, isolated from a wild urban rat

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    Shih Keng Loong

    Full Text Available Kocuria marina has recently emerged as a cause for catheter-related bloodstream infections in patients with underlying health complications. One K. marina strain was recently isolated from the lung tissues of a wild urban rat (Rattus rattus diardii caught during rodent surveillance. Here, we present the draft genome of the first K. marina animal isolate, K. marina TRE150902.

  18. Propranolol inhibits the in vitro conversion of thyroxine into triiodothyronine by isolated rat liver parenchymal cells

    NARCIS (Netherlands)

    van Noorden, C. J.; Wiersinga, W. M.; Touber, J. L.

    1979-01-01

    A model for the in vitro study of the conversion of thyroxine into triiodothyronine using isolated rat liver parenchymal cells is described. Isolated liver cells (mean protein content 18 mg/ml) convert approximately 0.8% of 1.3 microM exogenously added T4 into T3 during thirty minutes incubation.

  19. Increase vs. decrease of calcium uptake by isolated heart cells induced by H2O2 vs. HOCl

    International Nuclear Information System (INIS)

    Kaminishi, T.; Matsuoka, T.; Yanagishita, T.; Kako, K.J.

    1989-01-01

    Adult rat heart myocytes were labeled rapidly with exogenous [45Ca2+]. Addition of 2.5 mM H2O2 to the heart cell suspension raised the content of rapidly exchangeable intracellular Ca2+ twofold, whereas addition of 1-30 mM HOCl decreased the Ca2+ content. The H2O2-induced increase in Ca2+ content was dependent on the medium Na+, pH, and temperature but was not significantly affected by addition of verapamil, diltiazem, amiloride, or 3-aminobenzamide. The [3H]ouabain binding to myocytes was suppressed by H2O2, whereas the Ca2+ efflux from myocytes was not influenced. An uncoupler, carbonyl cyanide m-chlorophenylhydrazone, reduced Ca2+ content, implying that the H2O2-induced change in Ca2+ content was not directly related to ATP depletion. On the other hand, the H2O2-induced Ca2+ accumulation in myocytes was prevented by deferoxamine or o-phenanthroline. These results suggest that H2O2 inhibited Na+-K+-ATPase, resulting in an increase in intracellular Na+ concentration and stimulation of sarcolemmal Na+-Ca2+ exchange activity, which caused a transient net Ca2+ influx into myocytes. By contrast, HOCl decreased the Ca2+ content of the rapidly exchangeable pool below control levels and this action of HOCl was antagonized by 1,4-dithiothreitol. HOCl accelerated Ca2+ efflux from myocytes. Ca2+ uptake and Ca2+-ATPase of the isolated sarcoplasmic reticular (SR) fraction were highly sensitive to the action of HOCl. Ca2+ uptake by intracellular sites, studied with myocytes permeabilized with digitonin, was inhibited by both H2O2 and HOCl. Thus these results suggest that HOCl inhibits the SR Ca2+ pump, resulting in the observed acceleration of Ca2+ efflux from and decline in Ca2+ content of myocytes

  20. 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.

  1. [Contractile function of the heart and myocardium antioxidant system in rats of August and Wistar strains during ischemia and reperfusion].

    Science.gov (United States)

    Sazontova, T G; Belkina, L M; Zhukova, A G; Kirillina, T N; Arkhipenko, Iu V

    2004-01-01

    In August rats, local myocardial ischemia caused by 30-min occlusion of the coronary artery induced a slight depression of the contractile function of the heart; the latter was restored after 15-min reperfusion more rapidly than in Wistar rats. In August rats, the activities of antioxidant protection enzymes were lower than in Wistar rats. In comparison with Wistar rats, these enzyme activities were decreased in a lesser degree under ischemia and were restored in a greater degree under reperfusion. It may thus be concluded that the higher stability of antiradical protection parameters in August rats is one of the mechanisms responsible for the enhanced resistance of the heart to ischemia- and reperfusion-induced injuries.

  2. Congestive heart failure effects on atrial fibroblast phenotype: differences between freshly-isolated and cultured cells.

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    Kristin Dawson

    Full Text Available Fibroblasts are important in the atrial fibrillation (AF substrate resulting from congestive heart failure (CHF. We previously noted changes in in vivo indices of fibroblast function in a CHF dog model, but could not detect changes in isolated cells. This study assessed CHF-induced changes in the phenotype of fibroblasts freshly isolated from control versus CHF dogs, and examined effects of cell culture on these differences.Left-atrial fibroblasts were isolated from control and CHF dogs (ventricular tachypacing 240 bpm × 2 weeks. Freshly-isolated fibroblasts were compared to fibroblasts in primary culture. Extracellular-matrix (ECM gene-expression was assessed by qPCR, protein by Western blot, fibroblast morphology with immunocytochemistry, and K(+-current with patch-clamp. Freshly-isolated CHF fibroblasts had increased expression-levels of collagen-1 (10-fold, collagen-3 (5-fold, and fibronectin-1 (3-fold vs. control, along with increased cell diameter (13.4 ± 0.4 µm vs control 8.4 ± 0.3 µm and cell spreading (shape factor 0.81 ± 0.02 vs. control 0.87 ± 0.02, consistent with an activated phenotype. Freshly-isolated control fibroblasts displayed robust tetraethylammonium (TEA-sensitive K(+-currents that were strongly downregulated in CHF. The TEA-sensitive K(+-current differences between control and CHF fibroblasts were attenuated after 2-day culture and eliminated after 7 days. Similarly, cell-culture eliminated the ECM protein-expression and shape differences between control and CHF fibroblasts.Freshly-isolated CHF and control atrial fibroblasts display distinct ECM-gene and morphological differences consistent with in vivo pathology. Culture for as little as 48 hours activates fibroblasts and obscures the effects of CHF. These results demonstrate potentially-important atrial-fibroblast phenotype changes in CHF and emphasize the need for caution in relating properties of cultured fibroblasts to in vivo systems.

  3. Direct Effects of (−-Epicatechin and Procyanidin B2 on the Respiration of Rat Heart Mitochondria

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    Dalia M. Kopustinskiene

    2015-01-01

    Full Text Available Flavonol (−-epicatechin and its derived dimer procyanidin B2, present in high amounts in cocoa products, have been shown to exert beneficial effects on the heart and cardiovascular system; however, their mechanism of action has not been fully elucidated. We studied effects of (−-epicatechin and procyanidin B2 on the oxidative phosphorylation of isolated rat heart mitochondria. (−-Epicatechin and procyanidin B2 had stimulating effect (up to 30% compared to control on substrate-driven (State 2 mitochondrial respiration. Their effect was dependent on the respiratory substrates used. (−-Epicatechin at higher concentrations (from 0.27 µg/mL significantly decreased (up to 15% substrate- and ADP-driven (State 3 mitochondrial respiration in case of pyruvate and malate oxidation only. Procyanidin B2 (0.7–17.9 ng/mL inhibited State 3 respiration rate up to 19%, the most profound effect being expressed with succinate as the substrate. (−-Epicatechin at concentrations of 0.23 µg/mL and 0.46 µg/mL prevented loss of the cytochrome c from mitochondria when substrate was succinate, supporting the evidence of membrane stabilizing properties of this flavonol. Thus, both (−-epicatechin and procyanidin B2 directly influenced mitochondrial functions and the observed effects could help to explain cardiometabolic risk reduction ascribed to the consumption of modest amounts of cocoa products.

  4. N-acetylcysteine prevents nitrosative stress-associated depression of blood pressure and heart rate in streptozotocin diabetic rats.

    Science.gov (United States)

    Nagareddy, Prabhakara Reddy; Xia, Zhengyuan; MacLeod, Kathleen M; McNeill, John H

    2006-04-01

    Previous studies have indicated that cardiovascular abnormalities such as depressed blood pressure and heart rate occur in streptozotocin (STZ) diabetic rats. Chronic diabetes, which is associated with increased expression of inducible nitric oxide synthase (iNOS) and oxidative stress, may produce peroxynitrite/nitrotyrosine and cause nitrosative stress. We hypothesized that nitrosative stress causes cardiovascular depression in STZ diabetic rats and therefore can be corrected by reducing its formation. Control and STZ diabetic rats were treated orally for 9 weeks with N-acetylcysteine (NAC), an antioxidant and inhibitor of iNOS. At termination, the mean arterial blood pressure (MABP) and heart rate (HR) were measured in conscious rats. Nitrotyrosine and endothelial nitric oxide synthase (eNOS) and iNOS expression were assessed in the heart and mesenteric arteries by immunohistochemistry and Western blot experiments. Untreated diabetic rats showed depressed MABP and HR that was prevented by treatment with NAC. In untreated diabetic rats, levels of 15-F(2t)-isoprostane, an indicator of lipid peroxidation increased, whereas plasma nitric oxide and antioxidant concentrations decreased. Furthermore, decreased eNOS and increased iNOS expression were associated with elevated nitrosative stress in blood vessel and heart tissue of untreated diabetic rats. N-acetylcysteine treatment of diabetic rats not only restored the antioxidant capacity but also reduced the expression of iNOS and nitrotyrosine and normalized the expression of eNOS to that of control rats in heart and superior mesenteric arteries. The results suggest that nitrosative stress depress MABP and HR following diabetes. Further studies are required to elucidate the mechanisms involved in nitrosative stress mediated depression of blood pressure and heart rate.

  5. 3,5-Diiodo-l-Thyronine Increases Glucose Consumption in Cardiomyoblasts Without Affecting the Contractile Performance in Rat Heart

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    Ginevra Sacripanti

    2018-05-01

    Full Text Available 3,5-diiodo-l-thyronine (T2 is an endogenous derivative of thyroid hormone that has been suggested to regulate energy expenditure, resting metabolic rate and oxygen consumption with a mechanism that involves the activation of mitochondrial function. In this study, we focused on the cardiac effects of T2, which have been poorly investigated so far, by using both in vitro and ex vivo models. As a comparison, the response to T3 and T4 was also determined. Rat cardiomyoblasts (H9c2 cells were used to determine T2, T3, and T4 uptake by high-performance liquid chromatography–tandem mass spectrometry. In the same experimental model, MTT test, crystal violet staining, and glucose consumption were investigated, using T2 concentrations ranging from 0.1 to 10 µM. To assess cardiac functional effects, isolated working rat hearts were perfused with T2, T3, or T4 in Krebs-Ringer buffer, and the hemodynamic variables were recorded. T2 was taken up by cardiomyoblasts, and in cell lysate T2 levels increased slowly over time, reaching higher concentrations than in the incubation medium. T2 significantly decreased MTT staining at 0.5–10 µM concentration (P < 0.05. Crystal violet staining confirmed a reduction of cell viability only upon treatment with 10 µM T2, while equimolar T3 and T4 did not share this effect. Glucose consumption was also significantly affected as indicated by glucose uptake being increased by 24 or 35% in cells exposed to 0.1 or 1.0 µM T2 (P < 0.05 in both cases. On the contrary, T3 did not affect glucose consumption which, in turn, was significantly reduced by 1 and 10 µM T4 (−24 and −41% vs control, respectively, P < 0.05 and P < 0.01. In the isolated perfused rat heart, 10 µM T2 produced a slight and transient reduction in cardiac output, while T3 and T4 did not produce any hemodynamic effect. Our findings indicate that T2 is taken up by cardiomyoblasts, and at 0.1–1.0 µM concentration it can

  6. Immune system stimulation in rats by Lactobacillus sp. isolates from Raffia wine (Raphia vinifera).

    Science.gov (United States)

    Flore, Tiepma N E; François, Zambou N; Félicité, Tchouanguep M

    2010-01-01

    The immune system consists of organs and several cell types. Antigen interaction with these cells induces a cellular immune response mediated by activated cells. The effects of lactic acid bacteria on the systemic immune response and on the secretory immune system are described. The current investigation sets out to examine the possible effects of isolated wine lacto-bacilli upon various hematologic and immunologic parameters in rats. We have fed rats with probiotic isolates from Raffia wine and challenged with castor oil; two control groups were fed with castor oil and others were not. We counted blood cells at the end of the experiment; all isolates seemed to cause a decrease of circulating white blood cells. The percentage of lymphocytes and the total protein in the spleen increased in the treated animals; also a normal aspect of faeces was observed compared to the control. These isolates of Lactobacillus seem to occur to immune cell-mediated responses in rats.

  7. Effect of housing rats in dim light or long nights on heart rate.

    Science.gov (United States)

    Azar, Toni A; Sharp, Jody L; Lawson, David M

    2008-07-01

    Housing laboratory animals under lighting conditions that more closely mimic the natural environment may improve their wellbeing. This study examined the effects of dim light or a long-night photocycle on resting heart rate (HR) of rats and their HR responses to acute procedures. Male and female Sprague-Dawley (SD) and spontaneously hypertensive (SHR) rats, instrumented with radiotelemetry transmitters and housed individually under a 12:12-h light:dark photocycle with 10 lx illumination (dim light) or under an 8:16-h light:dark photocycle with 200 lx illumination (long nights), were compared with control rats individually housed under a 12:12-h light:dark photocycle with 200 lx illumination. Dim light and long nights significantly reduced the HR of undisturbed SD and SHR male and SHR female rats during the day and at night; however, the HR of undisturbed SD females was not affected. When rats were subjected acutely to husbandry, experimental, or stressful procedures, dim light or long nights (or both) reduced HR responses to some procedures, did not alter responses to others, and increased responses to yet other procedures. The pattern of effects varied between strains and between male and female rats. Because basal HR was reduced when rats were housed under 10 lx illumination or an 8:16-h light:dark photocycle, we concluded that housing rats under 12:12-h light:dark, 200 lx ambient light conditions was potentially stressful, We also concluded that dim light or long nights did not uniformly reduce the increased HR responses induced by acute procedures.

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

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    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

  9. Sex differences in the outcome of juvenile social isolation on HPA axis function in rats.

    Science.gov (United States)

    Pisu, M G; Garau, A; Boero, G; Biggio, F; Pibiri, V; Dore, R; Locci, V; Paci, E; Porcu, P; Serra, M

    2016-04-21

    Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. Social isolation is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like and depressive-like behaviors. Here we investigated the sex difference in the effects of post-weaning social isolation on acute stress sensitivity and behavior in rats. In both sexes, social isolation at weaning reduced basal levels of the neuroactive steroid allopregnanolone in the brain and of corticosterone in plasma. Moreover, acute stress increased plasma corticosterone levels in both group-housed and socially isolated male and female rats; however this effect was greater in male than female rats subjected to social isolation. Intriguingly, group-housed female rats showed no change in plasma and brain levels of allopregnanolone after acute foot-shock stress. The absence of stress-induced effects on allopregnanolone synthesis might be due to the physiologically higher levels of this hormone in females vs. males. Accordingly, increasing allopregnanolone levels in male rats blunted the response to foot-shock stress in these animals. Socially isolated male, but not female, rats also display depressive-like behavior and increased hippocampal brain-derived neurotrophic factor (BDNF). The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine

  10. 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

  11. 3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

    Science.gov (United States)

    Xu, He N; Zhou, Rong; Moon, Lily; Feng, Min; Li, Lin Z

    2014-03-01

    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 feasibility of 3D

  12. Effects of isolated vitamin B6 supplementation on oxidative stress and heart function parameters in experimental hyperhomocysteinemia

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    Roberta Hack Mendes

    2017-07-01

    Full Text Available Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 supplementation on experimental hyperhomocysteinemia (Hhe induced by homocysteine thiolactone (HcyT. Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6. On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6. After 60 days of treatment, homocysteine (Hcy, cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2-like 2 (NRF2 and glutathione S-transferase (GST immunocontent, and superoxide dismutase (SOD, catalase (CAT, and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62% in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51% in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17% in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53% compared to the CB6 group. Ejection fraction (EF was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI (r = 0.71; P = 0.06 and E/A ratio (r = 0.6; P = 0.01, and between EF and GST activity (r = 0.62; P = 0.02. Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters.   Keywords: Homocysteine; oxidative stress; vitamin B6.

  13. Iodine-131 metaiodobenzylguanidine intra- and extravesicular accumulation in the rat heart

    International Nuclear Information System (INIS)

    Nakajo, M.; Shimabukuro, K.; Yoshimura, H.; Yonekura, R.; Nakabeppu, Y.; Tanoue, P.; Shinohara, S.

    1986-01-01

    In order to establish the appropriate time for [ 123 I]MIBG human myocardial imaging to assess the adrenergic nerve activity, the time courses of metaiodobenzylguanidine (MIBG) intra- and extravesicular accumulation in the rat heart were estimated by using [ 131 I]MIBG and reserpine. In the heart, the intravesicular accumulation was relatively constant, while the extravesicular accumulation decreased rapidly from 5 min to 6 hr. The intravesicular percentage of the total cardiac tissue concentration reached a plateau value of 50% at 4 hr after i.v. injection of [ 131 I]MIBG. In the spleen, similar time courses were observed as those in the heart, both of these organs being richly innervated by adrenergic nerves. Along with the time activity difference previously observed in the human hearts, these results suggest that at 4 hr post i.v. injection, [ 123 I]MIBG myocardial imaging will best express the neuronal accumulation of the tracer and may be useful for the assessment of adrenergic function in various pathological conditions of the human heart

  14. The influx of amino acids into the heart of the rat

    International Nuclear Information System (INIS)

    Banos, G.; Moorhouse, S.R.; Pratt, O.E.; Wilson, P.A.; Daniel, P.M.

    1978-01-01

    The influx of nineteen amino acids into the heart of the living rat was studied by a method specially devised for experiments under controlled conditions in vivo. When, in separate experiments, the concentration of each amino acid in turn was artificially raised in the circulation, the influx of that amino acid into the heart increased. The data indicate that at least ten of these amino acids enter the heart in vivo by means of saturable carrier-mediated transport systems. The transport rates conform, at least approximately, to Michaelis kinetics and the transport systems are clearly, in the case of many amino acids, active, i.e. energy-dependent. The amino acids which were studied had rates of influx into the heart which differed from each other over a range of more than 10 to 1, even when allowances were made for the differences in their concentration in the circulating blood. These differences in influx were not related to such factors as the molecular size of the individual amino acids. The amino acids which have a high influx into the heart are mainly those which are needed either to re-synthesize contractile protein or as oxidizable substrates. (author)

  15. Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate.

    Science.gov (United States)

    Al Rasheed, N M; Al Sayed, M I; Al Zuhair, H H; Al Obaid, A R; Fatani, A J

    2001-04-01

    Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (Plidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl(2)significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential. Copyright 2001 Academic Press.

  16. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Effects of thapsigargin in isolated rat thoracic aorta

    DEFF Research Database (Denmark)

    Mikkelsen, E O; Thastrup, Ole; Christensen, S B

    1988-01-01

    The effect of thapsigargin (Tg) was studied in rat thoracic aorta. Tg (10(-8)-10(-5) M) had a dual effect on rat aorta. Thus, Tg induced a concentration dependent increase in basal tone in normal physiological salt solution (PSS), while Tg in potassium (K+) precontracted aortic rings caused a con...... A 23187 had an endothelium dependent relaxant effect on rat aorta different from that of carbachol. The results indicate that Tg in vascular smooth muscle acts by stimulating the transmembranal influx of extracellular calcium....

  18. Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction in the failing rat heart

    Science.gov (United States)

    Mulligan, Christopher M.; Sparagna, Genevieve C.; Le, Catherine H.; De Mooy, Anthony B.; Routh, Melissa A.; Holmes, Michael G.; Hickson-Bick, Diane L.; Zarini, Simona; Murphy, Robert C.; Xu, Fred Y.; Hatch, Grant M.; McCune, Sylvia A.; Moore, Russell L.; Chicco, Adam J.

    2012-01-01

    Aims Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L4CL). A selective loss of L4CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L4CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure. Methods and results Male spontaneously hypertensive heart failure rats (21 months of age) were administered diets supplemented with high-linoleate safflower oil (HLSO) or lard (10% w/w; 28% kilocalorie fat) or without supplemental fat (control) for 4 weeks. HLSO preserved L4CL and total CL to 90% of non-failing levels (vs. 61–75% in control and lard groups), and attenuated 17–22% decreases in state 3 mitochondrial respiration observed in the control and lard groups (P < 0.05). Left ventricular fractional shortening was significantly higher in HLSO vs. control (33 ± 2 vs. 29 ± 2%, P < 0.05), while plasma insulin levels were lower (5.4 ± 1.1 vs. 9.1 ± 2.3 ng/mL; P < 0.05), with no significant effect of lard supplementation. HLSO also increased serum concentrations of several eicosanoid species compared with control and lard diets, but had no effect on plasma glucose or blood pressure. Conclusion Moderate consumption of HLSO preserves CL and mitochondrial function in the failing heart and may be a useful adjuvant therapy for this condition. PMID:22411972

  19. Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

    Science.gov (United States)

    Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

    2018-02-17

    The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

  20. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    Directory of Open Access Journals (Sweden)

    Halina Baran*

    2016-01-01

    Full Text Available Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3, respiratory control index (RC and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM or succinate (10 mM and in the presence of L-tryptophan metabolites (1 mM or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver

  1. PFOS prenatal exposure induce mitochondrial injury and gene expression change in hearts of weaned SD rats

    International Nuclear Information System (INIS)

    Xia, Wei; Wan, Yanjian; Li, Yuan-yuan; Zeng, Huaicai; Lv, Ziquan; Li, Gengqi; Wei, Zhengzheng; Xu, Shun-qing

    2011-01-01

    Xenobiotics exposure in early life may have adverse effects on animals' development through mitochondrial injury or dysfunction. The current study demonstrated the possibility of cardiac mitochondrial injury in prenatal PFOS-exposed weaned rat heart. Pregnant Sprague-Dawley (SD) rats were exposed to perfluorooctane sulfonate (PFOS) at doses of 0.1, 0.6 and 2.0 mg/kg/d and 0.05% Tween 80 as control by gavage from gestation days 2-21. The dams were allowed to give nature delivery and then heart tissues from weaned (postnatal day 21) offspring rats were analyzed for mitochondrial injury through ultrastructure observation by electron microscope, global gene expression profile by microarray, as well as related mRNA and proteins expression levels by quantitative PCR and western blot. Ultrastructural analysis revealed significant vacuolization and inner membrane injury occurred at the mitochondria of heart tissues from 2.0 mg/kg/d dosage group. Meanwhile, the global gene expression profile showed significant difference in level of some mRNA expression associated with mitochondrial function at 2.0 mg/kg/d dosage group, compared to the control. Furthermore, dose-response trends for the expression of selected genes were analyzed by quantitative PCR and western blot analysis. The selected genes were mainly focused on those encoding for proteins involved in energy production, control of ion levels, and maintenance of heart function. The down-regulation of mitochondrial ATP synthetase (ATP5E, ATP5I and ATP5O) implicated a decrease in energy supply. This was accompanied by down-regulation of gene transcripts involved in energy consumption such as ion transporting ATPase (ATP1A3 and ATP2B2) and inner membrane protein synthesis (SLC25A3, SLC25A4, SLC25A10, SLC25A29). The up-regulation of gene transcripts encoding for uncoupling proteins (UCP1 and UCP3), epidermal growth factor receptor (EGFR) and connective tissue growth factor (CTGF), was probably a protective process to maintain

  2. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    International Nuclear Information System (INIS)

    Finan, A.; Cleary, M.P.

    1986-01-01

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either [1- 14 C] glucose or [6- 14 C] glucose resulted in significant decreases in CO 2 production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats

  3. Effects of salicylic acid on post-ischaemic ventricular function and purine efflux in isolated mouse hearts.

    Science.gov (United States)

    Farthing, Don; Gehr, Lynne; Karnes, H Thomas; Sica, Domenic; Gehr, Todd; Larus, Terri; Farthing, Christine; Xi, Lei

    2007-01-01

    Acetyl salicylic acid (aspirin) is one of the most widely used drugs in the world. Various plasma concentrations of aspirin and its predominant metabolite, salicylic acid, are required for its antiarthritic (1.5-2.5 mM), anti-inflammatory (0.5-5.0 mM) or antiplatelet (0.18-0.36 mM) actions. A recent study demonstrated the inhibitory effects of both aspirin and salicylic acid on oxidative phosphorylation and ATP synthesis in isolated rat cardiac mitochondria in a dose-dependent manner (0-10 mM concentration range). In this context, the present study was conducted to determine the effects of salicylic acid on inosine efflux (a potential biomarker of acute cardiac ischaemia) as well as cardiac contractile function in the isolated mouse heart following 20 min of zero-flow global ischaemia. Inosine efflux was found at significantly higher concentrations in ischaemic hearts perfused with Krebs buffer fortified with 1.0 mM salicylic acid compared with those without salicylic acid (12575+/-3319 vs. 1437+/-348 ng ml(-1) min(-1), mean+/-SEM, n=6 per group, psalicylic acid potentiates 8.8-fold ATP nucleotide purine catabolism into its metabolites (e.g. inosine, hypoxanthine). Salicylic acid (0.1 or 1.0 mM) did not appreciably inhibit purine nucleoside phosphorylase (the enzyme converts inosine to hypoxanthine) suggesting the augmented inosine efflux was due to the salicylic acid effect on upstream elements of cellular respiration. Whereas post-ischaemic cardiac function was further depressed by 1.0 mM salicylic acid, perfusion with 0.1 mM salicylic acid led to a remarkable functional improvement despite moderately increased inosine efflux (2.7-fold). We conclude that inosine is a sensitive biomarker for detecting cardiac ischaemia and salicylic acid-induced effects on cellular respiration. However, the inosine efflux level appears to be a poor predictor of the individual post-ischaemic cardiac functional recovery in this ex vivo model.

  4. 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.

  5. Morphological and functional changes in the rat heart after X irradiation: Strain differences

    International Nuclear Information System (INIS)

    Yeung, T.K.; Lauk, S.; Simmonds, R.H.; Hopewell, J.W.; Trott, K.R.

    1989-01-01

    The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change

  6. 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.

  7. Decreasing Compensatory Ability of Concentric Ventricular Hypertrophy in Aortic-Banded Rat Hearts

    Directory of Open Access Journals (Sweden)

    Alexandre Lewalle

    2018-02-01

    Full Text Available The cardiac system compensates for variations in physiological and pathophysiological conditions through a dynamic remodeling at the organ, tissue, and intracellular levels in order to maintain function. However, on longer time scales following the onset of ventricular pressure overload, such remodeling may begin to inhibit physiological function and ultimately lead to heart failure. This progression from compensatory to decompensatory behavior is poorly understood, in particular owing to the absence of a unified perspective of the concomitantly remodeling subsystems. To address this issue, the present study investigates the evolution of compensatory mechanisms, in response to overload, by integrating diffusion-tensor MRI, echocardiography, and intracellular and hemodynamic measurements within consistent computational simulations of aortic-banded rat hearts. This approach allows a comparison of the relative leverage of different cardiac properties (geometry, passive mechanical stiffness, fiber configuration, diastolic and peak calcium concentrations, calcium-binding affinity, and aortic impedance to affect cardiac contraction. Measurements indicate that, following aortic banding, an ejection fraction (EF of 75% was maintained, relative to control rats, despite significant remodeling of the left-ventricular wall thickness (increasing by ~90% over 4 weeks. Applying our framework, we identified the left-ventricular wall thickness (concentric hypertrophy and the intracellular calcium dynamics as playing the dominant roles in preserving EF acutely, whereas the significance of hypertrophy decreased subsequently. This trend suggests an increasing reliance on intracellular mechanisms (average increase ~50%, rather than on anatomical features (average decrease ~60%, to achieve compensation of pump function in the early phase of heart failure.

  8. Changes in expression of a functional Gi protein in cultured rat heart cells

    International Nuclear Information System (INIS)

    Allen, I.S.; Gaa, S.T.; Rogers, T.B.

    1988-01-01

    The muscarinic cholinergic agonist, carbachol, and pertussis toxin were used to examine the functional status of the guanine nucleotide-binding protein that inhibits adenylate cyclase (G i ) in cultured neonatal rat heart myocytes. The isoproterenol stimulation of adenylate cyclase activity in myocyte membranes and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in intact cells (4 days in culture) were insensitive to carbachol. However, in cells cultured for 11 days, carbachol inhibited isoproterenol-stimulated cAMP accumulation by 30%. Angiotensin II (ANG II) was also found to inhibit isoproterenol-stimulated cAMP accumulation in day 11 cells in a dose-dependent manner. Pertussis toxin treatment reversed the inhibitory effects of both ANG II and carbachol, suggesting a role for G i in the process. Carbachol binding to membranes from day 4 cells was relatively insensitive to guanine nucleotides when compared with binding to membranes from day 11 or adult cells. Furthermore, pertussis toxin-mediated 32 P incorporation into a 39- to 41-kDa substrate in day 11 membranes was increased 3.2-fold over that measured in day 4 membranes. These findings support the view that, although G i is expressed, it is nonfunctional in 4-day-old cultured neonatal rat heart myocytes and acquisition of functional G i is dependent on culture conditions. Furthermore, the ANG II receptor can couple to G i in heart

  9. Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes.

    Science.gov (United States)

    Zimmermann, W H; Fink, C; Kralisch, D; Remmers, U; Weil, J; Eschenhagen, T

    2000-04-05

    A technique is presented that allows neonatal rat cardiac myocytes to form spontaneously and coherently beating 3-dimensional engineered heart tissue (EHT) in vitro, either as a plane biconcaval matrix anchored at both sides on Velcro-coated silicone tubes or as a ring. Contractile activity was monitored in standard organ baths or continuously in a CO(2) incubator for up to 18 days (=26 days after casting). Long-term measurements showed an increase in force between days 8 and 18 after casting and stable forces thereafter. At day 10, the twitch amplitude (TA) of electrically paced EHTs (average length x width x thickness, 11 x 6 x 0.4 mm) was 0.51 mN at length of maximal force development (L(max)) and a maximally effective calcium concentration. EHTs showed typical features of neonatal rat heart: a positive force-length and a negative force-frequency relation, high sensitivity to calcium (EC(50) 0.24 mM), modest positive inotropic (increase in TA by 46%) and pronounced positive lusitropic effect of isoprenaline (decrease in twitch duration by 21%). Both effects of isoprenaline were sensitive to the muscarinic receptor agonist carbachol in a pertussis toxin-sensitive manner. Adenovirus-mediated gene transfer of beta-galactosidase into EHTs reached 100% efficiency. In summary, EHTs retain many of the physiological characteristics of rat cardiac tissue and allow efficient gene transfer with subsequent force measurement. Copyright 2000 John Wiley & Sons, Inc.

  10. Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart.

    Science.gov (United States)

    Granata, Riccarda; Trovato, Letizia; Gallo, Maria Pia; Destefanis, Silvia; Settanni, Fabio; Scarlatti, Francesca; Brero, Alessia; Ramella, Roberta; Volante, Marco; Isgaard, Jorgen; Levi, Renzo; Papotti, Mauro; Alloatti, Giuseppe; Ghigo, Ezio

    2009-07-15

    The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

  11. Glucose production and storage in hepatocytes isolated from normal versus diabetic rats

    International Nuclear Information System (INIS)

    Olivieri, M.C.; Dragland-Meserve, C.J.; Parker Botelho, L.H.

    1987-01-01

    The rates of glucose production and storage were compared in hepatocytes isolated from normal versus insulin-resistant diabetic rats. A single low-dose (40 mg/kg) IV injection of streptozotocin to 250 g rats resulted in a Type II diabetic animal model which was hyperglycemic with normal insulin levels. Addition of 8 mM 14 C-lactate and 2 mM pyruvate to hepatocytes resulted in a linear increase in total glucose production ( 14 C-glucose and unlabeled glucose) and incorporation into glycogen measured over 120 min. The rate of gluconeogenesis was estimated from the production of 14 C-glucose and the rate of glycogenolysis was estimated from the production of unlabeled glucose in cells incubated in the presence or absence of 14 C-labelled substrate. There was not significant difference in total glucose production in hepatocytes isolated from normal versus diabetic rats, however, the contribution from gluconeogenesis versus glycogenolysis was significantly different. Following a 1 h incubation of cells from normal rats, 42% of the total glucose production was due to gluconeogenesis and 58% was due to glycogenolysis. In cells from diabetic rats, 83% of total glucose production was from gluconeogenesis and 17% from glycogenolysis. Also, incubation with 14 C-lactate/pyruvate resulted in a 3.3-fold increase in 14 C-glucose incorporation into glycogen in hepatocytes isolated from normal rats compared to diabetic rats. These data suggest that alterations occur in the rate-limiting enzymes responsible for glucose production and storage in hepatocytes isolated from a rat model of insulin-resistant Type II diabetes

  12. Antispasmodic Effects of Yarrow (Achillea Millefolium L.) Extract in the Isolated Ileum of Rat

    OpenAIRE

    Moradi, Mohammad-Taghi; Rafieian-Koupaei, Mahmoud; Imani-Rastabi, Reza; Nasiri, Jafar; Shahrani, Mehrdad; Rabiei, Zahra; Alibabaei, Zahra

    2013-01-01

    Achillea millefolium L. is cultivated in Iran and widely used in traditional medicine for gastrointestinal disorders. The aim of this study was to determine the effect of hydroalcoholic extract of A. millefolium on the contraction and relaxation of isolated ileum in rat. In this experimental study, aerial parts of A. millefolium were extracted by maceration in ethanol 70% for 72h. Terminal portion of ileum in 100 male Wistar rats was dissected and its contractions were recorded isotonically i...

  13. Cardioprotection Resulting from Glucagon-Like Peptide-1 Administration Involves Shifting Metabolic Substrate Utilization to Increase Energy Efficiency in the Rat Heart.

    Science.gov (United States)

    Aravindhan, Karpagam; Bao, Weike; Harpel, Mark R; Willette, Robert N; Lepore, John J; Jucker, Beat M

    2015-01-01

    Previous studies have shown that glucagon-like peptide-1 (GLP-1) provides cardiovascular benefits independent of its role on peripheral glycemic control. However, the precise mechanism(s) by which GLP-1 treatment renders cardioprotection during myocardial ischemia remain unresolved. Here we examined the role for GLP-1 treatment on glucose and fatty acid metabolism in normal and ischemic rat hearts following a 30 min ischemia and 24 h reperfusion injury, and in isolated cardiomyocytes (CM). Relative carbohydrate and fat oxidation levels were measured in both normal and ischemic hearts using a 1-13C glucose clamp coupled with NMR-based isotopomer analysis, as well as in adult rat CMs by monitoring pH and O2 consumption in the presence of glucose or palmitate. In normal heart, GLP-1 increased glucose uptake (↑64%, pregions in response to this injury. In particular, a switch to anaerobic glycolysis in the ischemic area provides a compensatory substrate switch to overcome the energetic deficit in this region in the face of reduced tissue oxygenation, whereas a switch to more energetically favorable carbohydrate oxidation in more highly oxygenated remote regions supports maintaining cardiac contractility in a complementary manner.

  14. The Impact of Heart Irradiation on Dose-Volume Effects in the Rat Lung

    International Nuclear Information System (INIS)

    Luijk, Peter van; Faber, Hette; Meertens, Harm; Schippers, Jacobus M.; Langendijk, Johannes A.; Brandenburg, Sytze; Kampinga, Harm H.; Coppes, Robert P. Ph.D.

    2007-01-01

    Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. Methods and Materials: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data. Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung

  15. 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.

  16. Expression of classical mediators in hearts of rats with hepatic dysfunction.

    Science.gov (United States)

    Jarkovska, Dagmar; Bludovska, Monika; Mistrova, Eliska; Krizkova, Vera; Kotyzova, Dana; Kubikova, Tereza; Slavikova, Jana; Erek, Sumeyye Nur; Djordjevic, Aleksandar; Chottova Dvorakova, Magdalena

    2017-11-01

    Liver cirrhosis is associated with impairment of cardiovascular function including alterations of the heart innervation, humoral and nervous dysregulation, changes in systemic circulation and electrophysiological abnormalities. Choline acetyltransferase (ChAT), enzyme forming acetylcholine, tyrosine hydroxylase (TH), and dopamine-β-hydroxylase (DBH), enzymes participating in noradrenaline synthesis, are responsible for the production of classical neurotransmitters, and atrial natriuretic peptide (ANP) is produced by cardiomyocytes. The aim of this study was to evaluate the influence of experimentally induced hepatic dysfunction on the expression of proANP, ChAT, TH, and DBH in the heart. Hepatic dysfunction was induced by application of thioacetamide (TAA) or by ligation of bile duct. Biochemical parameters of hepatic injury and levels of peroxidation in the liver and heart were measured. Liver enzymes measured in the plasma were significantly elevated. Cardiac level of peroxidation was increased in operated but not TAA group animals. In the left atrium of operated rats, the expression of TH and DBH was lower, while expression of ChAT remained unchanged. In TAA group, no significant differences in the expression of the genes compared to controls were observed. Liver injury induced by ligation leads to an imbalance in the intracardiac innervation, which might impair nervous control of the heart.

  17. [Antiarrhythmic effect of oligonucleotides accompanied by activation of HSP70 protein in the heart of rats].

    Science.gov (United States)

    Kruglov, S V; Terekhina, O L; Smirnova, E A; Kashaeva, O V; Belkina, L M

    2015-01-01

    The mechanisms of the protective effect of oligonucleotides (OGN) during pathological processes are poorlyunderstood. The goal of this work was to study the effect of OGN on arrhythmias induced by myocardial ischemia and reperfusion, and the HSP70 level in the heart. As a source of OGN was used the drug "Derinat" ("Technomedservis", Russia). In male Wistar rats were pre-treated the drug for 7 days (i/m, 7.5 mg/kg).The intensity of the arrhythmias was assessed by ECG during 10 min occlusion of the left coronary artery and subsequent 5 min of reperfusion. Protein HSP70 determined in the left ventricle of the heart by Western-blot analysis. During ischemia, this drug reduced duration of extrasystolia by 13 times and the incidence of ventricular tachycardia by 1.5 times. During reperfusion the drug reduced the incidence of ventricular fibrillation, a more than 2-fold, as compared with the control (respectively 23% vs 56%) and by 5 times its duration (8,4 ± 2,3 48,1 ± sec vs 18 7 sec). "Derinat" increased the HSP70 level in the heart by 65% compared with control. These data support the fact that the activation of HSP70 synthesis, induced by OGN is one of the mechanisms that increases the heart resistance to the ischemic and reperfusion damages.

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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

    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...... robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal...

  20. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.

    Science.gov (United States)

    Hasan, Wohaib; Smith, Peter G

    2014-04-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Altered astrocyte glutamate transporter regulation of hypothalamic neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Potapenko, Evgeniy S; Biancardi, Vinicia C; Zhou, Yiqiang; Stern, Javier E

    2012-08-01

    Neurohumoral activation, which includes augmented plasma levels of the neurohormone vasopressin (VP), is a common finding in heart failure (HF) that contributes to morbidity and mortality in this disease. While an increased activation of magnocellular neurosecretory cells (MNCs) and enhanced glutamate function in HF is well documented, the precise underlying mechanisms remain to be elucidated. Here, we combined electrophysiology and protein measurements to determine whether altered glial glutamate transporter function and/or expression occurs in the hypothalamic supraoptic nucleus (SON) during HF. Patch-clamp recordings obtained from MNCs in brain slices show that pharmacological blockade of astrocyte glutamate transporter 1 (GLT1) function [500 μM dihydrokainate (DHK)], resulted in a persistent N-methyl-D-aspartate receptor (NMDAR)-mediated inward current (tonic I(NMDA)) in sham rats, an effect that was significantly smaller in MNCs from HF rats. In addition, we found a diminished GLT1 protein content in plasma membrane (but not cytosolic) fractions of SON punches in HF rats. Conversely, astrocyte GLAST expression was significantly higher in the SON of HF rats, while nonselective blockade of glutamate transport activity (100 μM TBOA) evoked an enhanced tonic I(NMDA) activation in HF rats. Steady-state activation of NMDARs by extracellular glutamate levels was diminished during HF. Taken together, these results support a shift in the relative expression and function of two major glial glutamate transporters (from GLT1 to GLAST predominance) during HF. This shift may act as a compensatory mechanism to preserve an adequate basal glutamate uptake level in the face of an enhanced glutamatergic afferent activity in HF rats.

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

    Directory of Open Access Journals (Sweden)

    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

  3. Peptide-evoked release of amylase from isolated acini of the rat parotid gland

    DEFF Research Database (Denmark)

    Goll, R; Poulsen, J H; Schmidt, P

    1994-01-01

    on isolated acini of the rat parotid gland. Furthermore, the occurrence and location of the peptides in the gland was studied. Finally, binding of 125I-BH-SP to isolated acini were studied in order to characterize their tachykinin receptor(s) and their binding kinetics. Only SP, NKA, NPK and VIP stimulated...... of NK1-receptors. Thus, the results of the present study support previous suggestions that the tachykinins and VIP are likely to be involved in amylase secretion in the rat parotid gland....

  4. Effect of UV-B (302 nm) irradiation on isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Lahiri, S.; Habibullah, C.M.; Ayesha, Q.; Khan, A.A.; Srinivas, V.K.; Naithani, R.

    1995-01-01

    The present study aimed to evaluate the effect of UV-B irradiation on the functional integrity, and the metabolic and detoxifying capacity of isolated rat hepatocytes. Isolated rat hepatocytes were irradiated in various doses (400 Jm -2 , 600 Jm -2 , 800 Jm -2 and 1000 Jm -2 ). The cells were assayed for total lactate dehydrogenase, Na + -K + -ATPase, ATPase, ornithine carbamyltransferase activity (OCT) and urea production capacity. Lactate dehydrogenase and Na + -K + -ATPase activity were significantly decreased in all four irradiated groups (P<0.001), whereas viability, OCT and urea production capacity showed no alterations. (au) 22 refs

  5. 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.

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

    Science.gov (United States)

    Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

    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.

  7. Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Deise M. Pacheco

    2016-01-01

    Full Text Available ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF following myocardial infarction. Method Twenty-seven male adult Wistar rats were randomized to CHF group (n=12 or Sham group (n=15. Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. Results The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs and the total lung capacity (TLC were lower (40% and 27%, respectively in the CHF rats when compared to the Sham group (P<0.01. There was also an increase in tissue resistance (Gti and elastance (Hti (28% and 45%, respectively in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01, while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02 in the CHF group when compared to the control. Pearson’s correlation coefficient showed a negative association between pulmonary edema and Crs (r=–0.70, P=0.0001 and between pulmonary edema and TLC (r=–0.67,P=0.0034. Pulmonary edema correlated positively with Gti (r=0.68, P=0.001 and Hti (r=0.68, P=0.001. Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001. Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions.

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

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    Chiaki Nagai-Okatani

    Full Text Available 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.

  9. Exposure to chronic isolation modulates receptors mRNAs for oxytocin and vasopressin in the hypothalamus and heart.

    Science.gov (United States)

    Pournajafi-Nazarloo, Hossein; Kenkel, William; Mohsenpour, Seyed Ramezan; Sanzenbacher, Lisa; Saadat, Habibollah; Partoo, Leila; Yee, Jason; Azizi, Fereidoun; Carter, C Sue

    2013-05-01

    The goal of our study was to explore the effect of social isolation stress of varying durations on the plasma oxytocin (OT), messenger ribonucleic acid (mRNA) for oxytocin receptor (OTR), plasma arginine vasopressin (AVP) and mRNA for V1a receptor of AVP (V1aR) expression in the hypothalamus and heart of socially monogamous female and male prairie voles (Microtus ochrogaster). Continuous isolation for 4 weeks (chronic isolation) increased plasma OT level in females, but not in males. One hour of isolation every day for 4 weeks (repeated isolation) was followed by a significant increase in plasma AVP level. Chronic isolation, but not repeated isolation, significantly decreased OTR mRNA in the hypothalamus and heart in both sexes. Chronic isolation significantly decreased cardiac V1aR mRNA, but no effect on hypothalamic V1aR mRNA expression. We did not find a gender difference within repeated social isolation groups. The results of the present study reveal that although chronic social isolation can down-regulate gene expression for the OTR in both sexes, the release of the OT peptide was increased after chronic isolation only in females, possibly somewhat protecting females from the negative consequences of isolation. In both sexes repeated, but not chronic, isolation increased plasma AVP, which could be permissive for mobilization and thus adaptive in response to a repeated stressor. The differential effects of isolation on OT and AVP systems may help in understanding mechanisms through social interactions can be protective against emotional and cardiovascular disorders. Published by Elsevier Inc.

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

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    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

  11. Forskolin- and dihydroalprenolol (DHA) binding sites and adenylate cyclase activity in heart of rats fed diets containing different oils

    International Nuclear Information System (INIS)

    Alam, S.Q.; Ren, Y.F.; Alam, B.S.

    1987-01-01

    The purpose of the present investigation was to determine if dietary lipids can induce changes in the adenylate cyclase system in rat heart. Three groups of male young Sprague-Dawley rats were fed for 6 weeks diets containing 10% corn oil (I), 8% coconut oil + 2% corn oil (II) or 10% menhaden oil (III). Adenylate cyclase activity (basal, fluoride-, isoproterenol-, and forskolin-stimulated) was higher in heart homogenates of rats in group III than in the other two groups. Concentration of the [ 3 H]-forskolin binding sites in the cardiac membranes were significantly higher in rats fed menhaden oil. The values (pmol/mg protein) were 4.8 +/- 0.2 (I), 4.5 +/- 0.7 (II) and 8.4 +/- 0.5 (III). There was no significant difference in the affinity of the forskolin binding sites among the 3 dietary groups. When measured at different concentrations of forskolin, the adenylate cyclase activity in cardiac membranes of rats fed menhaden oil was higher than in the other 2 groups. Concentrations of the [ 3 H]DHA binding sites were slightly higher but their affinity was lower in cardiac membranes of rats fed menhaden oil. The results suggest that diets containing fish oil increase the concentration of the forskolin binding sites and may also affect the characteristics of the β-adrenergic receptor in rat heart

  12. Analyzing the electrophysiological effects of local epicardial temperature in experimental studies with isolated hearts

    International Nuclear Information System (INIS)

    Tormos, Alvaro; Millet, José; Guill, Antonio; Chorro, Francisco J; Cánoves, Joaquín; Mainar, Luis; Such, Luis; Alberola, Antonio; Trapero, Isabel; Such-Miquel, Luis

    2008-01-01

    As a result of their modulating effects upon myocardial electrophysiology, both hypo- and hyperthermia can be used to study the mechanisms that generate or sustain cardiac arrhythmias. The present study describes an original electrode developed with thick-film technology and capable of controlling regional temperature variations in the epicardium while simultaneously registering its electrical activity. In this way, it is possible to measure electrophysiological parameters of the heart at different temperatures. The results obtained with this device in a study with isolated and perfused rabbit hearts are reported. An exploration has been made of the effects of local temperature changes upon the electrophysiological parameters implicated in myocardial conduction. Likewise, an analysis has been made of the influence of local temperature upon ventricular fibrillation activation frequency. It is concluded that both regional hypo- and hyperthermia exert reversible and opposite effects upon myocardial refractoriness and conduction velocity in the altered zone. The ventricular activation wavelength determined during constant pacing at 250 ms cycles is not significantly modified, however. During ventricular fibrillation, the changes in the fibrillatory frequency do not seem to be transmitted to normal temperature zones

  13. Validation of the Nonin 8600V Pulse Oximeter for heart rate and oxygen saturation measurements in rats.

    Science.gov (United States)

    Bernard, Susan L; An, Dowon; Glenny, Robb W

    2004-05-01

    This report validates the use and limitations of the Nonin Pulse Oximeter for measuring heart rate and oxygen saturation in rats. Eight anesthetized Sprague-Dawley rats were intubated and catheterized. Oxygen saturation was directly measured from arterial blood by using a Radiometer OSM3 Hemoximeter adjusted for rat blood as well as indirectly by using the Nonin Pulse Oximeter. Oxygen saturation was changed by varying the level of inhaled oxygen. Heart rate was measured in two ways: 1) by using the signal from the Nonin Pulse Oximeter and 2) by counting the pressure pulses from the transduced blood pressure. There was excellent agreement between heart rate values measured by the Nonin Pulse Oximeter and that measured by counting the pulses from the arterial blood pressure recording. The Nonin Pulse Oximeter underestimated oxygen saturations by about 3% to 5% compared to the Hemoximeter. Overall, the pulse oximeter reflected important trends in oxygen saturations, making it a useful tool for laboratory animal medicine.

  14. 45Ca2+movements induced by Ca2+chloride in isolated rat aorta under K+-free conditions

    NARCIS (Netherlands)

    Wermelskirchen, D.; Nebel, U.; Wirth, A.; Wilffert, B.

    1991-01-01

    Increasing the extracellular Ca2+concentration induced a dihydropyridine-insensitive contraction in the isolated rat aorta bathed in K+-free solution. To obtained further insight into the mechanisms of this contraction45Ca2+uptake measurements were carried out with isolated rat aorta. Increasing the

  15. CA-45(2+) MOVEMENTS INDUCED BY CA2+ CHLORIDE IN ISOLATED RAT AORTA UNDER K+-FREE CONDITIONS

    NARCIS (Netherlands)

    WERMELSKIRCHEN, D; NEBEL, U; WIRTH, A; WILFFERT, B

    1991-01-01

    Increasing the extracellular Ca2+ concentration induced a dihydropyridine-insensitive contraction in the isolated rat aorta bathed in K+-free solution. To obtain further insight into the mechanism of this contraction Ca-45(2+) uptake measurements were carried out with isolated rat aorta. Increasing

  16. Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition

    Directory of Open Access Journals (Sweden)

    M.L.N.M. Rosa

    2005-11-01

    Full Text Available Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing. These changes include deficits in prepulse inhibition (PPI of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse. PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group were housed in groups (5 per cage and handled three times a week or isolated (housed individually since weaning (21 days for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only or "handled" animals (handled three times a week. This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s. A statistically significant reduction (52% in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

  17. Routine post-weaning handling of rats prevents isolation rearing-induced deficit in prepulse inhibition.

    Science.gov (United States)

    Rosa, M L N M; Silva, R C B; Moura-de-Carvalho, F T; Brandão, M L; Guimarães, F S; Del Bel, E A

    2005-11-01

    Rats reared under isolation conditions from weaning present a number of behavioral changes compared to animals reared under social conditions (group housing). These changes include deficits in prepulse inhibition (PPI) of the startle reflex to a loud sound. PPI refers to the reduction of the magnitude of the startle reflex when a relatively weak stimulus (the prepulse) precedes by an appropriate time interval the intense startle-elicing stimulus (the pulse). PPI is useful for studying sensorimotor integration. The present study evaluated the effect of handling on the impairment of PPI induced by isolation-rearing. Male Wistar rats (N = 11-15/group) were housed in groups (5 per cage and handled three times a week) or isolated (housed individually) since weaning (21 days) for 10 weeks when they reach approximately 150 g. The isolated rats were divided into "minimally handled" animals (handled once a week for cleaning purposes only) or "handled" animals (handled three times a week). This handling consisted of grasping the rat by the tail and moving it to a clean cage (approximately 5 s). A statistically significant reduction (52%) in the PPI test was found only in the isolated group with minimal handling while no difference was seen between grouped animals and isolated handled animals. These results indicate that isolation rearing causes disruption in the PPI at adult age, which serves as an index of attention deficit. This change in the sensory processing of information induced by post-weaning isolation can be prevented by handling during the development of the animal.

  18. In vitro glucose uptake by isolated rat hemi-diaphragm study of Aegle marmelos Correa root

    Directory of Open Access Journals (Sweden)

    Subban Ravi

    2009-03-01

    Full Text Available The methanol extract of the root of Aegle marmelos, a medicinal plant, was fractionated into eight fractions using column chromatography. The anti-diabetic activity of all the fractions was studied using the glucose uptake by isolated rat hemi-diaphragm in vitro model. Using the bioassay-guided fractionation, two compounds 1 and 2 were isolated by column chromatography and identified as 6-methyl-4-chromanone and skimmianine respectively by NMR and mass spectral methods.

  19. Long term treadmill exercise performed to chronic social isolated rats regulate anxiety behavior without improving learning.

    Science.gov (United States)

    Cevik, Ozge Selin; Sahin, Leyla; Tamer, Lulufer

    2018-05-01

    The type and duration of exposure to stress is an important influence on emotional and cognitive functions. Learning is the adaptive response of the central nervous system that occurs in hippocampus which affects from environmental factors like exercise. In this study, we investigated effects of long term treadmill exercise on learning and behavior on chronic social isolated rat. Male Wistar rats (n = 32) randomly assigned into four groups: control, exercised, social isolation, social isolation + exercise during postnatal days (PNDs) 21-34. Social isolation protocol was applied during 14 days by placing rat in a cage one by one. Rats were exercised during 5 days, days were chosen randomly for overall 4 weeks (20, 30, 50, 60 min respectively). Finally, learning performance was evaluated by Morris water maze (MWM). Anxiety behavior was evaluated by Open field and elevated plus maze test. At the end of learning and behavior tests, the rats were decapitated to collect blood samples via intracardiac puncture and corticosterone analysis was performed with ELISA method. Animal weights and water consumption did not change significantly but food intake differed among groups. Corticosterone level did not change between groups. The frequency of entering to the target quadrant increased in exercised rat significantly. However, there was no difference in learning and memory in rats. Treadmill exercise reduced anxiety behavior significantly. Taken together these findings may point out that, long term treadmill exercise did not change learning and memory but reduced anxiety level of rat without changing corticosterone level. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Secondhand Smoke Exposure Reduced the Compensatory Effects of IGF-I Growth Signaling in the Aging Rat Hearts.

    Science.gov (United States)

    Wu, Jia-Ping; Hsieh, Dennis Jine-Yuan; Kuo, Wei-Wen; Han, Chien-Kuo; Pai, Peiying; Yeh, Yu-Lan; Lin, Chien-Chung; Padma, V Vijaya; Day, Cecilia Hsuan; Huang, Chih-Yang

    2015-01-01

    Secondhand smoke (SHS) exposure is associated with increased risk of cardiovascular disease. Aging is a physiological process that involves progressive impairment of normal heart functions due to increased vulnerability to damage. This study examines secondhand smoke exposure in aging rats to determine the age-related death-survival balance. Rats were placed into a SHS exposure chamber and exposed to smog. Old age male Sprague-Dawley rats were exposed to 10 cigarettes for 30 min, day and night, continuing for one week. After 4 weeks the rats underwent morphological and functional studies. Left ventricular sections were stained with hematoxylin-eosin for histopathological examination. TUNEL detected apoptosis cells and protein expression related death and survival pathway were analyzed using western blot. Death receptor-dependent apoptosis upregulation pathways and the mitochondria apoptosis proteins were apparent in young SHS exposure and old age rats. These biological markers were enhanced in aging SHS-exposed rats. The survival pathway was found to exhibit compensation only in young SHS-exposed rats, but not in the aging rats. Further decrease in the activity of this pathway was observed in aging SHS-exposed rats. TUNEL apoptotic positive cells were increased in young SHS-exposed rats, and in aging rats with or without SHS-exposure. Aging reduces IGF-I compensated signaling with accelerated cardiac apoptotic effects from second-hand smoke.

  1. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

    Directory of Open Access Journals (Sweden)

    Junhwan Kim

    2016-01-01

    Full Text Available Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  2. The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

    Science.gov (United States)

    Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

    2016-01-01

    Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

  3. 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% (Pproduct compared with hyperlipidemic control rats. Normalization of white blood cell populations was also detected. Monocyte and granulocyte counts in blood of rats fed the meat product decreased by 71.1% (Pproduct compared with hyperlipidemic control rats. The data confirmed the hypolipidemic action of the sterilized meat product. Normalization of white blood cell populations led us to hypothesize an anti-inflammatory action of the new meat product, which, therefore, could be recommended as a part of maintenance therapy for people with lipid disorders or atherosclerosis.

  4. Influence of N-acetylcysteine on oxidative stress in slow-twitch soleus muscle of heart failure rats

    OpenAIRE

    Martinez, Paula Felippe [UNESP; Bonomo, Camila [UNESP; Guizoni, Daniele Mendes [UNESP; Oliveira Junior, Silvio Assis [UNESP; Damatto, Ricardo Luiz [UNESP; Cezar, Marcelo Diarcadia Mariano [UNESP; Lima, Aline Regina Ruiz [UNESP; Pagan, Luana Urbano [UNESP; Seiva, Fabio Rodrigues; Fernandes, Denise Castro; Laurindo, Francisco Rafael Martins; Novelli, Ethel Lourenzi Barbosa [UNESP; Matsubara, Luiz Shiguero [UNESP; Zornoff, Leonardo Antonio Mamede [UNESP; Okoshi, Katashi [UNESP

    2015-01-01

    Background: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. Methods and Results: Four months after MI,...

  5. Separate neurochemical classes of sympathetic postganglionic neurons project to the left ventricle of the rat heart.

    Science.gov (United States)

    Richardson, R J; Grkovic, I; Allen, A M; Anderson, C R

    2006-04-01

    The sympathetic innervation of the rat heart was investigated by retrograde neuronal tracing and multiple label immunohistochemistry. Injections of Fast Blue made into the left ventricular wall labelled sympathetic neurons that were located along the medial border of both the left and right stellate ganglia. Cardiac projecting sympathetic postganglionic neurons could be grouped into one of four neurochemical populations, characterised by their content of calbindin and/or neuropeptide Y (NPY). The subpopulations of neurons contained immunoreactivity to both calbindin and NPY, immunoreactivity to calbindin only, immunoreactivity to NPY only and no immunoreactivity to calbindin or NPY. Sympathetic postganglionic neurons were also labelled in vitro with rhodamine dextran applied to the cut end of a cardiac nerve. The same neurochemical subpopulations of sympathetic neurons were identified by using this technique but in different proportions to those labelled from the left ventricle. Preganglionic terminals that were immunoreactive for another calcium-binding protein, calretinin, preferentially surrounded retrogradely labelled neurons that were immunoreactive for both calbindin and NPY. The separate sympathetic pathways projecting to the rat heart may control different cardiac functions.

  6. 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.

  7. Pharmacological effects of Eugenia uniflora (Myrtaceae) aqueous crude extract on rat's heart.

    Science.gov (United States)

    Consolini, Alicia E; Sarubbio, Marisol Gracía

    2002-06-01

    The effect of aqueous crude extract (ACE) of Eugenia uniflora L. (Myrtaceae) was studied on rat's perfused ventricles. This plant is used in South American traditional medicine as an antihypertensive and we already demonstrated previously its hypotensive properties. In this paper, maximal left intraventriclular pressure (P) of rat's hearts beating at 0.2 Hz firstly increased to 162.1+/-11.1% of basal value during 1-3 min of perfusing ACE 0.6%. Maximum rate of contraction (+P) also increased to duplicating +P/P ratio. Both types of effect were significantly decreased by either propranolol 0.35 microM, and pre-treatment with reserpine (5 mg/kg), suggesting that they were caused by a compound that releases cathecolamines with beta-adrenergic action. Nevertheless, after 20 min of perfusing ACE, ventricles decreased P to about 50% of their basal value, suggesting a negative-inotropic compound present in the extract. The perfusion of 1.2% ACE decreased P in a pressure-[Ca](o) curve (0.5-2 mM) in a non-competitive manner, suggesting that an irreversible Ca-blocking compound is also present in the extract. In summary, E. uniflora ACE has a dual effect on the heart related to its hypotensive action and is probably responsible for the therapeutic or adverse effects in patients under cardiac risk.

  8. Gamma radiation and its role in bio prosthetic aortic valves implanted in rat hearts

    International Nuclear Information System (INIS)

    Lamas, Gloria I.; Kairiyama, Eulogia; Navia, Jose

    2000-01-01

    Porcine heart valves glutaraldehyde fixed are implanted in patients with valvular deterioration. Mineralization may be the major factor in the long-term failure of tissue bio prosthesis. Gamma radiation randomly breaks some glutaraldehyde cross-links. As a consequence of irradiation, the polymeric fibers belonging to the valvular tissue are broken too, leading to sites of collagen fiber disorganisation. It is well known that the collagen fibers may act as a passive nucleator of salts where the calcium phosphate salts precipitate. This salt concentration has been described in association with disintegrated sites of protein fiber, which may favour new sites where the calcium salts would be deposit. The irradiation process is a technique used for sterilization of porcine heart valve. The main objective of this work was to study the effect of different doses of gamma radiation on the calcification process of subcutaneously implanted valves in rats. Small pieces from glutaraldehyde fixed valves, irradiated to different doses with a 60 Co sources were implanted subcutaneously in rats. The calcium was measured by X-ray and atomic absorption spectrophotometry. In our experimental conditions and at the radiation doses used in these tests, the calcium measurements on control and irradiated material were not significantly different. We conclude that, at the employed doses, the gamma radiation does not alter the process. (author) [es

  9. Neural activity in the prelimbic and infralimbic cortices of freely moving rats during social interaction: Effect of isolation rearing

    Science.gov (United States)

    Minami, Chihiro; Shimizu, Tomoko

    2017-01-01

    Sociability promotes a sound daily life for individuals. Reduced sociability is a central symptom of various neuropsychiatric disorders, and yet the neural mechanisms underlying reduced sociability remain unclear. The prelimbic cortex (PL) and infralimbic cortex (IL) have been suggested to play an important role in the neural mechanisms underlying sociability because isolation rearing in rats results in impairment of social behavior and structural changes in the PL and IL. One possible mechanism underlying reduced sociability involves dysfunction of the PL and IL. We made a wireless telemetry system to record multiunit activity in the PL and IL of pairs of freely moving rats during social interaction and examined the influence of isolation rearing on this activity. In group-reared rats, PL neurons increased firing when the rat showed approaching behavior and also contact behavior, especially when the rat attacked the partner. Conversely, IL neurons increased firing when the rat exhibited leaving behavior, especially when the partner left on its own accord. In social interaction, the PL may be involved in active actions toward others, whereas the IL may be involved in passive relief from cautionary subjects. Isolation rearing altered social behavior and neural activity. Isolation-reared rats showed an increased frequency and decreased duration of contact behavior. The increased firing of PL neurons during approaching and contact behavior, observed in group-reared rats, was preserved in isolation-reared rats, whereas the increased firing of IL neurons during leaving behavior, observed in group-reared rats, was suppressed in isolation-reared rats. This result indicates that isolation rearing differentially alters neural activity in the PL and IL during social behavior. The differential influence of isolation rearing on neural activity in the PL and IL may be one of the neural bases of isolation rearing-induced behavior. PMID:28459875

  10. Neural activity in the prelimbic and infralimbic cortices of freely moving rats during social interaction: Effect of isolation rearing.

    Science.gov (United States)

    Minami, Chihiro; Shimizu, Tomoko; Mitani, Akira

    2017-01-01

    Sociability promotes a sound daily life for individuals. Reduced sociability is a central symptom of various neuropsychiatric disorders, and yet the neural mechanisms underlying reduced sociability remain unclear. The prelimbic cortex (PL) and infralimbic cortex (IL) have been suggested to play an important role in the neural mechanisms underlying sociability because isolation rearing in rats results in impairment of social behavior and structural changes in the PL and IL. One possible mechanism underlying reduced sociability involves dysfunction of the PL and IL. We made a wireless telemetry system to record multiunit activity in the PL and IL of pairs of freely moving rats during social interaction and examined the influence of isolation rearing on this activity. In group-reared rats, PL neurons increased firing when the rat showed approaching behavior and also contact behavior, especially when the rat attacked the partner. Conversely, IL neurons increased firing when the rat exhibited leaving behavior, especially when the partner left on its own accord. In social interaction, the PL may be involved in active actions toward others, whereas the IL may be involved in passive relief from cautionary subjects. Isolation rearing altered social behavior and neural activity. Isolation-reared rats showed an increased frequency and decreased duration of contact behavior. The increased firing of PL neurons during approaching and contact behavior, observed in group-reared rats, was preserved in isolation-reared rats, whereas the increased firing of IL neurons during leaving behavior, observed in group-reared rats, was suppressed in isolation-reared rats. This result indicates that isolation rearing differentially alters neural activity in the PL and IL during social behavior. The differential influence of isolation rearing on neural activity in the PL and IL may be one of the neural bases of isolation rearing-induced behavior.

  11. Co-administration of trientine and flaxseed oil on oxidative stress, serum lipids and heart structure in diabetic rats.

    Science.gov (United States)

    Rezaei, Ali; Heidarian, Esfandiar

    2013-08-01

    The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats.

  12. Isolation and Osteogenic Differentiation of Rat Periosteum-derived Cells

    OpenAIRE

    Declercq, Heidi Andrea; De Ridder, Leo Isabelle; Cornelissen, Maria Jozefa

    2005-01-01

    Selection of appropriate cultures having an osteogenic potential is a necessity if cell/biomaterial interactions are studied in long-term cultures. Osteoblastic cells derived from rat long bones or calvaria have the disadvantage of being in an advanced differentiation stage which results in terminal differentiation within 21 days. In this regard, less differentiated periosteum-derived osteoprogenitors could be more suitable.

  13. Dietary manipulation and social isolation alter disease progression in a murine model of coronary heart disease.

    Directory of Open Access Journals (Sweden)

    Yumiko Nakagawa-Toyama

    Full Text Available BACKGROUND: Mice with a deficiency in the HDL receptor SR-BI and low expression of a modified apolipoprotein E gene (SR-BI KO/ApoeR61(h/h called 'HypoE' when fed an atherogenic, 'Paigen' diet develop occlusive, atherosclerotic coronary arterial disease (CHD, myocardial infarctions (MI, and heart dysfunction and die prematurely (50% mortality ~40 days after initiation of this diet. Because few murine models share with HypoE mice these cardinal, human-like, features of CHD, HypoE mice represent a novel, small animal, diet-inducible and genetically tractable model for CHD. To better describe the properties of this model, we have explored the effects of varying the composition and timing of administration of atherogenic diets, as well as social isolation vs. group housing, on these animals. METHODOLOGY/PRINCIPAL FINDINGS: HypoE mice were maintained on a standard lab chow diet (control until two months of age. Subsequently they received one of three atherogenic diets (Paigen, Paigen without cholate, Western or control diet for varying times and were housed in groups or singly, and we determined the plasma cholesterol levels, extent of cardiomegaly and/or survival. The rate of disease progression could be reduced by lowering the severity of the atherogenic diet and accelerated by social isolation. Disease could be induced by Paigen diets either containing or free of cholate. We also established conditions under which CHD could be initiated by an atherogenic diet and then subsequently, by replacing this diet with standard lab chow, hypercholesterolemia could be reduced and progression to early death prevented. CONCLUSIONS/SIGNIFICANCE: HypoE mice provide a powerful, surgery-free, diet-'titratable' small animal model that can be used to study the onset of recovery from occlusive, atherosclerotic CHD and heart failure due to MI. HypoE mice can be used for the analysis of the effects of environment (diet, social isolation on a variety of features of

  14. [Sodium hydrosulfide improves cardiac functions and structures in rats with chronic heart failure].

    Science.gov (United States)

    Li, Xiao-hui; Zhang, Chao-ying; Zhang, Ting

    2011-11-22

    To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling. A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared. At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed an amelioration of myocardial damage, an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-I collagen). Compared with the sham operation and shunt + NaHS groups, the shunt group displayed increased right ventricular hydroxyproline (mg×g(-1)·pro: 1.32 ± 0.25 vs 0.89 ± 0.18 and 0.83 ± 0.19, all P < 0

  15. Análise comparativa dos efeitos do diazepam, midazolam, propofol e etomidato na contratilidade miocárdica e no fluxo coronariano: estudo em corações isolados de ratos Effects of diazepam, midazolam, propofol and etomidate in myocardial contractility and coronary blood flow: comparative analysis in isolated rat's hearts

    Directory of Open Access Journals (Sweden)

    Carlos Geraldo Sobral de Medeiros

    2004-06-01

    Full Text Available OBJETIVO: Avaliar o efeito, na contratilidade miocárdica e no fluxo coronariano, de drogas comumente utilizadas na prática clínica (diazepam, midazolam, propofol e etomidato. MÉTODO: Foram estudados 50 corações isolados de ratos Wistar divididos em cinco grupos de dez, em preparação de Langendorff com líquido de perfusão de Krebs-Henseleit (K-H, mantendo-se constantes a pressão de perfusão (90 centímetros de água e a temperatura (37° + 0,5 graus Celsius. Com exceção do Grupo I (Controle, foram feitas infusões únicas, em um minuto, de diazepam (50 microgramas - Grupo II; midazolam (25 microgramas - Grupo III; propofol (25 e 50 microgramas - Grupo IV e etomidato (25 microgramas - Grupo V. Cada dose foi diluída e administrada em 0,1 mililitro de K-H, mantendo-se o fluxo e a pressão de perfusão coronarianos do sistema, durante sua infusão. Aferiu-se a freqüência cardíaca em batimentos por minuto (BPM, a tensão miocárdica em gramas (g, e o fluxo coronariano em mililitros por minuto (ml/min em 1, 3, 5, 10, 15, 20, 25 e 30 minutos; a contratilidade miocárdica foi avaliada pelo cálculo da primeira derivada tensão/tempo (dT/dtmax, naquelas marcas. RESULTADOS: A freqüência cardíaca apresentou variações nos Grupos I, III e IV. Em relação à tensão miocárdica, apenas o Grupo I não sofreu declínio; o fluxo coronariano, exceto no Grupo IV, apresentou variações para menos, ao longo do estudo; a contratilidade miocárdica decresceu em todos os grupos estudados, exceto no Grupo I. CONCLUSÃO: As drogas ensaiadas diminuíram a contratilidade miocárdica (p0,05.OBJECTIVE: The effects on myocardial contractility (dT/dtmax and coronary blood flow (CBF of common drugs used in clinical practice (diazepam, midazolam, propofol and etomidate were studied. METHOD: Fifty Wistar rat's hearts were divided into five groups of ten, and perfused by Langendorff method with Krebs-Henseleit solution (K-H, with the perfusion pressure

  16. Relations between fatty acid synthesis, pyruvate concentration and cell concentration of suspensions of isolated rat hepatocytes

    NARCIS (Netherlands)

    Beynen, A.C.; Geelen, M.J.H.

    1984-01-01

    1. 1. The cell concentration of suspensions of isolated rat hepatocytes affects both the rate of pyruvate accumulation in the incubation medium and the rate of fatty acid synthesis. 2. 2. At low cell concentrations pyruvate accumulation is directly related to the cell concentration but levels off

  17. Cell-swelling-induced taurine release from isolated perfused rat liver

    NARCIS (Netherlands)

    Brand, H. S.; Meijer, A. J.; Gustafson, L. A.; Jörning, G. G.; Leegwater, A. C.; Maas, M. A.; Chamuleau, R. A.

    1994-01-01

    Astrocytes and lymphocytes are able to release significant amounts of taurine during periods of hypotonicity to reduce the increase in cell volume. To investigate this mechanism in the liver, we studied the release of free amino acids from isolated perfused rat liver during hypotonicity. The

  18. Veratridine activates a silent sodium-channel in rat isolated aorta

    NARCIS (Netherlands)

    WERMELSKIRCHEN, D; WILFFERT, B; NEBEL, U; LEIDIG, A; WIRTH, A; Peters, Thies

    1992-01-01

    To investigate the existence of silent Na+ channels, isolated rat aorta was treated with veratridine (0.1 mM) and the resulting Ca2+ uptake was determined. After 30-min incubation the total tissue uptake of Ca2+ and Ca2+ uptake increased from 2.325 +/- 0.017 to 2.614 +/- 0.080 nmol/mg wet weight

  19. CRYOPRESERVATION OF FRESHLY ISOLATED SYNAPTOSOMES PREPARED FROM THE CEREBRAL-CORTEX OF RATS

    NARCIS (Netherlands)

    GLEITZ, J; BEILE, A; WILFFERT, B; TEGTMEIER, F

    In the present study, we established a cryopreservation method for freshly isolated synaptosomes prepared from the cerebral cortex of rats. Freshly prepared synaptosomes were either shock-frozen or frozen under temperature-controlled conditions using a programmable temperature controller. Each group

  20. The central responsiveness of the acute cerveau isolé rat.

    Science.gov (United States)

    User, P; Gottesmann, C

    1982-01-01

    The electrophysiological patterns of the frontal cortex and dorsal hippocampus were studied in the acute cerveau isolé rat. Central and peripheral stimulations were performed in order to modulate these patterns. The results showed that the permanent alternation of high amplitude spindle bursts and low voltage activity in the anterior neocortex of the acute cerveau isolé was influenced neither by olfactory nor by posterior hypothalamic stimulation. In contrast, these two kinds of stimulation easily modulated the continuous low frequency theta rhythm, recorded in the dorsal hippocampus, in terms of amplitude and in overall frequency. This modulation of the theta rhythm in the acute cerveau isolé rat mimics the changes observed when the normal rat comes from the intermediate stage of sleep (as characterized in the the acute intercollicular transected rat by high amplitude spindle bursts at frontal cortex level and low frequency theta activity in the dorsal hippocampus) to rapid sleep. These results further suggest that, during the intermediate stage (as in the cerveau isolé preparation), the hippocampus montonous theta activity appears through a brainstem disinhibitory process releasing the forebrain limbic pacemaker(s). During the following rapid sleep phase, the theta rhythm would be modulated by pontine activity influences acting on the theta generators.

  1. Intermediate stage of sleep and acute cerveau isolé preparation in the rat.

    Science.gov (United States)

    User, P; Gioanni, H; Gottesmann, C

    1980-01-01

    The acute cerveau isole rat shows spindle bursts of large amplitude alternating with low voltage activity in the frontal cortex and continuous theta rhythm in the dorsal hippocampus. These patterns closely resemble an "intermediate" stage of sleep-waking cycle, when the forebrain structures seem to be functionally disconnected from the brainstem.

  2. The effect of adrenaline and high Ca2+ on the mechanical performance and oxygen consumption of the isolated perfused trout (Oncorhynchus mykiss) heart

    DEFF Research Database (Denmark)

    Rytter, Dorte; Gesser, Hans

    2007-01-01

    In heart muscle from mammals, catecholamines frequently evoke an oxygen waste and reduce efficiency. It was examined if this also applies to fish in which heart muscle activity is often restricted by oxygen availability. In the isolated perfused heart from rainbow trout, adrenaline (0.5 micro...

  3. Early-life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats

    Directory of Open Access Journals (Sweden)

    Tomoko eSoga

    2015-11-01

    Full Text Available Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinising hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic–GnIH neuronal system using enhanced green fluorescent protein (EGFP-tagged GnIH-transgenic rats. Socially isolated rats were observed for anxious and depressive behaviours. Using immunohistochemistry, we examined c-Fos protein expression in EGFP–GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group -housing. We also inspected serotonergic fibre juxtapositions in EGFP–GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviours. The total number of EGFP–GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fibre juxtapositions on EGFP–GnIH neurons was also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  4. Early-Life Social Isolation Impairs the Gonadotropin-Inhibitory Hormone Neuronal Activity and Serotonergic System in Male Rats.

    Science.gov (United States)

    Soga, Tomoko; Teo, Chuin Hau; Cham, Kai Lin; Idris, Marshita Mohd; Parhar, Ishwar S

    2015-01-01

    Social isolation in early life deregulates the serotonergic system of the brain, compromising reproductive function. Gonadotropin-inhibitory hormone (GnIH) neurons in the dorsomedial hypothalamic nucleus are critical to the inhibitory regulation of gonadotropin-releasing hormone neuronal activity in the brain and release of luteinizing hormone by the pituitary gland. Although GnIH responds to stress, the role of GnIH in social isolation-induced deregulation of the serotonin system and reproductive function remains unclear. We investigated the effect of social isolation in early life on the serotonergic-GnIH neuronal system using enhanced green fluorescent protein (EGFP)-tagged GnIH transgenic rats. Socially isolated rats were observed for anxious and depressive behaviors. Using immunohistochemistry, we examined c-Fos protein expression in EGFP-GnIH neurons in 9-week-old adult male rats after 6 weeks post-weaning isolation or group housing. We also inspected serotonergic fiber juxtapositions in EGFP-GnIH neurons in control and socially isolated male rats. Socially isolated rats exhibited anxious and depressive behaviors. The total number of EGFP-GnIH neurons was the same in control and socially isolated rats, but c-Fos expression in GnIH neurons was significantly reduced in socially isolated rats. Serotonin fiber juxtapositions on EGFP-GnIH neurons were also lower in socially isolated rats. In addition, levels of tryptophan hydroxylase mRNA expression in the dorsal raphe nucleus were significantly attenuated in these rats. These results suggest that social isolation in early-life results in lower serotonin levels, which reduce GnIH neuronal activity and may lead to reproductive failure.

  5. 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); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons 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.

  6. 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.

  7. NF-κB involvement in hyperoxia-induced myocardial damage in newborn rat hearts.

    Science.gov (United States)

    Zara, Susi; De Colli, Marianna; Rapino, Monica; Di Valerio, Valentina; Marconi, Guya Diletta; Cataldi, Amelia; Macchi, Veronica; De Caro, Raffaele; Porzionato, Andrea

    2013-11-01

    Premature newborns are frequently exposed to hyperoxia ventilation and some literature data indicate the possibility of hyperoxia-induced myocardial damage. Since nuclear factor κB (NF-κB) is a crucial signaling molecule involved in physiological response to hyperoxia in different cell types as well as in various tissues, our attention has been focused on the role played by NF-κB pathway in response to moderate and severe hyperoxia exposure in rat neonatal heart tissue. Akt and IκBα levels, involved in NF-κB activation, along with the balance between apoptotic and survival pathways have also been investigated. Experimental design of the study has involved exposure of newborn rats to room air (controls), 60 % O2 (moderate hyperoxia), or 95 % O2 (severe hyperoxia) for the first two postnatal weeks. Morphological analysis shows a less compact tissue in rat heart exposed to moderate hyperoxia and a decreased number of nuclei in samples exposed to severe hyperoxia. A significant increase of NF-κB positive nuclei percentage and p-IκBα expression in samples exposed to 95 % hyperoxia compared to control and to 60 % hyperoxia is evidenced; in parallel, an increase of pAkt/Akt ratio in both samples exposed to 95 and 60 % hyperoxia is shown. Furthermore, a more evident cytochrome c/Apaf-1 immunocomplex and a decreased Bcl2 expression in 95 % hyperoxia-exposed sample compared to 60 % exposed one is evidenced. In conclusion, our findings suggest the involvement of the NF-κB pathway and Akt signaling in the mechanisms of myocardial hyperoxic damage in the newborns, with particular reference to the induction of oxidative stress-related apoptosis.

  8. Vitamin E and Hippophea rhamnoides L. extract reduce nicotine-induced oxidative stress in rat heart.

    Science.gov (United States)

    Gumustekin, Kenan; Taysi, Seyithan; Alp, Hamit Hakan; Aktas, Omer; Oztasan, Nuray; Akcay, Fatih; Suleyman, Halis; Akar, Sedat; Dane, Senol; Gul, Mustafa

    2010-06-01

    The effects of vitamin E and Hippophea rhamnoides L. extract (HRe-1) on nicotine-induced oxidative stress in rat heart were investigated. There were eight rats per group and supplementation period was 3 weeks. The groups were: nicotine [0.5 mg kg(-1)day(-1), intraperitoneal (i.p.)]; nicotine plus vitamin E [75 mg kg(-1)day(-1), intragastric (i.g.)]; nicotine plus HRe-1 (250 mg kg(-1)day(-1), i.g.); and the control group (receiving only vehicles). Nicotine increased the malondialdehyde level, which was prevented by both vitamin E and HRe-1. Glutathione peroxidase (GPx) activity in nicotine plus vitamin E supplemented group was higher than the others. Glutathione S-transferase (GST) activity in nicotine plus HRe-1 supplemented group was increased compared with the control group. Catalase activity was higher in nicotine group compared with others. GPx activity in nicotine plus vitamin E supplemented group was elevated compared with the others. Total and non-enzymatic superoxide scavenger activities in nicotine plus vitamin E supplemented group were lower than nicotine plus HRe-1 supplemented group. Superoxide dismutase (SOD) activity was higher in nicotine plus HRe-1 supplemented group compared with others. Glutathione reductase activity and nitric oxide level were not affected. Increased SOD and GST activities might have taken part in the prevention of nicotine-induced oxidative stress in HRe-1 supplemented group in rat heart. Flavonols such as quercetin, and isorahmnetin, tocopherols such as alpha-tocopherol and beta-tocopherol and carotenoids such as alpha-carotene and beta-carotene, reported to be present in H. rhamnoides L. extracts may be responsible for the antioxidant effects of this plant extract. 2010 John Wiley & Sons, Ltd.

  9. Socially isolated rats exhibit changes in dopamine homeostasis pertinent to schizophrenia

    DEFF Research Database (Denmark)

    Fabricius, Katrine; Steiniger-Brach, Björn; Helboe, Lone

    2011-01-01

    Post-weaning social isolation of rats produces an array of behavioral and neurochemical changes indicative of altered dopamine function. It has therefore been suggested that post-weaning social isolation mimics some aspects of schizophrenia. Here we replicate and extent these findings to include...... dopamine levels in the nucleus accumbens, it did cause a significant reduction of basal dopamine release in the prefrontal cortex. In addition, social isolation lead to a significantly larger dopamine response to an amphetamine challenge, in both the nucleus accumbens and the prefrontal cortex compared...

  10. Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Stern, Javier E; Potapenko, Evgeniy S

    2013-08-15

    An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca²⁺ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca²⁺ levels (NMDA-ΔCa²⁺) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa²⁺ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa²⁺ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca²⁺ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca²⁺ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa²⁺ signaling during HF are discussed.

  11. 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.

  12. Hyperglycemia raises the threshold of levosimendan- but not milrinone-induced postconditioning in rat hearts.

    Science.gov (United States)

    Matsumoto, Shuhei; Cho, Sungsam; Tosaka, Shinya; Higashijima, Ushio; Maekawa, Takuji; Hara, Tetsuya; Sumikawa, Koji

    2012-01-12

    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). 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. 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. 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.

  13. The protective effect of curcumin against sodium fluoride-induced oxidative stress in rat heart

    Directory of Open Access Journals (Sweden)

    Nabavi S.F.

    2011-01-01

    Full Text Available In the present study the cardioprotective effects of curcumin, a herbal polyphenolic compound, against sodium fluoride (NaF-induced toxicity in rat heart was evaluated. Fifty rats were divided into five experimental groups containing 10 rats each. Group I received standard water and diet and was used as a normal group; groups II and III were pretreated with curcumin intraperitoneally for 7 days prior to NaF intoxication. Group IV was pretreated with vitamin C, a standard antioxidant, intraperitoneally for 7 days prior to NaF intoxication and used as a positive control group. The animals in group V were intoxicated with NaF for the same time and used as a control group. There was a significant increase in lipid peroxidation along with a decrease in superoxide dismutase activity in the homogenates of tissues of the NaF-treated animals. Curcumin pretreatment in animals prior to fluoride intoxication normalized the levels of biochemical parameters measured.

  14. Studies on a novel peptide isolated and purified from rat insulinoma tissue

    Energy Technology Data Exchange (ETDEWEB)

    Al-Akhras, G N

    1987-01-01

    Rat insulinoma peptide (RIP) which appears to be either a fragment of, or an altered rat C-peptide was isolated and purified by dialysis. The purity of this peptide was investigated using polyacrylamide gel electrophoresis with sodium dodecyl sulfate, isoelectric focusing, and high performance liquid chromatography. RIP may contain two peptides similar to each other but differing in their isoelectric points. The molecular weight of RIP was found to be 1982 daltons by fast atoms bombardment mass spectrometry giving a chain length of approximately 22 amino acid residues. From information obtained using radioimmunoassay employing antiserum R901, RIP appears to share a common C-terminus with rat C-peptide. A radioimmunoassay for RIP was developed using the purified RIP as immunogen and for standards and tracers. An indirect enzyme linked immunosorbent assay (ELISA) for rat insulinoma peptide was developed using purified RIP for immunogen and semi-purified RIP as a standard.

  15. Effects of high-protein diet containing isolated whey protein in rats submitted to resistance training of aquatic jumps.

    Science.gov (United States)

    Avila, Eudes Thiago Pereira; da Rosa Lima, Thiago; Tibana, Ramires Alsamir; de Almeida, Paula Caroline; Fraga, Géssica Alves; de Souza Sena, Mariana; Corona, Luiz Felipe Petusk; Navalta, James Wilfred; Rezaei, Sajjad; Ghayomzadeh, Morteza; Damazo, Amílcar Sabino; Prestes, Jonato; Voltarelli, Fabrício Azevedo

    2018-02-13

    Isolated whey protein (IWP) can decrease body fat compared with other protein sources. The present study verified the effects of high protein diet (HD) containing IWP on several parameters of rats subjected to resistance training (RT). Thirty-two male Wistar rats (60 days of age) were separated into four groups (n = 8/group): sedentary normoproteic (IWP 14%; SN); sedentary hyperproteic (IWP 35%; SH); trained normoproteic (IWP 14%; TN), and trained hyperproteic (WPI 35%; TH). Relative tissue/organ weight (g): perirenal and retroperitoneal adipose tissues were lower in SH and TH compared with SN (no difference to TN); omental and subcutaneous adipose tissues were higher in SN compared with SH. Epididymal adipose tissue was higher in SN compared with other groups. Heart weight was higher in TH compared with TN and SN, but not SH; kidney and liver higher in TH and SH compared with SN and TN; gastrocnemius lower in SN compared with other groups; soleus higher in SH in relation to other groups. The triglycerides levels (mg/dL) was reduced in the TH groups compared with SH, TN, and SN. There were no changes both in the concentrations of adiponectin and leptin and in the protein expression of GLUT-4 and p70 s6k . HD containing WPI improved body composition, increased the weight of the heart, kidneys, liver and gastrocnemius and soleus muscles; however, this diet maintained the normal histomorphology of muscle and liver and, when associated with RT, reduced the serum levels of triglycerides. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. DA1 receptors modulation in rat isolated trachea.

    Science.gov (United States)

    Cabezas, Gloria A; Velasco, Manuel

    2010-01-01

    We have previously demonstrated that low dose of inhaled dopamine (0.5-2 microg kg(-1) min(-1)) induces broncodilatacion in patients with acute asthma attack, suggesting that this dopamine effect is mediated by dopaminergic rather than by adrenergic receptors. To understand better these dopamine effect, rat tracheal smooth muscle was used as a model to evaluate the responses of beta2-, alpha1-, alpha2-adrenergic and DA1 and DA2 dopaminergic antagonists. Tracheal rings from male Sprague-Dawley rats (n = 90) were excised and placed in an organ bath containing modified Krebs-Ringer bicarbonate buffer at 37 degrees C, and gassed with O2 (95%) and CO2 (5%). Contractile responses were recorded with an isometric transducer in a polygraph (Letica, Spain). Contraction was induced by accumulative doses of acetylcholine (0.1, 0.3, 1, 3, 10 mM) or by electric field stimulation (10 Hz at 2 milliseconds), and accumulative doses of dopamine were added to the bath. Low concentration (0.1-0.3 mM) elicited a small initial contraction, followed by a marked relaxation. Cholinergic contraction was completely reversed at 6 mM of dopamine. This biphasic dopaminergic response was not blocked by incubation with beta2-adrenergic antagonist propranolol (0.1 microM), alpha1-antagonist, terazosin (0.1 mM), alpha2-antagonist, yohimbine (0.1 mM), or by DA2 antagonist metoclopramide (1-8 mM); DA1 antagonist SCH23390 (0.1 microM) produced a sustained increase of basal tone but did not block initial dopaminergic contraction and partially inhibited bronchodilator effect of dopamine. Dopaminergic relaxation in rat trachea is mediated by DA1 rather than by DA2 receptors; and adrenergic receptors are not involved in such dopamine-induced response. Finally, DA1 antagonist SCH23390 exerts intrinsic contractile activity on airway smooth muscle that deserves further research.

  17. Isolation, separation, and characterization of epithelial and connective cells from rat palate

    Energy Technology Data Exchange (ETDEWEB)

    Terranova, Victor Paul [Univ. of Rochester, NY (United States)

    1979-01-01

    Epithelial and connective tissue cells were isolated from rat palate by sequential collagenase, hyaluronidase and trypsin digestion of the extracellular matrix. Differences between the two populations were noted with respect to total cell protein, total cell water, proline uptake and incorporation, percent collagen synthesized, effects of parathyroid hormone, metabolism of D-valine and cell density. Basal epithelial cells were subsequently separated from the heterogeneous epithelial cell population on shallow linear density gradients by velocity centrifugation. The type of collagen synthesized by the basal epithelial cells was compared to the type of collagen synthesized by the connective tissue cells by means of labeled amino acid incorporation ratios. Cells isolated from the epithelial and connective tissue were compared. From these studies it can be concluded that epithelial and connective tissue cells can be isolated from rat palate as viable and distinct populations with respect to the biochemical parameters examined. Furthermore, subpopulations can be separated and biochemically characterized.

  18. Imaging regional metabolic changes in the ischemic rat heart in vivo using hyperpolarized(1-13C)Pyruvate

    DEFF Research Database (Denmark)

    Lauritzen, Mette Hauge; Magnusson, Peter; Laustsen, Christoffer

    2017-01-01

    in the in vivo rat heart in an open-chest model of ischemia reperfusion. Hyperpolarized MRI enables new possibilities for evaluating changes in cardiac metabolism noninvasively and in real time, which potentially could be used for research to evaluate new treatments and metabolic interventions for myocardial......We evaluated the use of hyperpolarized 13C magnetic resonance imaging (MRI) in an open-chest rat model of myocardial infarction to image regional changes in myocardial metabolism. In total, 10 rats were examined before and after 30 minutes of occlusion of the left anterior descending coronary...

  19. Mitochondrial damage: An important mechanism of ambient PM2.5 exposure-induced acute heart injury in rats

    International Nuclear Information System (INIS)

    Li, Ruijin; Kou, Xiaojing; Geng, Hong; Xie, Jingfang; Tian, Jingjing; Cai, Zongwei; Dong, Chuan

    2015-01-01

    Highlights: • PM 2.5 induces heart mitochondrial morphological damage of rats. • Mitochondrial fission/fusion gene expression is important regulation mechanism. • Proinflammatoy cytokine level changes are accompanied with mitochondrial damage. • Alterations in oxidative stress and calcium homeostasis are focused on. - Abstract: Epidemiological studies suggested that ambient fine particulate matter (PM 2.5 ) exposure was associated with cardiovascular disease. However, the underlying mechanism, especially the mitochondrial damage mechanism, of PM 2.5 -induced heart acute injury is still unclear. In this study, the alterations of mitochondrial morphology and mitochondrial fission/fusion gene expression, oxidative stress, calcium homeostasis and inflammation in hearts of rats exposed to PM 2.5 with different dosages (0.375, 1.5, 6.0 and 24.0 mg/kg body weight) were investigated. The results indicated that the PM 2.5 exposure induced pathological changes and ultra-structural damage in hearts such as mitochondrial swell and cristae disorder. Furthermore, PM 2.5 exposure significantly increased specific mitochondrial fission/fusion gene (Fis1, Mfn1, Mfn2, Drp1 and OPA1) expression in rat hearts. These changes were accompanied by decreases of activities of superoxide dismutase (SOD), Na + K + -ATPase and Ca 2+ -ATPase and increases of levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) as well as levels of pro-inflammatory mediators including TNF-α, IL-6 and IL-1β in rat hearts. The results implicate that mitochondrial damage, oxidative stress, cellular homeostasis imbalance and inflammation are potentially important mechanisms for the PM 2.5 -induced heart injury, and may have relations with cardiovascular disease

  20. Na+/Ca2+ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart

    OpenAIRE

    Farkas, A S; Acsai, K; Nagy, N; Tóth, A; Fülöp, F; Seprényi, G; Birinyi, P; Nánási, P P; Forster, T; Csanády, M; Papp, J G; Varró, A; Farkas, A

    2008-01-01

    Background and purpose: The Na+/Ca2+ exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+ concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 μM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+ concentrations in rabbit and rat hearts.

  1. Influence of chronic prenatal hypoxia on the specialized contact apparatus of rat heart ventricles during ontogeny

    Directory of Open Access Journals (Sweden)

    N. S. Petruk

    2014-08-01

    Full Text Available Background. During prenatal development embryonic mammalian heart undergoes deep dynamic changes due to size, structure and functions. Pathological intrauterine hypoxia influences fetal development generally and cardiogeny particularly, it affects the structure and function of the heart muscle and can lead to a variety of cardiovascular abnormalities and congenital heart defects. It is known that as a result of chronic intrauterine hypoxia during the stages of prenatal ontogeny specialized intercellular apparatus of cardiomyocytes is damaged, which plays a role not only in the mechanical connections of the cardiomyocytes, but also in the electric cooperatives, metabolic conversions, the homeostasis of the ionic balance and transport morphogenetic signaling molecules which are involved into the mechanisms of cardiogeny. It contributes to the development of diseases that may be associated with impaired local distribution of specialized intercellular junctions, and manifests as arrhythmias and cardiac conduction. Objective. To determine the effects of chronic prenatal hypoxia on the structure and distribution of specialized intercellular junctions of typical cardiomyocytes in the rat ventricular myocardium at the stages of prenatal ontogeny and to evaluate morphometric parameters of intercalated disks in the postnatal period. Materials and methods. White rats were used as a material. Intrauterine hypoxia was modelled by intraperitoneal injection of sodium nitrite from 10th to 21st day of pregnancy. Hearts were investigated by the transmission electron microscopy during the stages of prenatal and postnatal ontogeny and in adult animals. Morphometric and statistical methods were applied. Pairwise comparisons between means of different groups were performed using Student’s t-test where, for each couple of normally distributed populations, the null hypothesis that the means are equal was verified. Results. The average length of desmosomes on the 20th

  2. Comparative proteomic analysis of 2-MCPD- and 3-MCPD-induced heart toxicity in the rat.

    Science.gov (United States)

    Schultrich, Katharina; Frenzel, Falko; Oberemm, Axel; Buhrke, Thorsten; Braeuning, Albert; Lampen, Alfonso

    2017-09-01

    The chlorinated propanols 2- and 3-monochloropropanediol (MCPD), and their fatty acid esters have gained public attention due to their frequent occurrence as heat-induced food contaminants. Toxic properties of 3-MCPD in kidney and testis have extensively been characterized. Other 3-MCPD target organs include heart and liver, while 2-MCPD toxicity has been observed in striated muscle, heart, kidney, and liver. Inhibition of glycolysis appears to be important in 3-MCPD toxicity, whereas mechanisms of 2-MCPD toxicity are still unknown. It is thus not clear whether toxicity by the two isomeric compounds is dependent on similar or dissimilar modes of action. A 28-day oral feeding study in rats was conducted using daily non-toxic doses of 2-MCPD or 3-MCPD [10 mg/kg body weight], or an equimolar (53 mg/kg body weight) or a lower (13.3 mg/kg body weight) dose of 2-MCPD dipalmitate. Comprehensive comparative proteomic analyses of substance-induced alterations in the common target organ heart revealed striking similarities between effects induced by 2-MCPD and its dipalmitate ester, whereas the degree of effect overlap between 2-MCPD and 3-MCPD was much less. The present data demonstrate that even if exerting effects in the same organ and targeting similar metabolic networks, profound differences between molecular effects of 2-MCPD and 3-MCPD exist thus warranting the necessity of separate risk assessment for the two substances. This study for the first time provides molecular insight into molecular details of 2-MCPD toxicity. Furthermore, for the first time, molecular data on 3-MCPD toxicity in the heart are presented.

  3. Time dependent changes in myocardial norepinephrine concentration and adrenergic receptor density following X-irradiation of the rat heart

    NARCIS (Netherlands)

    Franken, N. A.; van der Laarse, A.; Bosker, F. J.; Reynart, I. W.; van Ravels, F. J.; Strootman, E.; Wondergem, J.

    1992-01-01

    The hearts of 9 to 12-weeks-old Sprague-Dawley rats were locally irradiated with a single dose of 20 Gy. The effects on myocardial norepinephrine concentrations and on alpha-adrenergic and beta-adrenergic receptor densities was examined up to 16 months post-treatment. Myocardial norepinephrine

  4. One-step purification of rat heart-type fatty acid-binding protein expressed in Escherichia coli

    NARCIS (Netherlands)

    Schaap, F. G.; Specht, B.; van der Vusse, G. J.; Börchers, T.; Glatz, J. F.

    1996-01-01

    Heart-type fatty acid-binding protein (H-FABP) is a member of a family of 14-15 kDa lipid binding proteins which are believed to enhance intracellular transport of lipids by facilitating their cytoplasmic diffusion. To obtain sufficient amounts of protein for in vitro studies, we expressed rat

  5. 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

  6. Oxygen consumption and heart rate responses to isolated ballet exercise sets.

    Science.gov (United States)

    Rodrigues-Krause, Josianne; Dos Santos Cunha, Giovani; Alberton, Cristine Lima; Follmer, Bruno; Krause, Mauricio; Reischak-Oliveira, Alvaro

    2014-01-01

    Ballet stage performances are associated with higher cardiorespiratory demand than rehearsals and classes. Hence, new interest is emerging to create periodized training that enhances dancers' fitness while minimizing delayed exercise-induced fatigue and possible injuries. Finding out in what zones of intensity dancers work during different ballet movements may support the use of supplemental training adjusted to the needs of the individual dancer. Therefore, the main purpose of this study was to describe dancers' oxygen consumption (VO2) and heart rate (HR) responses during the performance of nine isolated ballet exercise sets, as correlated with their first and second ventilatory thresholds (VT1 and VT2). Twelve female ballet dancers volunteered for the study. Their maximum oxygen consumption (VO2max), VT1, and VT2 were determined by use of an incremental treadmill test. Nine sets of ballet movements were assessed: pliés, tendus, jetés, rond de jambes, fondus, grand adage (adage), grand battements, temps levés, and sautés. The sets were randomly executed and separated by 5 minute rest periods. ANOVA for repeated measurements followed by the Bonferroni Post-hoc test were applied (p ballet sets. This stratification followed closely, but not exactly, the variation in HR. For example, rond de jambes (156.8 ± 19 b·min(-1)) did not show any significant difference from all the other ballet sets, nor VT1 or VT2. It is concluded that the workloads of isolated ballet sets, based on VO2 responses, vary between low and moderate aerobic intensity in relation to dancers' VT1 and VT2. However, ballet set workloads may be higher when based on HR responses, due to the intermittent and isometric components of dance.

  7. Time-dependent changes in rat lymphocyte activity in response to isolation

    International Nuclear Information System (INIS)

    Jessop, J.J.; Bayer, B.M.

    1986-01-01

    The authors have found that isolation of rats, previously adapted to group-housing conditions, resulted in time-dependent changes in mitogenic and cytolytic responses of lymphocytes. A depression (40-60%) of the uptake of 3 H-thymidine by splenic and blood lymphocytes stimulated with either phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was observed during the first 48 hours after transfer of the animals to individual cages. Within 4 days the mitogenic response increased and was comparable to that of animals which had been continuously group-housed. The response continued to increase and by 10 days was enhanced by 2 to 4 fold and remained elevated for at least 8 weeks. Similar changes in activity were observed with both splenic and blood lymphocytes, however, thymic lymphocytes taken from isolated animals demonstrated no change in reactivity to PHA. As with mitogenic responses, the cytolytic activity of splenic lymphocytes was also depressed during the initial days of isolation and as isolation continued, the activity returned to normal and was significantly enhanced (80%) within 5 weeks. These data show that changes in lymphocyte activity are dependent on the duration of exposure to isolated housing conditions and may be a part of the acute, adaptive and chronic phases of the response of rats to the stress of isolation

  8. Anti-apoptosis effect of polysaccharide isolated from the seeds of Cuscuta chinensis Lam on cardiomyocytes in aging rats.

    Science.gov (United States)

    Sun, Shou-Li; Guo, Li; Ren, Ya-Chao; Wang, Bing; Li, Rong-Hui; Qi, Yu-Shan; Yu, Hui; Chang, Nai-Dan; Li, Ming-Hui; Peng, Hai-Sheng

    2014-09-01

    To investigate the mechanism of apoptosis in myocardial cells of aging rats induced by D-galactose and to study the effect of the Polysaccharide isolated from the seeds of Cuscuta chinensis Lam (PCCL) on apoptosis of cardiomyocytes and its corresponding machinasim in aging rat model. Fifty male SD rats were randomly divided into 5 groups. Normal control group (NC). D-galactose (100 mg · kg(-1)d(-1) for 56 day) indued aging group (MC), D-galactose plus 100 mg kg(-1) d(-1) PCCL group (ML), D-galactose plus 200 mg kg(-1) d(-1) PCCL group (MM), and D-galactose plus 400 mg kg(-1) d(-1) PCCL group (MH). Same volume of solution (water, or PCCL aqueous solution) was given by gavage for 56 days. Then the hearts were collected and apoptosis parameters were evaluated. Caspase-3 and Cyt c were determined by fluorescence spectrometer, the apoptosis rate was assessed by AnnexinV-FITC method by Flow-Cytometry, [Ca(2+)]i and [Ca(2+)]i overloaded by KCL were observed by laser scanning confocal microscopy (LSCM); Bcl-2 and Bax were examined by immunohistochemistry. The content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3, Bax expression level in D-galactose induced aging group were higher than NC (p < 0.05). The ratio of Bcl-2/Bax was decreased in D-galactose induced aging group compared to NC. On the other hand, the content of Cyt C, [Ca(2+)]i of cardiomyocytes, the activity of Caspase-3 and apoptosis rate, as well as Bax expression level in all three PCCL groups were decreased compared to galactose induced group (p < 0.05). Bcl-2/Bax ratio was increased in all PCCL groups compared to galactose induced aging group. PCCL could decrease the apoptosis of cardiomyocytes by the mitochondria apoptosis pathway.

  9. Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

    Science.gov (United States)

    Honda, H; Iwata, T; Mochizuki, T; Kogo, H

    2000-06-01

    Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

  10. 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.

  11. Change in the aldolase activity in rats' hearts after irradiation with. gamma. and. beta. rays

    Energy Technology Data Exchange (ETDEWEB)

    Kukulyanskaya, M F; Borodina, G N

    1973-01-01

    The activity of aldolase fructoso-1-phosphate (I) and aldolase fructoso-1, 6-diphosphate (II) has been studied at various periods after total ..gamma.. and ..beta.. irradiation of rats at a dose of 42 rads. It has been shown that after ..gamma.. irradiation the activity of I increases in the supernatant liquid of the heart muscle homogenate, but drops sharply in the nuclei. In total, the activity of the homogenate did not change. The activity of II dropped for seven days, and after 1 hour and 30 days it was above the normal level. After ..beta.. radiation the activity of II is slowed down after 1, 7, and 15 days. These changes occur in all subcellular fractions. The authors note that the changes in the activity of aldolases are more sharply demarcated after ..gamma.. irradiation and are more substantial for II. (JPRS)

  12. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses.

    Science.gov (United States)

    Songstad, Nils Thomas; Kaspersen, Knut-Helge Frostmo; Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

    2015-01-01

    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.

  13. 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

  14. 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.

  15. The effect of rigor mortis on the passage of erythrocytes and fluid through the myocardium of isolated dog hearts.

    Science.gov (United States)

    Nevalainen, T J; Gavin, J B; Seelye, R N; Whitehouse, S; Donnell, M

    1978-07-01

    The effect of normal and artificially induced rigor mortis on the vascular passage of erythrocytes and fluid through isolated dog hearts was studied. Increased rigidity of 6-mm thick transmural sections through the centre of the posterior papillary muscle was used as an indication of rigor. The perfusibility of the myocardium was tested by injecting 10 ml of 1% sodium fluorescein in Hanks solution into the circumflex branch of the left coronary artery. In prerigor hearts (20 minute incubation) fluorescein perfused the myocardium evenly whether or not it was preceded by an injection of 10 ml of heparinized dog blood. Rigor mortis developed in all hearts after 90 minutes incubation or within 20 minutes of perfusing the heart with 50 ml of 5 mM iodoacetate in Hanks solution. Fluorescein injected into hearts in rigor did not enter the posterior papillary muscle and adjacent subendocardium whether or not it was preceded by heparinized blood. Thus the vascular occlusion caused by rigor in the dog heart appears to be so effective that it prevents flow into the subendocardium of small soluble ions such as fluorescein.

  16. Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6 contents in rat heart and brain

    Directory of Open Access Journals (Sweden)

    Elżbieta Ciejka

    2017-08-01

    Full Text Available Background: The human population is exposed ever more frequently to magnetic fields (MF. This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF used in magnetotherapy on the concentration of interleukin 6 (IL-6 in rat heart and brain. Material and Methods: The male rats were randomly divided into 3 experimental groups: group I – control, without contact with magnetic field; group II − exposed to bipolar, rectangular magnetic field 40 Hz, induction “peak-to-peak” 7 mT 30 min/day for 2 weeks; and group III − exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Results: Exposure to ELFMF: 40 Hz, induction “peak-to-peak” 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05 and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05. Conclusions: The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4:517–523

  17. [Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6) contents in rat heart and brain].

    Science.gov (United States)

    Ciejka, Elżbieta; Skibska, Beata; Gorąca, Anna

    2017-06-27

    The human population is exposed ever more frequently to magnetic fields (MF). This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF) used in magnetotherapy on the concentration of interleukin 6 (IL-6) in rat heart and brain. The male rats were randomly divided into 3 experimental groups: group I - control, without contact with magnetic field; group II - exposed to bipolar, rectangular magnetic field 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks; and group III - exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Exposure to ELFMF: 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05) and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05). The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4):517-523. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  18. Characterization of thoracic spinal neurons with noxious convergent inputs from heart and lower airways in rats.

    Science.gov (United States)

    Qin, Chao; Foreman, Robert D; Farber, Jay P

    2007-04-13

    Respiratory symptoms experienced in some patients with cardiac diseases may be due to convergence of noxious cardiac and pulmonary inputs onto neurons of the central nervous system. For example, convergence of cardiac and respiratory inputs onto single solitary tract neurons may be in part responsible for integration of regulatory and defensive reflex control. However, it is unknown whether inputs from the lungs and heart converge onto single neurons of the spinal cord. The present aim was to characterize upper thoracic spinal neurons responding to both noxious stimuli of the heart and lungs in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer bradykinin (BK, 10 microg/ml, 0.2 ml, 1 min) as a noxious cardiac stimulus. The lung irritant, ammonia, obtained as vapor over a 30% solution of NH(4)OH was injected into the inspiratory line of the ventilator (0.5-1.0 ml over 20 s). Intrapericardial bradykinin (IB) altered activity of 58/65 (89%) spinal neurons that responded to inhaled ammonia (IA). Among those cardiopulmonary convergent neurons, 81% (47/58) were excited by both IA and IB, and the remainder had complex response patterns. Bilateral cervical vagotomy revealed that vagal afferents modulated but did not eliminate responses of individual spinal neurons to IB and IA. The convergence of pulmonary and cardiac nociceptive signaling in the spinal cord may be relevant to situations where a disease process in one organ influences the behavior of the other.

  19. Kidney in potassium depletion. II. K+ handling by the isolated perfused rat kidney

    International Nuclear Information System (INIS)

    Hayashi, M.; Katz, A.I.

    1987-01-01

    In a companion paper the authors reported a large increment in Na + -K + -ATPase activity and [ 3 H]ouabain binding the inner stripe of outer medullary collecting tubules from K-depleted rats. To test the hypothesis that the increased number of Na + -K + pumps in these animals may be involved in potassium reabsorption they examined the effect of ouabain on K excretion by isolated, perfused kidneys from rats fed a K-free diet for 3 wk. Kidneys from K-depleted rats retain potassium avidly, both the fractional (FE/sub K/) and absolute K excretion being approximately fivefold lower than in control kidneys. Ouabain (5 mM) increased FE/sub K/ in kidneys from each K-depleted rat; similar results were obtained when kidneys were perfused with low and high potassium concentrations. In contrast, ouabain produced a variable effect in control kidneys, that depended on the perfusate potassium concentration. In K-depleted rats amiloride did not significantly alter K excretion and did not block the ouabain-induced kaliuresis, suggesting that the latter is not due to enhanced secretion secondary to increased distal fluid delivery. These results provide evidence for ouabain-sensitive potassium reabsorption in kidneys of chronically K-depleted rats, and suggest an explanation for the increased Na + -K + -ATPase observed in such animals

  20. Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

    International Nuclear Information System (INIS)

    Claffey, K.P.; Herrera, V.L.; Brecher, P.; Ruiz-Opazo, N.

    1987-01-01

    A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a λ gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundant mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source

  1. Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Claffey, K.P.; Herrera, V.L.; Brecher, P.; Ruiz-Opazo, N.

    1987-12-01

    A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a lambda gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundant mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source.

  2. Melatonin Protects the Heart, Lungs and Kidneys from Oxidative Stress under Intermittent Hypobaric Hypoxia in Rats

    Directory of Open Access Journals (Sweden)

    Jorge G Farías

    2012-01-01

    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine is the main secretory product of the pineal gland in all mammals including humans, but it is also produced in other organs. It has been previously demonstrated to be a powerful organ-protective substance under oxidative stress conditions. The aim of this study was to evaluate the protective effect of melatonin in several organs such as heart, lung, kidney, and of the reproductive system, such as testis and epididymis in animals exposed to intermittent hypobaric hypoxia and therefore exposed to oxidative stress and analyzed by lipid peroxidation. Ten-week-old male Wistar rats were divided into 6 groups for 96 hours during 32 days under: 1 Normobaric conditions, 2 plus physiologic solution, 3 plus melatonin, 4 intermittent hypobaric hypoxia, 5 plus physiologic solution and 6 plus melatonin. The animals were injected with melatonin (10 mg/kg body weight at an interval of 96 hours during 32 days. Results indicated that melatonin decreased lipid peroxidation in heart, kidneys and lung under intermittent hypobaric hypoxia conditions. However, it did not exhibit any protective effect in liver, testis, epididymis and sperm count.

  3. Radiochromatographic method for determination of macroenergetic phosphorus compounds in the rat heart muscle

    International Nuclear Information System (INIS)

    Wajdowicz, A.

    1980-01-01

    The 32 P was injected intraperitoneally. After 20 min. a part of heart muscle was taken off under anaesthesia from which phosphorus compounds were extracted and separated by means of paper chromatography. Separation was performed on the Whatman 1 paper, in glass tank produced by Shandon by means of method replacing of two direction descending chromatography use together with three solvent system. Identification of nucleotides was conducted in the UV light, besides CP and inorganic phosphorus by means of chemical methods. For the qualitative analysis of separated phosphorus compounds autoradiography was applied. Quantitative analysis was conducted by means of radiogrametric method. Radioactivity for each of examined phosphorus compounds was computed from chromatograms. Radioactive curves were indicated for each stage of chromatography separation. It was found the peaks on the radioactive curves equal the black spots on the autoradiograms and the spots identified with optical test and by the chemical method. This method permits in constant condition absolute separation and quantitative determination of phosphorus compounds in the rat heart muscle. It is relatively simple and more specific than chemical methods. (author)

  4. Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats

    International Nuclear Information System (INIS)

    Bergsland, J.; Carr, E.A. Jr.; Carroll, M.; Feldman, M.J.; Kung, H.; Wright, J.R.

    1989-01-01

    There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection

  5. 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

  6. Measurement of functional cholinergic innervation in rat heart with a novel vesamicol receptor ligand

    International Nuclear Information System (INIS)

    Coffeen, Paul R.; Efange, S.M.N.; Haidet, George C.; McKnite, Scott; Langason, Rosemary B.; Khare, A.B.; Pennington, Jennifer; Lurie, Keith G.

    1996-01-01

    Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[ 125 I]iodobenzyl)trozamicol(+)-[ 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 (+)-[ 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 (+)-[ 125 I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[ 125 I]MIBT uptake revealed significantly greater (+)-[ 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 125 I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[ 125 I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system

  7. Modelled microgravity alters the Na+, K+-ATPase activity in rat heart homogenates

    Science.gov (United States)

    Peana, Alessandra T.; Pippia, Proto; Paci, Silvia; Tognacini, Christina; Assaretti, Anna Rita; Meloni, Antonietta M.; Galleri, Grazia; Bernardini, Federico

    2005-08-01

    This study was aimed at establishing whether modeled microgravity conditions, created in a three-dimensional clinostat (Random Positioning Machine, RPM), influence the membrane-associated Na+, K+- and Mg2+- ATPase activities in heart homogenates from rats (ex- posed to RPM for 48 hours). The experimental data indicate that modeled low g significantly decreased the total ATPase (p<0.01) and Na+, K+ -ATPase activities (p<0.05) with no change of the Mg2+-ATPase activity, compared to the respective rat control groups (ground). This Na+, K+- pump inhibition could cause a digital- like effect in response to several modifications of many physiological processes even if this inhibition might also be causally related to the physiological environment induced by RPM. The exact mechanism by which total A TPase and Na+, K+ -A TPase activities decrease in response to RPM conditions remains to be established. We cannot rule out that a reduced intracellular ATP production, previously demonstrated in other cellular systems submitted to modeled microgravity conditions, could be responsible for the effects reported here.

  8. Adrenaline and reactive oxygen species elicit proteome and energetic metabolism modifications in freshly isolated rat cardiomyocytes

    International Nuclear Information System (INIS)

    Costa, Vera Marisa; Silva, Renata; Tavares, Ludgero Canario; Vitorino, Rui; Amado, Francisco; Carvalho, Felix; Bastos, Maria de Lourdes; Carvalho, Marcia; Carvalho, Rui Albuquerque; Remiao, Fernando

    2009-01-01

    The sustained elevation of plasma and interstitial catecholamine levels, namely adrenaline (ADR), and the generation of reactive oxygen species (ROS) are well recognized hallmarks of several cardiopathologic conditions, like cardiac ischemia/reperfusion (I/R) and heart failure (HF). The present work aimed to investigate the proteomics and energetic metabolism of cardiomyocytes incubated with ADR and/or ROS. To mimic pathologic conditions, freshly isolated calcium-tolerant cardiomyocytes from adult rat were incubated with ADR alone or in the presence of a system capable of generating ROS [(xanthine with xanthine oxidase) (XXO)]. Two-dimensional electrophoresis with matrix-assisted laser desorption/ionization and time-of-flight mass spectrometer analysis were used to define protein spot alterations in the cardiomyocytes incubated with ADR and/or ROS. Moreover, the energetic metabolism and the activity of mitochondrial complexes were evaluated by nuclear magnetic resonance and spectrophotometric determinations, respectively. The protein extract was mainly constituted by cardiac mitochondrial proteins and the alterations found were included in five functional classes: (i) structural proteins, notably myosin light chain-2; (ii) redox regulation proteins, in particular superoxide dismutase (SOD); (iii) energetic metabolism proteins, encompassing ATP synthase alpha chain and dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex; (iv) stress response proteins, like the heat shock proteins; and (v) regulatory proteins, like cytochrome c and voltage-dependent anion channel 1. The XXO system elicited alterations in cardiac contractile proteins, as they showed high levels of cleavage, and also altered energetic metabolism, through increased lactate and alanine levels. The cardiomyocytes incubation with ADR resulted in an accentuated increase in mitochondrial complexes activity and the decrease in alanine/lactate ratio, thus reflecting a high

  9. Ischemic preconditioning fails to confer additional protection against ischemia-reperfusion injury in the hypothyroid rat heart.

    Science.gov (United States)

    Mourouzis, I; Dimopoulos, A; Saranteas, T; Tsinarakis, N; Livadarou, E; Spanou, D; Kokkinos, A D; Xinaris, C; Pantos, C; Cokkinos, D V

    2009-01-01

    There is accumulating evidence showing that ischemic preconditioning (PC) may lose its cardioprotective effect in the diseased states. The present study investigated whether PC can be effective in hypothyroidism, a clinical condition which is common and often accompanies cardiac diseases such as heart failure and myocardial infarction. Hypothyroidism was induced in rats by 3-week administration of 6n-propyl-2-thiouracil in water (0.05 %). Normal and hypothyroid hearts (HYPO) were perfused in Langendorff mode and subjected to 20 min of zero-flow global ischemia and 45 min of reperfusion. A preconditioning protocol (PC) was also applied prior to ischemia. HYPO hearts had significantly improved post-ischemic recovery of left ventricular developed pressure, end-diastolic pressure and reduced lactate dehydrogenase release. Furthermore, phospho-JNK and p38 MAPK levels after ischemia and reperfusion were 4.0 and 3.0 fold lower in HYPO as compared to normal hearts (Phearts. PC improved the post-ischemic recovery of function and reduced the extent of injury in normal hearts but had no additional effect on the hypothyroid hearts. This response, in the preconditioned normal hearts, resulted in 2.5 and 1.8 fold smaller expression of the phospho-JNK and phospho-p38 MAPK levels at the end of reperfusion, as compared to non-PC hearts (Phearts, no additional reduction in the phosphorylation of these kinases was observed after PC. Hypothyroid hearts appear to be tolerant to ischemia-reperfusion injury. This response may be, at least in part, due to the down-regulation of ischemia-reperfusion induced activation of JNKs and p38 MAPK kinases. PC is not associated with further reduction in the activation of these kinases in the hypothyroid hearts and fails to confer added protection in those hearts.

  10. Binding of [125I] Concanavalin A to isolated Langerhans islets of rats

    International Nuclear Information System (INIS)

    Prey, N.

    1983-01-01

    Langerhans islets of rats were isolated using Lacy's collagenase technique and were incubated in vitro. The binding of iodine-labelled Concanavalin A to isolated Langerhans islets was investigated. We were unable to decide whether multiple Concanavalin A binding sites are located on the cell membrane, or whether the Concanavalin A binding sites are negatively influenced via a allosteric protein. Although the secretion mechanism induced by sulfony urea is not influenced by Concanavalin A, enhanced binding of Concanavalin A indicates that the region of identification cannot be identical for glucose and sulfonyl urea. (orig./MG) [de

  11. Attenuated fatigue in slow twitch skeletal muscle during isotonic exercise in rats with chronic heart failure.

    Directory of Open Access Journals (Sweden)

    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.

  12. 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)

  13. 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.

  14. Effect of phenytoin on cortical epileptic foci in cerveau isolé rats.

    Science.gov (United States)

    Mares, P

    1994-01-01

    The action of phenytoin was studied in acute experiments in rats with brainstem transection at the midcollicular level. Symmetrical epileptogenic foci were elicited in sensorimotor cortical areas of both hemispheres by local application of penicillin. Seven rats formed a control group, ten animals were pretreated with phenytoin (60 mg/kg i.p., 10 min before penicillin application). Synchronization of interictal discharges in control rats was delayed in comparison to animals with an intact brainstem; phenytoin did not influence this synchronization. Spontaneous transition of interictal into ictal activity was not abolished by phenytoin, i.e. in cerveau isolé preparations phenytoin lost this activity. The loss of anticonvulsant activity was not complete. Ictal episodes were modified; they started as very short ones and their duration progressively increased. Structures localized below the level of transection represent a site of at least one of the mechanisms of phenytoin anticonvulsant action.

  15. Interaction of propionate and carnitine metabolism in isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Brass, E.P.; Beyerinck, R.A.

    1987-01-01

    Propionate (P) and its metabolic products P-CoA and methylmalonyl-CoA can disrupt normal hepatic metabolism. Carnitine (Cn) has been shown to partially restore cellular function in the presence of P. This effect of Cn may result from removal of propionyl groups as propionylcarnitine (P-Cn). The present study examined the kinetics of P-Cn formation in rat hepatocytes, and the consequence of P-Cn formation on P and Cn metabolism. 14 C-P was converted to CO 2 , glucose and P-Cn in the hepatocyte system. Increasing concentrations of Cn up to 10.0 mM increased P-Cn formation from P without affecting CO 2 or glucose formation. Thus, 10.0 mM Cn increased total P metabolism by 40%. Metabolism of P was associated with a decrease in Cn concentration and an increase in short chain acylcarnitines (SCCn). In the absence of added Cn, 60 min incubation with P decreased Cn from 6.8 to 2.5 μM with a corresponding increase in SCCn. This effect of P to deplete free Cn was not seen to the same degree with butyrate in place of P. Similar increases in the formation of SCCn in the presence of P at the expense of free Cn were seen when the incubation Cn concentration was increased to 50 μM or 150 μM. HPLC methodologies to study specific acylcarnitines demonstrated the accumulation of large amounts of P-Cn in the incubations containing P, accounting for the depletion of free Cn

  16. Isolated persistent left-sided superior vena cava, giant coronary sinus, atrial tachycardia and heart failure in a child

    Directory of Open Access Journals (Sweden)

    Nagaraja Moorthy

    2013-09-01

    Full Text Available Persistence of a left-sided superior vena cava (PLSVC with absent right superior vena cava (isolated PLSVC is a very rare venous malformation and commonly associated with congenital heart disease or alterations of the cardiac situs. We describe an unusual case of a young boy presenting with persistent atrial tachycardia and congestive heart failure. He was detected to have unexplained grossly dilated right atrium, right ventricle with systolic dysfunction and a giant coronary sinus (CS. The dilated CS closely mimicked a pseudo cor-triatriatum on echocardiography. Contrast echocardiography from both arms revealed opacification of the CS before the right atrium. Bilateral upper limb venography confirmed the presence of absent right SVC and isolated persistent left SVC draining into the giant coronary sinus.

  17. In vitro model to study the effects of matrix stiffening on Ca2+ handling and myofilament function in isolated adult rat cardiomyocytes.

    Science.gov (United States)

    van Deel, Elza D; Najafi, Aref; Fontoura, Dulce; Valent, Erik; Goebel, Max; Kardux, Kim; Falcão-Pires, Inês; van der Velden, Jolanda

    2017-07-15

    This paper describes a novel model that allows exploration of matrix-induced cardiomyocyte adaptations independent of the passive effect of matrix rigidity on cardiomyocyte function. Detachment of adult cardiomyocytes from the matrix enables the study of matrix effects on cell shortening, Ca 2+ handling and myofilament function. Cell shortening and Ca 2+ handling are altered in cardiomyocytes cultured for 24 h on a stiff matrix. Matrix stiffness-impaired cardiomyocyte contractility is reversed upon normalization of extracellular stiffness. Matrix stiffness-induced reduction in unloaded shortening is more pronounced in cardiomyocytes isolated from obese ZSF1 rats with heart failure with preserved ejection fraction compared to lean ZSF1 rats. Extracellular matrix (ECM) stiffening is a key element of cardiac disease. Increased rigidity of the ECM passively inhibits cardiac contraction, but if and how matrix stiffening also actively alters cardiomyocyte contractility is incompletely understood. In vitro models designed to study cardiomyocyte-matrix interaction lack the possibility to separate passive inhibition by a stiff matrix from active matrix-induced alterations of cardiomyocyte properties. Here we introduce a novel experimental model that allows exploration of cardiomyocyte functional alterations in response to matrix stiffening. Adult rat cardiomyocytes were cultured for 24 h on matrices of tuneable stiffness representing the healthy and the diseased heart and detached from their matrix before functional measurements. We demonstrate that matrix stiffening, independent of passive inhibition, reduces cell shortening and Ca 2+ handling but does not alter myofilament-generated force. Additionally, detachment of adult cultured cardiomyocytes allowed the transfer of cells from one matrix to another. This revealed that stiffness-induced cardiomyocyte changes are reversed when matrix stiffness is normalized. These matrix stiffness-induced changes in cardiomyocyte

  18. Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart

    DEFF Research Database (Denmark)

    Sonne, David P; Engstrøm, Thomas; Treiman, Marek

    2007-01-01

    to exert cardiovascular effects in a number of experimental models. Here we tested exendin-4 (Exe-4), a peptide agonist at GLP-1 receptors, and GLP-1(9-36) amide, the primary endogenous metabolite of GLP-1 (both in the concentration range 0.03-3.0 nM), for their protective effects against ischemia......-reperfusion injury (IRI) in an isolated rat heart preparation. When administered, the agents were only present for the first 15 min of a 120 min reperfusion period (postconditioning protocol). Exe-4, but not GLP-1(9-36) amide, showed a strong infarct-limiting action (from 33.2% +/-2.7% to 14.5% +/-2.......2% of the ischemic area, pamide were able to augment left ventricular performance (left ventricular developed pressure and rate-pressure product) during...

  19. Effect of ornithine on ammonia utilization and urea synthesis in isolated hepatocytes from fed rats

    International Nuclear Information System (INIS)

    Garwacki, S.; Wiechetek, M.; Souffrant, W.B.

    1988-01-01

    The effect of ornithine on the ammonia utilization and urea synthesis in hepatocytes isolated from fed male Wistar rats was investigated. On the basis of the 15 N tracer technique, it was found that ornithine stimulated urea synthesis with an increased utilization of the exogenously marked ammonia for urea, but deminished its utilization in other N-metabolic processes. The results also showed that the stimulation of urea synthesis due to ornithine resulted from the utilization of both exogenous and endogenous sources. (author)

  20. Relaxant effect of the ethanol extract of Helichrysum plicatum (Asteraceae) on isolated rat ileum contractions.

    Science.gov (United States)

    Bigovic, Dubravka; Brankovic, Suzana; Kitic, Dusanka; Radenkovic, Mirjana; Jankovic, Teodora; Savikin, Katarina; Zivanovic, Slavoljub

    2010-05-10

    Helichrysum plicatum (Turkish Helichrysum) has been used in folk medicine for the treatment of gastric and hepatic disorders. The aim of the present study was to examine the relaxant activity of an extract of H. plicatum flowers on isolated rat ileum. Segments of ileum of rats were suspended in an organ bath. Cumulative concentrations of H. plicatum ethanol extract induced a relaxant effect on spontaneous rat ileum contractions. H. plicatum extract caused a mean contractile response of 81.68 +/- 6.17% (at a dose of 0.01 mg/mL) and 30.08 +/- 9.07% (at a dose of 1 mg/mL). A similar effect was observed with papaverine (0.01-3 microg/mL). H. plicatum extract (0.01-1 mg/mL) relaxed high K+ (80 mM) precontractions, an effect similar to that caused by papaverine (0.01-3 microg/mL). The plant extract (0.03-0.3 mg/mL) also induced a significant depression of the cumulative concentration response curve for acetylcholine (5-1500 nM) (p Helichrysum plicatum flowers on the isolated rat intestine Extract of H. plicatum can inhibit the spontaneous ileum contractions and contractions induced by acetylcholine, histamine, barium and potassium ions.

  1. Kinetics of reversible-sequestration of leukocytes by the isolated perfused rat lung

    Energy Technology Data Exchange (ETDEWEB)

    Goliaei, B.

    1980-08-01

    The kinetics and morphology of sequestration and margination of rat leukocytes were studied using an isolated perfused and ventilated rat lung preparation. Whole rat blood, bone marrow suspension, or leukocyte suspensions, were used to perfuse the isolated rat lung. The lung was also perfused with latex particle suspensions and the passage of particles through the lung capillaries was studied. When a leukocyte suspension was perfused through the lung in the single-pass mode, the rate of sequestration decreased as more cells were perfused. In contrast, latex particles of a size comparable to that of leukocytes were totally stopped by the lung. When the leukocyte suspension was recirculated through the lung, cells were rapidly removed from circulation until a steady state was reached, after which no net removal of cells by the lung occurred. These results indicate that leukocytes are reversibly sequestered from circulation. The sequestered cells marginated and attached to the luminal surface of the endothelium of post-capillary venules and veins. A mathematical model was developed based on the assumption that the attachment and detachment of leukocytes to blood vessel walls follows first-order kinetics. The model correctly predicts the following characteristics of the system: (a) the kinetics of the sequestration of leukocytes by the lung; (b) the existence of a steady state when a suspension of leukocytes is recirculated through the lung; and (c) the independence of the fraction of cells remaining in circulation from the starting concentration for all values of starting concentration. (ERB)

  2. 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.)

  3. Effects of nitrous oxide on the rat heart in vivo: another inhalational anesthetic that preconditions the heart?

    NARCIS (Netherlands)

    Weber, Nina C.; Toma, Octavian; Awan, Saqib; Frässdorf, Jan; Preckel, Benedikt; Schlack, Wolfgang

    2005-01-01

    BACKGROUND: For nitrous oxide, a preconditioning effect on the heart has yet not been investigated. This is important because nitrous oxide is commonly used in combination with volatile anesthetics, which are known to precondition the heart. The authors aimed to clarify (1) whether nitrous oxide

  4. 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.

  5. Effect of eplerenone on serum TNF-α levels in adriamycin induced heart failure male rat models

    International Nuclear Information System (INIS)

    Xuan Nan; Song Liping; Xing Haiyan

    2009-01-01

    Objective: To investigate the effect of eplerenone on serum TNF-α levels in adriamycin induced heart failure male rat models. Methods: Forty male rat models of adriamycin-induced heart failure were prepared with weekly intraperitoneal injection of adriamycin (4/mg/kg) for six weeks. Twenty surviving models were randomly divided into two groups: (1)eplerenone-treated group, n=10, treated with garage of eplerenone 200mg/kg/d for 12 weeks (2) non-treated group n=10. All the surviving models (group (1) n=8, group (2) n=6) were sacrificed after 12 weeks with left ventricular hemodynamic function parameters tested and serum TNF-α levels measured. Ten male rats without adriamycin administration served as controls. Results: Left ventricular hemodynamic parameters in the non-treated group were significantly worse than those in controls (P<0.05). The parameters in the eplerenone treated group were significantly better than those in the non-treated group (P<0.05). The serum TNF-α levels in the non-treated group were significantly higher than those in controls (P<0.05). TNF-α levels in the eplerenone group were significantly lower than those in the non-treated group (P<0.05). Conclusion: Eplerenone could reduce the serum TNF-α levels in the rat models of heart failure. (authors)

  6. Action of a new cholinergic agonist, aclatonium napadisilate, on isolated rat pancreatic acini

    International Nuclear Information System (INIS)

    Fujii, M.; Okabayashi, Y.; Nakamura, T.; Tani, S.; Fujisawa, T.; Otsuki, M.

    1990-01-01

    The effect of aclatonium napadisilate, a newly synthesized choline ester, on pancreatic exocrine function was compared with that of the muscarinic agonist carbamylcholine in isolated rat pancreatic acini. Both compounds increased amylase release and 45 Ca 2+ efflux in a dose-dependent fashion, and similarly decreased the binding of [N-methyl- 3 H]scopolamine to isolated rat pancreatic acini. While aclatonium napadisilate was 20-30 times less potent than carbamylcholine in stimulations of amylase release and 45 Ca 2+ efflux, the potency of aclatonium napadisilate in inhibiting [N-methyl- 3 H]scopolamine binding was nearly the same as that of carbamylcholine. These results indicate that aclatonium napadisilate stimulates pancreatic exocrine secretion via muscarinic receptors and Ca 2+ mobilization, and its intrinsic activity is less than carbamylcholine in the isolated rat pancreatic acini. Since aclatonium napadisilate is known to increase motility and peristalsis of the gastrointestinal tract, stimulatory effects of aclatonium napadisilate, shown in the present study, on digestive enzyme secretion from the pancreas may provide additional benefit of aclatonium napadisilate in the treatment of various gastrointestinal disorders

  7. Effects of lysosomal inhibitors on 125I-insulin and 125I-asialofetuin degradation by the isolated, perfused rat liver and isolated rat hepatocytes

    International Nuclear Information System (INIS)

    Ward, W.F.; Moss, A.L.

    1985-01-01

    To further evaluate the role of the lysosomal system in insulin degradation, the authors have compared the effects of inhibitors of lysosomal function on the degradation of 125 I-insulin with 125 I-asialofetuin, a lysosomally targeted molecule, by the intact, perfused rat liver and the isolated rat hepatocyte. The inhibitors employed were chloroquine ( 125 microM), NH 4 Cl (10 mM), and leupeptin (50 micrograms/ml). In the intact, perfused liver the observed inhibition of 125 I-asialofetuin degradation at 30 min was as follows: chloroquine, 38%; NH 4 Cl, 32%; and leupeptin, 86%. Chloroquine also inhibited 125 I-insulin degradation in the intact, perfused liver (29%), but NH 4 Cl and leupeptin had no effect. Using the isolated hepatocyte, the observed values for inhibition of 125I-asialofetuin at 60 min were: chloroquine, 85%; NH 4 Cl, 76%; and leupeptin, 81%. Chloroquine produced a 28% inhibition of 125I-insulin degradation, while NH 4 Cl and leupeptin had no effect. Chloroquine and NH 4 Cl decreased cell-associated radioactivity when isolated hepatocytes were incubated with 125I-asialofetuin (leupeptin had no effect), whereas chloroquine caused a 107% increase in cell-associated radioactivity when 125I-i