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Sample records for diabetic rabbit heart

  1. Heart rate variability in isolated rabbit hearts.

    Science.gov (United States)

    Frey, B; Heger, G; Mayer, C; Kiegler, B; Stöhr, H; Steurer, G

    1996-11-01

    The presence of heart rate variability (HRV) in patients with cardiac denervation after heart transplantation raised our interest in HRV of isolated, denervated hearts. Hearts from seven adult white ELCO rabbits were transferred to a perfusion apparatus. All hearts were perfused in the working mode and in the Langendorff mode for 20 minutes each. HRV was analyzed in the frequency domain. A computer simulated test ECG at a constant rate of 2 Hz was used for error estimation of the system. In the isolated, denervated heart, HRV was of random, broadband fluctuations, different from the well-characterized oscillations at specific frequencies in intact animals. Mean NN was 423 +/- 51 ms in the Langendorff mode, 406 +/- 33 ms in the working heart mode, and 500 ms in the test ECG. Total power was 663 +/- 207 ms2, 817 +/- 318 ms2, and 3.7 ms2, respectively. There was no significant difference in any measure of HRV between Langendorff and working heart modes. The data provide evidence for the presence of HRV in isolated, denervated rabbit hearts. Left atrial and ventricular filling, i.e., the working heart mode, did not alter HRV, indicating that left atrial or ventricular stretch did not influence the sinus nodal discharge rate.

  2. Diabetic Heart Disease

    Science.gov (United States)

    ... be coronary heart disease (CHD), heart failure, and diabetic cardiomyopathy. Diabetes by itself puts you at risk for heart disease. Other risk factors include Family history of heart disease Carrying extra ...

  3. Diabetes, Heart Disease, and Stroke

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    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Diabetes, Heart Disease, and Stroke Having diabetes means that ... help to stop. What is the link between diabetes, heart disease, and stroke? Over time, high blood ...

  4. Living with Diabetic Heart Disease

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    ... from the NHLBI on Twitter. Living With Diabetic Heart Disease Diabetic heart disease (DHD) increases the likelihood of earlier and more ... also tend to have less success from certain heart disease treatments, such as coronary artery bypass grafting and ...

  5. Diabetic Heart Disease

    Science.gov (United States)

    ... develop DHD. The higher a person's blood sugar level is, the higher his or her risk of DHD. Diabetes affects heart disease risk in three major ways. ... is that many lifestyle changes help control multiple risk factors. For example, ... treatment plan for diabetes and see your doctor for ongoing care. If ...

  6. Diabetes - preventing heart attack and stroke

    Science.gov (United States)

    Diabetes complications - heart; Coronary artery disease - diabetes; CAD - diabetes; Cerebrovascular disease - diabetes ... People with diabetes have a higher chance of having heart attacks and strokes. Smoking and having high blood pressure and high ...

  7. Exogenous Streptococcus pneumoniae Endophthalmitis in Diabetic Rabbits

    Science.gov (United States)

    Benton, Angela H.; Fulton, Linda K.; Marquart, Mary E.

    2017-01-01

    Diabetics are at increased risk for eye infections including bacterial endophthalmitis. It is unclear whether the severity of endophthalmitis is greater in these patients due to confounding factors such as pre-existing ocular diseases in some but not others. Therefore, we tested the hypothesis that disease severity and/or bacterial loads would be significantly higher in a Type I diabetic rabbit model of Streptococcus pneumoniae endophthalmitis. Rabbits were treated with alloxan to destroy pancreatic islet cells, or mock-treated with vehicle, and maintained for 10 days before intravitreal infection with S. pneumoniae E353. Clinical scoring of the eyes was performed 24 and 48 hours after infection, followed by euthanasia and vitreous harvest to quantitate bacterial loads. There were no significant differences in clinical scores (P ≥ 0.440) or bacterial loads (P = 0.736), however, 4/12 (33%) of the diabetic rabbits became bacteremic. This finding not only indicates a breakdown in the blood-ocular barrier, but also prompts further investigation into the exploitation of the diabetic eye by the streptococci. PMID:28387365

  8. How Is Diabetic Heart Disease Treated?

    Science.gov (United States)

    ... from the NHLBI on Twitter. How Is Diabetic Heart Disease Treated? Diabetic heart disease (DHD) is treated with lifestyle changes, medicines, and ... treating DHD include: Controlling diabetes and any other heart disease risk factors you have, such as unhealthy blood ...

  9. 吡格列酮抑制糖尿病兔心房肌细胞离子通道重构%Pioglitazone inhibits atrial ionic channel remodeling in diabetic rabbits hearts

    Institute of Scientific and Technical Information of China (English)

    刘长乐; 李广平; 富华颖; 李健; 程立君; 杨万松; 刘彤

    2014-01-01

    Objective To investigate the effects of pioglitazone on atrial ionic channel remodeling in alloxan-induced diabetic rabbit models.Methods A total of 32 rabbits were randomly (random number) divided into control (CN) group,diabetes mellitus (DM) group,diabetes mellitus + pioglitazone 4 mg/ (d · kg) (DPG) group and diabetes mellitus + double pioglitazone 8 mg/ (d · kg) (DPI) group.The diabetic state was examined by quantitative determination of blood glucose levels of ≥ 14 mmol/L.Langendorff-perfused rabbit hearts were used to isolate single atrial myocyte,and whole-cell patch-clamp technique was used to record action potential duration (APD) and atrial ionic channel currents (ICa,L and INa).Variables with normal distribution were compared with One-way ANOVA and LSD-t test.Results Compared with controls,APD90 and APDS0 of left atrial myocytes were significantly prolonged in DM group (P <0.05 vs.CN),and there was no significant difference in APD90 frequency adaptation between them (P >0.05 vs.CN).The densities of INa were reduced and the densities of ICa,L were increased in DM group (P < 0.01 vs.CN).The above variables were markedly attenuated in DPG and DPI group.Conclusions Pioglitazone may inhibits atrial ionic channel remodeling in diabetic rabbit models.%目的 建立四氧嘧啶介导的兔糖尿病(DM)模型,评价吡格列酮对DM兔心房肌细胞离子通道重构的干预作用.方法 本实验在天津心脏病学研究所进行,选取健康成年日本大耳白兔32只随机(随机数字法)分为健康对照组(CN组)、糖尿病组(DM组)、糖尿病+吡格列酮A组[DPG组,4mg/ (d·kg)]和糖尿病+吡格列酮B组[DPI组,8mg/ (d·kg)].通过四氧嘧啶耳缘静脉注射建立兔DM模型,血糖水平≥14 mmol/L认为DM模型建立成功.模型建立成功后饲养8周取出心脏建立Langendorff灌流的离体兔心脏模型分离心房肌细胞,采用全细胞膜片钳技术记录细胞膜动作电位(AP)、L-型钙通道电

  10. Diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Bergmann, Natasha; Ballegaard, Søren; Holmager, Pernille

    2014-01-01

    The aim of this study was to test i) whether patients having diabetes and ischemic heart disease (IHD), i.e., patients suffering from two chronic diseases, demonstrate a higher degree of chronic stress when compared with patients suffering from IHD alone, and ii) whether suffering from the two...... chronic diseases results in an elevation in specific elements of the chronic stress concept. A total of 361 participants with IHD were included, of whom 47 suffered from concomitant diabetes. Stress was measured by pressure pain sensitivity (PPS) and by the following questionnaires: the Major Depression...

  11. What Are the Signs and Symptoms of Diabetic Heart Disease?

    Science.gov (United States)

    ... What Are the Signs and Symptoms of Diabetic Heart Disease? Some people who have diabetic heart disease (DHD) ... when it's given right after symptoms occur. Coronary Heart Disease A common symptom of coronary heart disease (CHD) ...

  12. Skin electrodes transduced signals to the bladder resulting in ameliorated hypomotility in a rabbit model of diabetes

    Institute of Scientific and Technical Information of China (English)

    Xinmin Wang; Qirui Fu; Qingmei Zhang; Ping Xu; Lin Cao; Meng Xue; Wei Wang

    2012-01-01

    Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projection area using three levels of exporting voltage (5.84 V, 8.00 V, and 11.00 V). Results demonstrated significantly attenuated electric signals from both groups, in particular the diabetes group. The skin electrode signals were conducted to the bladders, and all vesical signals increased according to strength of stimulating signals from the skin electrode. However, vesical signals from diabetic rabbits were less than those from normal rabbits at the same stimulating strength of exporting voltage. Vesical pressures from the two groups increased along with increased vesical signals, but vesical pressure was less those from diabetic rabbits than in normal rabbits (basic status and different stimulating levels). Linear correlation analysis showed a significantly positive correlation between vesical pressure and signal. These results demonstrated that electric signals from skin electrodes resulted in increased vesical pressure, and vesical pressure increased along with stimulation strength.

  13. Postnatal development of adrenergic responsiveness in the rabbit heart.

    Science.gov (United States)

    Feng, Z P; Dryden, W F; Gordon, T

    1989-08-01

    It is uncertain how changes in the beta-adrenoceptor population influence the contractility of developing heart. To resolve this we have examined postnatal developmental changes in the adrenergic responsiveness of the rabbit heart. The inotropic effect of isoproterenol on isolated left ventricular papillary muscles from rabbits aged 3, 21, and 90 days was compared with the relative number of beta-adrenoceptors at each age measured using [3H]dihydroalprenolol ([3H]DHA) as the specific ligand. The maximum tension developed in response to isoproterenol increases from 37 +/- 7 to 175 +/- 33% above control twitch tension between 3 and 21 days of age; this is followed by a decrease to 68 +/- 12% in the young adult. During this period of development, there is a decline in EC50 towards increased sensitivity. These differences are partially accounted for by an increase in the numbers of specific [3H]DHA binding sites from 17.3 +/- 2.3 to 56.6 +/- 9.9 fmol/mg wet tissue weight from 3 to 21 days, and a subsequent decrease to 32 +/- 4.5 fmol/mg tissue in the young adult. The proportionally larger increase in contractility compared with the number of beta-adrenoceptor binding sites during the first 3 weeks of life is discussed in terms of the developmental changes in the efficacy of coupling between receptor occupancy and contraction.

  14. Metabolism of lipids in experimental hypertrophic hearts of rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N.W.; Cameron, A.J.V.

    1979-06-01

    Cardiac hypertrophy was induced in rabbits by subcutaneous injection of thyroxine or isoprenaline or by surgically constricting the abdominal aorta. Alterations in lipid metabolism were observed in these hypertrophic hearts. Thyroxine or isoprenaline treatment increased the fatty acids in the serum and stimulated a marked increase in total lipids, triglycerides, and fatty acids in the hypertrophied myocardium. Coarctation of the aorta, in contrast, induced a significant increase in these lipids without significantly affecting serum free fatty acids. Histochemical and morphological studies confirmed an increase in neutral lipids. It is suggested that the observed increase in fatty acids in the heart following thyroxine or isoprenaline treatment is related to the increase in serum free fatty acids, which is followed by an increase in the removal of serum fatty acids by the heart. However, the amount of serum fatty acids that is removed exceeds the amount that is oxidized, which leads to an increase in lipid stores. The increase in lipid stores in the heart following coarctation of the aorta probably corresponds to the decrease in myocardial concentrations of carnitine. Serum lipid levels following coarctation were not significantly different from those of controls.

  15. Maternal diabetes and the fetal heart

    OpenAIRE

    Hornberger, L K

    2006-01-01

    Maternal diabetes mellitus significantly affects the fetal heart and fetal–placental circulation in both structure and function. The influence of pre‐conceptional diabetes begins during embryonic development in the first trimester, with altered cardiac morphogenesis and placental development. It continues to have an influence on the fetal circulation through the second and third trimesters and into the perinatal and neonatal period

  16. How Is Diabetic Heart Disease Diagnosed?

    Science.gov (United States)

    ... heart while you exercise. If you can’t exercise, you may be given medicine to raise your heart rate. Urinalysis For this test, you'll give a sample of urine for analysis. The sample is checked for abnormal levels of protein or blood cells. In people who have diabetes, protein in ...

  17. NADH fluorescence imaging of isolated biventricular working rabbit hearts.

    Science.gov (United States)

    Asfour, Huda; Wengrowski, Anastasia M; Jaimes, Rafael; Swift, Luther M; Kay, Matthew W

    2012-07-24

    that alter the rate of myocyte metabolism or induce hypoxia or create a combination of the two. Hearts from New Zealand white rabbits were connected to a biventricular working heart system (Hugo Sachs Elektronik) and perfused with modified Krebs-Henseleit solution(16) at 37 °C. Aortic, LV, pulmonary artery, and left & right atrial pressures were recorded. Electrical activity was measured using a monophasic action potential electrode. To image fNADH, light from a mercury lamp was filtered (350±25 nm) and used to illuminate the epicardium. Emitted light was filtered (460±20 nm) and imaged using a CCD camera. Changes in the epicardial fNADH of biventricular working hearts during different pacing rates are presented. The combination of the heart model and fNADH imaging provides a new and valuable experimental tool for studying acute cardiac pathologies within the context of realistic physiological conditions.

  18. Anti diabetic effect of Momordica charantia (bitter melone on alloxan induced diabetic rabbits.

    Directory of Open Access Journals (Sweden)

    Yakaiah Vangoori, Mishra SS, Ambudas B, Ramesh P, Meghavani G, Deepika K, Prathibha A

    2013-02-01

    Full Text Available Objective: to investigate the anti diabetic effect of the bitter melon on Alloxan induced diabetes in experimental animals (rabbits. Materials and Methods: the alcohol extract of whole fruit was tested for its efficacy in Alloxan (150mg/kg induced diabetic rabbit. The diabetic rabbits were divided into 5groups. Group I (control received 2% gumacasia, groupie (positive control received standard drug Metformin (62.5mg+2%GA, group III, IV, V (T1 T2 T3 were treated orally with a daily dose of 0.5(gm 1gm, 1.5gm respectively for 35 days, for all diabetic rabbits after giving TEST,NC,PC preparations, the blood samples were collected and determined the blood glucose level 0,1,3,24hrs intervals. 0hr reading is before drug giving and remaining 3 readings after drugs giving. 24th her reading is considered as 0hr reading for the next day. Results: administration of alcohol of an extract of bitter melon produced a dose dependent decrease in blood glucose levels in Alloxan induced rabbits. There was a significant fall in blood sugar level in High dose (1.5GM/kg in comparison to low dose (0.5gm/kg and median dose (1gm/kg shown by LSD test. This is comparable to the effect of Metformin. Conclusion: the results of this study show that chronic oral administration of an extract of Momordica charantia fruit at an appropriate dosage may be good alternative anti diabetic agent.

  19. The Diabetic Heart: Too Sweet for Its Own Good?

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    Hannah J. Whittington

    2012-01-01

    Full Text Available Diabetes mellitus is a major risk factor for ischemic heart disease (IHD. Patients with diabetes and IHD experience worse clinical outcomes, suggesting that the diabetic heart may be more susceptible to ischemia-reperfusion injury (IRI. In contrast, the animal data suggests that the diabetic heart may be either more, equally, or even less susceptible to IRI. The conflicting animal data may be due to the choice of diabetic and/or IRI animal model. Ischemic conditioning, a phenomenon in which the heart is protected against IRI by one or more brief nonlethal periods of ischemia and reperfusion, may provide a novel cardioprotective strategy for the diabetic heart. Whether the diabetic heart is amenable to ischemic conditioning remains to be determined using relevant animal models of IRI and/or diabetes. In this paper, we review the limitations of the current experimental models used to investigate IRI and cardioprotection in the diabetic heart.

  20. Hypoglycemic and Hypolipidemic Potential of a High Fiber Diet in Healthy versus Diabetic Rabbits

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    Raquel Díez

    2013-01-01

    Full Text Available The aim of this study was to investigate potential hypoglycaemic and hypolipidemic effects of Plantago ovata husk included in the diet, in healthy and diabetic rabbits. We also examined the effects of this fiber in other biochemical parameters. Two groups of 18 rabbits were used. The first group was fed with standard chow and the second with chow supplemented with Plantago ovata husk (3.5 mg/kg/day. On day 14 diabetes mellitus was induced by the intravenous administration of alloxan (80 mg/kg. After an oral glucose load (3 g, glucose, insulin, and other biochemical parameters were determined on day 14 (healthy rabbits and on day 28 (diabetic rabbits. In healthy rabbits, fiber did not modify glucose or insulin levels but decreased significantly total cholesterol, LDL-cholesterol, atherogenic index, and glycosylated hemoglobin. In diabetic rabbits, fiber was more beneficial in mild diabetics than in severe diabetics with significant decreases in glucose levels and increases in insulin concentrations. In these animals fiber caused an important reduction in cholesterol, indicating a beneficial effect of Plantago ovata husk in diabetic rabbits. Although further studies in patients are necessary, we think that Plantago ovata husk offers interesting perspectives to be administered to patients with diabetes mellitus.

  1. Microwave radiation and heart-beat rate of rabbits.

    Science.gov (United States)

    Chou, C K; Han, L F; Guy, A W

    1980-06-01

    Each of three adult New Zealand rabbits, 2 male and 1 female albinos, was exposed dorsally or ventrally, to 2450-MHz plane waves for 20 min under each of several field conditions: 1) to continuous waves (CW) at 5 mW/cm2; 2) to pulsed waves (PW) of 1-microsecond width that recurred 700 pps at an average of 5 mW/cm2 and at a peak of 7.1 W/cm2; 3) to PW of 10-microseconds width at a peak of 13.7 W/cm2 that were synchronized with and triggered by the R wave of the electrocardiogram (EKG) at various delay times (0, 100, and 200 ms; and 4) to CW at 80 mW/cm2. Carbon-loaded Teflon electrodes were used to record the EKG from forelimbs of an animal before, during, and after irradiation whilst it was maintained in a constant exposure geometry in a wooden squeeze box. Field induced changes in the heart-beat rate were observed at 80 mW/cm2 but not a lower average power densities, although a peak positive chronotropic effect might have been occasioned by PM introduced at 100 and 200 ms after the R wave peak. No cumulative effect was observed over a period of four months. Thermographic analysis revealed relatively little absorption of microwave energy by the myocardium irrespective of anatomical aspect of exposure.

  2. Diabetes, Dyslipidemia, and Heart Protection

    Science.gov (United States)

    ... blood. People usually have a lipid profile after fasting overnight. Many things can affect your lipid levels. They include • Age, sex, and family history of heart disease • Lifestyle factors such as what you eat, level of physical activity, alcohol use, and smoking • High blood pressure • High ...

  3. Effect of losartan on sarcoplasmic reticulum Ca2+ handing proteins in heart failure rabbit

    Institute of Scientific and Technical Information of China (English)

    姚艳

    2006-01-01

    Objective To investigate the effects of losartan on mRNA expression of myocardial sarcoplasmic reticulum calcium handling proteins (SERCA2, RyR2 and PLB) and the role of which in prevention of chronic heart failure in rabbit. Methods After chronic heart failure was

  4. Influence of diabetes mellitus on heart failure risk and outcome

    Directory of Open Access Journals (Sweden)

    Van Belle Eric

    2003-01-01

    Full Text Available Abstract Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure. The studies linking diabetes mellitus (DM with heart failure (HF The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy. Treatment of heart failure in diabetic patients The knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients.

  5. Evaluation of Stability of Surface-Treated Mini-Implants in Diabetic Rabbits

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    Nam-Hee Oh

    2014-01-01

    Full Text Available Introduction. The purpose of this study was to investigate effects of surface treatment of mini-implants in diabetes-induced rabbits by comparing osseointegration around mini-implants. Methods. Twelve New Zealand white rabbits were divided into two groups (alloxan-induced diabetic group and control group. A total of 48 mini-implants were placed after four weeks of diabetic induction. 24 mini-implants were surface-treated with SLA (sandblasted with large grit, and acid etched and the remaining 24 mini-implants had smooth surfaces. Four weeks after placement, 32 mini-implants were removed from 4 control and 4 diabetic rabbits. Insertion and removal torques were measured. The remaining 16 mini-implants from the two groups were histomorphometrically analyzed. Results. Maximum insertion torque showed no difference between diabetic and control groups, but total insertion energy was higher in control group. In surface-treated mini-implants, maximum removal torque was higher in both diabetic and control groups. Bone-implant contact (BIC was increased in the control group when compared to the diabetic group. Surface-treated group had higher BIC than smooth surface group in both control and diabetic groups. However, there was no significantly statistical difference. Conclusions. Type 1 diabetes mellitus and surface treatment method of mini-implant affected primary stability of mini-implants. In addition, the use of orthodontic mini-implants in a diabetic patient is likely to show results similar to the healthy patient.

  6. Effect of high-voltage impulse current on the structure and function of rabbit heart

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    Xin-ping XU

    2011-06-01

    Full Text Available Objective To explore the effect of high-voltage impulse current(HVIC on the structure and function of rabbit heart.Methods Sixty healthy male rabbits were involved in present study and divided into 6 groups randomly(n=10.The rabbits were then shocked using a high-voltage pulse generator with current intensity of 0,50,100,150,250 and 500mA(pulse width 100μs,duration 5s respectively.The heart rate and electrocardiogram(ECG of rabbits were detected before and 0,1,3,7,14 and 28 days after the electric shock.Moreover,the myocardial tissue of rabbits was obtained immediately and 28 days after shock to observe the pathological changes.Results Immediately after electric shock of 50 to 500mA,the heart rate of rabbit increased by different degree,and the ECG showed arrhythmia,myocardial ischemia,atrial fibrillation and atrioventricular block,and the changes recovered gradually one day later.The pathological observation showed cell swelling,separation of myofibril and sarcoplasmic condensation of Purkinje fibers immediately after electric shock of 50 to 500mA,and the changes recovered 28 days after shock.The cardiac injuries aggravated with the increasing of current intensity,especially when it exceeded 150mA,and the recovery time prolonged.Conclusion High-voltage impulse current may induce recoverable injuries on heart structure and function,and the damage effect shows a correlation with the current intensity.

  7. Arachidonic acid metabolism in the platelets and neutrophils of diabetic rabbit and human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Greco, N.J.

    1985-01-01

    An alteration of arachidonic acid metabolism to prostaglandins and leukotrienes from platelets and polymorphonuclear leukocytes respectively is evident in subjects with diabetes mellitus. There is evidence of altered platelet/vascular wall interactions in diabetes mellitus and evidence that polymorphonuclear leukocytes influence the vascular walls. Theories on the pathogenesis of atherosclerosis include both blood cells. Platelet hypersensitivity is evident in those platelets from the alloxan-induced diabetic rabbit either suspended in plasma or buffer. Arachidonic acid- and collagen-induced platelet aggregation, release of /sup 14/serotonin, and T x B/sub 2/ and 12-HETE production is enhanced when responses of diabetic platelets are compared to control platelets. Control rabbit neutrophils produce more LTB/sub 4/, LTB/sub 4/ isomers and 5-HETE than diabetic rabbits neutrophils. Decreased synthesis from diabetic rabbit neutrophils is not explained by increased catabolism of LTB/sub 4/, reesterification of 5-HETE, or increased eicosanoid formation. These experiments demonstrate both platelet and neutrophil dysfunction in diabetic subjects. Because of the involvement of these cells in regulating circulatory homeostatis, abnormal behavior could aggravate the atherosclerotic process. Platelet and neutrophil dysfunctions are noted before macroscopic vascular lesions are apparent suggesting an important role in the pathogenesis of atherosclerosis.

  8. Efficiently screening heart failure in patients with type 2 diabetes

    NARCIS (Netherlands)

    Boonman-de Winter, Leandra J M; Rutten, Frans H; Cramer, Maarten J; Landman, Marcel J; Zuithoff, Nicolaas P A; Liem, Anho H; Hoes, Arno W

    2015-01-01

    AIMS: Our aim was to develop a screening tool for heart failure in patients with type 2 diabetes. METHODS AND RESULTS: A total of 581 consecutive patients from 21 primary care practices in The Netherlands with type 2 diabetes, in whom the diagnosis of heart failure (HF) was not known, underwent an e

  9. Effects of Potassium Aspartate and Magnesium on Ventricular Arrhythmia in Ischemia-reperfusion Rabbit Heart

    Institute of Scientific and Technical Information of China (English)

    Jun PU; Ben HE; Cuntai ZHANG; Xiaoqing QUAN; Guoan ZHAO; Jiagao LV; Bo LI; Rong BAI; Nian LIU; Yanfei RUAN

    2008-01-01

    Summary: The aim of this study was to determine if the potassium aspartate and magnesium (PAM) prevent reperfusion-induced ventricular arrhythmias (RIVA) in ischcmia-reperfusion (IR) rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode's solution, and in ischemia group and PAM groups the perfusion of Tyrode's solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode's solution and the PAM group with Tyrode's solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion (TDR) and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group (P<0.05). The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group (P<0.05). Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.

  10. The Relationship between Ischemic Heart Disease and Diabete

    DEFF Research Database (Denmark)

    Norgaard, Mette Lykke

    2012-01-01

    THE FOLLOWING OBJECTIVES ON THE SUBJECT: The relationship between ischemic heart disease and diabetes: 1. To examine the short- and long-term risk of death and cardiovascular outcomes in patients with incident diabetes and in patients with first-time MI during a 10 year period in Denmark, using the general...... diabetes increases with increasing severity of heart failure. Focus on the development of diabetes in patients with ischemic heart disease with or without the presence of heart failure still compose a public health matter, because early and aggressive evidence-based therapy is thought to reduce......Diabetes is a well-established risk factor for cardiovascular disease and is common among patients with acute myocardial infarction (MI), where the prevalence is as high as 20%. Patients with diabetes requiring glucose-lowering medication (GLM) have been reported as having the same long-term risk...

  11. Effect of Camel Milk on Oxidative Stresses in Experimentally Induced Diabetic Rabbits

    Directory of Open Access Journals (Sweden)

    Esraa Tantawy

    2010-06-01

    Full Text Available Camel milk has an importance in the treatment of diabetes. It has been shown that the patients who drink camel milk daily, their need to insulin decrease. Therefore, this study aimed to investigate the effect of camel milk in comparison with insulin treatment in experimentally-induced diabetes. This study was carried out on forty male New Zealand rabbits, divided into four groups with ten rabbits in each. The first group G1 was considered as control non-diabetic group and received only normal saline solution. The other animals were injected intravenously with alloxan for induction of diabetes mellitus and then divided into three groups' ten rabbits each as the follows: G2 considered as control diabetic and left untreated, G3 was considered as diabetic and treated with insulin, and G4 was considered as diabetic and received camel milk. At the end of the experiment (4 weeks, blood (whole blood & serum and tissue samples (liver, kidney and pancreas were collected from all the animals for analysis of: enzymatic SOD and catalase, non-enzymatic GSH antioxidant enzyme activities. Serum malondialdeyde, glucose, insulin and lipid profile also were analyzed. The results showed that the camel milk was effective in the treatment of diabetes in comparison to insulin treatment alone. In addition to its hypoglycemic effect, camel milk improved the diabetes-induced oxidative stress. The histopathological evaluations demonstrated that there was a regeneration in β cells and the islets of Langerhans among the pancreatic acini in rabbits receiving camel milk. Our findings suggested that the camel milk administration in case of insulin dependant diabetes mellitus might be recommended as an oral anti-diabetic remedy.

  12. EFFECT OF ELECTROACUPUNCTURE OF THE HEART MERIDIAN ACUPOINTS ON ISCHEMIC CARDICA FUNCTION IN THE RABBIT

    Institute of Scientific and Technical Information of China (English)

    方志斌; 汪克明; 等

    2002-01-01

    Subjective:To observe the effect of electroacupuncture(EA) of acupoints of the Heart Meridian and Lung Meridian on ischemic cardiac systolic ability for analyzing the realtive specific relationship between the Heart Meridian and the heart.Methods:Acute myocardial ischemia(AMI) Was produced by intravenous infusion of pituitrin (40u+5% glucose injection 500 ml,60 drips/min)in the rabbit.Left intraventricular pressure(LVP),maximal rising velocity of LVP(dp/dt max),isovolumetric pressure(IP)and end-diastolic pressure(EDP)of the left cardiac ventricle were used as the indexes.Three points of Heart Meridian [HM,from"Shenmen")HT7)to "lingdan"(HT4)] and the three points of Lung Meridian[LM,from“Taiyuan”(LU9)to“Lieque”(LU7)]were punctured with filiform needles and stimulated with hand-manipulation and electrically with ZYZ-1 EA Therapeutic Apparatus.30 rabbits anes-thetized with urethane(1g/kg) were randomly and evenly divided into control group,HM group and LM group.Results:The effects of EA of HM points were evidently superior to those of EA of LM points in promoting the recovery of both AMI-induced decrease of LVP and dp/dtmax,and AMI-induced increase of IP and EDP.Conclusion:Acupoints of Heart Meridian has a relatively specific connection with the heart in comparison with those of Lung Meridian;and the Heart Meridian is a functionalo whole.

  13. EFFECT OF ELECTROACUPUNCTURE OF THE HEART MERIDIAN ACUPOINTS ON ISCHEMIC CARDIAC FUNCTION IN THE RABBIT

    Institute of Scientific and Technical Information of China (English)

    FANG Zhibin; WANG Keming; WANG Yuelan; ZHOU Yiping

    2002-01-01

    Subjective: To observe the effect of electroacupuncture (EA) of acupoints of the Heart Meridian and Lung Meridian on ischemic cardiac systolic ability for analyzing the relative specific relationship between the Heart Meridian and the heart. Methods: Acute myocardial ischemia (AMI) was produced by intravenous infusion of pituitrin (40 u + 5% glucose injection 500 mi, 60 drips/min) in the rabbit. Left intraventricular pressure (LVP), maximal rising velocity of LVP (dp/dt max), isovolumetric pressure (IP) and end-diastolic pressure (EDP) of the left cardiac ventricle were used as the indexes. Three points of Heart Meridian [HM, from "Shenmen" (HT 7) to "Lingdao" (HT 4)]and the three points of Lung Meridian [LM, from "Taiyuan" (LU 9) to "Lieque" (LU 7)] were punctured with filiform needles and stimulated with hand-manipulation and electrically with ZYZ-1 EA Therapeutic Apparatus. 30 rabbits anesthetized with urethane (1 g/kg) were randomly and evenly divided into control group, HM group and LM group. Result=s: The effects of EA of HM points were evidently superior to those of EA of LM points in promoting the recovery of both AMI-induced decrease of LVP and dp/dtmax, and AMI-induced increase of IP and EDP. Conclusion: Acupoints of Heart Meridian has a relatively specific connection with the heart in comparison with those of Lung Meridian; and the Heart Meridian is a functional whole.

  14. Topical Application of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP Accelerates Wound Healing in Diabetic Rabbits

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    Abdulmohsen H. Al-Elq

    2012-01-01

    Full Text Available Objective. Diminished wound healing is a common problem in diabetic patients due to diminished angiogenesis. SHMSP was found to promote angiogenesis. The present study was carried out to examine the effect of this peptide in healing of wounds in diabetic rabbits. Materials and Methods. Twenty male New Zealand rabbits were used in this study. Diabetes mellitus was induced and the rabbits were randomly divided into two equal groups: control group and peptide group. A-full thickness punch biopsy was made to create a wound of about 10 mm on the right ears of all rabbits. Every day, the wound was cleaned with saline in control groups. In the peptide group, 15 mg of SHMSP was applied after cleaning. On day 15th, all animals were sacrificed, and the wounds were excised with a rim of 5 mm of normal surrounding tissue. Histo-pathological assessment of wound healing, inflammatory cell infiltration, blood vessel proliferation, and collagen deposition was performed. Results. There were no deaths among the groups. There was significant increase in wound healing, blood vessel proliferation and collagen deposition, and significant decrease in inflammatory cell infiltration in the peptide group compared to the control group. Conclusion. Topical application of SHMSP improves wound healing in diabetic rabbits.

  15. Comparative hypoglycemic activity of different fractions of Thymus serpyllum L. in alloxan induced diabetic rabbits.

    Science.gov (United States)

    Alamgeer, -; Mushtaq, Muhammad Naveed; Bashir, Sajid; Ullah, Ikram; Karim, Sabeha; Rashid, Muhammad; Malik, Muhammad Nasir Hayat; Rashid, Haroonur

    2016-09-01

    The aim of present study was to evaluate and compare the hypoglycemic activity of different solvents extracts of Thymus serpyllum in rabbits. Diabetes was induced with single intravenous injection of alloxan monohydrate (150mg/kg). Glibenclamide and acarbose were used as standard drugs. The crude powder of Thymus serpyllum (500 mg/kg b.w) significantly reduced blood glucose level in both normal and diabetic rabbits. Various extracts of Thymus serpyllum were compared for their hypoglycemic activity in diabetic rabbits. Ether and aqueous extracts significantly reduced the blood glucose level with maximum effect (p<0.001) produced by aqueous extract, which was selected for further study. Aqueous extract significantly inhibited the rise in glucose level in oral glucose tolerance test. The extract showed synergistic effect with different doses of insulin; however serum insulin level of the diabetic rabbits was not significantly increased by the extract. HbA1c level was significantly (p<0.05) reduced whereas hemoglobin level was significantly increased in three months study. Phytochemical screening of the aqueous extract showed the presence of alkaloids, flavonoids, tannins, terpinoids, reducing sugar and cardiac glycosides. It is concluded that the aqueous extract might be used alone or in combination with insulin to manage diabetes and its associated complications.

  16. HEMATOLOGICAL AND IMMUNOBIOCHEMICAL STUDY OF GREEN TEA AND GINGER EXTRACTS IN EXPERIMENTALLY INDUCED DIABETIC RABBITS.

    Science.gov (United States)

    Elkirdasy, Ahmed; Shousha, Saad; Alrohaimi, Abdulmohsen H; Arshad, M Faiz

    2015-01-01

    The present study was designed to investigate the effects of the extract of green tea and/or ginger on some hematological and immunobiochemical profiles in alloxan-induced diabetic rabbits. The results revealed that treatment of diabetic animals with extract of green tea and/or ginger elevated the decreased HDL-c and LDL-c but significantly decreased triglycerides, the elevated glucose and GOT concentrations. The result also displayed a non-significant increase in the levels of CRP and fibrinogen. The experiment also revealed that the elevated MDA and GSH level fell down to the normal control group. The result also showed that after green tea and/or ginger extract treatment, the lowered RBC, WBC counts, PCV, percentage of neutrophils were increased and the elevated MCV, MCH, and MCHC of diabetic rabbits were decreased to normal levels. Thus, the overall results may indicate that green tea and/or ginger extracts have a significant hypoglycemic effect in diabetic rabbits. In addition, the extracts may be capable of improving hyperlipidemia, the impaired kidney function and hemogram in alloxan-induced diabetic rabbits.

  17. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-05-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls. All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p < 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p < 0.05) and pericardial effusion (p < 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p < 0.05) or IB (p < 0.01) and in the untreated, unirradiated rabbits (p < 0.01). Early administrative of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusin, and improved survival in this experimental model of radiation-induced heart disease.

  18. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-05-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug was administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls, All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p less than 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p less than 0.05) and pericardial effusion (p less than 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p less than 0.05) or IB (p less than 0.01) and in the untreated, unirradiated rabbits (p less than 0.01). Early administration of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusion, and improved survival in this experimental model of radiation-induced heart disease.

  19. Bone regeneration in cranioplasty and clinical complications in rabbits with alloxan-induced diabetes

    Directory of Open Access Journals (Sweden)

    Evanice Menezes Marçal Vieira

    2008-06-01

    Full Text Available This research evaluated the bone repair process in surgical defects created on the parietal bones of diabetic rabbits using the guided bone regeneration technique to observe the effects of alloxan in the induction of diabetes mellitus. Twenty-four adult rabbits were divided into three study groups: control (C, diabetic (D and diabetic associated to polytetrafluoroethylene (PTFE membrane (D-PTFE. For diabetes induction the animals received one dose of monohydrated alloxan (90 mg/kg by intravenous administration in the auricular or femoral vein. In group D-PTFE the membrane covered both the floor and the surface of the bone defect. In groups D and C, the bone defect was filled up with blood clot. The specimens were fixed in 10% formol and prepared for histomorphometric analysis. The results showed that the 90 mg/kg dose of monohydrate alloxan was sufficient to promote diabetes mellitus when administered in the auricular vein. Bone regeneration was slower in the diabetic group when compared with the control and diabetic-PTFE groups, but there was no significant statistical difference between the two experimental groups (D and D-PTFE. The oral and general clinical complications among the diabetics were weight loss, polyuria, polyphagia and severe chronic gingivitis.

  20. Antihyperglycemic and hypolipidemic potential of Caesalpinia decapetala in alloxan-induced diabetic rabbits

    Directory of Open Access Journals (Sweden)

    Liaqat Hussain

    2014-12-01

    Full Text Available The anti-hyperglycemic, anti-hyperlipidemic, kidney and hepatoprotective potential of Caesalpinia decapetala were evaluated in alloxan-induced diabetic rabbits. The plant extract showed concentration dependant significant (p<0.001 therapeutic potential in diabetic rabbits revealing improvement in lipid profile and liver and kidney functions. 300 mg/kg and 500 mg/kg oral extract were able to reduce average blood glucose levels from 250.6 mg/dL to 204.2 mg/dL and 188.2 mg/dL respectively during 14 days period, in comparison to 183.8 mg/dL of glibenclamide. There was no significant synergistic effect found, upon co-administration of both drug and extract representing the competitive binding to sulphonyl urea (SUR1, revealing possible mechanism of action for compounds in extract. Extract was found to be nephroprotective, hepatoprotective and improved lipid profile of alloxan-treated rabbits.

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

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    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. Saffron (Crocus sativus) pretreatment confers cardioprotection against ischemia-reperfusion injuries in isolated rabbit heart.

    Science.gov (United States)

    Nader, Moni; Chahine, Nathalie; Salem, Charelle; Chahine, Ramez

    2016-12-01

    Restoration of blood flow to the ischemic myocardium is imperative to avoid demise of cardiomyocytes, but is paradoxically associated with irreversible damage to cardiac tissues due to the excessive generation of reactive oxygen species (ROS). We have previously reported that saffron, a natural antioxidant, attenuated ischemia-reperfusion (IR) injuries in vitro; however, its role in a meaningful cardiac recovery remains unknown. Here, we show that saffron supplement (oral administration for 6 weeks) reduced myocardial damage and restored cardiac function in an IR model of rabbit hearts. This was evidenced by improved left ventricle pressure, heart rate and coronary flow, and left ventricle end diastolic pressure (LVEDP) in IR hearts (isolated from rabbits pre-exposed to saffron (S/IR)). Electrophysiological recordings revealed a significant decline in both premature ventricle contraction and ventricle tachycardia/fibrillation in S/IR compared to IR hearts. This was paralleled by increased expression of the contractile proteins α-actinin and Troponin C in the myocardium of S/IR hearts. Histological examination combined to biochemical analysis indicated that hearts pre-exposed to saffron exhibited reduced infarct size, lower lipid peroxidation, with increased glutathione peroxidase activity, and oxidation of nitro blue tetrazolium (by reactive oxygen species). Furthermore, in contrast with IR hearts, saffron pretreatment induced restoration of the phosphorylation level of the survival proteins Akt and 4EBP1 and reduced activity of p38. Collectively, our data demonstrate that the natural antioxidant saffron plays a pivotal role in halting IR-associated cardiac injuries and emerges as a novel preventive tool for ischemic heart disease.

  3. Heart rate variability in neonates of type 1 diabetic pregnancy.

    Science.gov (United States)

    Russell, Noirin E; Higgins, Mary F; Kinsley, Brendan F; Foley, Michael E; McAuliffe, Fionnuala M

    2016-01-01

    Cardiomyopathy is a common finding in offspring of pre-gestational type 1 diabetic pregnancy. Echocardiographic and biochemical evidence of fetal cardiac dysfunction have also been reported. Studies suggest that offspring of diabetic mothers (ODM) undergo a fetal programming effect due to the hyperglycaemic intrauterine milieu which increases their risk of cardiovascular morbidity in adult life. Decreased neonatal heart rate variability (HRV) has been described in association with in-utero growth restriction, prematurity, sudden infant death syndrome and congenital heart disease. The effect of in-utero exposure to hyperglycaemia in diabetic pregnancy on neonatal HRV is unknown. Our aim was to determine if neonatal HRV differs between normal and diabetic pregnancy. This was a prospective observational study of 38 patients with pregestational type 1 diabetes and 26 controls. HRV assessment was performed using Powerlab (ADI Instruments Ltd). Heart rate variability assessment and cord blood sampling for pH and glucose were performed for all neonates. Maternal glycaemic control was assessed via measurement of glycosylated haemoglobin in each trimester in the diabetic cohort. Neonates of diabetic mothers had evidence of altered heart rate variability, with increased low frequency to high frequency ratio (LF: HF), suggestive of a shift towards sympathetic predominance (pheart to fluctuations in maternal glycaemia with subsequent alterations in HRV may explain why infants of diabetic mothers are at greater risk of cardiovascular disease in later life. Copyright © 2015. Published by Elsevier Ireland Ltd.

  4. Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-an; FAN You-qi; LI Chang-ling; HE Hong; SUN Yong; LV Bin-jian

    2005-01-01

    Objective: The present study was designed to test whether transplantation of human bone marrow-derived mesenchymal stem cells (hMSCs) in New Zealand rabbits with myocardial infarction can improve heart function; and whether engrafted donor cells can survive and transdifferentiated into cardiomyocytes. Methods: Twenty milliliters bone marrow was obtained from healthy men by bone biopsy. A gradient centrifugation method was used to separate bone marrow cells (BMCs) and red blood cells.BMCs were incubated for 48 h and then washed with phosphate-buffered saline (PBS). The culture medium was changed twice a week for 28 d. Finally, hematopoietic cells were washed away to leave only MSCs. Human MSCs (hMSCs) were premarked by BrdU 72 h before the transplantation. Thirty-four New Zealand rabbits were randomly divided into myocardial infarction (MI)control group and cell treated group, which received hMSCs (MI+MSCs) through intramyocardial injection, while the control group received the same volume of PBS. Myocardial infarction was induced by ligation of the left coronary artery. Cell treated rabbits were treated with 5× 106 MSCs transplanted into the infarcted region after ligation of the coronary artery for 1 h, and the control group received the same volume of PBS. Cyclosporin A (oral solution; 10 mg/kg) was provided alone, 24 h before surgery and once a day after MI for 4 weeks. Echocardiography was measured in each group before the surgery and 4 weeks after the surgery to test heart function change. The hearts were harvested for HE staining and immunohistochemical studies after MI and cell transplantation for 4 weeks. Results: Our data showed that cardiac function was significantly improved by hMSC transplantation in rabbit infarcted hearts 4 weeks after MI (ejection fraction: 0.695±0.038 in the cell treated group (n=12) versus0.554±0.065 in the control group (n=13) (P<0.05). Surviving hMSCs were identified by BrdU positive spots in infarcted region and

  5. 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.

  6. Exogenous midkine administration prevents cardiac remodeling in pacing-induced congestive heart failure of rabbits.

    Science.gov (United States)

    Harada, Masahide; Hojo, Mayumi; Kamiya, Kaichiro; Kadomatsu, Kenji; Murohara, Toyoaki; Kodama, Itsuo; Horiba, Mitsuru

    2016-01-01

    Midkine (MK), a heparin-binding growth factor, has been shown to prevent cardiac remodeling after ischemic injury through its anti-apoptotic effect. Cell apoptosis is central to the pathophysiology of cardiac remodeling in congestive heart failure (CHF) of ischemic as well as non-ischemic origin. We hypothesized that MK exerts the anti-apoptotic cardioprotective effect in CHF of non-ischemic etiology. MK protein or vehicle (normal saline) was subcutaneously administered in tachycardia-induced CHF rabbits (right ventricular pacing, 350 beats/min, 4 weeks). The vehicle-treated rabbits (n = 19, control) demonstrated severe CHF and high mortality rate, whereas MK (n = 16) demonstrated a well-compensated state and a lower mortality rate. In echocardiography, left ventricular (LV) end-diastolic dimension decreased in MK versus control, whereas LV systolic function increased. In histological analysis (picrosirius red staining), MK decreased collagen deposition area compared with control. TUNEL staining showed that MK prevented cell apoptosis and minimized myocyte loss in the CHF rabbit ventricle, associated with activation of PI3-K/Akt signaling, producing a parallel decrease of Bax/Bcl-2 ratio. MK prevented progression of cardiac remodeling in the CHF rabbit, likely by activation of anti-apoptotic signaling. Exogenous MK application might be a novel therapeutic strategy for CHF due to non-ischemic origin.

  7. Sinusoidal Constriction and Vascular Hypertrophy in the Diabetes-Induced Rabbit Penis

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    Vivian Alves Pereira

    2013-06-01

    Full Text Available Objective To assess the morphological changes of penile vascular structures and the corpus cavernosum area in alloxan-induced diabetic rabbits. Materials and Methods Twenty male rabbits (2 months old were divided into two groups with 10 rabbits each, the control group (CG and the diabetic group (DG. The animals from DG received an intravenous injection of alloxan (100mg/kg to induce the diabetes. Ten weeks after the induction of diabetes, all animals were euthanized. Two fragments of the penile shaft were harvested and samples were processed and paraffin embedded. Sections (5µm were cut and stained for histological and immunohistochemical markers. Results Nuclear protrusion toward the lumen, and cytoplasmic vacuolization were observed in the tunica intima of the dorsal artery of the penis in DG. The thicknesses of the tunica media increased significantly in DG (p = 0.0350. It was also observed a significant increase in the area of the tunica media (p = 0.0179. There was no significant change in smooth muscle cell density in the tunica media of the dorsal artery of the penis (p = 0.0855. The collagen fiber pattern of the tunica adventitia of the dorsal artery of the penis was different between the control and diabetic groups. There was a significant decrease in the area occupied by the cavernous sinuses in DG (p = 0.0013. Conclusion Alloxan-induced diabetes mellitus in rabbits promotes important changes in penile vascular structures, thereby decreasing blood supply and affecting penile hemodynamics, leading to erectile dysfunction.

  8. VEGF-expressing Bone Marrow Mesenchymal Stem Cells Transplantation Improved Heart Function of Myocardial Infarct Rabbits

    Institute of Scientific and Technical Information of China (English)

    Sheng Xiaogang; Song Hui; Feng Jianzhang; Chen Qiuxiong; Wu Shulin

    2006-01-01

    Objectives To treat myocardial infarction with MSCs transplantation combined with VEGF gene therapy in rabbits and to study its mechanisms. Methods Forty-eight rabbits were randomly divided into MI group (n=12), MSCs group (n=12), VEGF group (n=12), MSCs+VEGF group (M+V group, n=12). Rabbit myocardial infarction models were founded by the ligation of left anterior descending artery. 107 MSCs were injected into the infarct-zone in four sites 2 weeks later in MSCs and M+V group. phVEGF gene were injected in infarct-zone in VEGF group and MSCs transfected with phVEGF gene were injected in M+V group. Heart function including LVEDP, LVSP, LVDP, -dp/dtmax, +dp/dtmax, were measured in vivo. The hearts were harvested at 4 weeks after transplantation and sectioned for HE stain,immunohistochemical stain of BrdU and Ⅷ factor antigen. Results The left ventricular hemodynamics parameters showed that heart function were improved more in M+V group than MSCs group, MI group and VEGF group. The numbers of BrdU positive cells in M+V group(61±8)were more than in MSCs group (44±8,P<0.01). The numbers of vessels in infarcted zone were more in M+V group (49±8) than in MSCs group (33±6, P<0.01)、VEGF group(30±8,P<0.01)and MI group (18±4,P<0.01). Conclusions VEGF-expressing MSCs transplantation could improve heart function after myocardial infarction, and they were more effective than sole MSCs transplantation. Keeping more MSCs survival and ameliorating the blood supply of infarct-zone might be involved in the mechanisms.

  9. Carvedilol protected diabetic rat hearts via reducing oxidative stress

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  10. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy.

    Science.gov (United States)

    Fillmore, N; Mori, J; Lopaschuk, G D

    2014-04-01

    Heart disease is a leading cause of death worldwide. In many forms of heart disease, including heart failure, ischaemic heart disease and diabetic cardiomyopathies, changes in cardiac mitochondrial energy metabolism contribute to contractile dysfunction and to a decrease in cardiac efficiency. Specific metabolic changes include a relative increase in cardiac fatty acid oxidation rates and an uncoupling of glycolysis from glucose oxidation. In heart failure, overall mitochondrial oxidative metabolism can be impaired while, in ischaemic heart disease, energy production is impaired due to a limitation of oxygen supply. In both of these conditions, residual mitochondrial fatty acid oxidation dominates over mitochondrial glucose oxidation. In diabetes, the ratio of cardiac fatty acid oxidation to glucose oxidation also increases, although primarily due to an increase in fatty acid oxidation and an inhibition of glucose oxidation. Recent evidence suggests that therapeutically regulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation can improve cardiac function of the ischaemic heart, the failing heart and in diabetic cardiomyopathies. In this article, we review the cardiac mitochondrial energy metabolic changes that occur in these forms of heart disease, what role alterations in mitochondrial fatty acid oxidation have in contributing to cardiac dysfunction and the potential for targeting fatty acid oxidation to treat these forms of heart disease.

  11. Primary Stability of Self-Drilling and Self-Tapping Mini-Implant in Tibia of Diabetes-Induced Rabbits

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    Jea-Beom Park

    2014-01-01

    Full Text Available Objective. This study aimed to evaluate effects of type 1 diabetes mellitus and mini-implant placement method on the primary stability of mini-implants by comparing mechanical stability and microstructural/histological differences. Methods. After 4 weeks of diabetic induction, 48 mini-implants (24 self-tapping and 24 self-drilling implants were placed on the tibia of 6 diabetic and 6 normal rabbits. After 4 weeks, the rabbits were sacrificed. Insertion torque, removal torque, insertion energy, and removal energy were measured with a surgical engine on 8 rabbits. Remaining 4 rabbits were analyzed by microcomputed tomography (micro-CT and bone histomorphometry. Results. Total insertion energy was higher in self-drilling groups than self-tapping groups in both control and diabetic groups. Diabetic groups had more trabecular separation in bone marrow than the control groups in both SD and ST groups. Micro-CT analysis showed deterioration of bone quality in tibia especially in bone marrow of diabetic rabbits. However, there was no statistically significant correlation between self-drilling and self-tapping group for the remaining measurements in both control and diabetic groups. Conclusions. Type 1 diabetes mellitus and placement method of mini-implant did not affect primary stability of mini-implants.

  12. Effects of high fat-, cholesterol-enriched diet on the antioxidant defence mechanisms in the rabbit heart.

    Science.gov (United States)

    Lapenna, D; Del Boccio, G; Porreca, E; Pennelli, A; Mezzetti, A; De Gioia, S; Marzio, L; Di Ilio, C; Cuccurullo, F

    1992-01-01

    In 7 rabbits fed on hyperlipidic diet (0.5% cholesterol, 5% peanut oil and 5% lard) for 4 weeks, the ventricular myocardium was tested for antioxidant defences and thiobarbituric acid reactive substances. Seven age-matched rabbits served as controls. The hearts were previously subjected to 45 min Langendorff perfusion to study coronary flow, developed tension and resting tension; coronary effluent values of CPK activity, pH and UV absorbance at 250 nm (i.e., low molecular weight ATP catabolites) were also investigated. After 4 weeks of diet, a significant rise of plasma cholesterol (P effluent of hyperlipidemic rabbits. In conclusion, high fat-, cholesterol-enriched diet induces an imbalance in the rabbit heart antioxidant defences, some of which are increased, whereas others are depressed, eventually resulting in enhanced myocardial lipid peroxidation. These biochemical changes are associated with higher perfusate values of UV absorbance at 250 nm, but not with significant CPK leakage or myocardial hemodynamics derangement.

  13. Differential cardiac responses to unilateral sympathetic nerve stimulation in the isolated innervated rabbit heart.

    Science.gov (United States)

    Winter, James; Tanko, Abdul Samed; Brack, Kieran E; Coote, John H; Ng, G André

    2012-01-26

    The heart receives both a left and right sympathetic innervation. Currently there is no description of an in vitro whole heart preparation for comparing the influence of each sympathetic supply on cardiac function. The aim was to establish the viability of using an in vitro model to investigate the effects of left and right sympathetic chain stimulation (LSS/RSS). For this purpose the upper sympathetic chain on each side was isolated and bipolar stimulating electrodes were attached between T2-T3 and electrically insulated from surrounding tissue in a Langendorff innervated rabbit heart preparation (n=8). Heart rate (HR) was investigated during sinus rhythm, whilst dromotropic, inotropic and ventricular electrophysiological effects were measured during constant pacing (250 bpm). All responses exhibited linear increases with increases in stimulation frequency (2-10 Hz). The change in HR was larger during RSS than LSS (P<0.01), increasing by 78±9 bpm and 49±8 bpm respectively (10 Hz, baseline; 145±7 bpm). Left ventricular pressure was increased from a baseline of 50±4 mmHg, by 22±5 mmHg (LSS, 10 Hz) and 4±1 mmHg (RSS, 10 Hz) respectively (P<0.001). LSS, but not RSS, caused a shortening of basal and apical monophasic action potential duration (MAPD90). We demonstrate that RSS exerts a greater effect at the sinoatrial node and LSS at the left ventricle. The study confirms previous experiments on dogs and cats, provides quantitative data on the comparative influence of right and left sympathetic nerves and demonstrates the feasibility of isolating and stimulating the ipsilateral cardiac sympathetic supply in an in vitro innervated rabbit heart preparation.

  14. Effects of Electric Stimulations Applied during Absolute Refractory Period on Cardiac Function of Rabbits with Heart Failure

    Institute of Scientific and Technical Information of China (English)

    张海柱; 崔长琮; 胡大一

    2010-01-01

    The effects of electric currents applied during absolute refractory period(ARP) on the cardiac function of rabbits with heart failure due to myocardial infarction(MI),and the safety of this method were investigated.Thirty rabbits were randomly assigned equally to 3 groups:sham-operated group,LV-anterior wall cardiac contractility modulation(LV-CCM) group,and septum-CCM(S-CCM) group.A thoracotomy was performed on all the rabbits.Electric pulses were delivered during the ARP on the anterior wall of left ventr...

  15. Stretchable, multiplexed pH sensors with demonstrations on rabbit and human hearts undergoing ischemia.

    Science.gov (United States)

    Chung, Hyun-Joong; Sulkin, Matthew S; Kim, Jong-Seon; Goudeseune, Camille; Chao, Hsin-Yun; Song, Joseph W; Yang, Sang Yoon; Hsu, Yung-Yu; Ghaffari, Roozbeh; Efimov, Igor R; Rogers, John A

    2014-01-01

    Stable pH is an established biomarker of health, relevant to all tissues of the body, including the heart. Clinical monitoring of pH in a practical manner, with high spatiotemporal resolution, is particularly difficult in organs such as the heart due to its soft mechanics, curvilinear geometry, heterogeneous surfaces, and continuous, complex rhythmic motion. The results presented here illustrate that advanced strategies in materials assembly and electrochemical growth can yield interconnected arrays of miniaturized IrOx pH sensors encapsulated in thin, low-modulus elastomers to yield conformal monitoring systems capable of noninvasive measurements on the surface of the beating heart. A thirty channel custom data acquisition system enables spatiotemporal pH mapping with a single potentiostat. In vitro testing reveals super-Nernstian sensitivity with excellent uniformity (69.9 ± 2.2 mV/pH), linear response to temperature (-1.6 mV °C(-1) ), and minimal influence of extracellular ions (sensor arrays on balloon catheters and on skin-like stretchable membranes. Real-time measurement of pH on the surfaces of explanted rabbit hearts and a donated human heart during protocols of ischemia-reperfusion illustrate some of the capabilities. Envisioned applications range from devices for biological research, to surgical tools and long-term implants.

  16. Poor Diet Tied to Half of U.S. Deaths from Heart Disease, Diabetes

    Science.gov (United States)

    ... Diet Tied to Half of U.S. Deaths From Heart Disease, Diabetes Study explores which foods and nutrients may ... HealthDay News) -- Nearly half of all deaths from heart disease, stroke and diabetes in the United States are ...

  17. Pathophysiology and Imaging Techniques of Diabetic Heart Disease

    Directory of Open Access Journals (Sweden)

    Danielle L. Harrop

    2014-10-01

    Full Text Available Diabetic patients are at an increased risk of developing heart failure. The aetiology of diabetic heart disease is likely to be multifactorial, ranging from altered myocardial metabolism, increased interstitial fibrosis, endothelial dysfunction, microvascular disease, and coronary atherosclerosis. These factors act synergistically with resultant myocardial systolic and diastolic dysfunction. The aim of the present review is to illustrate the role of multimodality cardiac imaging such as echocardiography, nuclear imaging, computed tomography, and magnetic resonance imaging in providing insights into these pathological processes, and to quantify the extent of myocardial diastolic and systolic dysfunction.

  18. Ultrasound Current Source Density Imaging in live rabbit hearts using clinical intracardiac catheter

    Science.gov (United States)

    Li, Qian

    Ultrasound Current Source Density Imaging (UCSDI) is a noninvasive modality for mapping electrical activities in the body (brain and heart) in 4-dimensions (space + time). Conventional cardiac mapping technologies for guiding the radiofrequency ablation procedure for treatment of cardiac arrhythmias have certain limitations. UCSDI can potentially overcome these limitations and enhance the electrophysiology mapping of the heart. UCSDI exploits the acoustoelectric (AE) effect, an interaction between ultrasound pressure and electrical resistivity. When an ultrasound beam intersects a current path in a material, the local resistivity of the material is modulated by the ultrasonic pressure, and a change in voltage signal can be detected based on Ohm's Law. The degree of modulation is determined by the AE interaction constant K. K is a fundamental property of any type of material, and directly affects the amplitude of the AE signal detected in UCSDI. UCSDI requires detecting a small AE signal associated with electrocardiogram. So sensitivity becomes a major challenge for transferring UCSDI to the clinic. This dissertation will determine the limits of sensitivity and resolution for UCSDI, balancing the tradeoff between them by finding the optimal parameters for electrical cardiac mapping, and finally test the optimized system in a realistic setting. This work begins by describing a technique for measuring K, the AE interaction constant, in ionic solution and biological tissue, and reporting the value of K in excised rabbit cardiac tissue for the first time. K was found to be strongly dependent on concentration for the divalent salt CuSO4, but not for the monovalent salt NaCl, consistent with their different chemical properties. In the rabbit heart tissue, K was determined to be 0.041 +/- 0.012 %/MPa, similar to the measurement of K in physiologic saline: 0.034 +/- 0.003 %/MPa. Next, this dissertation investigates the sensitivity limit of UCSDI by quantifying the relation

  19. Itraconazole decreases left ventricular contractility in isolated rabbit heart: Mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Yusheng, E-mail: yqu@amgen.com [Toxicology Science, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 (United States); Fang, Mei; Gao, BaoXi; Amouzadeh, Hamid R. [Toxicology Science, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 (United States); Li, Nianyu; Narayanan, Padma [Discovery Toxicology, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 (United States); Acton, Paul; Lawrence, Jeff; Vargas, Hugo M. [Toxicology Science, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320 (United States)

    2013-04-15

    Itraconazole (ITZ) is an approved antifungal agent that carries a “black box warning” in its label regarding a risk of negative cardiac inotropy based on clinical findings. Since the mechanism of the negative inotropic effect is unknown, we performed a variety of preclinical and mechanistic studies to explore the pharmacological profile of ITZ and understand the negative inotropic mechanism. ITZ was evaluated in: (1) an isolated rabbit heart (IRH) preparation using Langendorff retrograde perfusion; (2) ion channel studies; (3) a rat heart mitochondrial function profiling screen; (4) a mitochondrial membrane potential (MMP) assay; (5) in vitro pharmacology profiling assays (148 receptors, ion channels, transporters, and enzymes); and (6) a kinase selectivity panel (451 kinases). In the IRH, ITZ decreased cardiac contractility (> 30%) at 0.3 μM, with increasing effect at higher concentrations, which indicated a direct negative inotropic effect upon the heart. It also decreased heart rate and coronary flow (≥ 1 μM) and prolonged PR/QRS intervals (3 μM). In mechanistic studies, ITZ inhibited the cardiac NaV channel (IC{sub 50}: 4.2 μM) and was devoid of any functional inhibitory effect at the remaining pharmacological targets. Lastly, ITZ did not affect MMP, nor interfere with mitochondrial enzymes or processes involved with fuel substrate utilization or energy formation. Overall, the cardiovascular and mechanistic data suggest that ITZ-induced negative inotropy is a direct effect on the heart, in addition, the potential involvement of mitochondria function and L-type Ca{sup 2+} channels are eliminated. The exact mechanism underlying the negative inotropy is uncertain, and requires further study. - Highlights: ► Effect of itraconazole (ITZ) was assessed in the isolated rabbit heart (IRH) assay. ► ITZ decreased ventricular contractility in IRH, indicating a direct effect. ► IC{sub 50} of ITZ on L-type I{sub Ca} was greater than 30 μM, on I{sub Na} was 4

  20. Different sensitivity of rabbit heart and skeletal muscle to endotoxin-induced impairment of mitochondrial function.

    Science.gov (United States)

    Trumbeckaite, S; Opalka, J R; Neuhof, C; Zierz, S; Gellerich, F N

    2001-03-01

    The involvement of mitochondrial dysfunction in septic disturbances of tissues is controversial. The aim of this study was to investigate the effects of endotoxin-induced sepsis on the function of heart and skeletal muscle mitochondria. Rabbits were made septic by subcutaneous injection of endotoxin (lipopolysaccharide, LPS) from Escherichia coli at concentrations of 100 or 150 microg LPS.kg(-1) 24 h prior to the experiments. Mitochondrial respiration was measured in saponin-skinned muscle fibers and compared with photometrically detected activities of respiratory chain enzymes as well as with function of perfused hearts. In heart fibers a dosage of 100 microg LPS.kg(-1) caused a significant decrease of state 3-respiration for the substrates pyruvate (-38%), octanoyl-carnitine (-38%) and succinate (-30%) with correspondingly decreased respiratory control indexes (RCI). In addition, endotoxin caused a decreased temporal stability of the rate of state 3-respiration. At least in part these changes can be attributed to a reduced activity of complex I + III (-50%) of the respiratory chain. State 4-respiration rates were not significantly altered. The lowered state 3-respiration in heart mitochondria seems to contribute to the impairment of heart muscle function as detected by an increase of coronary vascular resistance (CVR) in endotoxin-treated hearts. Functional properties of mitochondria from M. Vastus lasteralis were not affected by 100 microg LPS.kg(-1) but a higher dosage of 150 microg LPS.kg(-1) caused decreased RCI for the substrates pyruvate (-29%) and octanoyl-carnitine (-32%). Also the activity of complex I + III was not significantly affected at lower dose of endotoxin but decreased (-42%) after treatment with 150 microg LPS.kg(-1). Results demonstrate the involvement of impaired mitochondria in the pathophysiology of septic organ failure and a tissue specificity of endotoxaemia.

  1. Regional cooling facilitates termination of spiral-wave reentry through unpinning of rotors in rabbit hearts.

    Science.gov (United States)

    Yamazaki, Masatoshi; Honjo, Haruo; Ashihara, Takashi; Harada, Masahide; Sakuma, Ichiro; Nakazawa, Kazuo; Trayanova, Natalia; Horie, Minoru; Kalifa, Jérôme; Jalife, José; Kamiya, Kaichiro; Kodama, Itsuo

    2012-01-01

    Moderate global cooling of myocardial tissue was shown to destabilize 2-dimensional (2-D) reentry and facilitate its termination. This study sought to test the hypothesis that regional cooling destabilizes rotors and facilitates termination of spontaneous and DC shock-induced subepicardial reentry in isolated, endocardially ablated rabbit hearts. Fluorescent action potential signals were recorded from 2-D subepicardial ventricular myocardium of Langendorff-perfused rabbit hearts. Regional cooling (by 5.9°C ± 1.3°C) was applied to the left ventricular anterior wall using a transparent cooling device (10 mm in diameter). Regional cooling during constant stimulation (2.5 Hz) prolonged the action potential duration (by 36% ± 9%) and slightly reduced conduction velocity (by 4% ± 4%) in the cooled region. Ventricular tachycardias (VTs) induced during regional cooling terminated earlier than those without cooling (control): VTs lasting >30 seconds were reduced from 17 of 39 to 1 of 61. When regional cooling was applied during sustained VTs (>120 seconds), 16 of 33 (48%) sustained VTs self-terminated in 12.5 ± 5.1 seconds. VT termination was the result of rotor destabilization, which was characterized by unpinning, drift toward the periphery of the cooled region, and subsequent collision with boundaries. The DC shock intensity required for cardioversion of the sustained VTs decreased significantly by regional cooling (22.8 ± 4.1 V, n = 16, vs 40.5 ± 17.6 V, n = 21). The major mode of reentry termination by DC shocks was phase resetting in the absence of cooling, whereas it was unpinning in the presence of cooling. Regional cooling facilitates termination of 2-D reentry through unpinning of rotors. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  2. Neurohormonal profile of patients with heart failure and diabetes

    NARCIS (Netherlands)

    van der Horst, I. C. C.; de Boer, R. A.; Hillege, H. L.; Boomsma, F.; Voors, A. A.; van Veldhuisen, D. J.

    2010-01-01

    Background. Neurohormonal activation is generally recognised to play an important role in the pathophysiology, prognosis and treatment of chronic heart failure (HF). While the number of patients with diabetes increases, little if anything is known about neurohormonal activation in HF patients with d

  3. Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease

    DEFF Research Database (Denmark)

    Øyen, Nina; Diaz, Lars Jorge; Leirgul, Elisabeth

    2016-01-01

    BACKGROUND: Maternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort. METHODS AND RESULTS: In a national cohort study, we...

  4. Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease

    DEFF Research Database (Denmark)

    Øyen, Nina; Diaz, Lars Jorge; Leirgul, Elisabeth;

    2016-01-01

    BACKGROUND: Maternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort. METHODS AND RESULTS: In a national cohort study, we...

  5. Association of heart failure severity with risk of diabetes

    DEFF Research Database (Denmark)

    Demant, Malene N; Gislason, Gunnar H; Køber, Lars;

    2014-01-01

    AIMS/HYPOTHESIS: Heart failure has been suggested to increase the risk of developing diabetes. We investigated the relation between heart failure severity, defined by loop-diuretic dosage, and the risk of developing diabetes in a nationwide cohort of patients with heart failure. METHODS: We...... discharge (study baseline) with risk of diabetes was estimated by multivariate Cox regression models. RESULTS: In total, 99,362 patients were included and divided into five loop-diuretic dose groups: 30,838 (31%) used no loop diuretics; 24,389 (25%) used >0-40 mg/day; 17,355 (17%) used >40-80 mg/day; 11......,973 (12%) used >80-159 mg/day; and 14,807 (15%) used ≥160 mg/day. A total of 7,958 patients (8%) developed diabetes. Loop-diuretic dosages were associated with an increased risk of developing diabetes in a dose-dependent manner. Concomitant use of renin-angiotensin system inhibitors (RASis) attenuated...

  6. HEART FAILURE, DIABETES, BETA-BLOCKERS AND RISK OF HYPOGLYCEMIA

    Directory of Open Access Journals (Sweden)

    A. A. Aleksandrov

    2008-01-01

    Full Text Available Aim. To evaluate an influence of carvedilol on risk of hypoglycemia in patients with diabetes type 2 (D2 and chronic heart failure (CHF treated with angiotensin converting enzyme (ACE inhibitors.Material and methods. 13 patients (10 men, 3 women; aged 59,8±6,7 y.o. with D2 and CHF caused by ischemic heart disease were included in the study. Before inclusion all patients were treated with ACE inhibitors and various beta-blockers (atenolol, metoprolol, bisoprolol. These beta-blockers were changed for carvedilol. Heart ultrasonography, blood pressure control, glycemia monitoring, HbA1c level determination were performed before, during and after carvedilol therapy.Results. Carvedilol reduces frequency and duration of hypoglycaemia episodes. There were not episodes of severe hypoglycaemia during carvedilol therapy.Conclusion. Carvedilol reduces risk of hypoglycemia when it is used in combination with ACE inhiditors in diabetic patients with CHF.

  7. Role of diabetes in heart rhythm disorders

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    The incidence of diabetes mellitus (DM) is increasingrapidly. DM is the leading cause of cardiovascular diseases,which can lead to varied cardiovascular complications byaggravated atherosclerosis in large arteries and coronaryatherosclerosis, thereby grows the risk for macro andmicroangiopathy such as myocardial infarction, stroke,limb loss and retinopathy. Moreover diabetes is one of thestrongest and independent risk factor for cardiovascularmorbidity and mortality, which associated frequentlyrhythm disorders such as atrial fibrillation (AF) andventricular arrhythmias (VA). The present article providesa concise overview of the association between DM andrhythm disorders such as AF and VA with underlyingpathophysiological mechanisms.

  8. Allograftic bone marrow-derived mesenchymal stem cells transplanted into heart infarcted model of rabbit to renovate infarcted heart

    Institute of Scientific and Technical Information of China (English)

    王建安; 李长岭; 樊友启; 何红; 孙勇

    2004-01-01

    Objective: To investigate the directed transplantation of allograftic bone marrow-derived mesenchymal stem cells (MSCs) in myocardial infarcted (MI) model rabbits. Materials and Methods: Rabbits were divided into 3 groups, heart infarcted model with MSCs transplanted treatment (MSCs group, n=12), heart infarcted model with PBS injection (control group, n=20), sham operation with PBS injection (sham group, n=17). MSCs labelled by BrdUrd were injected into the MI area of the MSCs group. The same volume of PBS was injected into the MI area of the control group and sham group. The mortality, LVIDd, LVIDs and LVEF of the two groups were compared 4 weeks later. Tropomyosin inhibitory component (Tn Ⅰ) and BrdUrd immunohistochemistry identified the engrafted cells 4 weeks after transplantation. Result: The mortality of the MSCs group was 16.7% (2/12), and remarkably lower than the control group's mortality [35% (7/20) (P<0.05)]. Among the animals that survived for 4 weeks, the LVIDd and LVIDs of the MSCs group after operation were 1.17±0.21cm and 0.74±0.13cm, and remarkably lower than those of the model group, which were 1.64±0.14cm and 1.19±0.12cm (P<0.05); the LVEF of the MSCs group after operation was 63±6%, and remarkably higher than that of the model group, which was 53±6% (P<0.05). Among the 10 cases of animals that survived for 4 weeks in the MSCs group, in 8 cases (80%), the transplanted cells survived in the non MI, MI region and its periphery, and even farther away; part of them differentiated into cardiomyocytes; in 7 cases (70%), the transplanted cells participated in the formation of blood vessel tissue in the MI region. Conclusion: Transplanted allograftic MSCs can survive and differentiate into cardiomyocytes, form the blood vessels in the MI region. MSCs transplantation could improve the heart function after MI.

  9. Allograftic bone marrow-derived mesenchymal stem cells transplanted into heart infarcted model of rabbit to renovate infarcted heart

    Institute of Scientific and Technical Information of China (English)

    王建安; 李长岭; 樊友启; 何红; 孙勇

    2004-01-01

    Objective: To investigate the directed transplantation of allograftic bone marrow-derived mesenchymal stem cells (MSCs) in myocardial infarcted (MI) model rabbits. Materials and Methods: Rabbits were divided into 3 groups, heart infarcted model with MSCs transplanted treatment (MSCs group, n=12), heart infarcted model with PBS injection (control group, n=20), sham operation with PBS injection (sham group, n=l 7). MSCs labelled by BrdUrd were injected into the MI area of the MSCs group. The same volume of PBS was injected into the MI area of the control group and sham group. The mortality, LVIDd, LVIDs and LVEF Of the two groups were compared 4 weeks later. Tropomyosin inhibitory component (Tn I) and BrdUrd immunohistochemistry identified the engrafted cells 4 weeks after transplantation. Result: The mortality of the MSCs group was 16.7% (2/12), and remarkably lower than the control group's mortality [35% (7/20) (P<0.05)].Among the animals that survived for 4 weeks, the LVIDd and LVIDs of the MSCs group after operation were 1.17±0.21 cm and 0.74±0.13 cm, and remarkably lower than those of the model group, which were 1.64±0.14 cm and 1.19±0.12 cm (P<0.05); the LVEF of the MSCs group after operation was 63±6%, and remarkably higher than that of the model group,which was 53±6% (P<0.05). Among the 10 cases of animals that survived for 4 weeks in the MSCs group, in 8 cases (80%),the transplanted cells survived in the non MI, MI region and its periphery, and even farther away; part of them differentiated into cardiomyocytes; in 7 cases (70%), the transplanted cells participated in the formation of blood vessel tissue in the MI region. Conclusion: Transplanted allograftic MSCs can survive and differentiate into cardiomyocytes, form the blood vessels in the MI region. MSCs transplantation could improve the heart function after MI.

  10. Heart rate variability in children with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Camila Balsamo Gardim

    2014-06-01

    Full Text Available OBJECTIVE:To gather current information about the effects of type 1 diabetes mellitus on children's cardiac autonomic behavior.DATA SOURCES: The search of articles was conducted on PubMed, Ibecs, Medline, Cochrane, Lilacs, SciELO and PEDro databases using the MeSH terms: "autonomic nervous system", "diabetes mellitus", "child", "type 1 diabetes mellitus", "sympathetic nervous system" and "parasympathetic nervous system", and their respective versions in Portuguese (DeCS. Articles published from January 2003 to February 2013 that enrolled children with 9-12 years old with type 1 diabetes mellitus were included in the review.DATA SYNTHESIS: The electronic search resulted in four articles that approached the heart rate variability in children with type 1 diabetes mellitus, showing that, in general, these children present decreased global heart rate variability and vagal activity. The practice of physical activity promoted benefits for these individuals.CONCLUSIONS: Children with type 1 diabetes mellitus present changes on autonomic modulation, indicating the need for early attention to avoid future complications in this group.

  11. High-energy phosphates and function in isolate, working rabbit hearts

    Energy Technology Data Exchange (ETDEWEB)

    Lewandowski, E.D.; Devous, M.D. Sr.; Nunnally, R.L. (Univ. of Texas Health Science Center, Dallas (USA))

    1987-11-01

    An isolated, working, rabbit heart has been developed for use with nuclear magnetic resonance (NMR) spectroscopy. This model is functionally stable over a 4-h period and displays classic hemodynamic responses to work-load changes. Control {sup 31}P spectra of this preparation were obtained with simultaneous recordings of left ventricular pressure (LVP), LVP differentiated with respect to time (dP/dt), heart rate (HR), and cardiac output (CO). ATP, phosphocreatine (PCr), and hemodynamics remained stable over a 90-min perfusion. Hearts were also subjected to 13.5 min of global ischemia (IS) at 37{degree}C followed by 60 min of reperfusion (RE) or 45 min of chronic IS. Contraction ceased within 60 s of IS. PCr loss was rapid, reaching undetectable limits by 11 min. ATP loss was gradual and bore no relationship to functional loss. ATP fell to 60 {+-} 4% of pre-IS levels after 13.5 min of IS. With RE, PCr returned to control levels, whereas ATP values remained depressed for the entire 60 min. Functional activity resumed with RE, but dP/dt did not rise above 85 {+-} 7% of preischemica values. No correlation between residual ATP at the end of IS and functional recovery during RE was evident.

  12. ANTI-DIABETIC EFFECT OF MORUS ALBA ON RABBIT AS ANIMAL MODEL

    Directory of Open Access Journals (Sweden)

    Laddha G. P.

    2012-04-01

    Full Text Available A study of ancient literature indicates that diabetes was fairly well known and well conceived as an entity in India. The nature has provided abundant plant wealth for all the living creatures, which possess medicinal virtues. Therefore, there is a necessity to explore their uses and to conduct Pharmacognostic and pharmacological studies to ascertain their therapeutic properties. In fact, nowadays diabetes is a global problem. Hence, the present study aims to open new avenues for the improvement of medicinal uses of Morus alba. for the area for diabetes. Another important objective of such study is to bring the anti-diabetic medicinal plants sector on a firm scientific footing, raise awareness and add value to the resource. Dried petroleum ether (60-80°C extracts of leaves of Morus alba. were subjected for hypoglycemic activity in New Zealand rabbits (1.5-3.5 kg. Blood sugar level was determined using digital glucometer. The oral administration of leaf extracts at doses of 200 mg/ kg− lead to a significant blood glucose reduction. This laid the foundation to study the active compounds of such anti-diabetic plants that are responsible for the hypoglycemic activities. It also proves the traditional claim of Kachh region with regard to Morus Alba for its anti-diabetic activity.

  13. Terminating Ventricular Fibrillation Using Pulsed Far-Field Stimulation in Whole Rabbit Hearts

    Science.gov (United States)

    Squires, Amgad; Hornung, Daniel; Bittihn, Philip; Xia Wu, Dong; Krinsky, Valentin; Zabel, Markus; Bodenschatz, Eberhard; Luther, Stefan

    2010-03-01

    During life-threatening cardiac fibrillation, chaotic spatio-temporal dynamics is mediated by vortex-like rotating waves. Current defibrillation strategies rely on global control through high-energy shocks, which may have severe side-effects including traumatic pain and tissue damage. Far-field antifibrillation pacing terminates fibrillation using a train of low-energy electric pulses [1,2]. Using optical mapping in isolated rabbit heart preparations, we evaluate the efficiency and robustness of this approach. We found that a series of pulses at low energies (ventricular fibrillation with a success rate of 95%. We will discuss the physical mechanisms involved.[4pt] [1] F.H. Fenton et al, Circulation 120 467-476 (2009).[0pt] [2] A. Pumir et al., Phys. Rev. Lett. 99, 208101 (2007).

  14. In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits.

    Science.gov (United States)

    Bakirel, Tülay; Bakirel, Utku; Keleş, Oya Ustüner; Ulgen, Sinem Güneş; Yardibi, Hasret

    2008-02-28

    Rosemary (Rosmarinus officinalis), used in traditional Turkish folk medicine for the treatment of hyperglycaemia, is widely accepted as one of the medicinal herb with the highest antioxidant activity. Accordingly, the present study was designed to investigate the possible actions of ethanolic extract of the leaves of Rosmarinus officinalis on glucose homeostasis and antioxidant defense in rabbits. In the first set of experiments, hypoglycaemic effects of oral administration of various doses (50, 100 and 200 mg/kg) of the extract were examined in normoglycaemic and glucose-hyperglycaemic rabbits. Optimal effect was observed in both of the animal groups with a dose of 200 mg/kg of the extract and this activity was independent from the effects of insulin. In another part of experiments, acute effect of various doses of the Rosmarinus officinalis extract on blood glucose and serum insulin levels was studied in alloxan-induced diabetic rabbits. Of the three doses of extract, the highest dose (200 mg/kg) significantly lowered blood glucose level and increased serum insulin concentration in alloxan-diabetic rabbits. The last set of experiments designed to investigate the subacute effect of the Rosmarinus officinalis extract on repeated administration in alloxan-diabetic rabbits. At the doses of 100 and 200 mg/kg, antihyperglycaemic effect of extract was accompanied by a significant increase in serum insulin levels in diabetic rabbits. Furthermore, during 1 week of treatment of diabetic rabbits with a dose of 200 mg/kg of the extract showed that the extract possessed a capability to inhibit the lipid peroxidation and activate the antioxidant enzymes. It was concluded that probably, due to its potent antioxidant properties, the Rosmarinus officinalis extract exerts remarkable antidiabetogenic effect.

  15. [Effects of xinshuaikang granule on cardiac function and atrial natriuretic polypeptide levels in rabbits with experimental congestive heart failure].

    Science.gov (United States)

    Jin, X C; Sun, J Z; Wang, X

    1996-07-01

    Xinshuaikang (XSK) granule mainly consisted of Radix Ginseng, Aconifum carmichaeli, Ligustici wallichii, Semen Lepidii seu Descurainiae, etc. Thirty-five white rabbits of Japanese strain with big ears were used and five groups were divided randomly. The models of chronic heart failure (CHF) was made by injection of adriamycin through the marginal vein of rabbit's ear. Only one group without adriamycin injection was taken as blank group. After the making of models, Xinbao (XB) was used to treat one group which was regarded as control group, XSK was used to treat two model groups, one used higher dose, the other one used lower dose. Fifteen days was taken as a course of treatment. The results were: the body weight of all model groups was heavier than that without adriamycin. After a course of treatment, the body weight of the groups treated by XSK or XB decreased rapidly, the general conditions of the three groups were improved; the two drugs could reduce heart rate and enhance heart function, at the same time they reduced the level of atrial natriuretic polypeptide (ANP) in plasma. The best results was obtained in XSK group with higher dose, the effect of XSK group with lower dose was equivalent to that of XB group. Hence, XSK granule could enhance the CHF rabbits' heart function, improve their heart endocrine activity, this drug had a reliable effect on CHF.

  16. Influence of Drugs Carried in Lipid Nanoparticles in Coronary Disease of Rabbit Transplanted Heart.

    Science.gov (United States)

    Barbieri, Lucas R; Lourenço-Filho, Domingos D; Tavares, Elaine R; Carvalho, Priscila O; Gutierrez, Paulo S; Maranhão, Raul C; Stolf, Noedir A G

    2017-08-01

    Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and currently has no effective prevention and treatment. Lipid nanoparticles, termed LDE can carry chemotherapeutic agents in the circulation and concentrates them in the heart. Twenty-eight rabbits fed a cholesterol-rich diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg/kg daily) and allocated to four groups of 7 animals treated with intravenous LDE-methotrexate (MTX; 4 mg/kg weekly), with LDE-paclitaxel (PACLI; 4 mg/kg weekly), or with LDE-PACLI (4 mg/kg weekly) and LDE-MTX (4 mg/kg weekly). A control group was treated with only weekly intravenous saline solution. Animals were euthanized 6 weeks later for morphometric, histologic, immunohistochemical, and gene expression analysis of the graft and native hearts. Compared with controls, grafts of rabbits treated with LDE-PACLI showed 50% reduction of coronary stenosis, and in the LDE-MTX and LDE-MTX/PACLI stenosis was approximately 18% less than in control, but this difference was not statistically significant. In the three treatment groups, macrophage infiltration was decreased. In the LDE-MTX group, gene expression of proinflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein 1, interleukin 18, vascular cellular adhesion molecule 1, and matrix metalloproteinase 12 was strongly diminished, whereas expression of antiinflammatory interleukin 10 increased. In the LDE-PACLI and LDE-PACLI/MTX groups, proinflammatory and antiinflammatory gene expressions were not consistently changed by the treatments. LDE-PACLI promoted strong improvement of cardiac allograft vasculopathy, but the decrease in coronary stenosis by LDE-MTX and LDE-MTX/PACLI was not significant. All three treatments decreased macrophage infiltration in the graft. These results may encourage future clinical trials to test this new therapeutic approach

  17. Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits

    Directory of Open Access Journals (Sweden)

    Živadinović Milka

    2016-01-01

    Full Text Available Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm, which were grafted with autogenous bone and β-tricalcium phosphate (n = 4 or served as unfilled controls (n = 4. After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53% compared with β-tricalcium phosphate (30%, (p < 0.030 and control (7%, (p < 0.000 groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008. Conclusion. In the present

  18. Wave front fragmentation due to ventricular geometry in a model of the rabbit heart

    Science.gov (United States)

    Rogers, Jack M.

    2002-09-01

    The role of the heart's complex shape in causing the fragmentation of activation wave fronts characteristic of ventricular fibrillation (VF) has not been well studied. We used a finite element model of cardiac propagation capable of simulating functional reentry on curved two-dimensional surfaces to test the hypothesis that uneven surface curvature can cause local propagation block leading to proliferation of reentrant wave fronts. We found that when reentry was induced on a flat sheet, it rotated in a repeatable meander pattern without breaking up. However, when a model of the rabbit ventricles was formed from the same medium, reentrant wave fronts followed complex, nonrepeating trajectories. Local propagation block often occurred when wave fronts propagated across regions where the Gaussian curvature of the surface changed rapidly. This type of block did not occur every time wave fronts crossed such a region; rather, it only occurred when the wave front was very close behind the previous wave in the cycle and was therefore propagating into relatively inexcitable tissue. Close wave front spacing resulted from nonstationary reentrant propagation. Thus, uneven surface curvature and nonstationary reentrant propagation worked in concert to produce wave front fragmentation and complex activation patterns. None of the factors previously thought to be necessary for local propagation block (e.g., heterogeneous refractory period, steep action potential duration restitution) were present. We conclude that the complex geometry of the heart may be an important determinant of VF activation patterns.

  19. Safety of diabetes drugs in patients with heart failure.

    Science.gov (United States)

    Carrasco-Sánchez, F J; Ostos-Ruiz, A I; Soto-Martín, M

    2017-08-28

    Heart failure (HF) and diabetes mellitus are 2 clinical conditions that often coexist, particularly in patients older than 65 years. Diabetes mellitus promotes the development of HF and confers a poorer prognosis. Hypoglycaemic agents (either by their mechanism of action, hypoglycaemic action or adverse effects) can be potentially dangerous for patients with HF. In this study, we performed a review of the available evidence on the safety of diabetes drugs in HF, focused on the main observational and experimental studies. Recent studies on cardiovascular safety have evaluated, although as a secondary objective, the impact of new hypoglycaemic agents on HF, helping us understand the neutrality, risks and potential benefits of these agents. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  20. Relationship of literacy and heart failure in adults with diabetes

    Directory of Open Access Journals (Sweden)

    Morris Nancy

    2007-07-01

    Full Text Available Abstract Background Although reading ability may impact educational strategies and management of heart failure (HF, the prevalence of limited literacy in patients with HF is unknown. Methods Subjects were drawn from the Vermont Diabetes Information System Field Survey, a cross-sectional study of adults with diabetes in primary care. Participants' self-reported characteristics were subjected to logistic regression to estimate the association of heart failure and literacy while controlling for social and economic factors. The Short Test of Functional Health Literacy was used to measure literacy. Results Of 172 subjects with HF and diabetes, 27% had limited literacy compared to 15% of 826 subjects without HF (OR 2.05; 95% CI 1.39, 3.02; P P = .05. After adjusting for education, however, HF was no longer independently associated with literacy (OR 1.31; 95% CI 0.82 – 2.08; P = 0.26. Conclusion Over one quarter of diabetic adults with HF have limited literacy. Although this association is no longer statistically significant when adjusted for education, clinicians should be aware that many of their patients have important limitations in dealing with written materials.

  1. Boosting autophagy in the diabetic heart: a translational perspective.

    Science.gov (United States)

    Sciarretta, Sebastiano; Boppana, V Subbarao; Umapathi, Mahaa; Frati, Giacomo; Sadoshima, Junichi

    2015-10-01

    Diabetes, obesity, and dyslipidemia are main risk factors that promote the development of cardiovascular diseases. These metabolic abnormalities are frequently found to be associated together in a highly morbid clinical condition called metabolic syndrome. Metabolic derangements promote endothelial dysfunction, atherosclerotic plaque formation and rupture, cardiac remodeling and dysfunction. This evidence strongly encourages the elucidation of the mechanisms through which obesity, diabetes, and metabolic syndrome induce cellular abnormalities and dysfunction in order to discover new therapeutic targets and strategies for their prevention and treatment. Numerous studies employing both dietary and genetic animal models of obesity and diabetes have demonstrated that autophagy, an intracellular system for protein degradation, is impaired in the heart under these conditions. This suggests that autophagy reactivation may represent a future potential therapeutic intervention to reduce cardiac maladaptive alterations in patients with metabolic derangements. In fact, autophagy is a critical mechanism to preserve cellular homeostasis and survival. In addition, the physiological activation of autophagy protects the heart during stress, such as acute ischemia, starvation, chronic myocardial infarction, pressure overload, and proteotoxic stress. All these aspects will be discussed in our review article together with the potential ways to reactivate autophagy in the context of obesity, metabolic syndrome, and diabetes.

  2. Trimetazidine therapy for diabetic mouse hearts subjected to ex vivo acute heart failure.

    Science.gov (United States)

    Breedt, Emilene; Lacerda, Lydia; Essop, M Faadiel

    2017-01-01

    Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart diseases in Africa. As increased fatty acid β-oxidation (FAO) during heart failure triggers detrimental effects on the myocardium, we hypothesized that trimetazidine (TMZ) (partial FAO inhibitor) offers cardioprotection under normal and obese-related diabetic conditions. Hearts were isolated from 12-14-week-old obese male and female diabetic (db/db) mice versus lean non-diabetic littermates (db/+) controls. The Langendorff retrograde isolated heart perfusion system was employed to establish an ex vivo AHF model: a) Stabilization phase-Krebs Henseleit buffer (10 mM glucose) at 100 mmHg (25 min); b) Critical Acute Heart Failure (CAHF) phase-(1.2 mM palmitic acid, 2.5 mM glucose) at 20 mmHg (25 min); and c) Recovery Acute Heart Failure phase (RAHF)-(1.2 mM palmitic acid, 10 mM glucose) at 100 mmHg (25 min). Treated groups received 5 μM TMZ in the perfusate during either the CAHF or RAHF stage for the full duration of each respective phase. Both lean and obese males benefited from TMZ treatment administered during the RAHF phase. Sex differences were observed only in lean groups where the phases of the estrous cycle influenced therapy; only the lean follicular female group responded to TMZ treatment during the CAHF phase. Lean luteal females rather displayed an inherent cardioprotection (without treatments) that was lost with obesity. However, TMZ treatment initiated during RAHF was beneficial for obese luteal females. TMZ treatment triggered significant recovery for male and obese female hearts when administered during RAHF. There were no differences between lean and obese male hearts, while lean females displayed a functional recovery advantage over lean males. Thus TMZ emerges as a worthy therapeutic target to consider for AHF treatment in normal and obese-diabetic individuals (for both sexes), but only when administered during the recovery phase and not during the very acute

  3. Antihyperlipidemic and renoprotective activities of methanolic extract of Canscora decussata extract in alloxan-induced diabetic rabbits

    Directory of Open Access Journals (Sweden)

    Nadeem Irshad

    2013-08-01

    Full Text Available The current study was designed to evaluate the hypolipidemic and renopro-tective effects of methanolic extract of powdered Canscora decussata whole plant in the diabetic rabbits. Thirty rabbits were divided into five groups having 6 animals each including normal and diabetic controls groups, the remaining groups received methanolic extract in 400 and 600 mg/kg doses and another group got pioglitazone (3 mg/kg for 30 days. Serum levels of triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, albumin, globulin and total proteins were estimated by using commercially available kits. The results showed that extract significantly (p<0.01 decreased the raised parameters including triglyceride, total cholesterol and LDL-cholesterol, atherogenic index, Coronary risk index up to normal values compared to diabetic rabbits. However, it significantly increased HDL-cholesterol, albumin, globulin and total protein levels. Therefore, it is suggested that methanolic extract of C. decussata exerts hypolipidemic and renoprotective effects in the alloxan-induced diabetic rabbits.

  4. [Effect of acute stress on the fatty acid composition of lipids of adrenal and heart mitochondria in rabbits].

    Science.gov (United States)

    Mandrik, K A; Doroshkevich, N A; Buko, V U; Vinogradov, V V

    1985-01-01

    A comparative study of changes in the fatty acid composition of rabbit heart and adrenal mitochondria was carried out after acute (1h) immobilization stress. In heart mitochondria the stress induced a decrease in the content of capric, lauric, myristic and pentadecanic acids. A statistically significant reduction of the amount of heptadecanoic, linoleic, arachidonic acids and an increase in the level of palmitic acid was noted in adrenal mitochondria. The acute stress resulted in differently directed shifts in the saturation of fatty acids. An elevation of the sum of unsaturated fatty acids was observed in the heart, and a decrease was detected in the adrenal glands. The above shifts in the fatty acid composition of adrenal and heart mitochondria provide evidence for different directions of lipid metabolism in these organs following stress.

  5. Diabetes, Glycemic Control, and New-Onset Heart Failure in Patients With Stable Coronary Artery Disease Data from the Heart and Soul Study

    NARCIS (Netherlands)

    van Melle, Joost P.; Bot, Marisica; De Jonge, Peter; De Boer, Rudolf A.; van Veldhuisen, Dirk J.; Whooley, Mary A.

    2010-01-01

    OBJECTIVE- Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS- We evaluated the association of diabetes and

  6. Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease : data from the heart and soul study

    NARCIS (Netherlands)

    van Melle, J.P.; Bot, M.; de Jonge, P.; de Boer, R.A.; van Veldhuisen, D.J.; Whooley, M.A.

    2010-01-01

    OBJECTIVE Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS We evaluated the association of diabetes and A

  7. Diabetes, glycemic control, and new-onset heart failure in patients with stable coronary artery disease : data from the heart and soul study

    NARCIS (Netherlands)

    van Melle, J.P.; Bot, M.; de Jonge, P.; de Boer, R.A.; van Veldhuisen, D.J.; Whooley, M.A.

    2010-01-01

    OBJECTIVE Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS We evaluated the association of diabetes and

  8. Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure

    DEFF Research Database (Denmark)

    Gustafsson, Ida; Brendorp, Bente; Seibaek, Marie;

    2004-01-01

    OBJECTIVES: The purpose of this study was to investigate the influence of diabetes on long-term mortality in a large cohort of patients hospitalized with heart failure (HF). BACKGROUND: Diabetes is common in HF patients, but information on the prognostic effect of diabetes is sparse. METHODS: The...

  9. Evolution of Action Potential Alternans in Rabbit Heart during Acute Regional Ischemia

    Directory of Open Access Journals (Sweden)

    Irma Martišienė

    2015-01-01

    Full Text Available This study investigates the development of the spatiotemporal pattern of action potential alternans during acute regional ischemia. Experiments were carried out in isolated Langendorff-perfused rabbit heart using a combination of optical mapping and microelectrode recordings. The alternans pattern significantly changed over time and had a biphasic character reaching maximum at 6–9 min after occlusion. Phase I (3–11 minutes of ischemia is characterized by rapid increase in the alternans magnitude and expansion of the alternans territory. Phase I is followed by gradual decline of alternans (Phase II in both magnitude and territory. During both phases we observed significant beat-to-beat variations of the optical action potential amplitude (OAPA alternans. Simultaneous microelectrode recordings from subepicardial and subendocardial layers showed that OAPA alternans coincided with intramural 2 : 1 conduction blocks. Our findings are consistent with the modeling studies predicting that during acute regional ischemia alternans can be driven by 2 : 1 conduction blocks in the ischemic region.

  10. Phosphatidylinositol 4,5-bisphosphate formation in rabbit skeletal and heart muscle membranes.

    Science.gov (United States)

    Varsányi, M; Messer, M; Brandt, N R; Heilmeyer, L M

    1986-08-14

    Incubation of rabbit skeletal muscle microsomes or isolated triads with gamma 32P-ATP/Mg2+ in the absence and in the presence of added phosphatidylinositol resulted in the formation of phosphatidylinositol 4-phosphate catalyzed by phosphatidylinositol kinase. When phosphatidylinositol 4-phosphate was added as exogenous substrate, phosphatidylinositol 4,5-bisphosphate was also formed demonstrating the presence of a membrane bound phosphatidylinositol 4-phosphate kinase. Triads were broken mechanically in a French press and separated on a continuous sucrose gradient. Incubation of these fractions with gamma 32P-ATP/Mg2+ resulted in a rapid labeling of phospholipid in a membrane fraction banding between transverse tubules and the terminal cisternae. Partial triad breakage and triad reformation experiments indicated that this phosphatidylinositol kinase was associated with T-tubules. When exogenous phosphatidylinositol 4-phosphate was employed as substrate phosphatidylinositol 4,5-bisphosphate and phosphatidic acid were formed, indicating the presence of all the enzymes of the polyphosphoinositide signaling system in this special membrane fraction. In contrast, heart muscle microsomes or plasma membranes can catalyze this reaction sequence from endogenous formed phosphatidylinositol 4-phosphate.

  11. Heart Failure Considerations of Antihyperglycemic Medications for Type 2 Diabetes.

    Science.gov (United States)

    Standl, Eberhard; Schnell, Oliver; McGuire, Darren K

    2016-05-27

    Prevalent and incident heart failure (HF) is increased in people with type 2 diabetes mellitus, with risk directly associated with the severity of hyperglycemia. Furthermore, in patients with type 2 diabetes mellitus, mortality is increased ≈10-fold in patients with versus without HF. Reducing HF with antihyperglycemic therapies, however, has been unsuccessful until recently. In fact, HF as an important outcome in patients with type 2 diabetes mellitus seems to be heterogeneously modulated by antihyperglycemic medications, as evidenced by results from cardiovascular outcome trials (CVOTs) and large observational cohort studies. Appropriately powered and executed CVOTs are necessary to truly evaluate cardiovascular safety and efficacy of new antihyperglycemic medications, as reflected by the guidance of the US Food and Drug Administration and other regulatory agencies since 2008. In light of the best available evidence at present, metformin and the sodium-glucose-co-transporter 2-inhibitor empagliflozin seem to be especially advantageous with regard to HF effects, with their use associated with reduced HF events and improved mortality. Acarbose, the dipeptidyl-peptidase 4-inhibitor sitagliptin, the glucagon-like peptide 1-receptor agonist lixisenatide based on presently available CVOT results comprise reasonable additional options, as significant harm in terms of HF has been excluded for those drugs. Additions to this list are anticipated pending results of ongoing CVOTs. Although no HF harm was seen in CVOTs for insulin or sulfonylureas, they should be used only with caution in patients with HF, given their established high risk for hypoglycemia and some uncertainties on their safety in patients with HF derived from epidemiological observations. Pioglitazone is contraindicated in patients with HF>New York Heart Association I, despite some benefits suggested by CVOT subanalyses. © 2016 American Heart Association, Inc.

  12. Protection of the ischemic diabetic heart by L-propionylcarnitine therapy.

    Science.gov (United States)

    Paulson, D J; Shug, A L; Zhao, J

    1992-10-21

    Diabetics suffer from an increased incidence of myocardial infarction and are less likely to survive an ischemic insult. Since L-propionylcarnitine (LPC) has been shown to protect against ischemic/reperfusion injury, we hypothesized that LPC may be of even greater benefit to the diabetic heart. Diabetes was induced by i.v. streptozotocin, 60 mg/kg; duration: 12 wks. The chronic effect of LPC was determined by daily i.p. injections (100 mg/kg) for 8 wks. The acute effects of LPC were determined by adding it to the perfusion medium (5 mM) of control and diabetic hearts. Initial cardiac contractile performance of isolated perfused working hearts was assessed by varying left atrial filling pressure. Hearts were then subjected to 90 min of low flow global ischemia followed by 30 min reperfusion. Chronic LPC treatment had no effect on initial cardiac performance in either control or diabetic hearts. Acute addition of LPC to the perfusion medium enhanced pump performance of control hearts, but had no effect in diabetic hearts. Both acute and chronic LPC significantly improved the ability of control and diabetic hearts to recover cardiac contractile performance after ischemia and reperfusion, however, chronic treatment was more effective in diabetic hearts.

  13. Heart failure therapy in diabetic patients-comparison with the recent ESC/EASD guideline

    Directory of Open Access Journals (Sweden)

    Angermann Christiane E

    2011-02-01

    Full Text Available Abstract Background To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function. Methods 3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years; out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50% and 994 patients in the whole cohort suffered from diabetes. Results The majority (>90% of heart failure patients with reduced ejection fraction (SHF and diabetes were treated with an ACE inhibitor (ACEi or angiotensin receptor blocker (ARB or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF were less likely to receive these substance classes (p Conclusions Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.

  14. Effects of acute exposure to WIFI signals (2.45GHz) on heart variability and blood pressure in Albinos rabbit.

    Science.gov (United States)

    Saili, Linda; Hanini, Amel; Smirani, Chiraz; Azzouz, Ines; Azzouz, Amina; Sakly, Mohsen; Abdelmelek, Hafedh; Bouslama, Zihad

    2015-09-01

    Electrocardiogram and arterial pressure measurements were studied under acute exposures to WIFI (2.45GHz) during one hour in adult male rabbits. Antennas of WIFI were placed at 25cm at the right side near the heart. Acute exposure of rabbits to WIFI increased heart frequency (+22%) and arterial blood pressure (+14%). Moreover, analysis of ECG revealed that WIFI induced a combined increase of PR and QT intervals. By contrast, the same exposure failed to alter maximum amplitude and P waves. After intravenously injection of dopamine (0.50ml/kg) and epinephrine (0.50ml/kg) under acute exposure to RF we found that, WIFI alter catecholamines (dopamine, epinephrine) action on heart variability and blood pressure compared to control. These results suggest for the first time, as far as we know, that exposure to WIFI affect heart rhythm, blood pressure, and catecholamines efficacy on cardiovascular system; indicating that radiofrequency can act directly and/or indirectly on cardiovascular system.

  15. Effect of Lidocaine and Amiodarone on Transmural Heterogeneityricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

    Institute of Scientific and Technical Information of China (English)

    YOU Binquan; PU Jun; LIU Nian; YU Ronghui; RUAN Yanfei; LI Yang; WANG Lin

    2005-01-01

    To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of recorded across the left ventricular free wall in rabbit hearts perfused transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5 %), but no case in lidocaine group (P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia (P< 0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.

  16. Lipid peroxide levels of serum lipoprotein fractions of diabetic patients with angiopathy and /sup 60/Co-irradiated rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Tsunekawa, Hiroshi (Nagoya Univ. (Japan). Faculty of Medicine)

    1982-09-01

    For a better understanding of the relationship between lipid peroxide (LPO) and vascular diseases, the author determined LPO levels and lipid contents of serum lipoprotein fractions of diabetics with angiopathy. The LPO level in high density lipoprotein (HDL) fraction of diabetic serum was significantly higher than that of normal serum whereas no significant increase was observed in the levels of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions of diabetic serum. As to the ratios of LPO to total lipids in these lipoprotein fractions, it was found that the ratio in HDL fraction of the diabetics was markedly higher than that of the normals. These results suggest that the increase in LPO levels in the sera of diabetic patients is due to that in HDL fraction. To study further this problem, the author employed /sup 60/Co-irradiated rabbit as a model, since it was already reported that radiation affects lipid metabolism and LPO formation, and that it induces the development of atherosclerosis. Upon irradiation with /sup 60/Co ranging from 100R to 700R, serum LPO level of rabbit was significantly increased. Although elevation of LPO level was found in each serum lipoprotein fraction of VLDL, LDL and HDL, LPO level per lipid content was significantly increased only in HDL fraction. In the irradiated rabbit, significant elevation of the level of LPO was also observed in the liver, while no significant increase was found in the kidney and spleen. These results indicate that high level of LPO observed in the serum of irradiated rabbit would be the reflection of the increased LPO in the liver.

  17. Heart failure in sub-Saharan Africa: A literature review with emphasis on individuals with diabetes

    Directory of Open Access Journals (Sweden)

    Andre Pascal Kengne

    2008-02-01

    Full Text Available Andre Pascal Kengne1, Anastase Dzudie2, Eugene Sobngwi31The George Institute for International Health, University of Sydney, Australia; 2Heart failure and transplantation Unit, Louis Pradel’s Cardiovascular Hospital, Lyon, France; 3National Obesity Centre, Yaounde Central Hospital, CameroonPurpose: Heart failure is the ultimate complication of cardiac involvements in diabetes. The purpose of this review was to summarize current literature on heart failure among people with diabetes mellitus in sub-Saharan Africa (SSA.Method: Bibliographic search of published data on heart failure and diabetes in sub-Saharan Africa over the past 26 years.Results: Heart failure remains largely unexplored in general population and among people with diabetes in Africa. Heart failure accounts for over 30% of hospital admission in specialized cardiovascular units and 3%–7% in general internal medicine. Over 11% of adults with heart failure have diabetes. Risk factors for heart failure among those with diabetes include classical cardiovascular risk factors, without evidence of diabetes distinctiveness for other predictors common in Africa. Prevention, management, and outcomes of heart failure are less well known; recent data suggest improvement in the management of risk factors in clinical settings.Conclusions: Diabetes mellitus is growing in SSA. Related cardiovascular diseases are emerging as potential health problem. Heart failure as cardiovascular complication remains largely unexplored. Efforts are needed through research to improve our knowledge of heart failure at large in Africa. Multilevel preventive measures, building on evidences from other parts of the world must go along side.Keywords: diabetes mellitus, cardiovascular diseases, heart failure, sub-Saharan Africa

  18. Validation of pulse rate variability as a surrogate for heart rate variability in chronically instrumented rabbits.

    Science.gov (United States)

    Pellegrino, Peter R; Schiller, Alicia M; Zucker, Irving H

    2014-07-01

    Heart rate variability (HRV) is a function of cardiac autonomic tone that is widely used in both clinical and animal studies. In preclinical studies, HRV measures are frequently derived using the arterial pulse waveform from an implanted pressure telemetry device, termed pulse rate variability (PRV), instead of the electrocardiogram signal in accordance with clinical guidelines. The acceptability of PRV as a surrogate for HRV in instrumented animals is unknown. Using rabbits implanted with intracardiac leads and chronically implanted pressure transducers, we investigated the correlation and agreement of time-domain, frequency-domain, and nonlinear indexes of HRV and PRV at baseline. We also investigated the effects of ventricular pacing and autonomic blockade on both measures. At baseline, HRV and PRV time- and frequency-domain parameters showed robust correlations and moderate to high agreement, whereas nonlinear parameters showed slightly weaker correlations and varied agreement. Ventricular pacing almost completely eliminated HRV, and spectral analysis of the PRV signal revealed a HRV-independent rhythm. After cardiac autonomic blockade with atropine or metoprolol, the changes in time- and non-normalized frequency-domain measures of PRV continued to show strong correlations and moderate to high agreement with corresponding changes in HRV measures. Blockade-induced changes in nonlinear PRV indexes correlated poorly with HRV changes and showed weak agreement. These results suggest that time- and frequency-domain measures of PRV are acceptable surrogates for HRV even in the context of changing cardiac autonomic tone, but caution should be used when nonlinear measures are a primary end point or when HRV is very low as HRV-independent rhythms may predominate.

  19. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    Science.gov (United States)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  20. The influence of diabetes mellitus and insulin therapy on biomechanical retention around dental implants: a study in rabbits.

    Science.gov (United States)

    Margonar, Rogério; Sakakura, Celso E; Holzhausen, Marinella; Pepato, Maria Teresa; Alba, júnior Rodolfo Cândia; Marcantonio, júnior Elcio

    2003-01-01

    The oral rehabilitation by dental implants in patients with diabetes remains a controversial issue. The aim of this study was to evaluate the influence of diabetes mellitus and insulin therapy on the bone healing around dental implants using torque removal. Twenty-seven rabbits were randomly divided into 3 groups with 9 animals each: control (C) group, induced diabetic (D) group, and insulin-treated diabetic (ITD) group (10 U/day). After 1 week, one implant was inserted at the tibial metaphysis of the animals. The glucose levels were periodically evaluated through the glucose-oxidase enzymatic method. The animals were killed at 4, 8, and 12 weeks after surgery and the biomechanical test was performed using a torque manometer. Statistically significant differences regarding the removal torque of the implant could not be found at 4 weeks (P = 0.2) among groups. Group C showed statistically higher values than groups D and ITD at the experimental periods of 8 (P = 0.0001 and P = 0.0002, respectively) and 12 weeks (P = 0.0053 and P = 0.001, respectively). There were no statistical differences between D and ITD groups in any of the experimental periods. Diabetes mellitus has negatively influenced the mechanical retention of implants placed at the tibial metaphysis of rabbits. Therapy with insulin did not induce any changes.

  1. Exercise Heart Rate Reserve and Recovery as Predictors of Incident Type 2 Diabetes.

    Science.gov (United States)

    Jae, Sae Young; Kurl, Sudhir; Laukkanen, Jari A; Zaccardi, Francesco; Choi, Yoon-Ho; Fernhall, Bo; Carnethon, Mercedes; Franklin, Barry A

    2016-05-01

    We tested the hypothesis that selected exercise heart rate responses, specifically those providing indices of autonomic dysfunction, may be associated with incident type 2 diabetes in 2231 apparently healthy men with normal baseline fasting glucose levels. Heart rate reserve was calculated as the difference between the maximal attained heart rate and the supine resting heart rate, whereas heart rate recovery was defined as the maximal heart rate minus the heart rate measured at 2 minutes of recovery after peak or symptom-limited cardiopulmonary exercise testing. Type 2 diabetes was defined as glycated hemoglobin >6.5% or fasting plasma glucose >126 mg/dL at the follow-up examination. During a median follow-up interval of 5 years, 90 of the 2231 men (4.0%) developed type 2 diabetes. The relative risks of incident type 2 diabetes in men within the lowest quartiles of heart rate reserve and heart rate recovery versus men comprising the highest quartiles of heart rate reserve and heart rate recovery were 2.71 (95% confidence interval, 1.20-6.11) and 2.81 (95% confidence interval, 1.36-5.78) after adjusting for potential confounding variables. Each unit increment (1 beat/min) in heart rate reserve and heart rate recovery was associated with a 2% to 3% decreased incidence of type 2 diabetes. Exercise heart rate reserve and recovery predicted incidence of type 2 diabetes in healthy men, suggesting that autonomic dysfunction may be associated with an increased likelihood for the development of this cardiometabolic risk factor. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Impaired Heart Rate Response to Exercise in Diabetes and Its Long-term Significance.

    Science.gov (United States)

    Sydó, Nóra; Sydó, Tibor; Merkely, Béla; Carta, Karina Gonzales; Murphy, Joseph G; Lopez-Jimenez, Francisco; Allison, Thomas G

    2016-02-01

    To investigate the effect of diabetes mellitus on exercise heart rate and the role of impaired heart rate in excess mortality in diabetes. Patients without cardiovascular disease who underwent exercise testing from September 1, 1993, through December 31, 2010, were included. Mortality was determined from Mayo Clinic records and the Minnesota Death Index. Multivariate linear regression was used to compare heart rate responses in patients with vs without diabetes. Cox regression was used to determine the effect of abnormal heart rate recovery and abnormal chronotropic index on survival. A total of 21,396 patients (65.4% men) with a mean ± SD age of 51±11 years, including 1200 patients with diabetes (5.4%), were included. Patients with diabetes had a higher resting heart rate (81±14 vs 77±13 beats/min), lower peak heart rate (154±20 vs 165±19 beats/min), heart rate reserve (73±19 vs 88±19 beats/min), chronotropic index (0.86±0.22 vs 0.99±0.20), and heart rate recovery (15±8 vs 19±9 beats/min) vs patients without diabetes. There were 1362 deaths (6.4%) during a mean ± SD follow-up of 11.9±4.9 years. Adjusting for age, sex, and heart rate-lowering drug use, a chronotropic index less than 0.8 contributed significantly to risk in patients with diabetes (hazard ratio [HR], 2.21; 95% CI, 1.62-3.00; Pheart rate recovery (patients with diabetes: HR, 2.21; 95% CI, 1.60-5.05; Pheart rate responses to exercise, which are independently predictive of reduced long-term survival in patients with diabetes as in patients without diabetes. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  3. Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes without known heart disease

    DEFF Research Database (Denmark)

    Jensen, Magnus T; Sogaard, Peter; Andersen, Henrik U;

    2014-01-01

    AIMS/HYPOTHESIS: Heart failure is one of the leading causes of mortality in type 1 diabetes. Early identification is vitally important. We sought to determine the prevalence and clinical characteristics associated with subclinical impaired systolic and diastolic function in type 1 diabetes patients...... without known heart disease. METHODS: In this cross-sectional examination of 1,093 type 1 diabetes patients without known heart disease, randomly selected from the Steno Diabetes Center, complete clinical and echocardiographic examinations were performed and analysed in uni- and multivariable regression...... known heart disease. Type 1 diabetes patients with albuminuria are at greatly increased risk of having subclinical abnormal myocardial function compared with patients without albuminuria. Echocardiography may be particularly warranted in patients with albuminuria....

  4. Heart rate recovery after exercise and incidence of type 2 diabetes in men.

    Science.gov (United States)

    Jae, Sae Young; Carnethon, Mercedes R; Heffernan, Kevin S; Fernhall, Bo; Lee, Moon-Kyu; Park, Won Hah

    2009-06-01

    We tested that slow heart rate recovery (HRR) after exercise testing, indicative of decreased parasympathetic nervous system activity, is associated with the development of type 2 diabetes in 1,813 healthy men. Heart rate recovery was calculated as the difference between maximum heart rate during the exercise test and heart rate 1 min after cessation of the exercise test. During an average of 6.4 years of follow-up, 64 (3.5%) subjects developed type 2 diabetes. The unadjusted relative risk (RR) of developing incident diabetes in the slowest versus the fastest HRR quartile was 3.13 (95% CI, 1.28-7.65). However, the association was no longer significant after adjustment for diabetes risk factors and baseline glucose (RR = 2.28, 95% CI, 0.87-5.95). Slow HRR is associated with the development of type 2 diabetes, but these relationships were largely explained by baseline fasting glucose in healthy men.

  5. Morphological and electrophysiological properties of single myocardial cells from Koch triangle of rabbit heart

    Institute of Scientific and Technical Information of China (English)

    REN Fu-xian; NIU Xiao-lin; OU Yan; HAN Zhen-hua; LING Feng-dong; ZHOU Shi-sheng; LI Ya-jie

    2006-01-01

    Background The morphological and electrophysiological characteristics of cardiac cells in Koch triangle are still disputed. We studied the appearance and electrical properties of these diverse myocytes to elucidate their complex electrophysiological phenomena.Methods Experiments were conducted using cooled charge coupling device (CCD) system and whole cell,patch clamp technique to determine the morphology, action potential and sodium current density of single viable myocytes enzymatically isolated from the Koch triangle of rabbit hearts.Results Morphologically, cardiac cells in shape of spider, tiny spindle, slender spindle, rod and strip were observed in percentage of 3.0±0.3, 35.0±5.0, 15.0±2.0, 40.0±5.0 and 6.0±0.7 respectively. The cellular dimensions and capacitance gradually increased in the above order (all P<0.05). Electrophysiologically, action potential configurations recorded from them were similar respectively to nodal (N), atrial nodal (AN), nodal Hisian (NH), atrial (A) and Hisian like potentials obtained from the intact atrioventricular nodal preparations.Diastolic depolarization appeared in all myocytes except for rod cells. Sodium current density increased in the order of tiny spindle, strip, rod, slender spindle cell (all P<0.05), but could not be detected in spider-shaped cells.Linear regression analysis revealed that membrane capacitance was correlated negatively to the rate of diastolic depolarization r=-0.70, P<0.001, but positively to maximum depolarization potential, amplitude of action potential, upstroke velocity and maximum peak value of sodium current density r=-0.84, 0.80, 0.87 and 0.75,respectively; all P<0.001.Conclusions The results demonstrated that spider-shaped, spindle, rod and strip cells in Koch triangle might correspond to pacemaking, transitional, atrial and Purkinje like cells, respectively. Furthermore, tiny spindle and slender spindle cells were referred to transitional cell α (TCα) and β (TCβ) accordingly

  6. Diabetes and Cardiovascular Disease: Original Insights from the Framingham Heart Study

    OpenAIRE

    Qazi, Mohammad U.; Malik, Shaista

    2013-01-01

    The role of diabetes in the pathogenesis of cardiovascular disease (CVD) was unclear until 1979 when Kannel et al used data from the Framingham Heart Study (FHS) to identify diabetes as a major cardiovascular risk factor. It was also one of the first studies to demonstrate the higher risk of CVD in women with diabetes compared to men with diabetes. Since then, multiple studies have been done to recognize and curtail cardiovascular risk factors such as smoking, obesity, hypertension, hyperlipi...

  7. 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.

  8. Association of Diabetes Related Complications with Heart Rate Variability among a Diabetic Population in the UAE

    Science.gov (United States)

    Khandoker, Ahsan H.; Al-Angari, Haitham M.; Khalaf, Kinda; Lee, Sungmun; Almahmeed, Wael; Al Safar, Habiba S.

    2017-01-01

    Microvascular, macrovascular and neurological complications are the key causes of morbidity and mortality among type II diabetes mellitus (T2DM) patients. The aim of this study was to investigate the alterations of cardiac autonomic function of diabetic patients in relation to three types of diabetes-related complications. ECG recordings were collected and analyzed from 169 T2DM patients in supine position who were diagnosed with nephropathy (n = 55), peripheral neuropathy (n = 64) and retinopathy (n = 106) at two hospitals in the UAE. Comparison between combinations of patients with complications and a control diabetic group (CONT) with no complication (n = 34) was performed using time, frequency and multi-lag entropy measures of heart rate variability (HRV). The results show that these measures decreased significantly (p<0.05) depending on the presence and type of diabetic complications. Entropy, (median, 1st- 3rd interquartile range) for the group combining all complications (1.74,1.37–2.09) was significantly lower than the corresponding values for the CONT group (1.77, 1.39–2.24) with lag-1 for sequential beat-to-beat changes. Odds ratios (OR) from the entropy analysis further demonstrated a significantly higher association with the combination of retinopathy and peripheral neuropathy versus CONT (OR: 1.42 at lag 8) and an even OR for the combination of retinopathy and nephropathy (OR: 2.46 at lag 8) compared to the other groups with complications. Also, the OR of low frequency power to high frequency power ratio (LF/HF) showed a higher association with these diabetic-related complications compared to CONT, especially for the patient group combining all complications (OR: 4.92). This study confirms that the type of microvascular or peripheral neuropathy complication present in T2DM patients have different effects on heart rate entropy, implying disorders of multi-organ connectivity are directly associated with autonomic nervous system dysfunction. Clinical

  9. Role of Ca2+ in protecting the heart from hyperkalemia and acidosis in the rabbit: implications for exercise.

    Science.gov (United States)

    Leitch, S P; Paterson, D J

    1994-11-01

    Catecholamines can offset the negative effect of acidosis and raised extracellular K+ concentration in the isolated rabbit heart when these factors are changed with similar kinetics and concentrations as those observed in exercise. This effect appears to be mediated by changes in Ca2+ handling in the heart. To test the role of Ca2+ in vivo, we studied the interactive effects of infusions of KCl, lactic acid, norepinephrine (NE), and CaCl2 on cardiovascular performance in the anesthetized rabbit. After propranolol, CaCl2 was given during acidosis and hyperkalemia. Acidosis (arterial pH 7.17 +/- 0.3) markedly reduced cardiac performance, and its effects were exacerbated by hyperkalemia (7.3 +/- 0.4 mM). NE reversed the cardiac response to combined acidosis and hyperkalemia. After propranolol, arterial pH and arterial K+ concentration changed more rapidly with acidosis and hyperkalemia, combined with a faster fall in cardiac performance, but CaCl2 offset these negative hemodynamic effects. The rises in plasma Ca2+, NE, and sympathetic activity during exercise may therefore interact to ameliorate the harmful effects of acidosis and hyperkalemia.

  10. Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.

    Science.gov (United States)

    Thaung, H P Aye; Baldi, J Chris; Wang, Heng-Yu; Hughes, Gillian; Cook, Rosalind F; Bussey, Carol T; Sheard, Phil W; Bahn, Andrew; Jones, Peter P; Schwenke, Daryl O; Lamberts, Regis R

    2015-08-01

    Elevated sympathetic nerve activity (SNA) coupled with dysregulated β-adrenoceptor (β-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the β-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to β-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular β1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial β2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac β-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. The American Heart Association Ideal Cardiovascular Health and Incident Type 2 Diabetes Mellitus Among Blacks: The Jackson Heart Study.

    Science.gov (United States)

    Effoe, Valery S; Carnethon, Mercedes R; Echouffo-Tcheugui, Justin B; Chen, Haiying; Joseph, Joshua J; Norwood, Arnita F; Bertoni, Alain G

    2017-06-21

    The concept of ideal cardiovascular health (CVH), defined by the American Heart Association primarily for coronary heart disease and stroke prevention, may apply to diabetes mellitus prevention among blacks. Our sample included 2668 adults in the Jackson Heart Study with complete baseline data on 6 of 7 American Heart Association CVH metrics (body mass index, healthy diet, smoking, total cholesterol, blood pressure, and physical activity). Incident diabetes mellitus was defined as fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes mellitus drugs, or glycosylated hemoglobin ≥6.5%. A summary CVH score from 0 to 6, based on presence/absence of ideal CVH metrics, was derived for each participant. Cox regression was used to estimate adjusted hazard ratios. Mean age was 55 years (65% women) with 492 incident diabetes mellitus events over 7.6 years (24.6 cases/1000 person-years). Three quarters of participants had only 1 or 2 ideal CVH metrics; no participant had all 6. After adjustment for demographic factors (age, sex, education, and income) and high-sensitivity C-reactive protein, each additional ideal CVH metric was associated with a 17% diabetes mellitus risk reduction (hazard ratio, 0.83; 95% CI, 0.74-0.93). The association was attenuated with further adjustment for homeostasis model assessment for insulin resistance (hazard ratio, 0.89; 95% CI, 0.79-1.00). Compared with participants with 1 or no ideal CVH metric, diabetes mellitus risk was 15% and 37% lower in those with 2 and ≥3 ideal CVH metrics, respectively. The AHA concept of ideal CVH is applicable to diabetes mellitus prevention among blacks. These associations were largely explained by insulin resistance. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  12. Comparing maximum rate and sustainability of pacing by mechanical vs. electrical stimulation in the Langendorff-perfused rabbit heart.

    Science.gov (United States)

    Quinn, T Alexander; Kohl, Peter

    2016-12-01

    Mechanical stimulation (MS) represents a readily available, non-invasive means of pacing the asystolic or bradycardic heart in patients, but benefits of MS at higher heart rates are unclear. Our aim was to assess the maximum rate and sustainability of excitation by MS vs. electrical stimulation (ES) in the isolated heart under normal physiological conditions. Trains of local MS or ES at rates exceeding intrinsic sinus rhythm (overdrive pacing; lowest pacing rates 2.5±0.5 Hz) were applied to the same mid-left ventricular free-wall site on the epicardium of Langendorff-perfused rabbit hearts. Stimulation rates were progressively increased, with a recovery period of normal sinus rhythm between each stimulation period. Trains of MS caused repeated focal ventricular excitation from the site of stimulation. The maximum rate at which MS achieved 1:1 capture was lower than during ES (4.2±0.2 vs. 5.9±0.2 Hz, respectively). At all overdrive pacing rates for which repetitive MS was possible, 1:1 capture was reversibly lost after a finite number of cycles, even though same-site capture by ES remained possible. The number of MS cycles until loss of capture decreased with rising stimulation rate. If interspersed with ES, the number of MS to failure of capture was lower than for MS only. In this study, we demonstrate that the maximum pacing rate at which MS can be sustained is lower than that for same-site ES in isolated heart, and that, in contrast to ES, the sustainability of successful 1:1 capture by MS is limited. The mechanism(s) of differences in MS vs. ES pacing ability, potentially important for emergency heart rhythm management, are currently unknown, thus warranting further investigation. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  13. An intriguing association between congestive heart failure and An intriguing association between congestive heart failure and diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    SHEN Wei-feng

    2010-01-01

    @@ The prevalence of type 2 diabetes is rising at an alarming rate in China due to aging of the population,increased frequency of obesity, and suboptimal nutritional habits.~1 Although many diabetic Patients now survive severe coronary lesions or myocardial infarction as a result of dramatic advances in the management of ischemic heart disease in general and acute myocardial infarction specifically,~(2,3) they are subsequently succumbing to the consequences of myocardial damage, with an increased incidence of congestive heart failure (CHF).~4

  14. Common Virus May Be Linked to Heart Disease, Diabetes in Some Women

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_163761.html Common Virus May Be Linked to Heart Disease, Diabetes in ... THURSDAY, Feb. 23, 2017 (HealthDay News) -- A common virus may make some women more susceptible to both ...

  15. Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure

    Directory of Open Access Journals (Sweden)

    Ullmann Cris

    2006-06-01

    Full Text Available Abstract Background Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation. Methods White male New Zealand rabbits were treated with doxorubicine (3 mg/kg/week; 6 weeks to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained autologous bone marrow stem cells (BMSC and injected 1.5–2.0 Mio cells in 1 ml medium by infiltrating the myocardium via a left anterolateral thoracotomy in comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was determined in-vivo using a Millar catheter. Thereafter, the heart was excised and processed for radioligand binding assays to detect β1- and β2-adrenoceptor density. In addition, catecholamine plasma levels were determined via HPLC. In a subgroup we investigated cardiac electrophysiology by use of 256 channel mapping. Results In doxorubicine-treated animals β-adrenoceptor density was significantly down-regulated in left ventricle and septum, but not in right ventricle, thereby indicating a typical left ventricular heart failure. Sham-operated rabbits exhibited the same down-regulation. In contrast, BMSC transplantation led to significantly less β-adrenoceptor down-regulation in septum and left ventricle. Cardiac contractility was significantly decreased in heart failure and sham-operated rabbits, but was significantly higher in BMSC-transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced in heart failure and sham-operated animals, while these were not different from normal in BMSC-transplanted animals. Electrophysiological mapping revealed unaltered electrophysiology and did not show signs of arrhythmogeneity. Conclusion BMSC transplantation improves sympathoadrenal dysregualtion in non-ischemic heart failure.

  16. Influence of baroreflex on volume elasticity of heart and aorta in the rabbit.

    Science.gov (United States)

    Wronski, T; Seeliger, E; Persson, P B; Harnath, A; Flemming, B

    2002-03-01

    Optimal ventriculoaortic coupling includes tuning of elastic properties. The ratio of effective arterial elastance and left ventricular endsystolic elastance is often taken as a measure for mechanical and energetical efficiency. The present study determined the time course of ventricular and aortic volume elasticity (VE = dp/dV) throughout a complete heartbeat. This was achieved by using changes of eigenfrequency of two catheter-transducer systems under closed chest conditions in rabbits. Short-term VE modulation was studied by a baroreflex response, as induced by pressure changes applied to the carotid sinus. Long-term changes were studied in atherosclerotic rabbits (12 wk of high-cholesterol feeding). The time course and mean values of ventricular and aortic VE were changed by the baroreflex stimulus. Cholesterol feeding diminished the response. The degree of ventriculoaortic coupling, as quantified by VE(Aorta)/VE(Ventricle) ratio, varied during a single ejection period. The large span allows either maximal energetical efficiency or maximal stroke work. Although normal rabbits adjusted their ventriculoaortic coupling during baroreflex input, the cholesterol-fed rabbits failed to do so.

  17. Paradoxically enhanced heart tolerance to ischaemia in type 1 diabetes and role of increased osmolarity.

    Science.gov (United States)

    Chen, Hong; Shen, Wei-Li; Wang, Xu-Hui; Chen, Hong-Zhuan; Gu, Jian-Zhong; Fu, Jie; Ni, Ya-Feng; Gao, Ping-Jin; Zhu, Ding-Liang; Higashino, Hideaki

    2006-10-01

    There is considerable controversy regarding the tolerance of diabetic hearts to ischaemia and the underlying mechanisms responsible for the increased heart tolerance to ischamia remain uncertain. In the present study, we observed, in vitro, type 1 diabetic heart responses to ischaemia and reperfusion at different degrees of hyperglycaemia. In addition, the possible role of increased osmolarity in cardioprotection due to hyperglycaemia was evaluated. Hearts from 3 week streptozocin-induced diabetic rats were isolated and perfused in a Langendorff apparatus and subjected to 30 min ischaemia and 30 min reperfusion. Cardiac function and the electrocardiogram were recorded. Myocardial content of osmolarity associated heat shock protein (hsp) 90, heme oxygenase (HO)-1 and anti-oxidant enzymes were determined in diabetic or hyperosmotic solution-perfused hearts using western blot. The hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG; 2 x 10(-7) mol/L) or the nitric oxide synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester (1 x 10(-5) mol/L) was added to the perfusate to observe the effects of hsp90 inhibition and hsp90-associated endothelial NOS on ischaemic responses of diabetic hearts. Compared with normal control rats, diabetic hearts with severe hyperglycaemia (blood glucose > 20 mmol/L) showed markedly improved postischaemic heart function with fewer reperfusion arrhythmias. Mild hyperglycaemia (< 12 mmol/L) exhibited no significant cardioprotection. Elevated expression of hsp90 accompanied the enhanced resistance to ischaemia in diabetic hearts, which was abrogated by 17-AAG. In the presence of the NOS inhibitor, heart function was preserved, whereas reperfusion arrhythmias were increased in diabetes. Diabetic hearts also had markedly elevated HO-1 and catalase, with no significant change in superoxide dismutase. Hyperosmotic perfusion with glucose or mannitol also increased myocardial hsp90 and catalase. The present findings reveal that

  18. Type 2 diabetes, obesity, and sex difference affect the fate of glucose in the human heart

    OpenAIRE

    Peterson, Linda R.; Herrero, Pilar; Coggan, Andrew R.; Kisrieva-Ware, Zulia; Saeed, Ibrahim; Dence, Carmen; Koudelis, Deborah; McGill, Janet B.; Lyons, Matthew R.; Novak, Eric; Dávila-Román, Víctor G.; Waggoner, Alan D.; Gropler, Robert J.

    2015-01-01

    Type 2 diabetes, obesity, and sex difference affect myocardial glucose uptake and utilization. However, their effect on the intramyocellular fate of glucose in humans has been unknown. How the heart uses glucose is important, because it affects energy production and oxygen efficiency, which in turn affect heart function and adaptability. We hypothesized that type 2 diabetes, sex difference, and obesity affect myocardial glucose oxidation, glycolysis, and glycogen production. In a first-in-hum...

  19. Associaton between plasma osteopontin levels and severity of coronary heart disease in non-diabetic subjects

    Institute of Scientific and Technical Information of China (English)

    魏芹

    2014-01-01

    Objective To seek the association between plasma osteopontin(OPN)levels and severity of coronary heart disease in non-diabetic subjects.Methods A total of 166stable angina patients free of diabetes were enrolled in the study.Clinical characteristic of patients was recorded.Plasma OPN levels were measured by an enzymelinked immunosorbent assay method.Coronary heart disease was determined by coronary artery angiography.The extent of coronary artery stenosis was represented as the

  20. The administration of folic acid improves erectile function and reduces intracavernosal oxidative stress in the diabetic rabbit.

    Science.gov (United States)

    Shukla, Nilima; Hotston, Matthew; Persad, Raj; Angelini, Gianni D; Jeremy, Jamie Y

    2009-01-01

    To test the possibility that folic acid (FA) may be a means of treating erectile dysfunction (ED) in diabetes mellitus (DM), by studying the effect of FA administration to DM rabbits on cavernosal function and intrapenile oxidative stress. To investigate the effect of administering FA to DM rabbits on erectile function and oxidative stress the formation of superoxide (O(2)(-)), 8-isoprostane F(2 alpha) (8-IPF(2 alpha)) and prostacyclin (as 6-keto-PGF(1 alpha)) were assessed, as well as carbachol- and electrical field stimulated (EFS) relaxation and p47(phox) content (active component of NADPH oxidase complex). Non-ketotic DM was induced in New Zealand rabbits with alloxan and FA administered orally daily for 1 month. Rabbits were killed, penises excised and segments prepared. These were mounted in an organ bath and relaxation elicited with carbachol or EFS. O(2)(-) release was measured spectrophotometrically, p47(phox) expression by Western blotting and 8-IPF(2 alpha) and 6-keto-PGF(1 alpha) formation by enzyme-linked immunosorbant assay. Blood was collected for measurement of homocysteine, red blood cell (RBC) folate and glucose. In cavernosal tissue from DM rabbits, carbachol-and EFS-induced relaxation was significantly impaired compared with the untreated controls. O(2)(-) release, p47(phox) expression and 8-IPF(2 alpha) formation were all enhanced and 6-keto-PGF(1 alpha) formation reduced compared with the controls. All these effects were reversed by FA. Plasma total homocysteine was reduced and RBC folate elevated. The administration of FA may constitute a strategy for reducing ED in patients with DM.

  1. Novel Risk Factors for Type II Diabetes Mellitus and Coronary Heart Disease

    NARCIS (Netherlands)

    A. Dehghan (Abbas)

    2010-01-01

    textabstractDespite the huge advances made in the understanding of type II diabetes and coronary heart disease (CHD), these diseases still constitute a major health problem. Since the 1950s, epidemiologists focused on chronic disorders, including type II diabetes and CHD. Major aims of their researc

  2. Heart failure progression is accelerated following myocardial infarction in type II diabetic rats

    Science.gov (United States)

    Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients and following an infarction, diabetes is associated with an increased risk for the development of left ventricular dysfunction and heart failure. The goal of this study was to determine if the progression o...

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

    Directory of Open Access Journals (Sweden)

    Behrouz Ilkhanizadeh

    2016-02-01

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

  4. Congenital Heart Diseases in the Newborns of Diabetic Mothers: an Echocardiographic Study

    Directory of Open Access Journals (Sweden)

    S Rahimpour

    2011-10-01

    Full Text Available Introduction: Despite the discovery of insulin and current improvement in diabetics care, congenital malformations in diabetics are still more frequent than in the general population. The aim of this study was to identify congenital heart dieases (CHD in the newborns of diabetic mothers (IDMS. Methods: In our prospective study, color doppler echocardiography was performed in 75 consecutive full- term newborns of diabetic mothers by GE Vivid3 echocardiographic device. Newborns were classified into two subgroups according to the type of the mothers’ diabetes: pre-gestational and gestational. They were also those were classified into three subgroups according to their birth weight: appropriate, large and small for gestational age. Data analysis was made by Fisher exact test and Chi-Square test. Results: Forty nine (65% and thirty six (35% of subjects were infants of gestational (IGDM and pre-gestational diabetic mothers (IPDM, respectively. Fifty five Newborns (73% were apropriate, fourteen (19% were large and six (8% were small for gestational age. The most common echocardiographic findings included: patent ductus arteriosus (PDA: 54.7%, hypertrophic cardiomyopathy (HCMP: 24%, ventricular septal defect (VSD: 4%, atrial septal defect (ASD: 2.7%, transposition of great arteries (TGA: 1.3% and coarctation of the Aorta (COA: 1.3%. Overall incidence of congenital heart diseases was 9.3 after exclusion of PDA and HCMP cases. The incidence of congenital heart diseases was higher in macrosomic than nonmacrosomic infants of diabetic mothers (P<0.001. Congenital heart diseases were more common in infants of pre-gestational than gestational diabetic mothers (P=0.004. Conclusion: Our results showed that diabetic mothers are at increased risk of giving birth to a newborn with congenital heart disease, and transthoracic echocardiography is recommended for all infants of diabetic mothers.

  5. Tissue Doppler echocardiography in persons with hypertension, diabetes, or ischaemic heart disease: the Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Sogaard, Peter; Pedersen, Sune A

    2009-01-01

    AIMS: To test the hypothesis that echocardiographic tissue Doppler imaging (TDI) reveals reduced myocardial function in hypertension, diabetes, and ischaemic heart disease (IHD) in the general population. METHODS AND RESULTS: Within a large, community-based population study, cardiac function...... and diastolic cardiac function in hypertension [n = 345; LD 10.1 (+/-standard deviation, SD 2.0 mm), P diabetes [n = 65; LD 9.8 (+/-SD 2.2 mm), P ....001] compared with controls [n = 533; LD 11.4 (+/-SD 2.0 mm); E/e' 9.0 (x/SD 1.3)]. This pattern remained significant after adjusting for age, sex, body mass index, heart rate, and the results of conventional echocardiography. CONCLUSION: In the general population, persons with hypertension, diabetes, or IHD...

  6. Treatment of feline asthma with ciclosporin in a cat with diabetes mellitus and congestive heart failure.

    Science.gov (United States)

    Nafe, Laura A; Leach, Stacey B

    2015-12-01

    A 5-year-old domestic shorthair cat that had been previously diagnosed with diabetes mellitus was presented for episodes of coughing and respiratory distress. Diagnostic testing revealed congestive heart failure secondary to hypertrophic cardiomyopathy and concurrent asthma. All clinical signs and eosinophilic airway inflammation resolved with oral ciclosporin while the cat was concurrently receiving medications for treatment of heart failure (furosemide and enalapril). Ciclosporin should be considered for treatment of feline asthma in patients with concurrent diseases (eg, diabetes mellitus, severe heart disease) that may contraindicate use of oral glucocorticoid therapy.

  7. Sudden cardiac death in patients with diabetes mellitus and chronic heart failure.

    Science.gov (United States)

    Walker, Andrew Mn; Cubbon, Richard M

    2015-07-01

    In patients with diabetes mellitus, around 50% of deaths due to cardiovascular causes are sudden cardiac deaths. The prevalence of diabetes in cohorts with chronic heart failure is increasing, and while sudden cardiac death is an increasingly rare mode of death in chronic heart failure patients as a whole, the risk of this outcome remains high in those with diabetes. This review summarises the current knowledge on the incidence of sudden cardiac death in patients with diabetes and chronic heart failure, before discussing the causes of the excess risk seen in those with these coexistent conditions. We then describe current strategies for risk stratification and prevention of sudden cardiac death in these patients before discussing the priorities for further study in this area.

  8. Genetically Low Antioxidant Protection and Risk of Cardiovascular Disease and Heart Failure in Diabetic Subjects

    DEFF Research Database (Denmark)

    Kobylecki, Camilla J; Afzal, Shoaib; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased...... risk of cardiovascular disease and heart failure. METHODS: We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization...... and death registers to assess cardiovascular disease and heart failure. FINDINGS: Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G...

  9. Inhalation of ultrafine carbon particles alters heart rate and heart rate variability in people with type 2 diabetes.

    Science.gov (United States)

    Vora, Rathin; Zareba, Wojciech; Utell, Mark J; Pietropaoli, Anthony P; Chalupa, David; Little, Erika L; Oakes, David; Bausch, Jan; Wiltshire, Jelani; Frampton, Mark W

    2014-07-16

    Diabetes may confer an increased risk for the cardiovascular health effects of particulate air pollution, but few human clinical studies of air pollution have included people with diabetes. Ultrafine particles (UFP, ≤100 nm in diameter) have been hypothesized to be an important component of particulate air pollution with regard to cardiovascular health effects. 17 never-smoker subjects 30-60 years of age, with stable type 2 diabetes but otherwise healthy, inhaled either filtered air (0-10 particles/cm3) or elemental carbon UFP (~107 particles/cm3, ~50 ug/m3, count median diameter 32 nm) by mouthpiece, for 2 hours at rest, in a double-blind, randomized, crossover study design. A digital 12-lead electrocardiogram (ECG) was recorded continuously for 48 hours, beginning 1 hour prior to exposure. Analysis of 5-minute segments of the ECG during quiet rest showed reduced high-frequency heart rate variability with UFP relative to air exposure (p = 0.014), paralleled by non-significant reductions in time-domain heart rate variability parameters. In the analysis of longer durations of the ECG, we found that UFP exposure increased the heart rate relative to air exposure. During the 21- to 45-hour interval after exposure, the average heart rate increased approximately 8 beats per minute with UFP, compared to 5 beats per minute with air (p = 0.045). There were no UFP effects on cardiac rhythm or repolarization. Inhalation of elemental carbon ultrafine particles alters heart rate and heart rate variability in people with type 2 diabetes. Our findings suggest that effects may occur and persist hours after a single 2-hour exposure.

  10. L-propionylcarnitine enhancement of substrate oxidation and mitochondrial respiration in the diabetic rat heart.

    Science.gov (United States)

    Broderick, T L; Haloftis, G; Paulson, D J

    1996-02-01

    This study was designed to determine whether L-propionylcarnitine (LPC) treatment is beneficial in preventing the depression in cardiac function from occurring in chronic diabetes. Diabetes was induced by tail vein injection of streptozotocin (60 mg/kg). Two weeks later, treatment was initiated by supplementing the drinking water with LPC at the concentration of 1 mg/ml. Following a 6-week treatment period, myocardial substrate utilization and cardiac function were determined in isolated working hearts. In a separate group of hearts, the effects of LPC treatment on mitochondrial respiration were also determined. The results showed that diabetic hearts, compared with those of controls, oxidized glucose at a much lower rate, but oxidized palmitate at a similar rate. The effect of diabetes compared a controls was also characterized by a pronounced decrease in cardiac pump function. Following treatment with LPC, however, there was a marked increase in the rates at which glucose and palmitate were oxidized by diabetic hearts, and a significant improvement in cardiac pump performance. In addition, the depression of cardiac mitochondrial respiration seen in diabetes was prevented with LPC treatment. Our findings show that the depression of cardiac pump function by diabetes can be prevented with chronic LPC treatment. Possible mechanisms for this beneficial effect include an energetically favorable shift in glucose and fatty acid metabolism.

  11. Exercise mediated protection of diabetic heart through modulation of microRNA mediated molecular pathways.

    Science.gov (United States)

    Lew, Jason Kar Sheng; Pearson, James T; Schwenke, Daryl O; Katare, Rajesh

    2017-01-13

    Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfunction, and left ventricular remodelling and dysfunction. Diabetic heart disease (DHD) is the term used to describe the presence of heart disease specifically in diabetic patients. Despite significant advances in medical research and long clinical history of anti-diabetic medications, the risk of heart failure in people with diabetes never declines. Interestingly, sustainable and long-term exercise regimen has emerged as an effective synergistic therapy to combat the cardiovascular complications in people with diabetes, although the precise molecular mechanism(s) underlying this protection remain unclear. This review provides an overview of the underlying mechanisms of hyperglycaemia- and insulin resistance-mediated DHD with a detailed discussion on the role of different intensities of exercise in mitigating these molecular alterations in diabetic heart. In particular, we provide the possible role of exercise on microRNAs, the key molecular regulators of several pathophysiological processes.

  12. 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

  13. The association of atopy with incidence of ischemic heart disease, stroke, and diabetes

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Thuesen, Betina Heinsbæk;

    2015-01-01

    Allergy is a systemic inflammatory disease that could theoretically affect the risk of cardiovascular disease (CVD) and diabetes through inflammatory pathways or mast cell-induced coronary spasm. Whether allergy is associated with an increased risk of CVD and diabetes is largely unknown. We...... investigated the association between atopy as assessed by IgE sensitization, a well-accepted biomarker of allergy, and incidence of ischemic heart disease, stroke, and diabetes in five Danish population-based cohorts. A total of 14,849 participants were included in the study. Atopy was defined as serum......-specific IgE positivity to inhalant allergens. The Danish National Diabetes Register enabled identification of incident diabetes. Likewise, the Danish Registry of Causes of Death and the Danish National Patient Register provided information on fatal and non-fatal ischemic heart disease and stroke. Data were...

  14. Lagged Poincar\\'{e} and auto-correlation analysis of Heart rate variability in diabetes

    CERN Document Server

    Ghatak, S K

    2010-01-01

    The heart rate variability (HRV) in diabetic human subjects, has been analyzed using lagged Poincar\\'{e} plot, auto-correlation and the detrended fluctuation analysis methods. The parameters $SD1$, and $SD12 (= SD1/SD2)$ for Poincar\\'{e} plot for diabetic are lower than that for non-diabetic subjects and reverse is case for $SD2$ for all lagged number (m). The slope and the curvature of the plot SD12 vs m is much reduced for diabetic subject. The scatter plot of two successive interbeat intervals points out smaller variability in diabetic heart. The detrended fluctuation exponent has a higher value for diabetic group. The auto-correlation function of the deviation of interbeat interval in diabetic group shows highly correlated pattern when compared to that of normal one. The study suggests that the curvature of $SD12$ and auto-correlation method appear to be better way to assess the alteration of regulatory system on heart dynamics in diabetic condition.

  15. H2S对兔离体心脏心率的影响%Effects of Hydrogen Sulfide on Heart Rate of Rabbit Hearts in Vitro

    Institute of Scientific and Technical Information of China (English)

    陈立锋; 徐涛; 范凌; 赵兰平; 陈少峰; 温晓竞; 张晓云; 马建伟; 尹万斌

    2009-01-01

    Objective:To explore the effects of hydrogen sulfide (H2S)on the rabbit's heart rate in vitro.Method:By using standard intracellular microelectrode technique to record Ap,hydrogen sulfide was used to investigate the rate of action potential of right atrium myocytes.Electrophysiological porameters examined were:rates of pacemaker firing,RPF.Results:(1)Perfusion with NaHS(H2S donor,200μmol/L) led to a significant decrease in RPF(P<0.01).(2)Application of 400μmol/L NaHS resulted in a significant decrease in RPF(P<0.01).Compared with the result of 200μmol/L NaHS,400μmol/L NaHS showed a significant decrease in RPF(P<0.01).(3) The above mentioned effects occurred after 3~5min of NaHS superfusion,had a significant decrease(P<0.01)after 10 min,and reached the peak within 25~30min.Conclusion:H2S could significantly affect the heart rate of rabbit hearts in vitro in a concentration-depedent manner.%目的:探讨硫化氢(H2S)对兔离体心脏心率的影响.方法:用标准微电极细胞内记录技术,观测硫化氢对兔右心房心肌细胞动作电位频率的影响.观测指标:自发放电频率(rate of pacemaker firing,RPF).结果:(1) 用200μmol/LNaHS 灌流时,和正常对照组相比,RPF显著减小(P<0.01).(2) 400μmol/L NaHS与对照组比较, RPF显著减小(P<0.01).和200μmol/LNaHS相比,RPF显著减小(P<0.01).(3)以上使RPF减小的效应在NaHS灌流3~5min出现,10min时已经有显著减小(P<0.01),25~30min达到高峰.结论:H2S可浓度依赖性的影响兔离体心脏的心率.

  16. Mapping the ECG in the live rabbit heart using Ultrasound Current Source Density Imaging with coded excitation.

    Science.gov (United States)

    Qin, Yexian; Li, Qian; Ingram, Pier; Witte, Russell S

    2012-10-01

    Ultrasound current source density imaging (UCSDI) is a noninvasive technique for mapping electric current fields in 4D (space + time) with the resolution of ultrasound imaging. This approach can potentially overcome limitations of conventional electrical mapping procedures often used during treatment of cardiac arrhythmia or epilepsy. However, at physiologic currents, the detected acoustoelectric (AE) interaction signal in tissue is very weak. In this work, we evaluated coded ultrasound excitation (chirps) for improving the sensitivity of UCSDI for mapping the electrocardiogram (ECG) in a live rabbit heart preparation. Results confirmed that chirps improved detection of the AE signal by as much as 6.1 dB compared to a square pulse. We further demonstrated mapping the ECG using a clinical intracardiac catheter, 1 MHz ultrasound transducer and coded excitation. B-mode pulse echo and UCSDI revealed regions of high current flow in the heart wall during the peak of the ECG. These improvements to UCSDI are important steps towards translation of this new technology to the clinic for rapidly mapping the cardiac activation wave.

  17. Impact of hypokalemia on electromechanical window, excitation wavelength and repolarization gradients in guinea-pig and rabbit hearts.

    Science.gov (United States)

    Osadchii, Oleg E

    2014-01-01

    Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM) window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K(+)) was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients.

  18. Impact of hypokalemia on electromechanical window, excitation wavelength and repolarization gradients in guinea-pig and rabbit hearts.

    Directory of Open Access Journals (Sweden)

    Oleg E Osadchii

    Full Text Available Normal hearts exhibit a positive time difference between the end of ventricular contraction and the end of QT interval, which is referred to as the electromechanical (EM window. Drug-induced prolongation of repolarization may lead to the negative EM window, which was proposed to be a novel proarrhythmic marker. This study examined whether abnormal changes in the EM window may account for arrhythmogenic effects produced by hypokalemia. Left ventricular pressure, electrocardiogram, and epicardial monophasic action potentials were recorded in perfused hearts from guinea-pig and rabbit. Hypokalemia (2.5 mM K(+ was found to prolong repolarization, reduce the EM window, and promote tachyarrhythmia. Nevertheless, during both regular pacing and extrasystolic excitation, the increased QT interval invariably remained shorter than the duration of mechanical systole, thus yielding positive EM window values. Hypokalemia-induced arrhythmogenicity was associated with slowed ventricular conduction, and shortened effective refractory periods, which translated to a reduced excitation wavelength index. Hypokalemia also evoked non-uniform prolongation of action potential duration in distinct epicardial regions, which resulted in increased spatial variability in the repolarization time. These findings suggest that arrhythmogenic effects of hypokalemia are not accounted for by the negative EM window, and are rather attributed to abnormal changes in ventricular conduction times, refractoriness, excitation wavelength, and spatial repolarization gradients.

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

    Science.gov (United States)

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

    2015-05-01

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

  20. The surface microstructure of cusps and leaflets in rabbit and mouse heart valves

    Directory of Open Access Journals (Sweden)

    Xia Ye

    2014-05-01

    Full Text Available In this investigation, scanning electron microscopy was used to characterize the microstructure on the surfaces of animal heart valve cusps/leaflets. The results showed that though these surfaces appear smooth to the naked eye, they are actually comprised of a double hierarchical structure consisting of a cobblestone-like microstructure and nano-cilia along with mastoids with a directional arrangement. Such nanostructures could play a very important role in the hemocompatibility characteristics of heart valves. On this basis, the model of the microstructure was constructed and theoretical analysis was used to obtain optimal geometric parameters for the rough surface of artificial valve cusps/leaflets. This model may help improve reconstructive techniques and it may be beneficial in the design and fabrication of valve substitutes or partial substitutes. Namely, the model may help ameliorate heart valve replacement surgery.

  1. Effects of Simvastatin on Ion Channel Currents in Ventricular Myocytes from Acute Infarcted Heart of Normocholesterolemic Rabbits

    Institute of Scientific and Technical Information of China (English)

    Chao Ding; Xianghua Fu; Li Yang; Huixiao Chen; Junxia Li; Yuying Zhao; Jie Li; Jie Wang

    2008-01-01

    Objectives To investigate the effects of simvastatin on membrane ionic currents in left ventricular myocytes of rab-bit heart suffering from acute myocardial infarction (AMI), so as to explore the ionic mechanism of statin treatment for antiarrhythmia. Methods Forty-five New Zealand rabbits were randomly divided into three groups: AMI group, simv-astatin intervention group (Statin group) and sham-operated control group (CON). Rabbits were infarcted by ligation of the left anterior descending coronary artery after administration of oral simvastatin 5 mg · kg-1 · d-1 (Statin group) or placebo (AMI group) for 3 days. Single ventricular myocytes were isolated enzymatically from the epicardial zone of the infracted region 72 h later. Whole cell patch clamp technique was used to record membrane ionic currents, inclu-ding sodium current (Ina), L-type calcium current (Ica-L) and transient outward potassium current (Ito). Results ① There was not significant difference in serum cholesterol concentration among three groups. ② The peak Ina current den-sity (at -30 mV) was significantly decreased in AMI group (-25.26±5. 28, n = 13), comparing with CON (-42. 78±5.48, n = 16), P < 0. 05, while it was significantly increased in Statin group (-39. 83±5. 65 pA/pF, n = 12) comparing with AMI group, P <0. 01; The peak I Ca-L current density (at 0 mV) was significantly decreased in AMI group (- 3.43±0. 92 pA/pF, n = 13) comparing with CON (- 4. 56±1.01 pA/pF, n = 15), P < 0. 05, while it was significantly increased in Statin group (-4. 18±0. 96 pA/pF, n = 12) comparing with AMI group, P <0. 05; The Ito current density (at + 60 mV) was significantly decreased in AMI group (11.41±1.94 pA/pF, n = 13) compa-ring with CON (17. 41±3. 13 pA/pF, n = 15), P <0. 01, while it was significantly increased in Statin group (16. 11±2. 43 pA/pF, n = 14) comparing with AMI group, P < 0. 01. Conclusions AMI induces significant down-regula-tion of Ina, I Ca-L and Ito. Pretreatment with

  2. Natriuretic Peptide System Activation in Acute Heart Failure Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    Filipe M. Cunha

    2017-01-01

    Full Text Available Background. Elevated B-type natriuretic peptide (BNP is a hallmark in heart failure (HF. Diabetic patients with chronic HF seem to have higher BNP than nondiabetics. We studied, in acute HF, if BNP levels are different between diabetics and nondiabetics. Methods. From a prospectively recruited population of acute HF patients, we selected a convenience sample. In pair-matched analysis, each diabetic patient was matched with a nondiabetic of the same age (±1 year, gender, and according to left ventricular systolic dysfunction. Diabetics and nondiabetics were compared. Cox-regression analysis was used to analyse the prognostic impact of diabetes. Results. We studied 328 patients, mean age: 78 years, 44.5% male. Diabetics were more often hypertensive and had ischemic HF; they had higher body mass index, lower haemoglobin, and worse renal function. Diabetics were more often discharged on ACE inhibitors/ARB, antiplatelet therapy, and statins. Neither admission nor discharge BNP values differed between diabetics and pair-matched nondiabetics. One-year mortality was also nondifferent between pairs of diabetics and nondiabetics: 44 (26.8% and 46 (28.0%, respectively. HR for 1-year mortality in diabetics was 1.00 (95% CI: 0.82–1.24 compared with nondiabetics. Conclusions. HF patients with diabetes have similar neurohumoral activation when compared with nondiabetics. One-year mortality is also nondifferent after matching for age, gender, and systolic function.

  3. β1 -Adrenoceptor, but not β2 -adrenoceptor, subtype regulates heart rate in type 2 diabetic rats in vivo.

    Science.gov (United States)

    Cook, Rosalind F; Bussey, Carol T; Mellor, Kimberley M; Cragg, Patricia A; Lamberts, Regis R

    2017-08-01

    What is the central question of the study? The sympathetic system regulates heart rate via β-adrenoceptors; this is impaired during diabetes. However, the specific β-adrenoceptor subtype contributions in heart rate regulation in diabetes in vivo are unknown. What is the main finding and its importance? Telemetric recordings in conscious non-diabetic and type 2 diabetic rats demonstrated that the β1 -adrenoceptor subtype, and not the β2 -adrenoceptor, regulated the lower resting heart rate and increased β-adrenoceptor responsiveness in diabetes in vivo. This provides new physiological insight into the dysregulation of heart rate in type 2 diabetes, which is important for improving therapeutic strategies targeting the diabetic chronotropic incompetence. β-Adrenoceptor blockers are widely used to reduce heart rate, the strongest predictor of mortality in cardiac patients, but are less effective in diabetic patients. This study aimed to determine the specific contributions of β1 - and β2 -adrenoceptor subtypes to chronotropic responses in type 2 diabetes in vivo, which are currently unknown. Type 2 diabetic and non-diabetic rats were implanted with radiotelemeters to measure arterial blood pressure and derive heart rate in conscious conditions. Vascular access ports were implanted to inject isoprenaline (β1 - and β2 -adrenoceptor agonist, 0.1-300 μg kg(-1) ) in the presence of atenolol (β1 -adrenoceptor antagonist, 2000 μg kg(-1) ) or nadolol (β1 - and β2 -adrenoceptor agonist, 4000 μg kg(-1) ) to determine the chronotropic contributions of the β-adrenoceptor subtypes. Resting heart rate was reduced in diabetic rats (388 ± 62 versus 290 ± 37 beats min(-1) non-diabetic versus diabetic, P heart rate at highest dose of isoprenaline: 135 ± 66 versus 205 ± 28 beats min(-1) , non-diabetic versus diabetic, P heart rate at highest dose of isoprenaline: 205 ± 37 versus 195 ± 22 beats min(-1) , non-diabetic versus diabetic, P heart

  4. Molecular Mechanisms of Increased Heart Rate in Shenxianshengmai-treated Bradycardia Rabbits

    Directory of Open Access Journals (Sweden)

    Zhou-Ying Liu

    2017-01-01

    Conclusions: Long-term SXSM stimulates sympathetic transmission by increasing the expression of acetylcholinesterase and reduces the expression of nicotinic receptor to increase heart rate. SXSM also restored the calcium handling genes and altered genes involved in signaling. In addition, SXSM improves the ATP supply of ventricular myocardium by increasing proteins involved in TCA cycle and oxidation-respiratory chain.

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

    Science.gov (United States)

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

    2015-09-01

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

  6. Development of a Coronary Heart Disease Risk Prediction Model for Type 1 Diabetes: The Pittsburgh CHD in Type 1 Diabetes Risk Mode

    NARCIS (Netherlands)

    Zgibor, J.C.; Ruppert, K.; Orchard, T.J.; Soedamah-Muthu, S.S.; Fuller, J.H.; Chaturvedi, N.; Roberts, M.S.

    2010-01-01

    Aim - To create a coronary heart disease (CHD) risk prediction model specific to type 1 diabetes. Methods - Development of the model used data from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC). EDC subjects had type 1 diabetes diagnosed between 1950 and 1980, received their

  7. Boosting autophagy in the diabetic heart: a translational perspective

    OpenAIRE

    Sciarretta, Sebastiano; Boppana, V. Subbarao; Umapathi, Mahaa; Frati, Giacomo; Sadoshima, Junichi

    2015-01-01

    Diabetes, obesity, and dyslipidemia are main risk factors that promote the development of cardiovascular diseases. These metabolic abnormalities are frequently found to be associated together in a highly morbid clinical condition called metabolic syndrome. Metabolic derangements promote endothelial dysfunction, atherosclerotic plaque formation and rupture, cardiac remodeling and dysfunction. This evidence strongly encourages the elucidation of the mechanisms through which obesity, diabetes, a...

  8. Investigation of the Protective Effects of Taurine against Alloxan-Induced Diabetic Retinal Changes via Electroretinogram and Retinal Histology with New Zealand White Rabbits

    Directory of Open Access Journals (Sweden)

    Samuel Tung-Hsing Chiang

    2014-01-01

    Full Text Available The purpose of this study was to investigate the protective role of orally administered taurine against diabetic retinal changes via electroretinogram (ERG and retinal histology on rabbits. Rabbits were randomly assigned into groups: Group I (vehicle administration only; Group II (diabetes: induced by 100 mg/kg alloxan injection; Group III (diabetes and fed with 200 mg/kg taurine; and Group IV (diabetes and fed with 400 mg/kg taurine. The body weight and blood glucose levels of the rabbits were monitored weekly. The ERG was measured on weeks 5 and 15. Retinal histology was analyzed in the end of the experiment. Results revealed that a taurine supplement significantly ameliorates the alloxan-induced hyperglycemia and protects the retina from electrophysiological changes. Group II showed a significant (P0.05 between all groups and when compared with those of Group I. Our study provides solid evidences that taurine possesses an antidiabetic activity, reduced loss of body weight, and less electrophysiological changes of the diabetic retina.

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

    Directory of Open Access Journals (Sweden)

    Anil Kumar Singhal

    2012-01-01

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

  10. [New markers of progression of chronic heart failure in patients with myocardial infarction, type 2 diabetes and obesity].

    Science.gov (United States)

    Kravchun, P P; Kadykova, O I; Gabisonia, T N

    2015-01-01

    Currently identified a large number of biomarkers that are closely linked with the development of chronic heart failure, some of which are clusterin and fractalkine. Accordingly, the purpose of our study was - to evaluate the role of clusterin and fractalkine in progression of chronic heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. We investigated 71 patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. All patients with postinfarction cardiosclerosis, diabetes and obesity were divided into groups according to the functional class of chronic heart failure (CHF). It was found that an increase the level of fractalkine and reduced clusterin leads due to the development of systolic dysfunction and heart failure progression in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity. Fractalkine and clusterin play an important role in progression of the heart failure in patients with postinfarction cardiosclerosis, type 2 diabetes and obesity, and this gives them the right to be considered indicators of the severity of CHF.

  11. Comparison in conscious rabbits of the baroreceptor-heart rate reflex effects of chronic treatment with rilmenidine, moxonidine, and clonidine

    Directory of Open Access Journals (Sweden)

    Monique L Parkin

    2016-11-01

    Full Text Available We investigated the effects of chronic subcutaneous treatment with centrally-acting antihypertensive agents moxonidine, rilmenidine and clonidine on the baroreflex control of heart rate (HR in conscious normotensive rabbits over 3 weeks. Infusions of phenylephrine and nitroprusside were performed at week 0 and at weeks 1 and 3 of treatment to determine mean arterial pressure (MAP-HR baroreflex relationships. A second curve was performed after intravenous methscopolamine to determine the sympathetic baroreflex relationship. The vagal component of the reflex was determined by subtracting the sympathetic curve from the intact curve. Clonidine and moxonidine (both 1 mg/kg/day, and rilmenidine (5 mg/kg/day, reduced MAP by 13  3, 15  2 and 13  2 mmHg, respectively, but had no effect on HR over the 3-week treatment period. Whilst all three antihypertensive agents shifted baroreflex curves to the left, parallel to the degree of hypotension, moxonidine and rilmenidine decreased the vagal contribution to the baroreflex by decreasing the HR range of the reflex whilst moxonidine also increased sympathetic baroreflex range and sensitivity. By contrast clonidine had little chronic effect on the cardiac baroreflex. The present study shows that second generation agents moxonidine and rilmenidine but not first generation agent clonidine chronically shift the balance of baroreflex control of HR toward greater sympathetic and lesser vagal influences. These changes if translated to hypertensive subjects, may not be particularly helpful in view of the already reduced vagal contribution in hypertension.

  12. The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning.

    Directory of Open Access Journals (Sweden)

    Vladimir Vinokur

    Full Text Available Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC, we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation. Diabetic hearts were less sensitive to ischemia-reperfusion stress, as indicated by functional parameters and histology. Mechanistically, since ferritin has been shown to provide cellular protection against insults, including ischemia-reperfusion stress and as the basal ferritin level in diabetic heart was 2-fold higher than in controls, these are in accord with the greater resistance of the diabetic heart to ischemia-reperfusion. Additionally, during ischemia-reperfusion, preceded by IPC, a rapid and extensive loss in ferritin levels, during the prolonged ischemia, in diabetic heart but not in non-diabetic controls, provide additional substantiation to the explanation for loss of respond to IPC. Current research is shedding light on the mechanism behind ferritin degradation as well, suggesting a novel explanation for diabetes-induced loss of cardioprotection.

  13. The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning.

    Science.gov (United States)

    Vinokur, Vladimir; Berenshtein, Eduard; Bulvik, Baruch; Grinberg, Leonid; Eliashar, Ron; Chevion, Mordechai

    2013-01-01

    Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation. Diabetic hearts were less sensitive to ischemia-reperfusion stress, as indicated by functional parameters and histology. Mechanistically, since ferritin has been shown to provide cellular protection against insults, including ischemia-reperfusion stress and as the basal ferritin level in diabetic heart was 2-fold higher than in controls, these are in accord with the greater resistance of the diabetic heart to ischemia-reperfusion. Additionally, during ischemia-reperfusion, preceded by IPC, a rapid and extensive loss in ferritin levels, during the prolonged ischemia, in diabetic heart but not in non-diabetic controls, provide additional substantiation to the explanation for loss of respond to IPC. Current research is shedding light on the mechanism behind ferritin degradation as well, suggesting a novel explanation for diabetes-induced loss of cardioprotection.

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

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    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.

  15. Nonlinear Methods to Assess Changes in Heart Rate Variability in Type 2 Diabetic Patients

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    Bhaskar, Roy, E-mail: imbhaskarall@gmail.com [Indian Institute of Technology (India); University of Connecticut, Farmington, CT (United States); Ghatak, Sobhendu [Indian Institute of Technology (India)

    2013-10-15

    Heart rate variability (HRV) is an important indicator of autonomic modulation of cardiovascular function. Diabetes can alter cardiac autonomic modulation by damaging afferent inputs, thereby increasing the risk of cardiovascular disease. We applied nonlinear analytical methods to identify parameters associated with HRV that are indicative of changes in autonomic modulation of heart function in diabetic patients. We analyzed differences in HRV patterns between diabetic and age-matched healthy control subjects using nonlinear methods. Lagged Poincaré plot, autocorrelation, and detrended fluctuation analysis were applied to analyze HRV in electrocardiography (ECG) recordings. Lagged Poincare plot analysis revealed significant changes in some parameters, suggestive of decreased parasympathetic modulation. The detrended fluctuation exponent derived from long-term fitting was higher than the short-term one in the diabetic population, which was also consistent with decreased parasympathetic input. The autocorrelation function of the deviation of inter-beat intervals exhibited a highly correlated pattern in the diabetic group compared with the control group. The HRV pattern significantly differs between diabetic patients and healthy subjects. All three statistical methods employed in the study may prove useful to detect the onset and extent of autonomic neuropathy in diabetic patients.

  16. Comparable long-term mortality risk associated with individual sulfonylureas in diabetes patients with heart failure

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Gislason, Gunnar H; Jørgensen, Casper H

    2011-01-01

    The aim was to investigate the outcomes of individual sulfonylureas in patients with heart failure (HF). Methods All patients hospitalized with HF for the first time in 1997–2006, alive 30 days after discharge, and who received anti-diabetic monotherapy with glimepiride (n = 1097), glibenclamide...... was not dependent on prior acute myocardial infarction or ischemic heart disease (p for interactions >0.3). Conclusions In current clinical practice, it is unlikely that there are considerable differences in risk of mortality associated with individual sulfonylureas in patients with heart failure....

  17. Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

    Science.gov (United States)

    Howard, Barbara V.; Umans, Jason G.; Gribble, Matthew O.; Best, Lyle G.; Francesconi, Kevin A.; Goessler, Walter; Lee, Elisa; Guallar, Eliseo; Navas-Acien, Ana

    2015-01-01

    OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism. PMID:25583752

  18. Insulin growth factor adjustment in preimplantation rabbit blastocysts and uterine tissues in response to maternal type 1 diabetes.

    Science.gov (United States)

    Thieme, René; Schindler, Maria; Ramin, Nicole; Fischer, Sünje; Mühleck, Britta; Fischer, Bernd; Navarrete Santos, Anne

    2012-07-06

    Insulin-like growth factors (IGFs) are well-known regulators of embryonic growth and differentiation. IGF function is closely related to insulin action. IGFs are available to the preimplantation embryo through maternal blood (endocrine action), uterine secretions (paracrine action) and by the embryo itself (autocrine action). In rabbit blastocysts, embryonic IGF1 and IGF2 are specifically strong in the embryoblast (ICM). Signalling of IGFs and insulin in blastocysts follows the classical pathway with Erk1/2 and Akt kinase activation. The aim of this study was to analyse signalling of IGFs in experimental insulin dependent diabetes (exp IDD) in pregnancy, employing a diabetic rabbit model with uterine hypoinsulinemia and hyperglycaemia. Exp IDD was induced in female rabbits by alloxan treatment prior to mating. At 6 days p.c., the maternal and embryonic IGFs were quantified by RT-PCR and ELISA. In pregnant females, hepatic IGF1 expression and IGF1 serum levels were decreased while IGF1 and IGF2 were increased in endometrium. In blastocysts, IGF1 RNA and protein was approx. 7.5-fold and 2-fold higher, respectively, than in controls from normoglycemic females. In cultured control blastocysts supplemented with IGF1 or insulin in vitro for 1 or 12 h, IGF1 and insulin receptors as well as IGF1 and IGF2 were downregulated. In cultured T1D blastocysts activation of Akt and Erk1/2 was impaired with lower amounts of total Akt and Erk1/2 protein and a reduced phosphorylation capacity after IGF1 supplementation. Our data show that the IGF axis is severely altered in embryo-maternal interactions in exp IDD pregnancy. Both, the endometrium and the blastocyst produce more IGF1 and IGF2. The increased endogenous IGF1 and IGF2 expression by the blastocyst compensates for the loss of systemic insulin and IGF. However, this counterbalance does not fill the gap of the reduced insulin/IGF sensitivity, leading to a developmental delay of blastocysts in exp IDD pregnancy.

  19. The influence of diabetes mellitus on midregional proadrenomedullin concentrations and prognostic value in heart failure outpatients

    DEFF Research Database (Denmark)

    Holmager, Pernille; Schou, Morten; Egstrup, Michael;

    2015-01-01

    BACKGROUND: Diabetes mellitus (DM) is associated with an adverse outcome in heart failure (HF). Increased concentrations of midregional proadrenomedullin (MR-proADM) have been associated with DM and are predictors of mortality in HF patients. The aim of this study was to elucidate the impact of DM...

  20. Multimorbidity and Persistent Depression among Veterans with Diabetes, Heart Disease, and Hypertension

    Science.gov (United States)

    Findley, Patricia; Shen, Chan; Sambamoorthi, Usha

    2011-01-01

    This study investigated the association between multimorbidity and persistent depression among cohorts of veterans with diabetes, heart disease, or hypertension. The retrospective longitudinal analysis used national administrative data on around 1.38 million Veteran Health Administration clinic users merged with Medicare claims data.…

  1. GLUT12 deficiency during early development results in heart failure and a diabetic phenotype in zebrafish

    NARCIS (Netherlands)

    Jiménez-Amilburu, Vanesa; Jong-Raadsen, Susanne; Bakkers, Jeroen; Spaink, Herman P; Marín-Juez, Rubén

    2015-01-01

    Cardiomyopathies-associated metabolic pathologies (e.g., type 2 diabetes and insulin resistance) are a leading cause of mortality. It is known that the association between these pathologies works in both directions, for which heart failure can lead to metabolic derangements such as insulin resistanc

  2. The Impact of Personalized Risk Feedback on Mexican Americans' Perceived Risk for Heart Disease and Diabetes

    Science.gov (United States)

    Hovick, Shelly R.; Wilkinson, Anna V.; Ashida, Sato; de Heer, Hendrik D.; Koehly, Laura M.

    2014-01-01

    Little is known about the effect of personalized risk information on risk perceptions over time, particularly among ethnically diverse subpopulations. The present study examines Mexican American's (MAs) risk perceptions for heart disease and diabetes at baseline and following receipt of risk feedback based on family health history. Participants…

  3. Multimorbidity and Persistent Depression among Veterans with Diabetes, Heart Disease, and Hypertension

    Science.gov (United States)

    Findley, Patricia; Shen, Chan; Sambamoorthi, Usha

    2011-01-01

    This study investigated the association between multimorbidity and persistent depression among cohorts of veterans with diabetes, heart disease, or hypertension. The retrospective longitudinal analysis used national administrative data on around 1.38 million Veteran Health Administration clinic users merged with Medicare claims data.…

  4. Prevalence and characteristics of diabetic patients in a chronic heart failure population

    DEFF Research Database (Denmark)

    Kistorp, Caroline; Galatius, Søren; Gustafsson, Finn

    2005-01-01

    Previously, estimates of the prevalence of diabetes mellitus (DM) in patients with chronic heart failure (CHF) have solely been based on history in retrospective studies. The aim of this study was to investigate the prevalence of DM and glucose abnormalities in patients with CHF in accordance...

  5. Selective block of IKs plays a significant role in MAP triangulation induced by IKr block in isolated rabbit heart.

    Science.gov (United States)

    Guérard, N C; Traebert, M; Suter, W; Dumotier, B M

    2008-01-01

    The role of IKr (rapidly-activating delayed rectifier K(+) current) block in triangulation of monophasic action potentials (MAP) and in development of torsade de pointes (TdP) arrhythmia is known. Combined IKr and IKs (slowly-activating delayed rectifier K(+) current) block has been demonstrated to promote TdP. The aim of this study was to describe a possible implication of IKs block in MAP triangulation. Four contact electrodes were placed on the epicardium of the left ventricle of Langendorff-perfused rabbit hearts to record monophasic action potentials (MAP), with an IKr blocker d,l-sotalol (3 to 100 microM, n=6) or a non-selective IKr blocker, quinidine (1 to 30 microM, n=6). Their effects were assessed with or without a specific IKs blocker chromanol 293B (20 microM, n=6), on MAP duration at 30, 60 and 90% of repolarization (APD30, 60 and 90, respectively) and MAP triangulation (APD90-APD30) at 1 and 0.2 Hz. D,L-sotalol increased significantly APD90 and triangulation with reverse use-dependency for concentrations > or =10 microM. Quinidine markedly prolonged APD90 and triangulation with reverse use-dependency at concentrations > or =3 microM. Chromanol 293B alone had no effects on APD, but when combined with D,L-sotalol or quinidine (i) increased APD prolonging effects, (ii) lowered values of pro-arrhythmic concentrations, (iii) increased incidence and length of D,L-sotalol- or quinidine-induced Early Afterdepolarizations (EADs) and TdP. All these events were primarily due to an important slowing of final repolarization, i.e. a marked increased triangulation. IKs, even of low amplitude in rabbits, plays a key role in ventricular repolarization. IKs is involved in prolonged MAP duration mainly by triangulation and subsequent increased drug arrhythmogenicity. Therefore drug affinity for IKs must be evaluated with IKr studies as part of preclinical drug cardiac safety assessment.

  6. Complex regulation of PKCβ2 and PDK-1/AKT by ROCK2 in diabetic heart.

    Directory of Open Access Journals (Sweden)

    Guorong Lin

    Full Text Available OBJECTIVES: The RhoA/ROCK pathway contributes to diabetic cardiomyopathy in part by promoting the sustained activation of PKCβ2 but the details of their interaction are unclear. The purpose of this study was to investigate if over-activation of ROCK in the diabetic heart leads to direct phosphorylation and activation of PKCβ2, and to determine if their interaction affects PDK-1/Akt signaling. METHODS: Regulation by ROCK of PKCβ2 and related kinases was investigated by Western blotting and co-immunoprecipitation in whole hearts and isolated cardiomyocytes from 12 to 14-week diabetic rats. Direct ROCK2 phosphorylation of PKCβ2 was examined in vitro. siRNA silencing was used to confirm role of ROCK2 in PKCβ2 phosphorylation in vascular smooth muscle cells cultured in high glucose. Furthermore, the effect of ROCK inhibition on GLUT4 translocation was determined in isolated cardiomyocytes by confocal microscopy. RESULTS: Expression of ROCK2 and expression and phosphorylation of PKCβ2 were increased in diabetic hearts. A physical interaction between the two kinases was demonstrated by reciprocal immunoprecipitation, while ROCK2 directly phosphorylated PKCβ2 at T641 in vitro. ROCK2 siRNA in vascular smooth muscle cells or inhibition of ROCK in diabetic hearts reduced PKCβ2 T641 phosphorylation, and this was associated with attenuation of PKCβ2 activity. PKCβ2 also formed a complex with PDK-1 and its target AKT, and ROCK inhibition resulted in upregulation of the phosphorylation of PDK-1 and AKT, and increased translocation of glucose transporter 4 (GLUT4 to the plasma membrane in diabetic hearts. CONCLUSION: This study demonstrates that over-activation of ROCK2 contributes to diabetic cardiomyopathy by multiple mechanisms, including direct phosphorylation and activation of PKCβ2 and interference with the PDK-1-mediated phosphorylation and activation of AKT and translocation of GLUT4. This suggests that ROCK2 is a critical node in the

  7. Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes.

    Science.gov (United States)

    Fukushima, Arata; Lopaschuk, Gary D

    2016-10-01

    Obesity and diabetes are major public health problems, and are linked to the development of heart failure. Emerging data highlight the importance of alterations in cardiac energy metabolism as a major contributor to cardiac dysfunction related to obesity and diabetes. Increased rates of fatty acid oxidation and decreased rates of glucose utilization are two prominent changes in cardiac energy metabolism that occur in obesity and diabetes. This metabolic profile is probably both a cause and consequence of a prominent cardiac insulin resistance, which is accompanied by a decrease in both cardiac function and efficiency, and by the accumulation of potentially toxic lipid metabolites in the heart that can further exaggerate insulin resistance and cardiac dysfunction. The high cardiac fatty acid oxidation rates seen in obesity and diabetes are attributable to several factors, including: 1) increased fatty acid supply and uptake into the cardiomyocyte, 2) increased transcription of fatty acid metabolic enzymes, 3) decreased allosteric control of mitochondrial fatty acid uptake and fatty acid oxidation, and 4) increased post-translational acetylation control of various fatty acid oxidative enzymes. Emerging evidence suggests that therapeutic approaches aimed at switching the balance of cardiac energy substrate preference from fatty acid oxidation to glucose use can prevent cardiac dysfunction associated with obesity and diabetes. Modulating acetylation control of fatty acid oxidative enzymes is also a potentially attractive strategy, although presently this is limited to precursors of nicotinamide adenine or nonspecific activators of deacetylation such as resveratrol. This review will focus on the metabolic alterations in the heart that occur in obesity and diabetes, as well as on the molecular mechanisms controlling these metabolic changes. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk.

  8. Age-related differences in biomedical and folk beliefs as causes for diabetes and heart disease among Mexican origin adults.

    Science.gov (United States)

    Palmquist, Aunchalee E L; Wilkinson, Anna V; Sandoval, Juan-Miguel; Koehly, Laura M

    2012-08-01

    An understanding of health beliefs is key to creating culturally appropriate health services for Hispanic populations in the US. In this study we explore age-based variations in causal beliefs for heart disease and diabetes among Mexican origin adults in Houston, TX. This cross-sectional study included 497 adults of Mexican origin. Participants were asked to indicate the importance of biomedically defined and folk illness-related risk factors as causes for heart disease and diabetes. Biomedical risk factors were ranked highest as causes of diabetes and heart disease among all participants. Folk illness-related factors were ranked below biomedical factors as causes of heart disease among all age groups. Susto was ranked above the median as a risk factor for diabetes among older participants. Age-related differences in causal beliefs may have implications for designing culturally appropriate health services, such as tailored diabetes interventions for older Mexican origin adults.

  9. Oxidative stress and inflammation modulate peroxisome proliferator-activated receptors with regional discrepancy in diabetic heart.

    Science.gov (United States)

    Lee, Ting-I; Kao, Yu-Hsun; Chen, Yao-Chang; Pan, Nan-Hung; Chen, Yi-Jen

    2010-08-01

    Peroxisome proliferator-activated receptors (PPARs) play a pivotal role in myocardial lipid and glucose homeostasis. We investigated the effects of diabetes on PPAR isoforms in different cardiac regions and explored whether proinflammatory cytokines or oxidative stress modulate PPARs in diabetic hearts. Male Wistar rats were separated into control, diabetes and ascorbate-treated diabetes groups. Real-time PCR and Western blot analysis were performed on PPAR isoforms, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6, from left and right atria and ventricles. Nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase activity was quantified through photometric measurements. In control hearts, PPAR-alpha was most expressed, and PPAR-gamma least expressed in mRNA and protein levels. Diabetes decreased the protein and mRNA levels of PPAR-alpha and PPAR-delta. Ascorbate attenuated the diabetes-induced down-regulations of PPAR-alpha and PPAR-delta proteins in all cardiac regions and down-regulation of PPAR-alpha mRNA in the left atrium. In PPAR-gamma, the protein and mRNA levels were increased in diabetic atria and ventricles, which were decreased by ascorbate. Moreover, diabetes increased the TNF-alpha and IL-6 protein levels, and NAD(P)H oxidase activities in atria and ventricles. Ascorbate attenuated the increase of TNF-alpha, IL-6 protein levels and NAD(P)H oxidase activity in the atria, but only attenuated the increase of NAD(P)H oxidase activities in the ventricles. Peroxisome proliferator-activated receptor isoforms are differentially expressed in the atria and ventricles. Diabetes can modulate PPARs through increased inflammatory cytokines and oxidative stress, which are attenuated by ascorbate treatment.

  10. Heart Rate Variability as Early Biomarker for the Evaluation of Diabetes Mellitus Progress

    Science.gov (United States)

    Arroyo-Carmona, Rosa Elena; López-Serrano, Ana Laura; Albarado-Ibañez, Alondra; Mendoza-Lucero, Francisca María Fabiola; Medel-Cajica, David; López-Mayorga, Ruth Mery; Torres-Jácome, Julián

    2016-01-01

    According to the American Diabetes Association (ADA), the side effects of diabetes mellitus have recently increased the global health expenditure each year. Of these, the early diagnostic can contribute to the decrease on renal, cardiovascular, and nervous systems complications. However, the diagnostic criteria, which are commonly used, do not suggest the diabetes progress in the patient. In this study, the streptozotocin model in mice (cDM) was used as early diagnostic criterion to reduce the side effects related to the illness. The results showed some clinical signs similarly to five-year diabetes progress without renal injury, neuropathies, and cardiac neuropathy autonomic in the cDM-model. On the other hand, the electrocardiogram was used to determine alterations in heart rate and heart rate variability (HRV), using the Poincaré plot to quantify the HRV decrease in the cDM-model. Additionally, the SD1/SD2 ratio and ventricular arrhythmias showed increase without side effects of diabetes. Therefore, the use of HRV as an early biomarker contributes to evaluating diabetes mellitus complications from the diagnostic. PMID:27191000

  11. Heart Rate Variability as Early Biomarker for the Evaluation of Diabetes Mellitus Progress

    Directory of Open Access Journals (Sweden)

    Rosa Elena Arroyo-Carmona

    2016-01-01

    Full Text Available According to the American Diabetes Association (ADA, the side effects of diabetes mellitus have recently increased the global health expenditure each year. Of these, the early diagnostic can contribute to the decrease on renal, cardiovascular, and nervous systems complications. However, the diagnostic criteria, which are commonly used, do not suggest the diabetes progress in the patient. In this study, the streptozotocin model in mice (cDM was used as early diagnostic criterion to reduce the side effects related to the illness. The results showed some clinical signs similarly to five-year diabetes progress without renal injury, neuropathies, and cardiac neuropathy autonomic in the cDM-model. On the other hand, the electrocardiogram was used to determine alterations in heart rate and heart rate variability (HRV, using the Poincaré plot to quantify the HRV decrease in the cDM-model. Additionally, the SD1/SD2 ratio and ventricular arrhythmias showed increase without side effects of diabetes. Therefore, the use of HRV as an early biomarker contributes to evaluating diabetes mellitus complications from the diagnostic.

  12. Overweight, resting heart rate, and prediabetes/diabetes: A population-based prospective cohort study among Inner Mongolians in China.

    Science.gov (United States)

    Zhang, Shao Yan; Wu, Jia Hui; Zhou, Jing Wen; Liang, Zhu; Qiu, Qiao Yan; Xu, Tian; Zhang, Ming Zhi; Zhong, Chong Ke; Jiang, Wei; Zhang, Yong Hong

    2016-03-31

    We aimed to investigate the cumulative effect of overweight and resting heart rate on prediabetes/diabetes incidence in an 10-year follow-up study in Inner Mongolians. Among 1729 participants who were free from prediabetes and diabetes at baseline, 503 and 155 subjects developed prediabetes and diabetes, respectively. We categorized the participants into 4 subgroups according to overweight and resting heart rate status. The multivariate-adjusted OR (95% CI) in normal weight with heart rate ≥80 bpm, overweight with heart rate overweight with heart rate ≥80 bpm were 1.24 (0.95-1.61), 1.83 (1.29-2.61), 2.20 (1.41-3.45) for prediabetes and 1.52 (0.97-2.40), 3.64 (2.21-6.01), 4.61 (2.47-8.61) for diabetes, respectively, compared with normal weight with heart rate overweight and resting heart rate, along with conventional factors (AUC = 0.751), was significantly (P = 0.003) larger than the one containing only conventional factors (AUC = 0.707). Our study indicated that overweight was an independent risk factor of prediabetes and diabetes, and overweight with faster resting heart rate might further increase the risk of prediabetes and diabetes.

  13. The impact of heart failure on prognosis of diabetic and non-diabetic patients with myocardial infarction: a 15-year follow-up study

    DEFF Research Database (Denmark)

    Melchior, T; Rask-Madsen, C; Torp-Pedersen, C;

    2001-01-01

    BACKGROUND: Information about the occurrence of heart failure in the acute phase of myocardial infarction (MI) in diabetic patients and its impact on prognosis are sparse. AIM: The purpose of the present study was to describe how MI patients with diabetes mellitus (DM) differed from MI patients...... to the development of heart failure. In acute myocardial infarction diabetic patients with heart failure have a worse prognosis than non-diabetic patients with heart failure....... admitted to one coronary care unit (CCU) between 1979 and 1983. DM was diagnosed in 10% (n=194), with 17% (n=33) on insulin therapy. Patients with DM comprised of a higher proportion of women (DM 36% vs. no DM 26%, P

  14. 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.

  15. Circadian rhythm of heart rate in the rabbit: prolongation of action potential duration by sustained beta adrenoceptor blockade is not due to associated bradycardia.

    Science.gov (United States)

    Vaughan Williams, E M; Dennis, P D; Garnham, C

    1986-07-01

    Six litters of six young rabbits were injected intraperitoneally, two per litter, with saline, alinidine, or nadolol once or twice daily for two weeks. In four litters successful radiotransmissions of electrocardiograms were recorded once hourly for four days before and during treatment. Alinidine and nadolol produced an overall mean bradycardia in comparison with saline treated animals, the effect of alinidine exceeding that of nadolol. At 48-70 hours after the end of treatment the hearts were used for in vitro electrophysiological study. Nadolol, but not alinidine, induced a prolongation of action potential duration compared with that of saline treated littermates in both atrial and ventricular muscle. An incidental observation was that heart rate in the rabbit followed a circadian rhythm, heart rates being slower in the morning and faster in late afternoon and evening. The circadian rhythm was attenuated but not abolished by alinidine and nadolol. These results suggest that if prolongation of action potential duration by sustained beta blockade in patients after myocardial infarction contributes to protection against sudden death (by a class III antiarrhythmic action) then alinidine would not be expected to provide a comparable prophylaxis.

  16. Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress, and apoptosis

    Science.gov (United States)

    Wu, Yanqing; Reece, E. Albert; Zhong, Jianxiang; Dong, Daoyin; Shen, Wei-Bin; Harman, Christopher R.; Yang, Peixin

    2017-01-01

    BACKGROUND Maternal type 1 and 2 diabetes mellitus are strongly associated with high rates of severe structural birth defects, including congenital heart defects. Studies in type 1 diabetic embryopathy animal models have demonstrated that cellular stress-induced apoptosis mediates the teratogenicity of maternal diabetes leading to congenital heart defect formation. However, the mechanisms underlying maternal type 2 diabetes mellitus–induced congenital heart defects remain largely unknown. OBJECTIVE We aim to determine whether oxidative stress, endoplasmic reticulum stress, and excessive apoptosis are the intracellular molecular mechanisms underlying maternal type 2 diabetes mellitus–induced congenital heart defects. STUDY DESIGN A mouse model of maternal type 2 diabetes mellitus was established by feeding female mice a high-fat diet (60% fat). After 15 weeks on the high-fat diet, the mice showed characteristics of maternal type 2 diabetes mellitus. Control dams were either fed a normal diet (10% fat) or the high-fat diet during pregnancy only. Female mice from the high-fat diet group and the 2 control groups were mated with male mice that were fed a normal diet. At E12.5, embryonic hearts were harvested to determine the levels of lipid peroxides and superoxide, endoplasmic reticulum stress markers, cleaved caspase 3 and 8, and apoptosis. E17.5 embryonic hearts were harvested for the detection of congenital heart defect formation using India ink vessel patterning and histological examination. RESULTS Maternal type 2 diabetes mellitus significantly induced ventricular septal defects and persistent truncus arteriosus in the developing heart, along with increasing oxidative stress markers, including superoxide and lipid peroxidation; endoplasmic reticulum stress markers, including protein levels of phosphorylated-protein kinase RNA-like endoplasmic reticulum kinase, phosphorylated-IRE1α, phosphorylated-eIF2α, C/EBP homologous protein, and binding immunoglobulin

  17. Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart disease.

    Science.gov (United States)

    Rawal, Shruti; Manning, Patrick; Katare, Rajesh

    2014-02-14

    Diabetic heart disease (DHD) is the leading cause of morbidity and mortality among the people with diabetes, with approximately 80% of the deaths in diabetics are due to cardiovascular complications. Importantly, heart disease in the diabetics develop at a much earlier stage, although remaining asymptomatic till the later stage of the disease, thereby restricting its early detection and active therapeutic management. Thus, a better understanding of the modulators involved in the pathophysiology of DHD is necessary for the early diagnosis and development of novel therapeutic implications for diabetes-associated cardiovascular complications. microRNAs (miRs) have recently been evolved as key players in the various cardiovascular events through the regulation of cardiac gene expression. Besides their credible involvement in controlling the cellular processes, they are also released in to the circulation in disease states where they serve as potential diagnostic biomarkers for cardiovascular disease. However, their potential role in DHD as modulators as well as diagnostic biomarkers is largely unexplored. In this review, we describe the putative mechanisms of the selected cardiovascular miRs in relation to cardiovascular diseases and discuss their possible involvement in the pathophysiology and early diagnosis of DHD.

  18. [Cardiovascular disease prevention in adults with type 2 diabetes mellitus according to the recent statement from the American Heart Association/American Diabetes Association].

    Science.gov (United States)

    Avogaro, Angelo

    2016-03-01

    There is a clear epidemiologic association between glycemic control and cardiovascular disease. There is strong evidence of a microvascular benefit by lowering glycated hemoglobin diabetic patients, to control all major cardiovascular risk factors such as obesity, hypertension, and dyslipidemia. These risk factors, easily measurable, account for 90% of acute myocardial infarction. In this review, the update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus from the American Heart Association and the American Diabetes Association is discussed and commented.

  19. Effect of Shengmai Injection on Vascular Endothelial and Heart Functions in Patients with Coronary Heart Disease Complicated with Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ya-chen; LU Bao-jing; ZHAO Mei-hua; RONG Ye-zhi; CHEN Rui-ming

    2008-01-01

    Objective: To study the effect of Shengrnai injection (生脉注射液, SMI) on vascular endothelial and heart functions in coronary heart disease patients complicated with diabetes mellitus (CHD-DM). Methods: One hundred and twenty patients with CHD-DM, their diagnosis confirmed by coronary arteriography, were equally randomized into a control group treated with conventional treatment and a treated group treated with conventional treatment plus SMI. The changes in blood levels of nitric oxide (NO), endothelin-1 (ET-1) and angiotensin Ⅱ (Ang Ⅱ ), as well as endothelium-dependent vascular dilating function and heart function in the patients were observed before treatment and after the 3-week treatment. Results: After being treated with SMI for 3 weeks, in the treated group, blood level of NO was raised significantly from 69.8 ± 33.1 μ mol/L to 120.1 ± 50.8 μ mol/L, and ET-1 was lowered from 70.1 ± 32.1 ng/L to 46.2±21.3 ng/L, respectively (P<0.01); that of Ang Ⅱ was lowered from 81.3 ± 24.3 ng/L to 50.2 ± 27.3 ng/L (P<0.01); brachial arterial post-congestion blood flow increasing rate was raised from 389.4 ± 26.3% to 459.3 ± 27.8% (P<0.01); and the improvement in heart function as seen through the ejection fraction (EF) was increased from 44 ± 5% to 68 ± 6% (P<0.01), all the changes being more significant than those in the control group (all P<0.01). Conclusion: SMI can improve not only the endothelial function in CHD-DM patients, but also heart contraction significantly.

  20. Monitoring Heart Disease and Diabetes with Mobile Internet Communications

    Directory of Open Access Journals (Sweden)

    David Mulvaney

    2012-01-01

    Full Text Available A telemedicine system is described for monitoring vital signs and general health indicators of patients with cardiac and diabetic conditions. Telemetry from wireless sensors and readings from other instruments are combined into a comprehensive set of measured patient parameters. Using a combination of mobile device applications and web browser, the data can be stored, accessed, and displayed using mobile internet communications to the central server. As an extra layer of security in the data transmission, information embedded in the data is used in its verification. The paper highlights features that could be enhanced from previous systems by using alternative components or methods.

  1. Effect of fiberoptic intubation on myocardial ischemia and hormonal stress response in diabetics with ischemic heart disease

    Directory of Open Access Journals (Sweden)

    Nashwa Nabil Mohamed

    2014-01-01

    Conclusion: The optimum use of fiberoptic bronchoscope with avoidance of jaw thrust maneuver attenuates the hemodynamic response to intubation which is beneficial in diabetic patients with ischemic heart disease. Stress response hormones showed no statistically significant difference between groups.

  2. Resting heart rate and measures of effort-related cardiac autonomic dysfunction predict cardiovascular events in asymptomatic type 2 diabetes.

    Science.gov (United States)

    Zafrir, Barak; Azencot, Mali; Dobrecky-Mery, Idit; Lewis, Basil S; Flugelman, Moshe Y; Halon, David A

    2016-08-01

    Autonomic control of the cardiovascular system may be impaired in type 2 diabetes and is associated with increased morbidity and mortality. Parameters obtained during stress testing may reflect early stages of cardiac autonomic dysfunction and provide prognostic information in asymptomatic type 2 diabetes. We performed maximal exercise treadmill testing in 594 patients with type 2 diabetes without known coronary heart disease. The prognostic significance of physiological parameters associated with autonomic dysfunction was assessed, including chronotropic incompetence (heart rate reserve), abnormal heart rate recovery at 1 minute 100 beats/minute. Cox proportional hazards analysis was used to determine the association of exercise parameters with a composite outcome of all-cause mortality, myocardial infarction or stroke. Resting heart rate >100 beats/minute was observed in 18% of patients, chronotropic incompetence in 30% and heart rate recovery at 1 minute heart rate ≥100 beats/minute (hazard ratio 1.97, 95% confidence interval 1.19-3.26; P = 0.008) and heart rate recovery at 1 minute heart rate recovery are independently and additively associated with long-term mortality, myocardial infarction or stroke in type 2 diabetes without known coronary heart disease. © The European Society of Cardiology 2015.

  3. Nanosecond pulse electric field activation of platelet-rich plasma reduces myocardial infarct size and improves left ventricular mechanical function in the rabbit heart.

    Science.gov (United States)

    Hargrave, Barbara; Li, Francis

    2012-12-01

    In the current study, we used the novel, nonchemical method of nanosecond pulsed electric fields (nsPEF) to investigate the efficiency of a protocol involving the in vivo treatment of the ischemic and reperfused heart and heart cells in culture with platelet-rich plasma (PRP). Associated with the restoration of blood flow to the ischemic tissue is a phenomenon referred to as "ischemic reperfusion injury." Clinically a type of reperfusion injury occurs during coronary bypass surgery once blood perfusion to the heart is restarted. Although the restoration of oxygen to ischemic myocardial cells is critical for tissue survival, reperfusion causes myocardial oxidative stress, attributable in part to the increased production of reactive oxygen species (ROS). Enhanced ROS production is associated with mitochondrial damage. Adult female New Zealand white rabbits were anesthetized and a left thoracotomy performed to expose the heart. The distal segment of the left anterior descending coronary artery was occluded for 15 minutes and then released so reperfusion of the tissue could occur. PRP (.21 mg/heart) or saline was injected into the ischemic area of the myocardium. Mechanical function of the left ventricle was analyzed using a Millar catheter attached to a Micro-Med Analysis System. H9c2 cells in culture were treated with 1 mL of nsPEF activated PRP (1.05 mg/flask) for 24 hours before analysis for ROS production or mitochondrial depolarization damage). The left ventricle contracted and relaxed faster and infarct size was reduced in hearts treated with PRP compared with saline. ROS production and mitochondrial depolarization were reduced in H9c2 cells treated with PRP and stimulated with hydrogen peroxide. These results provide evidence that nsPEFs can successfully be used to prepare PRP and that the PRP is functional in heart protection possibly by reducing ROS generation and stabilizing the mitochondria of the ischemic/reperfused heart.

  4. Maternal Diabetes Leads to Unphysiological High Lipid Accumulation in Rabbit Preimplantation Embryos

    NARCIS (Netherlands)

    Schindler, Maria; Pendzialek, Mareike; Santos, Alexander Navarrete; Ploesch, Torsten; Seyring, Stefanie; Guerke, Jacqueline; Haucke, Elisa; Knelangen, Julia Miriam; Fischer, Bernd; Santos, Anne Navarrete

    2014-01-01

    According to the "developmental origin of health and disease" hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation devel

  5. Maternal Diabetes Leads to Unphysiological High Lipid Accumulation in Rabbit Preimplantation Embryos

    NARCIS (Netherlands)

    Schindler, Maria; Pendzialek, Mareike; Santos, Alexander Navarrete; Ploesch, Torsten; Seyring, Stefanie; Guerke, Jacqueline; Haucke, Elisa; Knelangen, Julia Miriam; Fischer, Bernd; Santos, Anne Navarrete

    According to the "developmental origin of health and disease" hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation

  6. Vitamin D Insufficiency Is Associated with Lower Physical Function in Patients with Heart Failure and Diabetes

    Directory of Open Access Journals (Sweden)

    M. R. Lopes

    2014-01-01

    Full Text Available Vitamin D deficiency is frequent among patients with heart failure (HF and diabetes, disorders associated with exercise intolerance and muscle weakness. This study aims to search for associations between vitamin D sufficiency and physical function indexes in patients with HF and diabetes. A cross-sectional study of 146 HF patients, 39.7% with diabetes, at a Brazilian tertiary outpatient clinic was performed. Patients underwent clinical evaluation, 6-minute walk test (6 MWT, handgrip strength, physical activity level (IPAQ, and biochemical evaluations including serum 25-hydroxyvitamin D. Classification was done according to vitamin D status (≥30 ng/dL, sufficient and presence/absence of diabetes in vitamin sufficient, no diabetes (DS-C, n=25, vitamin sufficient, diabetes (DS-DM, n=18, vitamin deficient, no diabetes (DD-C, n= 63, and vitamin deficient, diabetes (DD-DM, n=40. Patients age was 55.4 ± 8 yrs; 70.5% had vitamin D deficiency. Clinical characteristics were similar among groups. Total time expended in physical activity was similar among groups (P=0.26. DS-C covered higher distances in the 6 MWT (392 ± 60 m versus DD-DM (309 ± 116 m; P=0.024. Handgrip strength was similar among groups but tended to lower levels in DD-DM (P=0.074 even after being adjusted to physical activity (P=0.069. Vitamin D deficiency can influence physical function in HF diabetic patients.

  7. Prevalence and characteristics of diabetic patients in a chronic heart failure population

    DEFF Research Database (Denmark)

    Kistorp, Caroline; Galatius, Søren; Gustafsson, Finn;

    2005-01-01

    Previously, estimates of the prevalence of diabetes mellitus (DM) in patients with chronic heart failure (CHF) have solely been based on history in retrospective studies. The aim of this study was to investigate the prevalence of DM and glucose abnormalities in patients with CHF in accordance...... with the modern diagnostic criteria of DM. A second aim was to characterize patients with DM with respect to severity of CHF....

  8. Heart Rate and Systolic Blood Pressure Variability on Recently Diagnosed Diabetics

    Directory of Open Access Journals (Sweden)

    Anaclara Michel-Chávez

    2015-01-01

    Full Text Available Background: Diabetes affects approximately 250 million people in the world. Cardiovascular autonomic neuropathy is a common complication of diabetes that leads to severe postural hypotension, exercise intolerance, and increased incidence of silent myocardial infarction. Objective: To determine the variability of heart rate (HR and systolic blood pressure (SBP in recently diagnosed diabetic patients. Methods: The study included 30 patients with a diagnosis of type 2 diabetes of less than 2 years and 30 healthy controls. We used a Finapres® device to measure during five minutes beat-to-beat HR and blood pressure in three experimental conditions: supine position, standing position, and rhythmic breathing at 0.1 Hz. The results were analyzed in the time and frequency domains. Results: In the HR analysis, statistically significant differences were found in the time domain, specifically on short-term values such as standard deviation of NN intervals (SDNN, root mean square of successive differences (RMSSD, and number of pairs of successive NNs that differ by more than 50 ms (pNN50. In the BP analysis, there were no significant differences, but there was a sympathetic dominance in all three conditions. The baroreflex sensitivity (BRS decreased in patients with early diabetes compared with healthy subjects during the standing maneuver. Conclusions: There is a decrease in HR variability in patients with early type 2 diabetes. No changes were observed in the BP analysis in the supine position, but there were changes in BRS with the standing maneuver, probably due to sympathetic hyperactivity.

  9. Revascularization for patients with diabetes mellitus and stable ischemic heart disease: an update.

    Science.gov (United States)

    Mancini, G B John; Farkouh, Michael; Verma, Subodh

    2017-09-01

    To provide an update on the management of patients with diabetes mellitus and requiring coronary revascularization. Evidence continues to show that patients with diabetes mellitus and ischemic heart disease represent a very high-risk group of patients. Choice of stent appears important for minimizing target lesion and target vessel adverse events with everolimus eluting stents having the best performance, particularly in patients being treated with insulin. The higher risk of adverse angioplasty results in patients with diabetes appears most related to the disease state per se and not necessarily to anatomical complexities. Interestingly, physiologic documentation of nonischemia producing lesions with use of fractional flow reserve appears less reassuring in this setting of aggressive and rapid atherosclerosis progression, particularly if myocardial infarction has occurred previously, than in patients without diabetes. Coronary artery bypass surgery in patients with appropriate anatomy and diabetes continues to emerge in many analyzes as the optimal, long-term therapy. The treatment of diabetes per se, advances in stent technology and optimization of coronary artery bypass techniques are all occurring in parallel making it very critical for the design of modern era trials that keep pace with these advances. Currently, in patients with appropriate anatomy who are willing candidates, bypass surgery remains the optimal, long-term therapeutic option.

  10. Slowing of electrical activity in ventricular fibrillation is not associated with increased defibrillation energies in the isolated rabbit heart

    Directory of Open Access Journals (Sweden)

    Jane eCaldwell

    2011-04-01

    Full Text Available Prolonged out-of-hospital ventricular fibrillation (VF arrests are associated with reduced ECG dominant frequency (DF and diminished defibrillation success. Partial reversal of ischaemia increases ECG DF and improves defibrillation outcome. We have investigated the metabolic components of ischaemia responsible for the decline in ECG DF and defibrillation success.Isolated Langendorff-perfused rabbit hearts were loaded with the voltage-sensitive dye RH237. Using a photodiode array, epicardial membrane potentials were recorded at 252 sites (15x15mm on the anterior surface of the left & right ventricles. Simultaneously, a global ECG was recorded. VF was induced by burst pacing, and after 60s, perfusion was either reduced to 6ml/min or the perfusate composition changed to impose hypoxia (95%N2/5%CO2, pH 6.7 (80%O2/20%CO2, or hyperkalaemia (8mM. Using Fast Fourier Transform, power spectra were created from the optical signals and the global ECG. The optical power spectra were summated to give a global power spectrum (pseudoECG. At 600s the minimum defibrillation voltage (MDV was determined by step-up protocol.During VF, the ECG and pseudoECG DF were reduced by low-flow ischaemia (9.0±1.0Hz, p<0.01, n=5 and raised [K+]o (12.2±1.3 Hz, p<0.05, n=7 compared to control (19.2±1.5 Hz, n=20, but were unaffected by acidic pHo (16.7±1.1 Hz, n=11 and hypoxia (14.0±1.2 Hz, n=10. In contrast, the MDV was raised by acidic pH (156.1±26.4V, p<0.001 and hypoxia (154.1±22.1V, p<0.01 compared to control (65.6±2.3V, but comparable changes were not observed in low-flow ischaemia (61.0±0.5V or raised [K+]o (56±3V. In summary, different metabolites are responsible for the reduction in DF and the increase in defibrillation energy during ischaemic VF.

  11. The use of metoprolol CR/XL in the treatment of patients with diabetes and chronic heart failure

    Directory of Open Access Journals (Sweden)

    Ovidio De Freitas

    2006-06-01

    Full Text Available Ovidio De Freitas, Oliver Lenz, Alessia Fornoni, Barry J MatersonDivision of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida, USAAbstract: About 5 million Americans suffer from heart failure. Given the correlation of heart failure with age and the rising life expectancy, the prevalence of heart failure continues to increase in the general population. Sympathetic stimulation intensifies with progressive heart failure. The rationale to use β-blockers in individuals with impaired myocardial function is based on experimental evidence supporting the notion that prolonged α- and β-adrenergic stimulation leads to worsening heart failure. Until recently, safety concerns have precluded the use of β-blockers in patients with diabetes and heart failure. However, several large, randomized, placebo-controlled clinical trials such as Metoprolol Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF have shown that β-blockers can be safely used in patients with diabetes and heart failure. Moreover, β-blockers significantly improved morbidity and mortality in this population. Based on this evidence, it is now recommended to add β-blockers such as metoprolol CR/XL with an escalating dosage regimen to the treatment of patients with symptomatic heart failure who already are receiving a stable medical regimen including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, diuretics, vasodilators, or digitalis.Keywords: metoprolol, heart failure, diabetes mellitus, β-adrenergic blocking agents, MERITHF

  12. Novel insight into the dangerous connection between diabetes and heart failure.

    Science.gov (United States)

    Lombardi, C; Spigoni, V; Gorga, E; Dei Cas, A

    2016-05-01

    Heart failure (HF) affects approximately 1-2 % of the adult population. Diabetes mellitus (DM) is one of the most frequent comorbidities in HF, portending a worse prognosis. DM is associated with an increased risk of artery disease, and consequently of post-ischemic HF, but it may also alter directly the myocardial structure and function. Insights into the pathophysiological mechanisms of diabetic cardiomyopathy have been provided by both experimental and clinical investigations. In recent years, it has emerged that the fibrotic process is a result of the convergence of multiple neurohormonal alterations in diabetic cardiomyopathy at the basis of disease progression and phenotype determination: HF with reduced or preserved ejection fraction. Therapies for HF and DM should demonstrate an improved prognosis and have a neutral effect on glucose homeostasis and the risk of HF development.

  13. Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy.

    Science.gov (United States)

    Sacre, J W; Jellis, C L; Coombes, J S; Marwick, T H

    2012-09-01

    Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type 2 diabetes. Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type 2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥ 2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Patients with cardiac autonomic neuropathy (n = 27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P Heart-rate recovery demonstrated univariate associations with autonomic function markers (r-values 0.20-0.46, P heart-rate recovery parameters (range 0.80-0.83, P heart-rate recovery at 1-, 2- and 3-min post-exercise were ≤ 28 beats/min (sensitivity 93%, specificity 69%), ≤ 50 beats/min (sensitivity 96%, specificity 63%) and ≤ 52 beats/min (sensitivity 70%, specificity 84%), respectively. These criteria predicted cardiac autonomic neuropathy independently of relevant clinical and exercise test information (adjusted odds ratios 7-28, P exercise heart-rate recovery provides an accurate diagnostic test for cardiac autonomic neuropathy in Type 2 diabetes. The high sensitivity and modest specificity suggests heart-rate recovery may be useful to screen for patients requiring clinical autonomic evaluation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  14. Diabetes Increases Cryoinjury Size with Associated Effects on Cx43 Gap Junction Function and Phosphorylation in the Mouse Heart

    Directory of Open Access Journals (Sweden)

    Joseph A. Palatinus

    2016-01-01

    Full Text Available Diabetic patients develop larger myocardial infarctions and have an increased risk of death following a heart attack. The poor response to myocardial injury in the diabetic heart is likely related to the many metabolic derangements from diabetes that create a poor substrate in general for wound healing, response to injury and infection. Studies in rodents have implicated a role for the gap junction protein connexin 43 (Cx43 in regulating the injury response in diabetic skin wounds. In this study, we sought to determine whether diabetes alters Cx43 molecular interactions or intracellular communication in the cryoinjured STZ type I diabetic mouse heart. We found that epicardial cryoinjury size is increased in diabetic mice and this increase is prevented by preinjury insulin administration. Consistent with these findings, we found that intercellular coupling via gap junctions is decreased after insulin administration in diabetic and nondiabetic mice. This decrease in coupling is associated with a concomitant increase in phosphorylation of Cx43 at serine 368, a residue known to decrease channel conductance. Taken together, our results suggest that insulin regulates both gap junction-mediated intercellular communication and injury propagation in the mouse heart.

  15. Diabetes is a predictor of coronary artery stenosis in patients hospitalized with heart failure.

    Science.gov (United States)

    Kosuga, Tsuneharu; Komukai, Kimiaki; Miyanaga, Satoru; Kubota, Takeyuki; Nakata, Kotaro; Suzuki, Kenichiro; Yamada, Takayuki; Yoshida, Jun; Kimura, Haruka; Yoshimura, Michihiro

    2016-05-01

    In patients with heart failure, coronary artery disease is the most common underlying heart disease, and is associated with increased mortality. However, estimating the presence or absence of coronary artery disease in patients with heart failure is sometimes difficult without coronary imaging. We reviewed 155 consecutive patients hospitalized with heart failure who underwent coronary angiography. The patients were divided into two groups: patients with (N = 59) and without (N = 96) coronary artery stenosis. The clinical characteristics and blood sampling data were compared between the two groups. The patients with coronary artery stenosis were older than those without. The prevalence of diabetes mellitus (DM), dyslipidemia and a history of revascularization was higher in the patients with coronary artery stenosis. Patients with coronary artery stenosis tended to have wall motion asynergy more frequently than those without. On the other hand, the prevalence of atrial fibrillation (AF) was lower in patients with coronary artery stenosis. The serum hemoglobin level and estimated glomerular filtration rate were lower in patients with coronary artery stenosis than in those without. In the multivariate analysis, DM (odds ratio 3.517, 95 % CI 1.601-7.727) was found to be the only the predictor of the presence of coronary artery stenosis in patients with heart failure. In conclusion, coronary imaging is strongly recommended for heart failure patients with DM to confirm the presence of coronary artery stenosis.

  16. Uncovering heart failure with preserved ejection fraction in patients with type 2 diabetes in primary care : Time for a change

    NARCIS (Netherlands)

    Boonman-de Winter, L. J M; Cramer, M. J.; Hoes, A. W.; Rutten, F. H.

    2016-01-01

    Undetected heart failure appears to be an important health problem in patients with type 2 diabetes and aged ≥ 60 years. The prevalence of previously unknown heart failure in these patients is high, steeply rises with age, and is overall higher in women than in men. The majority of the patients with

  17. Tissue advanced glycation end products are associated with diastolic function and aerobic exercise capacity in diabetic heart failure patients

    NARCIS (Netherlands)

    Willemsen, Suzan; Hartog, Jasper W. L.; Hummel, Yoran M.; van Ruijven, Marieke H. I.; van der Horst, Iwan C. C.; van Veldhuisen, Dirk J.; Voors, Adriaan A.

    2011-01-01

    Aims Advanced glycation end products (AGEs) are increased in patients with diabetes and are associated with diastolic dysfunction through the formation of collagen crosslinks in the heart. The association among AGEs, diastolic function, and aerobic capacity in heart failure (HF) patients with and wi

  18. The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive

    DEFF Research Database (Denmark)

    Falskov, Britt; Hermann, Thomas Steffen; Rask-Madsen, Christian;

    2011-01-01

    AIM: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes. ME...

  19. Heart lesions associated with anabolic steroid abuse: comparison of post-mortem findings in athletes and norethandrolone-induced lesions in rabbits.

    Science.gov (United States)

    Fanton, Laurent; Belhani, Dalila; Vaillant, Fanny; Tabib, Alain; Gomez, Ludovic; Descotes, Jacques; Dehina, Leila; Bui-Xuan, Bernard; Malicier, Daniel; Timour, Quadiri

    2009-07-01

    Among 15,000 forensic post-mortem examinations performed on the coroner's order over a 24-year period (January 1981-December 2004) in the area of Lyon, France (population: 2,000,000), 2250 cases of unexpected cardiac sudden death were identified retrospectively according to WHO criteria. Of these, 108 occurred during recreational sport and 12 occurred in athletes. In the latter category, a history of anabolic steroid abuse was found in 6 cases, whereas pre-existing ordinary cardiac lesions were observed in the 6 remaining cases. To shed light on the possible role of anabolic steroids in the induction of cardiac lesions, an experimental study was conducted in rabbits that were treated orally with norethandrolone 8mg/kg/day for 60 days, and sacrificed at day 90. The histopathological examination of the heart from treated animals showed coronary thrombosis associated with left ventricle hypertrophy in 3 cases, and lesions analogous to toxic or adrenergic myocarditis in all other treated animals. These findings were very similar to those observed after cardiac sudden death in the 6 athletes with a history of anabolic steroid abuse. In addition, elevated caspase-3 activity in the heart of treated rabbits as compared to controls suggests that apoptosis is involved in the induction of norethandrolone-induced cardiac lesions. These results confirm the cardiotoxic potential of anabolic steroid abuse.

  20. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations.

    Science.gov (United States)

    Low Wang, Cecilia C; Hess, Connie N; Hiatt, William R; Goldfine, Allison B

    2016-06-14

    Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting.

  1. Establishment of ischemia-induced atrial fibrillation model in isolated rabbit heart%离体兔缺血性心房颤动模型的建立

    Institute of Scientific and Technical Information of China (English)

    陈晓丽

    2012-01-01

    目的 建立离体兔的缺血性心房颤动模型.方法 40只健康雄性的新西兰兔(2.2 ~2.5 kg),随机分为正常流量灌流组、正常流量灌流+短促高频电刺激组、低灌流模拟心肌缺血组、低灌流模拟心肌缺血+短促高频电刺激组,每组10只.采用Langendorff灌流装置行主动脉逆行灌流,通过缺血和短促高频电刺激诱发心房颤动.结果 正常流量灌流组、正常流量灌流+短促高频电刺激、低灌流模拟心肌缺血组心房颤动的发生率为0%,而低灌流模拟心肌缺血+短促高频电刺激组心房颤动的发生率为90%.结论 通过Langendorff心脏灌流中模拟心肌缺血,并给予短促高频电刺激模拟应激事件,可以稳定地诱导心房颤动的发生.%Objective To establish an ischemia-induced atrial fibrillation (AF) model in the isolated rabbit heart. Methods Forty healthy male New Zealand white rabbits (2. 2 -2.5 kg) were used in experiments. The isolated heart were randomly assigned to normal perfusion, normal perfusion with burst high-frequency electric stimulation, low perfusion, and low perfusion with burst high-frequency electric stimulation with 10 in each group. The isolated hearts were perfused with Langendorff perfusion system. Results The incidence of AF in group with burst electric stimulation during low perfusion was 90% ; while no AF was induced in other three groups. Conclusion Atrial fibrillation can be stably induced by ischemia with burst electric stimulation in isolated rabbit heart.

  2. New-Onset Diabetes Mellitus After Heart Transplantation - Incidence, Risk Factors and Impact on Clinical Outcome.

    Science.gov (United States)

    Kim, Ho Jin; Jung, Sung-Ho; Kim, Jae-Joong; Yun, Tae-Jin; Kim, Joon Bum; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won

    2017-05-25

    New-onset diabetes mellitus (DM) can occur as a serious complication after heart transplantation, but the comparative data on its clinical impact on survival and on transplant-related adverse events are limited.Methods and Results:We reviewed a total of consecutive 391 patients aged ≥17 years undergoing isolated orthotopic heart transplantation at the present institution from 1992 to 2013. The entire cohort was divided into 3 groups: (1) no diabetes (n=257); (2) pre-existing DM (n=46); and (3) new-onset DM (n=88). Early and long-term clinical outcomes were compared across the 3 groups. Early death occurred in 8 patients (2.0%). Of the 345 non-diabetic patients before transplantation, 88 (25.5%) developed new-onset DM postoperatively. During follow-up, 83 (21.2%) died. On time-varying Cox analysis, new-onset DM was associated with increased risk for overall death (HR, 2.11; 95% CI: 1.26-3.55) and tended to have a greater risk for severe chronic kidney disease (HR, 1.77; 95% CI: 0.94-3.44). Compared with the no-diabetes group, the new-onset DM group had a worse survival rate (P=0.035), but a similar survival rate to that of the pre-existing DM group (P=0.364). New-onset DM has a negative effect on long-term survival and kidney function after heart transplantation. Further studies are warranted to evaluate the relevance of early diagnosis and timely control of new-onset DM to improve long-term survival.

  3. Physical Exercise Improves Heart Rate Variability in Patients with Type 2 Diabetes: A Systematic Review.

    Science.gov (United States)

    Villafaina, Santos; Collado-Mateo, Daniel; Fuentes, Juan Pedro; Merellano-Navarro, Eugenio; Gusi, Narcis

    2017-09-23

    The aim of the present systematic review is to provide an up-to-date analysis of the research on the effects of exercise programs on heart rate variability (HRV) in individuals with type 2 diabetes mellitus (T2DM). An electronic search of the literature (PubMed, PEDro and Web of Science) was performed. "HRV", "heart rate variability", "exercise", "physical" and "diabetes" were the terms used for article retrieval. Lastly, 15 articles were selected. PRISMA methodology was employed and data were extracted according to the PICOS approach. Although HRV is not routinely measured in the management of T2DM, it is an important measure due to its relation with mortality and diabetic neuropathy. Physical exercise has become a therapy for T2DM, because it improves physical fitness and functional capacity, enhances metabolic control and insulin sensitivity, reduces inflammatory markers and neuropathy symptoms and can increase the regenerative capacity of cutaneous axons, slowing or preventing neuropathy progression. However, it is not clear to what extent physical exercise can improve HRV in this population. Participation in the 15 selected studies was similar in men and women (48.01% men and 51.99% women). All the intervention programs included aerobic training, and it was complemented by strength training in four studies. Duration of physical exercise sessions ranged between 30 and 75 min, the frequency being between 2 and 7 days/week. Statistically significant improvements in groups with diabetes, relative to baseline, were observed in nine studies. More than 3 days per week of aerobic training, complemented by strength training, during at least 3 months seems to improve HRV in T2DM. Weekly frequency might be the most important factor to improve HRV. These aspects could help to design better programs based in scientific evidence, incorporating HRV as an important variable associated with diabetic neuropathy and mortality.

  4. Dimensions of compartments and membrane surfaces in the intact rabbit heart of importance in studies on intramyocardial transfer of blood-borne substances.

    Science.gov (United States)

    van der Vusse, Ger J; Verheyen, Fons; Reneman, Robert S; Arts, Theo

    2016-01-01

    Cardiac studies on the uptake, storage and intramyocardial transfer of blood-borne substances require detailed information on the geometric ultrastructural dimensions of myocardial compartments and parts thereof, and the membranes separating these compartments. Such a specific ultrastructural set of data of the heart is yet lacking. In the present study, we quantitatively assessed these dimensions in glutaraldehyde-perfusion fixed rabbit hearts by means of histological and tailored mathematical techniques. We showed the true ellipsoid nature of the myocardial capillary cross section and estimated the mean capillary diameter dcap. After correction for the ellipsoid shape, dcap was found to be 5.21±1.41 µm. Effective widths of the endothelial cell and the pericapillary interstitium (is1), dimensions of importance in diffusion, amounted to 187±7 and 160±10 nm, respectively. The fractional volume of the large vessels (arteries and veins larger than 10 µm), capillaries, endothelium, is1, cardiomyocytes, non-pericapillary interstitium is2, t-tubular compartment and interstitial cells amounted on average to 5.92%, 9.36%, 1.83%, 1.94%, 73.07%, 5.97%, 0.95% and 0.96%, respectively, of total myocardial volume, defined as the cardiac tissue volume, the large blood vessels included. Normalized to total myocardial volume, the surface area of the luminal and abluminal endothelial membranes and of the cardiomyocyte membrane opposing the endothelial cells amounted to 75.2±5.5·10³, 82.2±6.0·10³ and 89.1±6.5·10³ m²/m³, respectively. The present study provides quantitative information about ultrastructural dimensions of the adult rabbit heart, among others, of importance for studies on cardiac uptake, and intramyocardial transfer and storage of blood-supplied substances.

  5. [Correlation between resting heart rate and blood glucose level in elderly patients with coronary heart disease and diabetes mellitus].

    Science.gov (United States)

    Liang, Dong-Liang; Li, Xiao-Ying; Wang, Lin; Xu, Hao; Tuo, Xi-Ping; Jian, Zai-Jin; Wang, Xiao-Na; Yun, Ji-Li; Zhang, Xu; Wang, Si-Yue

    2016-05-01

    To explore the correlation between resting heart rate (RHR) and blood glucose level in elderly patients with coronary heart disease (CHD) complicated by diabetes mellitus. Between April and July, 2011, a total of 1336 outpatients over 60 years of age recruited from 165 hospitals were asked to complete a questionnaire and received blood glucose and RHR examination. According to baseline RHR, the patients were divided into 3 groups with HRH blood glucose control rate. HbA1c levels in the total, male and female patients differed significantly among the 3 groups (F=15.436, 15.436, and 24.270, respectively, PBlood glucose control rate in the total, male and female patients also differed significantly among the 3 groups (χ(2)=13.471, 6.752, and 6.522, respectively, Pblood glucose control failure of 1.99 (95% CI: 1.23-2.37, Pblood glucose level, and an increased RHR is associated with an increased risk of poor blood glucose control. Rigorous RHR control in such high-risk patients may prove beneficial for both blood glucose control and secondary prevention of CHD.

  6. Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study

    National Research Council Canada - National Science Library

    Hanley, Anthony J G; Williams, Ken; Gonzalez, Clicerio; D'Agostino, Jr, Ralph B; Wagenknecht, Lynne E; Stern, Michael P; Haffner, Steven M

    2003-01-01

    ...) to predict type 2 diabetes, we used combined prospective data from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study, which include well...

  7. The Relationship between Serum Lipid Fractions and Heart Rate Variability in Diabetic Patients with Statin Therapy.

    Science.gov (United States)

    Badea, Anamaria Raluca; Nedelcu, Laurentiu; Valeanu, Madalina; Zdrenghea, Dumitru

    2014-01-01

    The aim of this study is to identify and highlight the relationship between serum lipid fractions and heart rate variability in diabetic patients receiving statin therapy. The study was performed in a group of 87 type 2 diabetic patients on statin associated therapy. All patients were on Holter ECG 24 hours monitored with three channel monitor (Labtech ECG Holter monitor), and data were analyzed on a commercially available software (Cardiospy PC SW/EV 5.02.06.02). Concentrations of biochemical parameters were determined using specific enzymatic assays on an autoanalyzer Olympus AU 680. In the studied patients, we analyzed Holter/24 hours monitoring reports with respect to heart rate variability indexes, arrhythmic events and myocardial ischemia. It was noticed that the mean values of serum TG were slightly elevated, TC levels were close to the limits specified by the guidelines for diabetic patients and for patients with cardiovascular diseases, with no significant differences between males and females. After analyzing the HRV in both time and frequency domains, we found no strong correlations between any of the HRV indexes and any of the lipid fractions. The results suggest that statin therapy may reduce the autonomic impairment secondary to dyslipidemia.

  8. Heart rate complexity and cardiac sympathetic dysinnervation in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Baumert, Mathias; Sacre, Julian W

    2013-01-01

    Cardiovascular autonomic neuropathy (CAN) is one of the most severe complications of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate associations of cardiac sympathetic dysinnervation (CSD; by (123)I-MIBG scintigraphy) with short-term heart rate variability (HRV) measured by traditional vs. complexity markers. ECG was measured in 31 diabetic patients during rest over a period of 5 minutes and HRV quantified in different domains (time and frequency domain, scaling properties, symbolic dynamics). (123)I-MIBG scintigraphy identified 16 patients with CSD. Resting heart rate was increased and HRV reduced in these patients. In a subgroup of 16 patients ECG was also measured during standing. Changes in several HRV measures upon standing demonstrated cardiac responsiveness to orthostatic stress. Strong correlations between HRV, measured during standing, and CSD were observed with metrics based on symbolic dynamics. In conclusion, HRV assessment during standing may be useful for assessing cardiac sympathetic dysinnervation in patients with type 2 diabetes mellitus.

  9. Hypovitaminosis D: a novel risk factor for coronary heart disease in type 2 diabetes?

    Science.gov (United States)

    Muscogiuri, Giovanna; Nuzzo, Vincenzo; Gatti, Adriano; Zuccoli, Alfonso; Savastano, Silvia; Di Somma, Carolina; Pivonello, Rosario; Orio, Francesco; Colao, Annamaria

    2016-02-01

    Vitamin D (25(OH)D) levels have been associated with cardiovascular disease. Thus, the aim of our study was to investigate the association of 25(OH)D levels with coronary heart disease (CHD) in 698 consecutive type 2 diabetic outpatients. 698 consecutive type 2 diabetic outpatients (25.2 % men, age 66 ± 9 years) and 100 (90 % men, age 65 ± 13 years) age-matched non-diabetic volunteers were enrolled. 25(OH)D assay and the main cardiovascular risk factors were explored. 25(OH)D concentration was 22 ± 10 ng/ml in control subjects and 18.23 ± 10 ng/ml in diabetic patients (p hypovitaminosis D was higher in diabetic patients than in control subjects (90 vs. 83 %, p hypovitaminosis D had higher prevalence of high values of A1C (p < 0.01), BMI (p < 0.01), LDL cholesterol (p < 0.01), triglycerides (p < 0.01), and glycemia (p < 0.01) than their vitamin D-sufficient counterparts. 25(OH)D and HDL cholesterol were lower (p < 0.01), while BMI (p < 0.01), age (p < 0.01), systolic (p < 0.01) and diastolic blood pressure (p < 0.01), diabetes duration (p < 0.01), A1C (p < 0.01), glycemia (p < 0.01), fibrinogen (p < 0.01), triglycerides (p < 0.01), and total (p < 0.01) and LDL cholesterol (p < 0.01) were higher in diabetic subjects with CHD than diabetic subjects without CHD. At the logistic regression analysis, the association of vitamin D with CHD was lost, while sex (p = 0.026), diabetes duration (p = 0.023), and age (p = 0.024) were the most powerful predictors of CHD. The current study demonstrates that 25(OH)D does not have a direct effect on CHD but may have an indirect effect mediated by cardiovascular risk factors such as diabetes duration, age, and sex.

  10. Sensitivity, Specificity and Predictive Value of Heart Rate Variability Indices in Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Anne Kastelianne França da Silva

    Full Text Available Abstract Background: Heart rate variability (HRV indices may detect autonomic changes with good diagnostic accuracy. Type diabetes mellitus (DM individuals may have changes in autonomic modulation; however, studies of this nature in this population are still scarce. Objective: To compare HRV indices between and assess their prognostic value by measurements of sensitivity, specificity and predictive values in young individuals with type 1 DM and healthy volunteers. Methods: In this cross-sectional study, physical and clinical assessment was performed in 39 young patients with type 1 DM and 43 young healthy controls. For HRV analysis, beat-to-beat heart rate variability was measured in dorsal decubitus, using a Polar S810i heart rate monitor, for 30 minutes. The following indices were calculated: SDNN, RMSSD, PNN50, TINN, RRTri, LF ms2, HF ms2, LF un, HF un, LF/HF, SD1, SD2, SD1/SD2, and ApEn. Results: Type 1 DM subjects showed a decrease in sympathetic and parasympathetic activities, and overall variability of autonomic nervous system. The RMSSD, SDNN, PNN50, LF ms2, HF ms2, RRTri, SD1 and SD2 indices showed greater diagnostic accuracy in discriminating diabetic from healthy individuals. Conclusion: Type 1 DM individuals have changes in autonomic modulation. The SDNN, RMSSD, PNN50, RRtri, LF ms2, HF ms2, SD1 and SD2 indices may be alternative tools to discriminate individuals with type 1 DM.

  11. Sensitivity, Specificity and Predictive Value of Heart Rate Variability Indices in Type 1 Diabetes Mellitus

    Science.gov (United States)

    da Silva, Anne Kastelianne França; Christofaro, Diego Giuliano Destro; Bernardo, Aline Fernanda Barbosa; Vanderlei, Franciele Marques; Vanderlei, Luiz Carlos Marques

    2017-01-01

    Background Heart rate variability (HRV) indices may detect autonomic changes with good diagnostic accuracy. Type diabetes mellitus (DM) individuals may have changes in autonomic modulation; however, studies of this nature in this population are still scarce. Objective To compare HRV indices between and assess their prognostic value by measurements of sensitivity, specificity and predictive values in young individuals with type 1 DM and healthy volunteers. Methods In this cross-sectional study, physical and clinical assessment was performed in 39 young patients with type 1 DM and 43 young healthy controls. For HRV analysis, beat-to-beat heart rate variability was measured in dorsal decubitus, using a Polar S810i heart rate monitor, for 30 minutes. The following indices were calculated: SDNN, RMSSD, PNN50, TINN, RRTri, LF ms2, HF ms2, LF un, HF un, LF/HF, SD1, SD2, SD1/SD2, and ApEn. Results Type 1 DM subjects showed a decrease in sympathetic and parasympathetic activities, and overall variability of autonomic nervous system. The RMSSD, SDNN, PNN50, LF ms2, HF ms2, RRTri, SD1 and SD2 indices showed greater diagnostic accuracy in discriminating diabetic from healthy individuals. Conclusion Type 1 DM individuals have changes in autonomic modulation. The SDNN, RMSSD, PNN50, RRtri, LF ms2, HF ms2, SD1 and SD2 indices may be alternative tools to discriminate individuals with type 1 DM. PMID:28443958

  12. Fasting plasma glucose and hemoglobin A1c in identifying and predicting diabetes: the strong heart study.

    Science.gov (United States)

    Wang, Wenyu; Lee, Elisa T; Howard, Barbara V; Fabsitz, Richard R; Devereux, Richard B; Welty, Thomas K

    2011-02-01

    To compare fasting plasma glucose (FPG) and HbA(1c) in identifying and predicting type 2 diabetes in a population with high rates of diabetes. Diabetes was defined as an FPG level ≥ 126 mg/dL or an HbA(1c) level ≥ 6.5%. Data collected from the baseline and second exams (1989-1995) of the Strong Heart Study were used. RESULTS For cases of diabetes identified by FPG ≥ 126 mg/dL, using HbA(1c) ≥ 6.5% at the initial and 4-year follow-up diabetes screenings (or in identifying incident cases in 4 years) among undiagnosed participants left 46% and 59% of cases of diabetes undetected, respectively, whereas for cases identified by HbA(1c) ≥ 6.5%, using FPG ≥ 126 mg/dL left 11% and 59% unidentified, respectively. Age, waist circumference, urinary albumin-to-creatinine ratio, and baseline FPG and HbA(1c) levels were common significant risk factors for incident diabetes defined by either FPG or HbA(1c); triglyceride levels were significant for diabetes defined by HbA(1c) alone, and blood pressure and sibling history of diabetes were significant for diabetes defined by FPG alone. Using both the baseline FPG and HbA(1c) in diabetes prediction identified more people at risk than using either measure alone. CONCLUSIONS Among undiagnosed participants, using HbA(1c) alone in initial diabetes screening identifies fewer cases of diabetes than FPG, and using either FPG or HbA(1c) alone cannot effectively identify diabetes in a 4-year periodic successive diabetes screening or incident cases of diabetes in 4 years. Using both criteria may identify more people at risk. The proposed models using the commonly available clinical measures can be applied to assessing the risk of incident diabetes using either criterion.

  13. Diabetes-specific genetic effects on obesity traits in American Indian populations: the Strong Heart Family Study

    Directory of Open Access Journals (Sweden)

    Howard Barbara V

    2008-10-01

    Full Text Available Abstract Background Body fat mass distribution and deposition are determined by multiple environmental and genetic factors. Obesity is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes. We previously identified evidence for genotype-by-diabetes interaction on obesity traits in Strong Heart Family Study (SHFS participants. To localize these genetic effects, we conducted genome-wide linkage scans of obesity traits in individuals with and without type 2 diabetes, and in the combined sample while modeling interaction with diabetes using maximum likelihood methods (SOLAR 2.1.4. Methods SHFS recruited American Indians from Arizona, North and South Dakota, and Oklahoma. Anthropometric measures and diabetes status were obtained during a clinic visit. Marker allele frequencies were derived using maximum likelihood methods estimated from all individuals and multipoint identity by descent sharing was estimated using Loki. We used variance component linkage analysis to localize quantitative trait loci (QTLs influencing obesity traits. We tested for evidence of additive and QTL-specific genotype-by-diabetes interactions using the regions identified in the diabetes-stratified analyses. Results Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (P P Conclusion These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.

  14. Peculiarities of Ischemic Heart Disease Course and Treatment in Patients with Glucose Metabolism Impairment and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    O.M. Radchenko

    2015-11-01

    Full Text Available Combination of ischemic heart disease and diabetes mellitus is characterized by certain features of clinical picture and insufficient effectiveness of treatment of ischemic heart disease. With the aim of investigation of pathogenic mechanisms and features of the clinical course of ischemic heart disease associated with glucose homeostasis violation we examined 116 patients (51 women, 65 men, median of age 63 years old with normal regulation of glucose metabolism (NRG, n = 24, changes in fasting glucose (n = 23, violated glucose tolerance (n = 21, combined violation (n = 24 and diabetes mellitus (n = 24. We also conducted their prospective observation for 40 months with the following endpoints — hospitalization because of cardiovascular complications, death from them and the emergence of diabetes. It was established that ischemic heart disease associated with prediabetic disorders and diabetes mellitus has the following peculiarities: earlier clinical manifestation in women; more frequent and severe heart failure; lower tolerance to physical load in patients with angina pectoris; atypical manifestation of ischemic pain: longer attacks, atypical localization or absent pain; frequent combination with arrhythmias and conduction disorders; frequent affection of multiple coronary arteries, which leads to myocardial infarction with complicated course; eccentric type of left ventricle remodeling; significant calcification of mitral and aortic valves of heart. The main principles of treatment of ischemic heart disease: weight loss; active correction of glucose metabolism violations using medications (metformin even at the stage of prediabetes, because in chronic stable forms of ischemic heart disease metformin significantly improves glucose metabolism, decreases insulin resistance and does not increase the incidence of cardiovascular complications and decompensations of heart failure; the basic drugs for treatment of ischemic heart disease should be

  15. Homogenous demineralized dentin matrix and platelet-rich plasma for bone tissue engineering in cranioplasty of diabetic rabbits: biochemical, radiographic, and histological analysis.

    Science.gov (United States)

    Gomes, M F; Valva, V N; Vieira, E M M; Giannasi, L C; Salgado, M A C; Vilela-Goulart, M G

    2016-02-01

    This study evaluated the effects of homogenous demineralized dentin matrix (HDDM) slices and platelet-rich plasma (PRP) in surgical defects created in the parietal bones of alloxan-induced diabetic rabbits, treated with a guided bone regeneration technique. Biochemical, radiographic, and histological analyses were performed. Sixty adult New Zealand rabbits were divided into five groups of 12: normoglycaemic (control, C), diabetic (D), diabetic with a PTFE membrane (DM), diabetic with a PTFE membrane and HDDM slices (DM-HDDM), and diabetic with PTFE membrane and PRP (DM-PRP). The quantity and quality of bone mass was greatest in the DM-HDDM group (respective radiographic and histological analyses: at 15 days, 71.70 ± 16.50 and 50.80 ± 1.52; 30 days, 62.73 ± 16.51 and 54.20 ± 1.23; 60 days, 63.03 ± 11.04 and 59.91 ± 3.32; 90 days, 103.60 ± 24.86 and 78.99 ± 1.34), followed by the DM-PRP group (respective radiographic and histological analyses: at 15 days 23.00 ± 2.74 and 20.66 ± 7.45; 30 days 31.92 ± 6.06 and 25.31 ± 5.59; 60 days 25.29 ± 16.30 and 46.73 ± 2.07; 90 days 38.10 ± 14.04 and 53.38 ± 9.20). PRP greatly enhanced vascularization during the bone repair process. Abnormal calcium metabolism was statistically significant in the DM-PRP group (P<0.001) for all four time intervals studied, especially when compared to the DM-HDDM group. Alkaline phosphatase activity was significantly higher in the DM-HDDM group (P<0.001) in comparison to the C, D, and DM-PRP groups, confirming the findings of intense osteoblastic activity and increased bone mineralization. Thus, HDDM promoted superior bone architectural microstructure in bone defects in diabetic rabbits due to its effective osteoinductive and osteoconductive activity, whereas PRP stimulated angiogenesis and red bone marrow formation. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  16. CLINICAL PROFILE OF PATTERN OF DYSLIPIDAEMIA AND ISCHAEMIC HEART DISEASE IN TYPE II DIABETES MELLITUS PATIENTS

    Directory of Open Access Journals (Sweden)

    Atul Vijayrao Rajkondawar

    2017-07-01

    Full Text Available BACKGROUND The present research was undertaken to study the pattern of dyslipidaemia and varied clinical manifestations of ischaemic heart disease, its risk factors in type 2 diabetes mellitus patients. Diabetes Mellitus (DM has become major public health problem in India. It is not only increasing in morbidity and mortality, but also decreases the quality of life. Also, disease and its complications are causing heavy economic burden for patients suffering from it.1,2 Diabetes is endemic globally with increasing prevalence in both developing and developed countries. Diabetes is a major cause of mortality, but several studies indicate that it is likely underreported as a cause of death. A recent estimate suggested that diabetes was the fifth leading cause of death worldwide and was responsible for almost 3 million deaths annually (1.7-5.2% of all deaths. MATERIALS AND METHODS A total of 100 patients attending the outpatient department or admitted to medical wards, ICU of tertiary care centre and fulfilling the inclusion criteria were evaluated clinically. A baseline Electrocardiogram (ECG was taken in all cases irrespective of clinical evidence of cardiac involvement. Patients with normal ECG pattern were further evaluated by Treadmill Testing (TMT or stress test for subclinical cardiac involvement. Risk factor evaluation was done in all cases. RESULTS Prevalence of IHD was found to be 41% with a male predominance (1.067:1. Evaluation of risk factors has shown its strong association with IHD. Incidence of IHD was high when low HDL (P 25 had negatively significant association with IHD in type 2 diabetics (P=0.072. Smoking was not statistically associated (P=0.577 and in male alcoholics, IHD had positive association with alcohol (P=0.193. CONCLUSION The current study points out that there exists an increased incidence of ischaemic heart disease in diabetics with few, but not all risk factors contributing to it. Early detection, optimal glycaemic

  17. Maternal diabetes induces congenital heart defects in mice by altering the expression of genes involved in cardiovascular development

    Directory of Open Access Journals (Sweden)

    Tay Samuel

    2007-10-01

    Full Text Available Abstract Background Congenital heart defects are frequently observed in infants of diabetic mothers, but the molecular basis of the defects remains obscure. Thus, the present study was performed to gain some insights into the molecular pathogenesis of maternal diabetes-induced congenital heart defects in mice. Methods and results We analyzed the morphological changes, the expression pattern of some genes, the proliferation index and apoptosis in developing heart of embryos at E13.5 from streptozotocin-induced diabetic mice. Morphological analysis has shown the persistent truncus arteriosus combined with a ventricular septal defect in embryos of diabetic mice. Several other defects including defective endocardial cushion (EC and aberrant myofibrillogenesis have also been found. Cardiac neural crest defects in experimental embryos were analyzed and validated by the protein expression of NCAM and PGP 9.5. In addition, the protein expression of Bmp4, Msx1 and Pax3 involved in the development of cardiac neural crest was found to be reduced in the defective hearts. The mRNA expression of Bmp4, Msx1 and Pax3 was significantly down-regulated (p p p Conclusion It is suggested that the down-regulation of genes involved in development of cardiac neural crest could contribute to the pathogenesis of maternal diabetes-induced congenital heart defects.

  18. 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.

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

    Science.gov (United States)

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

    2015-02-01

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

  20. Substrate-Specific Derangements in Mitochondrial Metabolism and Redox Balance in Atrium of Type 2 Diabetic Human Heart

    Science.gov (United States)

    Anderson, Ethan J.; Kypson, Alan P.; Rodriguez, Evelio; Anderson, Curtis A.; Lehr, Eric J.; Neufer, P. Darrell

    2009-01-01

    Objective This aim of this study was to determine the impact of diabetes on oxidant balance and mitochondrial metabolism of carbohydrate- and lipid-based substrates in myocardium of type 2 diabetic patients. Background Heart failure represents a major cause of death among diabetics, and it has been proposed that derangements in cardiac metabolism and oxidative stress may underlie the progression of this co-morbidity, but scarce evidence exists in support of this mechanism in humans. Methods Mitochondrial O2 consumption and H2O2 emission were measured in permeabilized myofibers prepared from samples of right atrial appendage obtained from non-diabetic (n=13) and diabetic (n=11) patients undergoing non-emergent coronary artery bypass graft surgery. Results Mitochondria in atrial tissue of type 2 diabetic individuals display a sharply decreased capacity for glutamate and fatty acid-supported respiration, in addition to an increased content of myocardial triglycerides, as compared to non-diabetics. Furthermore, diabetics display an increased mitochondrial H2O2 emission during oxidation of carbohydrate- and lipid-based substrates, depleted glutathione, and evidence of persistent oxidative stress in their atrial tissue. Conclusions These findings are the first to directly investigate the effects of type 2 diabetes on a panoply of mitochondrial functions in the human myocardium using cellular and molecular approaches, and they demonstrate that mitochondria in diabetic human heart have specific impairments in maximal capacity to oxidize fatty acids and glutamate, yet increased mitochondrial H2O2 emission, providing insight into the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of heart failure in diabetic patients. PMID:19892241

  1. Mobile biofeedback of heart rate variability in patients with diabetic polyneuropathy: a preliminary study.

    Science.gov (United States)

    Druschky, Katrin; Druschky, Achim

    2015-09-01

    Biofeedback of heart rate variability (HRV) was applied to patients with diabetic polyneuropathy using a new mobile device allowing regularly scheduled self-measurements without the need of visits to a special autonomic laboratory. Prolonged generation of data over an eight-week period facilitated more precise investigation of cardiac autonomic function and assessment of positive and negative trends of HRV parameters over time. Statistical regression analyses revealed significant trends in 11 of 17 patients, while no significant differences were observed when comparing autonomic screening by short-term HRV and respiratory sinus arrhythmia at baseline and after the 8 weeks training period. Four patients showed positive trends of HRV parameters despite the expected progression of cardiac autonomic dysfunction over time. Patient compliance was above 50% in all but two patients. The results of this preliminary study indicate a good practicality of the handheld device and suggest a potential positive effect on cardiac autonomic neuropathy in patients with type 2 diabetes.

  2. Conditioning-specific reflex modification of the rabbit's nictitating membrane response and heart rate: behavioral rules, neural substrates, and potential applications to posttraumatic stress disorder.

    Science.gov (United States)

    Burhans, Lauren B; Smith-Bell, Carrie; Schreurs, Bernard G

    2008-12-01

    Interest in classical conditioning is usually focused on anticipatory responses to a stimulus associated with a significant event, and it is assumed that responses to the event itself are reflexive, involuntary, and relatively invariant. However, there is compelling evidence that both the rabbit nictitating membrane response (NMR) and heart rate response (HR), well-known reflexive reactions to aversive events, can change quite dramatically as a function of learning when measured in the absence of the conditioned stimulus. In the case of NMR conditioning, a simple blink is transformed into a larger and more complex response. For HR conditioning, reflexive heart rate acceleration can actually change to heart rate deceleration. In both cases, the reflex comes to resemble the conditioned response and follows some of the same behavioral laws. This change in response to the aversive event itself or weaker forms of that event is called conditioning-specific reflex modification (CRM). CRM may force us to reevaluate the behavioral and neural consequences of classical conditioning and may have important consequences for the treatment of conditions such as posttraumatic stress disorder.

  3. Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction

    Directory of Open Access Journals (Sweden)

    Raffaele Altara

    2017-07-01

    Full Text Available Heart failure with preserved ejection fraction (HFpEF is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes. Thus, pharmacological strategies to supplement nitric oxide and subsequent cyclic guanosine monophosphate (cGMP—protein kinase G (PKG signaling may have therapeutic promise. Other potential approaches include exercise and lifestyle modifications, as well as targeting endothelial cell mineralocorticoid receptors, non-coding RNAs, sodium glucose transporter 2 inhibitors, and enhancers of natriuretic peptide protective NO-independent cGMP-initiated and alternative signaling, such as LCZ696 and phosphodiesterase-9 inhibitors. Additionally, understanding the role of adipokines in HFpEF may lead to new treatments. Identifying novel drug targets based on the shared underlying microvascular disease process may improve the quality of life and lifespan of those afflicted with both HFpEF and obesity or diabetes, or even prevent its occurrence.

  4. Relationship between diabetic autonomic dysfunction and heart rate variability assessed by recurrence plot.

    Science.gov (United States)

    Mestivier, D; Chau, N P; Chanudet, X; Bauduceau, B; Larroque, P

    1997-03-01

    Beat-to-beat heart rate (HR) and blood pressure were measured by the Finapres system in 44 healthy and 64 diabetic subjects in the at-rest condition. Autonomic control in diabetic subjects was assessed by the Ewing test. HR variability was explored by both linear and nonlinear methods. Linear methods used HR standard deviation and power spectrum. The percentage of the spectrum in the low frequencies was used to assess the sympathetic tone of the autonomic control. The nonlinear method used the "recurrence plot." This method explored long parallel subsequences in the HR time series. These sequences characterize the dependence of the HR dynamics on initial values. The HR standard deviation was reduced in the diabetic subjects compared with the healthy subjects (2.80 +/- 1.17 vs. 3.64 +/- 1.45 beats/min; P 0.10). In contrast, the longest length index was very strongly correlated to the Ewing score (r = -0.60; P < 0.0001). The results suggest that nonlinear methods might be powerful to explore the autonomic dysfunction in diabetic subjects.

  5. [Relationship between blood pressure, heart rate and cardiac autonomic dysfunction in non-diabetic obese patients].

    Science.gov (United States)

    Banu, I; Nguyen, M T; Hamo-Tchatchouang, E; Cosson, E; Valensi, P

    2015-06-01

    Some studies suggest that a high heart rate (HR) would be predictive of the incidence of an elevated blood pressure (BP). Cardiac autonomic dysfunction (CAD) affects a high proportion of obese patients. CAD could be involved in BP increase. Our aim was to examine the relationship between CAD, HR and BP in obese patients without known diabetes. We included 428 overweight or obese patients. CAD was assessed by analyzing HR variations during three standard tests (Valsalva, deep breathing, lying-to-standing), which are mostly dependent on vagal control. An oral load in glucose was performed and the Matsuda index was calculated. The population was separated in 4 groups according to the grade of CAD (no or only one abnormal test, 2 or 3 abnormal tests) and HR (heart rate, which is indicative of a more marked insulin resistance and probably an excess in sympathetic activity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Risk factors for coronary heart disease and actual diagnostic criteria for diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mitrović-Perišić Nataša

    2009-01-01

    Full Text Available Background/Aim. Recent studies indicate that the prevalence of diabetes mellitus (DM type 2 is increasing in the world. Chronic hyperglycemia in DM is associated with a long term damage, dysfunction and failure of various organs, especially retina, kidney, nerves and, in addition, with an increased risk of cardiovasclar disease. For a long time the illness has been unknown. Early diagnosis of diabetes could suspend the development of diabetic complications. The aim of the study was to establish risk for the development of coronary disease in the patients evaluated by the use of new diagnostic criteria for DM. Methods. The study included 930 participants without diagnosis of DM, hypertension, dyslipidemia, nor coronary heart disease two years before the study. The patients went through measuring of fasting plasma glycemia, erythrocytes, hematocrit, cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase. In the group with hyperglycemia the 2-hour oral glucose tolerance test was performed. We analyzed ECG and made blood pressure monitoring, and also measured body mass, height, waist and hip circumference. We analyzed life style, especially smoking, and exercise and family history. Results. Diabetes prevalence was 2.68%, and prevalences of impaired fasting glucose, impaired glucose tolerance and DM were 12.15%. Average age of males and females was 38 and 45 years, respectively. In the healthy population there was higher frequency of smokers (55% vs 42%, but in the population with hyperglycemia there were more obesity (23% vs 10.5%, hypertension (39% vs 9%, hypercholesterolemia (76% vs 44.1%, lower HDL-C (52.2% vs 25.7%. Cummulative risk factor in healthy subjects, and those with hyperglycemia were 5.6% and 14%, respectively. Conclusion. Subjects with hyperglicemia without diagnosis of DM have higher risk factors for coronary heart disease.

  7. Heart rate recovery after exercise is a predictor of silent myocardial ischemia in patients with type 2 diabetes.

    Science.gov (United States)

    Yamada, Tomohide; Yoshitama, Takashi; Makino, Kunihiko; Lee, Tetsuo; Saeki, Fumihiko

    2011-03-01

    Slow heart rate recovery (HRR) predicts all-cause mortality. This study investigated the relationship between silent myocardial ischemia (SMI) and HRR in type 2 diabetes. The study enrolled 87 consecutive patients with type 2 diabetes and no chest symptoms. They underwent treadmill exercise testing and single-photon emission computed tomography imaging with thallium scintigraphy. Patients with abnormal myocardial perfusion images also underwent coronary angiography. SMI was diagnosed in 41 patients (47%). The SMI group showed slower HRR than the non-SMI group (18 ± 6 vs. 30 ± 12 bpm; P exercise workload, resting heart rate, maximum heart rate, rate pressure product, HbA(1c), use of sulfonamides, and a history of cardiovascular disease. HRR can predict SMI in patients with type 2 diabetes.

  8. In-hospital and 1-year mortality associated with diabetes in patients with acute heart failure: results from the ESC-HFA Heart Failure Long-Term Registry.

    Science.gov (United States)

    Targher, Giovanni; Dauriz, Marco; Laroche, Cécile; Temporelli, Pier Luigi; Hassanein, Mahmoud; Seferovic, Petar M; Drozdz, Jaroslaw; Ferrari, Roberto; Anker, Stephan; Coats, Andrew; Filippatos, Gerasimos; Crespo-Leiro, Maria G; Mebazaa, Alexandre; Piepoli, Massimo F; Maggioni, Aldo Pietro; Tavazzi, Luigi

    2017-01-01

    The aim of this study was to evaluate the in-hospital and 1-year prognostic impact of diabetes and elevated blood glucose levels at hospital admission in patients with acute heart failure (HF). We studied a multinational cohort of 6926 hospitalized patients with acute HF enrolled in the European Society of Cardiology (ESC) and Heart Failure Association (HFA) Long-Term Registry, of whom 49.4% (n = 3422) had known or previously undiagnosed diabetes (defined as self-reported history, or medication use, or fasting glucose levels ≥7.0 mmol/L or haemoglobin A1c ≥6.5%). Compared with those without diabetes, patients with known or previously undiagnosed diabetes had higher cumulative rates of in-hospital mortality, 1-year mortality, and 1-year HF re-hospitalization that occurred independently of multiple clinical risk factors: in-hospital mortality [6.8 vs. 4.4%; adjusted hazard ratio (HR) 1.774; 95% confidence interval (CI) 1.282-2.456, P year all-cause mortality (27.5 vs. 24%; adjusted HR 1.162; 95% CI 1.020-1.325, P = 0.024), and 1-year hospital re-admissions for HF (23.2 vs. 18.5%; adjusted HR 1.320; 95% CI 1.139-1.530, P year mortality or re-hospitalizations, in both patients with and without diabetes. Among patients hospitalized for acute HF, the presence of diabetes is independently associated with an increased risk of in-hospital mortality, 1-year all-cause mortality, and 1-year re-hospitalizations for HF, underscoring the need for more effective and personalized treatments of diabetes in this particularly high-risk patient population. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

  9. Increased expression and local accumulation of the Prion Protein, Alzheimer Aβ peptides, superoxide dismutase 1, and Nitric oxide synthases 1 & 2 in muscle in a rabbit model of diabetes

    Directory of Open Access Journals (Sweden)

    Bitel Claudine L

    2010-09-01

    Full Text Available Abstract Background Muscle disease associated with different etiologies has been shown to produce localized accumulations of amyloid and oxidative stress-related proteins that are more commonly associated with neurodegeneration in the brain. In this study we examined changes in muscle tissue in a classic model of diabetes and hyperglycemia in rabbits to determine if similar dysregulation of Alzheimer Aβ peptides, the prion protein (PrP, and superoxide dismutase 1 (SOD1, as well as nitric oxide synthases is produced in muscle in diabetic animals. This wild-type rabbit model includes systemic physiological expression of human-like Alzheimer precursor proteins and Aβ peptides that are considered key in Alzheimer protein studies. Results Diabetes was produced in rabbits by injection of the toxic glucose analogue alloxan, which selectively enters pancreatic beta cells and irreversibly decreases insulin production, similar to streptozotocin. Quadriceps muscle from rabbits 16 wks after onset of diabetes and hyperglycemia were analyzed with biochemical and in situ methods. Immunoblots of whole muscle protein samples demonstrated increased PrP, SOD1, as well as neuronal and inducible Nitric oxide synthases (NOS1 and NOS2 in diabetic muscle. In contrast, we detected little change in Alzheimer Aβ precursor protein expression, or BACE1 and Presenilin 1 levels. However, Aβ peptides measured by ELISA increased several fold in diabetic muscle, suggesting a key role for Aβ cleavage in muscle similar to Alzheimer neurodegeneration in this diabetes model. Histological changes in diabetic muscle included localized accumulations of PrP, Aβ, NOS1 and 2, and SOD1, and evidence of increased central nuclei and cell infiltration. Conclusions The present study provides evidence that several classic amyloid and oxidative stress-related disease proteins coordinately increase in overall expression and form localized accumulations in diabetic muscle. The present study

  10. Heart rate variability and heart rate turbulence in patients with type 2 diabetes mellitus with versus without cardiac autonomic neuropathy.

    Science.gov (United States)

    Balcioğlu, Serhat; Arslan, Uğur; Türkoğlu, Sedat; Ozdemir, Murat; Cengel, Atiye

    2007-09-01

    Cardiac autonomic neuropathy (CAN) is an important complication of diabetes mellitus (DM) and confers an increased cardiovascular risk. The aim of this study was to disclose the place of heart rate (HR) variability and HR turbulence for the detection of CAN in patients with type 2 DM and no obvious heart disease. Ninety patients who were /=2 years were studied. CAN was diagnosed with a battery of cardiovascular reflex tests and the degree of neuropathic involvement was graded by the Ewing score. Time-domain HR variability and HR turbulence parameters were assessed on 24-hour digital Holter recordings. Thirty-five patients were found to have CAN. The clinical characteristics of patients with and without CAN were similar, except that the mean duration of DM and the number of patients using insulin were significantly increased in the group with CAN. All time-domain HR variability parameters were significantly lower in the group with CAN. Of the 2 HR turbulence parameters studied, turbulence onset was similar but turbulence slope was significantly lower in the group with CAN. The Ewing score significantly correlated negatively with all HR variability parameters and turbulence slope, and among all, turbulence slope was the most strongly correlated (r = -0.617, p <0.01). Receiver-operating characteristics analysis revealed a sensitivity of 97% and a specificity of 71% at a turbulence slope cut-off value of 3.32 for the detection of CAN. In conclusion, time-domain HR variability and HR turbulence parameters, except turbulence, onset were found to be significantly depressed in patients with type 2 DM and CAN. Decreases in all these parameters were found to correlate significantly with degree of neuropathic involvement. The most strongly correlated parameter, turbulence slope, was found to be highly sensitive and specific for the detection of CAN at a cut-off value of 3.32.

  11. Construction of a New Zealand rabbit model of diabetic nephropathy%新西兰兔糖尿病肾病模型的建立方法

    Institute of Scientific and Technical Information of China (English)

    陈小明; 黄丹丹; 李自成

    2012-01-01

    AIM: To establish a method to produce animal model of diabetic nephropathy (DN) in New Zealand rabbits using alloxan (ALX). METHODS: Twenty male New Zealand rabbits were randomly divided into 2 groups: 8 rabbits in control group were fed with conventional feed such as buffer solution ; 12 in diabetes milleuts (DM) group were fed with high - sugar and high - fat diet (conventional feed plus 5% sucrose, 5 % pork fat and 1 % cholesterol) for 2 weeks , then intravenous injection of ALX at 50 mg/kg was given , and another dosage of 100 mg/kg ALX was intravenously injected after 48 h. The levels of blood glucose , blood cholesterol, triglyceride , urine microalbumin , and serum creatinine were detected before and 12 weeks after the processes of modeling. After 12 weeks , the rabbits were sacrificed , and the kidneys were taken for pathological examination . RESULTS : The successful model of DN in the rabbits had the characteristics of high blood glucose , abundant urine microalbumin (P < 0. 01) , and corresponding morphological and functional changes of the kidneys. CONCLUSION: Rabbits with high - sugar and high - fat diet plus twice intravenous injection of ALX at a total dose of 150 mg/kg (50 mg/kg and 100 mg/kg, respectively) shows low mortality and stable diabetes mellitus state . This method induces a typical DN model in 12 weeks.%目的:探讨小剂量四氧嘧啶(ALX)建立新西兰兔糖尿病肾病(diabetic nephropathy,DN)模型的可行性.方法:雄性新西兰兔20只,8只为对照组,给予常规饲料,12只为糖尿病组,给予高糖高脂饮食(常规饲料加5%蔗糖、5%猪油和1%胆固醇)喂养2周,再加用小剂量ALX耳缘静脉注射,分别检测造模前与造模12周后兔血糖、血脂、尿蛋白和肾功能指标,并于12周后进行组织形态学观察.结果:建模成功动物具有"多饮、多食、多尿、体重减轻"的特点,并出现DN相应的形态及功能改变.结论:高脂高糖饮食加ALX药物诱导的方法,12 周

  12. The association between resting heart rate and type 2 diabetes and hypertension in Korean adults.

    Science.gov (United States)

    Kim, Dong-Il; Yang, Hyuk In; Park, Ji-Hye; Lee, Mi Kyung; Kang, Dong-Woo; Chae, Jey Sook; Lee, Jong Ho; Jeon, Justin Y

    2016-11-01

    The purpose of this study was to analyse the association between resting heart rate (RHR) and type 2 diabetes and hypertension in Korean adults. A total of 5124 participants, who participated in the exercise programme at the National Health Promotion Center between 2007 and 2010 (male=904, female=4220) were analysed in this study. Anthropometrics, body mass index (BMI), blood pressure (BP) and RHR were measured, and blood samples were collected after fasting for at least 12 hours. To investigate the association between RHR and metabolic parameters, participants were divided into quartiles. Participants in the fourth quartile (RHR >80 beats per minute (bpm) showed significantly higher systolic and diastolic BP and glucose compared with participants in the first quartile (RHR type 2 diabetes and 1.27 times (95% CI 1.04 to 1.55; AR: 22.2% (304/1371)) higher odds of hypertension compared with those in the first quartile of RHR (type 2 diabetes AR: 5.3% (71/1346); hypertension AR: 18.9% (254/1346)). Multiple regression analyses showed that both BMI and RHR were significantly associated with glucose and mean arterial pressure. RHR is significantly associated with type 2 diabetes and hypertension independent of age, gender, BMI, smoking, drinking and family history of disease. RHR in combination with BMI, and multiple linear regression analyses emphasise the importance of the association of RHR with type 2 diabetes and hypertension in Korean adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Evaluating the Effect of Sarconesiopsis magellanica (Diptera: Calliphoridae Larvae-Derived Haemolymph and Fat Body Extracts on Chronic Wounds in Diabetic Rabbits

    Directory of Open Access Journals (Sweden)

    Jennifher Góngora

    2015-01-01

    Full Text Available We evaluated extracts taken from S. magellanica third instar larvae fat body and haemolymph using a diabetic rabbit model and compared this to the effect obtained with the same substances taken from Lucilia sericata larvae. Alloxan (a toxic glucose analogue was used to induce experimental diabetes in twelve rabbits. Dorsal wounds were made in each animal and they were infected with Staphylococcus aureus and Pseudomonas aeruginosa. They were then treated with haemolymph and lyophilized extracts taken from the selected blowflies’ larvae fat bodies. Each wound was then evaluated by using rating scales and histological analysis. More favourable scores were recorded on the PUSH and WBS scales for the wounds treated with fat body derived from the larvae of both species compared to that obtained with haemolymph; however, wounds treated with the substances taken from S. magellanica had better evolution. Histological analysis revealed that treatment led to tissue proliferation and more effective neovascularisation in less time with both species’ fat body extracts compared to treatment with just haemolymph. The results suggest the effectiveness of the substances evaluated and validate them in the animal model being used here as topical agents in treating chronic wounds.

  14. Identification of metabolic biomarkers in patients with type 2 diabetic coronary heart diseases based on metabolomic approach

    OpenAIRE

    2016-01-01

    Type 2 diabetic coronary heart disease (T2DM-CHD) is a kind of serious and complex disease. Great attention has been paid to exploring its mechanism; however, the detailed understanding of T2DM-CHD is still limited. Plasma samples from 15 healthy controls, 13 coronary heart disease (CHD) patients, 15 type 2 diabetes mellitus (T2DM) patients and 28 T2DM-CHD patients were analyzed in this research. The potential biomarkers of CHD and T2DM were detected and screened out by 1H NMR-based plasma me...

  15. Effect of tolvaptan in patients with chronic kidney disease due to diabetic nephropathy with heart failure.

    Science.gov (United States)

    Sato, Eiichi; Nakamura, Tsukasa; Amaha, Mayuko; Nomura, Mayumi; Matsumura, Daisuke; Yamagishi, Hidetsugu; Ono, Yuko; Ueda, Yoshihiko

    2014-01-01

    The efficacy of tolvaptan for treating heart failure has already been shown. Adequate data relating to the effect of tolvaptan on the correlation of water balance in renal disease are not available. A retrospective study was conducted on the efficacy and adverse reactions of tolvaptan for treating nephrotic syndrome.The subjects were 26 patients with chronic kidney failure due to diabetic nephropathy with heart failure who were administered tolvaptan and seen between December 2011 and October 2013. The endpoints were urinary output, physical findings, and blood analyses. The expression of aquaporin-2 in the collecting duct, which is related to the action of tolvaptan, was investigated by immunohistochemistry using the kidney tissue obtained for the diagnosis.Responses were seen in 19 of the patients. In the histopathological investigation there was severe glomerulosclerosis in patients with diabetic nephropathy, but the responders were noticeable in that they only had mild tubulointerstitial damage. Non-responders exhibited profound tubulointerstitial damage. The expression of aquaporin-2 was determined in 8 patients, of which 7 were responders who tested positive for aquaporin-2. The remaining case was a non-responder who showed no expression of aquaporin-2.Tolvaptan is considered effective for some cases of nephrotic syndrome. There are no clear parameters for predicting an effect, but the present study showed that aquaporin-2 was expressed in the epithelial cells of the collecting ducts of tolvaptan responders.

  16. Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts

    Directory of Open Access Journals (Sweden)

    O. M. Duicu

    2016-01-01

    Full Text Available Mitochondria-related oxidative stress is a pathomechanism causally linked to coronary heart disease (CHD and diabetes mellitus (DM. Recently, mitochondrial monoamine oxidases (MAOs have emerged as novel sources of oxidative stress in the cardiovascular system and experimental diabetes. The present study was purported to assess the mitochondrial impairment and the contribution of MAOs-related oxidative stress to the cardiovascular dysfunction in coronary patients with/without DM. Right atrial appendages were obtained from 75 patients randomized into 3 groups: (1 Control (CTRL, valvular patients without CHD; (2 CHD, patients with confirmed CHD; and (3 CHD-DM, patients with CHD and DM. Mitochondrial respiration was measured by high-resolution respirometry and MAOs expression was evaluated by RT-PCR and immunohistochemistry. Hydrogen peroxide (H2O2 emission was assessed by confocal microscopy and spectrophotometrically. The impairment of mitochondrial respiration was substrate-independent in CHD-DM group. MAOs expression was comparable among the groups, with the predominance of MAO-B isoform but no significant differences regarding oxidative stress were detected by either method. Incubation of atrial samples with MAOs inhibitors significantly reduced the H2O2 in all groups. In conclusion, abnormal mitochondrial respiration occurs in CHD and is more severe in DM and MAOs contribute to oxidative stress in human diseased hearts with/without DM.

  17. Lifetime Risk of Cardiovascular Disease Among Individuals With and Without Diabetes Stratified by Obesity Status in the Framingham Heart Study

    OpenAIRE

    Pencina, Michael J.; Wilson, Peter W. F.; Vasan, Ramachandran S; D’Agostino, Ralph B.; Fox, Caroline; Paynter, Nina Palanza

    2008-01-01

    Objective: We assessed the lifetime risk of cardiovascular disease (CVD) among individuals with and without obesity and diabetes. Research Design and Methods: Participants were drawn from the original and offspring cohorts of the Framingham Heart Study. Lifetime (30-year) risk of CVD was assessed using a modified Kaplan-Meier approach adjusting for the competing risk of death, beginning from age 50 years. Results: Over 30 years, the lifetime risk of CVD among women with diabetes was 54.8% amo...

  18. ROLE OF GLYCAEMIA LEVEL IN THE DEVELOPMENT OF INTERSTITIAL COLLAGEN IN PATIENTS WITH CORONARY HEART DISEASE AND TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    T. Rudenko

    2015-12-01

    Full Text Available A role of blood glucose levels in the development of interstitial collagen has been studied in 84 patients (53 women and 31 men, average age 60 ± 2.4 years with coronary heart disease (CHD. All patients were divided into twocomparable groups: a study group including patients with coronary heart disease andtype 2 diabetes mellitus (DM and a control group consisting of patients with coronary heart disease without DM. All patients received standard medical therapy as recommended by the European Society of Cardiology. The level of blood glucose in both groups was assessed by the standard technique, a degree of interstitial collagen volume fraction (ICVF was measured using the formula of J. Shirani et al. The data were processed by parametric and nonparametric statistical methods. It has been proved that hyperglycemia in type 2 diabetes contributes to the development of ICVF, the degree of which increases with the rise of blood glucose level. A high level ofICVF in patients with coronary heart disease and diabetes type 2 can be a predictor of myocardial dyssynchrony development and heart failure progression, therefore, a close monitoring and timely correction of changes of blood glucose levelsare recommended to prevent the complication development. ICVF evaluation should become a routine diagnostic method in all patients with type 2 diabetes.

  19. Biomarkers of endothelial dysfunction are elevated and related to prognosis in chronic heart failure patients with diabetes but not in those without diabetes

    DEFF Research Database (Denmark)

    Kistorp, C.; Chong, A.Y.; Gustafsson, F.;

    2008-01-01

    Biomarkers of endothelial dysfunction, such as soluble E-selectin, and von Willebrand factor (vWf) are elevated in patients with chronic heart failure (CHF). The impact of diabetes mellitus (DM) on these biomarkers, and their relation to prognosis remains unknown....

  20. A six-month exercise intervention in subclinical diabetic heart disease: effects on exercise capacity, autonomic and myocardial function.

    Science.gov (United States)

    Sacre, Julian W; Jellis, Christine L; Jenkins, Carly; Haluska, Brian A; Baumert, Mathias; Coombes, Jeff S; Marwick, Thomas H

    2014-09-01

    Autonomic dysfunction may contribute to the etiology and exercise intolerance of subclinical diabetic heart disease. This study sought the efficacy of exercise training for improvement of peak oxygen uptake (VO₂(peak)) and cardiac autonomic function in type 2 diabetic patients with non-ischemic subclinical left-ventricular (LV) dysfunction. Forty-nine type 2 diabetic patients with early diastolic tissue Doppler velocity >1 standard deviation below the age-based mean entered an exercise intervention (n=24) or usual care (n=25) for 6-months (controlled, pre-/post- design). Co-primary endpoints were treadmill VO₂(peak) and 5-min heart-rate variability (by the coefficient of variation of normal RR intervals [CVNN]). Autonomic function was additionally assessed by resting heart-rate (for sympathovagal balance estimation), baroreflex sensitivity, cardiac reflexes, and exercise/recovery heart-rate profiles. Echocardiography was performed for LV function (systolic/diastolic tissue velocities, myocardial deformation) and myocardial fibrosis (calibrated integrated backscatter). VO₂(peak) increased by 11% during the exercise intervention (p=0.001 vs. -1% in controls), but CVNN did not change (p=0.23). Reduction of resting heart-rate in the intervention group (pheart-rate variability total spectral power (pexercise/recovery heart-rate profiles showed no significant benefit. No effects on LV function were observed despite favorable reduction of calibrated integrated backscatter in the intervention group (pexercise intolerance of subclinical diabetic heart disease was amenable to improvement by exercise training. Despite a reduction in resting heart-rate and potential attenuation of myocardial fibrosis, no other cardiac autonomic or LV functional adaptations were detected. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Contextual and individual influences on diabetes and heart disease in Havana primary care catchment areas.

    Science.gov (United States)

    Díaz-Perera, Georgia; Bacallao, Jorge; Alemañy, Eduardo

    2013-04-01

    A population health profile is a cumulative product of socioenvironmental and political factors that create the contexts in which health problems arise, as well as opportunities and barriers to addressing them. Research on context has focused on demonstrating its effects, direct or indirect, on health indicators, but has made few incursions into assessing its role as a mediator of other factors. While individual risk factors for chronic diseases are well known, the same cannot be said for the complex of contextual factors operating at various levels and over the lifespan. Estimate relative influences by contextual versus individual factors as determinants of diabetes type 2 and heart disease. A cross-sectional study was carried out in populations served by 12 family doctor-and-nurse practices in Havana, in 840 families selected by simple random sampling, 70 per practice. Principal components analysis was used, as well as contextual logistic regression models with a nested model strategy, whose fit was meant to estimate the relative contributions of contextual compared to individual risk factors for diabetes and heart disease. Context was described and analyzed at two levels: that of the family or household and that of the catchment area served by a family doctor-and-nurse practice (geographically defined as a neighborhood). For diabetes, the contextual effect of neighborhood was modified when household effect was removed; that is, the effect of neighborhood was indirect and mediated by household. Individual coefficients were practically invariant; the principal effect of household changed noticeably on removal of individual effects, while age maintained its effect without variation. For heart disease, the effect of neighborhood was slightly modified when household effect was controlled for. Individual coefficients showed little change. There was an important direct effect of household on risk of heart disease. Age and high blood pressure coefficients hardly varied

  2. The changes of serum BDNF, blood lipid and PCI in the elderly patients with coronary heart disease complicated with diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Chun-Xia He; Jing-Jing Yang; Mei-Jin Yuan; Xiao-Juan Ding

    2016-01-01

    Objective:To compare the clinic from coronary heart disease complicated with diabetes mellitus patients serum BDNF changes, blood tests and PCI, for the clinical treatment of coronary heart disease in patients with diabetes mellitus provide certain reference and ideas.Methods: In outpatient of our hospital of elderly patients with coronary heart disease in patients with diabetes mellitus complicated with 126 cases into coronary heart disease combined with diabetes mellitus group, CHD patients admitted in the same period of 125 cases into coronary heart disease group and healthy subjects during the same period in 120 cases into the healthy control group, 61 males, 59 females, aged 58 to 79 years old, mean age (64.36± 2.20) to exclude coronary heart disease, diabetes and liver and other diseases. All patients according to Gensini integration system and coronary artery vascular image segmentation evaluation criteria for each of the degree of vascular stenosis were evaluated. Total cholesterol (TC), glycerin three fat (TG), low density protein (LDL-C), high density protein (HDL-C), apolipoprotein A1 (APOA-1) and apolipoprotein B (APOB) and other indicators were detected. The number of stents, mean diameter and length of stent in patients with coronary heart disease combined with diabetes mellitus and coronary heart disease group were compared. Results: Coronary heart disease with diabetes mellitus group Gensini score and serum BDNF concentrations were higher in CHD group and control group, CHD group Gensini score and serum BDNF concentrations were significantly higher than the control group, the differences were statistically significant; coronary heart disease and coronary heart disease group and blood fat group in TC, TG, LDL-C, diabetes, APO-B levels were significantly higher than that of control group HDL-C and APOA-1 were significantly lower than control group, coronary heart disease and diabetes group in TC, TG, LDL-C, blood lipid and APO-B level were

  3. Increased persistent sodium current due to decreased PI3K signaling contributes to QT prolongation in the diabetic heart.

    Science.gov (United States)

    Lu, Zhongju; Jiang, Ya-Ping; Wu, Chia-Yen C; Ballou, Lisa M; Liu, Shengnan; Carpenter, Eileen S; Rosen, Michael R; Cohen, Ira S; Lin, Richard Z

    2013-12-01

    Diabetes is an independent risk factor for sudden cardiac death and ventricular arrhythmia complications of acute coronary syndrome. Prolongation of the QT interval on the electrocardiogram is also a risk factor for arrhythmias and sudden death, and the increased prevalence of QT prolongation is an independent risk factor for cardiovascular death in diabetic patients. The pathophysiological mechanisms responsible for this lethal complication are poorly understood. Diabetes is associated with a reduction in phosphoinositide 3-kinase (PI3K) signaling, which regulates the action potential duration (APD) of individual myocytes and thus the QT interval by altering multiple ion currents, including the persistent sodium current INaP. Here, we report a mechanism for diabetes-induced QT prolongation that involves an increase in INaP caused by defective PI3K signaling. Cardiac myocytes of mice with type 1 or type 2 diabetes exhibited an increase in APD that was reversed by expression of constitutively active PI3K or intracellular infusion of phosphatidylinositol 3,4,5-trisphosphate (PIP3), the second messenger produced by PI3K. The diabetic myocytes also showed an increase in INaP that was reversed by activated PI3K or PIP3. The increases in APD and INaP in myocytes translated into QT interval prolongation for both types of diabetic mice. The long QT interval of type 1 diabetic hearts was shortened by insulin treatment ex vivo, and this effect was blocked by a PI3K inhibitor. Treatment of both types of diabetic mouse hearts with an INaP blocker also shortened the QT interval. These results indicate that downregulation of cardiac PI3K signaling in diabetes prolongs the QT interval at least in part by causing an increase in INaP. This mechanism may explain why the diabetic population has an increased risk of life-threatening arrhythmias.

  4. Effect of icodextrin on heart rate variability in diabetic patients on peritoneal dialysis.

    Science.gov (United States)

    Orihuela, Oscar; de Jesús Ventura, María; Ávila-Díaz, Marcela; Cisneros, Alejandra; Vicenté-Martínez, Marlén; Furlong, María-del-Carmen; García-González, Zuzel; Villanueva, Diana; Alcántara, Guadalupe; Lindholm, Bengt; García-López, Elvia; Villanueva, Cleva; Paniagua, Ramón

    2014-01-01

    Spectral analysis of heart rate variability is a noninvasive method for evaluating autonomic cardiovascular dysfunction under various clinical conditions, such as in dialysis patients, in whom an imbalance between the sympathetic and parasympathetic nervous system appears to be an important risk factor for sudden cardiovascular death and arrhythmia. ♢ We compared the effect of icodextrin-based dialysis solution, an option that allows for better metabolic and fluid overload control, with that of glucose-based dialysis fluid on sympathetic and parasympathetic activity in the heart, as assessed by heart rate variability, in diabetic patients on peritoneal dialysis (PD). ♢ This secondary analysis uses data from a randomized controlled trial in diabetic PD patients with high or high-average peritoneal transport using icodextrin-based (ICO group, n = 30) or glucose-based (GLU group, n = 29) solutions for the long dwell. All patients underwent 24-hour electrocardiographic Holter monitoring at baseline, and at 6 and 12 months of follow-up. ♢ We observed no significant differences between the groups in most of the variables analyzed, although values were, in general, below reference values. In the ICO group, total power and both low- and high-frequency power in normalized units increased, but the percentage of RR intervals with variation of more than 50 ms declined over time; in the GLU group, all those values declined. Plasma catecholamine levels were higher at baseline and declined over time. ♢ These results indicate a partial recovery of sympathetic activity in the ICO group, probably because of better extracellular fluid control and lower exposure to glucose with the use of icodextrin-based dialysis solutions.

  5. Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart.

    Science.gov (United States)

    Anderson, Ethan J; Kypson, Alan P; Rodriguez, Evelio; Anderson, Curtis A; Lehr, Eric J; Neufer, P Darrell

    2009-11-10

    The aim of this study was to determine the impact of diabetes on oxidant balance and mitochondrial metabolism of carbohydrate- and lipid-based substrates in myocardium of type 2 diabetic patients. Heart failure represents a major cause of death among diabetic patients. It has been proposed that derangements in cardiac metabolism and oxidative stress may underlie the progression of this comorbidity, but scarce evidence exists in support of this mechanism in humans. Mitochondrial oxygen (O(2)) consumption and hydrogen peroxide (H(2)O(2)) emission were measured in permeabilized myofibers prepared from samples of the right atrial appendage obtained from nondiabetic (n = 13) and diabetic (n = 11) patients undergoing nonemergent coronary artery bypass graft surgery. Mitochondria in atrial tissue of type 2 diabetic individuals show a sharply decreased capacity for glutamate and fatty acid-supported respiration, in addition to an increased content of myocardial triglycerides, as compared to nondiabetic patients. Furthermore, diabetic patients show an increased mitochondrial H(2)O(2) emission during oxidation of carbohydrate- and lipid-based substrates, depleted glutathione, and evidence of persistent oxidative stress in their atrial tissue. These findings are the first to directly investigate the effects of type 2 diabetes on a panoply of mitochondrial functions in the human myocardium using cellular and molecular approaches, and they show that mitochondria in diabetic human hearts have specific impairments in maximal capacity to oxidize fatty acids and glutamate, yet increased mitochondrial H(2)O(2) emission, providing insight into the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of heart failure in diabetic patients. 2009 by the American College of Cardiology Foundation

  6. Ultrathin, Stretchable, Multiplexing pH Sensor Arrays on Biomedical Devices With Demonstrations on Rabbit and Human Hearts Undergoing Ischemia

    OpenAIRE

    Chung, Hyun-Joong; Sulkin, Matthew S.; Kim, Jong-Seon; Goudeseune, Camille; Chao, Hsin-Yun; Song, Joseph W.; Yang, Sang Yoon; Hsu, Yung-Yu; Ghaffari, Roozbeh; Efimov, Igor R.; Rogers, John A.

    2013-01-01

    Stable pH is an established biomarker of health, relevant to all tissues of the body, including the heart. Clinical monitoring of pH in a practical manner, with high spatiotemporal resolution, is particularly difficult in organs such as the heart due to its soft mechanics, curvilinear geometry, heterogeneous surfaces and continuous, complex rhythmic motion. The results presented here illustrate that advanced strategies in materials assembly and electrochemical growth can yield interconnected ...

  7. Inactivation of the central nucleus of the amygdala blocks classical conditioning but not conditioning-specific reflex modification of rabbit heart rate.

    Science.gov (United States)

    Burhans, Lauren B; Schreurs, Bernard G

    2013-02-01

    Heart rate (HR) conditioning in rabbits is a widely used model of classical conditioning of autonomic responding that is noted for being similar to the development of conditioned heart rate slowing (bradycardia) in humans. We have shown previously that in addition to HR changes to a tone conditioned stimulus (CS), the HR reflex itself can undergo associative change called conditioning-specific reflex modification (CRM) that manifests when tested in the absence of the CS. Because CRM resembles the conditioned bradycardic response to the CS, we sought to determine if HR conditioning and CRM share a common neural substrate. The central nucleus of the amygdala (CeA) is a critical part of the pathway through which conditioned bradycardia is established. To test whether the CeA is also involved in the acquisition and/or expression of CRM, we inactivated the CeA with muscimol during HR conditioning or CRM testing. CeA inactivation blocked HR conditioning without completely preventing CRM acquisition or expression. These results suggest that the CeA may therefore only play a modulatory role in CRM. Theories on the biological significance of conditioned bradycardia suggest that it may represent a state of hypervigilance that facilitates the detection of new and changing contingencies in the environment. We relate these ideas to our results and discuss how they may be relevant to the hypersensitivity observed in fear conditioning disorders like post-traumatic stress.

  8. Acetylation control of cardiac fatty acid β-oxidation and energy metabolism in obesity, diabetes, and heart failure.

    Science.gov (United States)

    Fukushima, Arata; Lopaschuk, Gary D

    2016-12-01

    Alterations in cardiac energy metabolism are an important contributor to the cardiac pathology associated with obesity, diabetes, and heart failure. High rates of fatty acid β-oxidation with cardiac insulin resistance represent a cardiac metabolic hallmark of diabetes and obesity, while a marginal decrease in fatty acid oxidation and a prominent decrease in insulin-stimulated glucose oxidation are commonly seen in the early stages of heart failure. Alterations in post-translational control of energy metabolic processes have recently been identified as an important contributor to these metabolic changes. In particular, lysine acetylation of non-histone proteins, which controls a diverse family of mitochondrial metabolic pathways, contributes to the cardiac energy derangements seen in obesity, diabetes, and heart failure. Lysine acetylation is controlled both via acetyltransferases and deacetylases (sirtuins), as well as by non-enzymatic lysine acetylation due to increased acetyl CoA pool size or dysregulated nicotinamide adenine dinucleotide (NAD(+)) metabolism (which stimulates sirtuin activity). One of the important mitochondrial acetylation targets are the fatty acid β-oxidation enzymes, which contributes to alterations in cardiac substrate preference during the course of obesity, diabetes, and heart failure, and can ultimately lead to cardiac dysfunction in these disease states. This review will summarize the role of lysine acetylation and its regulatory control in the context of mitochondrial fatty acid β-oxidation. The functional contribution of cardiac protein lysine acetylation to the shift in cardiac energy substrate preference that occurs in obesity, diabetes, and especially in the early stages of heart failure will also be reviewed. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.

  9. Loss of Breathing Modulation of Heart Rate Variability in Patients with Recent and Long Standing Diabetes Mellitus Type II

    Science.gov (United States)

    Estañol, Bruno; Fossion, Ruben; Toledo-Roy, Juan C.; Callejas-Rojas, José A.; Gien-López, José A.; Delgado-García, Guillermo R.; Frank, Alejandro

    2016-01-01

    Healthy subjects under rhythmic breathing have heart interbeat intervals with a respiratory band in the frequency domain that can be an index of vagal activity. Diabetes Mellitus Type II (DM) affects the autonomic nervous system of patients, thus it can be expected changes on the vagal activity. Here, the influence of DM on the breathing modulation of the heart rate is evaluated by analyzing in the frequency domain heart interbeat interval (IBI) records obtained from 30 recently diagnosed, 15 long standing DM patients, and 30 control subjects during standardized clinical tests of controlled breathing at 0.1 Hz, supine rest and standing upright. Fourier spectral analysis of IBI records quantifies heart rate variability in different regions: low-frequencies (LF, 0.04–0.15 Hz), high-frequencies (HF, 0.15–0.4 Hz), and a controlled breathing peak (RP, centered around 0.1 Hz). Two new parameters are introduced: the frequency radius rf (square root of the sum of LF and HF squared) and β (power of RP divided by the sum of LF and HF). As diabetes evolves, the controlled breathing peak loses power and shifts to smaller frequencies, indicating that heart rate modulation is slower in diabetic patients than in controls. In contrast to the traditional parameters LF, HF and LF/HF, which do not show significant differences between the three populations in neither of the clinical tests, the new parameters rf and β, distinguish between control and diabetic subjects in the case of controlled breathing. Sympathetic activity that is driven by the baroreceptor reflex associated with the 0.1 Hz breathing modulations is affected in DM patients. Diabetes produces not only a rigid heartbeat with less autonomic induced variability (rf diminishes), but also alters the coupling between breathing and heart rate (reduced β), due to a progressive decline of vagal and sympathetic activity. PMID:27802329

  10. Fall in population-based mortality from coronary heart disease negated in people with diabetes mellitus: data from England.

    Science.gov (United States)

    Ecclestone, T C; Yeates, D G R; Goldacre, M J

    2015-10-01

    Mortality rates for coronary heart disease (CHD) have declined substantially in developed countries. Diabetes mellitus is an important risk factor for CHD; its prevalence is increasing. We aimed to compare trends in population-based mortality for CHD without diabetes on the death certificate with trends for CHD with diabetes on the same certificate. Analysis of an all-England dataset with multiple-cause coded mortality records from 1995 to 2010. Analysis of a similar dataset for Oxford, because it has the longest run of multiple-cause coded mortality in England, from 1979. Age-specific and age-standardized mortality rates were calculated. In the all-England dataset, there were 1 772 760 deaths with CHD and no mention of diabetes; and 173 184 deaths with CHD and diabetes on the same death certificate. Of deaths with CHD without a mention of diabetes, rates per million men fell by more than half from 2843 (95% confidence interval: 2822-2862) in 1995 to 1379 (1366-1391) in 2010; and those in women halved from 1324 (1314-1336) to 628 (621-635). Of deaths with CHD and diabetes, rates per million men increased from 194 (188-200) to 215 (210-220); and those for women fell, but only very slightly, from 114 (111-118) to 101 (98-104). The longer run in Oxford, from 1979, showed that rates in men and women without diabetes had fallen by two-thirds; but that rates for CHD with diabetes had not fallen. The fall in mortality from CHD without diabetes has been spectacular. There has been no comparable fall in mortality from CHD with diabetes. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  11. Association Between a Genetic Variant Related to Glutamic Acid Metabolism and Coronary Heart Disease in Type 2 Diabetes

    Science.gov (United States)

    Qi, Qibin; Prudente, Sabrina; Mendonca, Christine; Andreozzi, Francesco; di Pietro, Natalia; Sturma, Mariella; Novelli, Valeria; Mannino, Gaia Chiara; Formoso, Gloria; Gervino, Ernest V.; Hauser, Thomas H.; Muehlschlegel, Jochen D.; Niewczas, Monika A.; Krolewski, Andrzej S.; Biolo, Gianni; Pandolfi, Assunta; Rimm, Eric; Sesti, Giorgio; Trischitta, Vincenzo; Hu, Frank

    2013-01-01

    IMPORTANCE Diabetes is associated with an elevated risk of coronary heart disease (CHD). Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and non-diabetic participants. OBJECTIVE To identify genetic determinants of CHD that are specific to diabetic patients. DESIGN, SETTING, AND PARTICIPANTS We studied five independent sets of CHD cases and CHD-negative controls from the Nurses Health Study (NHS; enrolled in 1976 and followed through 2008), Health Professionals Follow-up Study (HPFS; enrolled in 1986 and followed through 2008), Joslin Heart Study (enrolled in 2001-2008), Gargano Heart Study (enrolled in 2001-2008), and Catanzaro Study (enrolled in 2004-2010). Included were a total of 1,517 CHD cases and 2,671 CHD-negative controls, all with type 2 diabetes. Results in diabetic patients were compared with those in 737 non-diabetic CHD cases and 1,637 non-diabetic CHD-negative controls from the NHS and HPFS cohorts. EXPOSURE 2,543,016 common genetic variants occurring throughout the genome. MAIN OUTCOME CHD defined as fatal or non-fatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or angiographic evidence of significant stenosis of the coronary arteries. RESULTS We identified a variant on chromosome 1q25 (rs10911021) consistently associated with CHD risk among diabetic participants with an odds ratio of 1.36 (95% confidence interval [CI] 1.22-1.51, P=2×10−8). No association between this variant and CHD was detected among non-diabetic participants (OR=0.99, P=0.89), consistent with a significant gene-by-diabetes interaction on CHD risk (P=2×10−4). As compared to protective allele homozygotes, rs10911021 risk allele homozygotes were characterized by a 32% decrease in the expression of the neighboring glutamate-ammonia ligase (GLUL) gene in human endothelial cells (P=0.0048). They also showed a decreased ratio between plasma

  12. Prediction of risk of diabetic retinopathy for all-cause mortality, stroke and heart failure

    Science.gov (United States)

    Zhu, Xiao-Rong; Zhang, Yong-Peng; Bai, Lu; Zhang, Xue-Lian; Zhou, Jian-Bo; Yang, Jin-Kui

    2017-01-01

    Abstract To examine and quantify the potential relation between diabetic retinopathy (DR) and risk of all-cause mortality, stroke and heart failure (HF). The resources of meta-analysis of epidemiological observational studies were from Pub-med, EMBASE, CINAHL, Cochrane Library, conference, and proceedings. Random/fixed effects models were used to calculate pooled subgroup analysis stratified by different grades of DR was performed to explore the potential source of heterogeneity. Statistical manipulations were undertaken using program STATA. Of the included 25 studies, comprising 142,625 participants, 19 studies were concluded to find the relation of DR to all-cause mortality, 5 for stroke, and 3 for HF. Risk ratio (RR) for all-cause mortality with the presence of DR was 2.33 (95% CI 1.92–2.81) compared with diabetic individuals without DR. Evidences showed a higher risk of all-cause mortality associated with DR in patients with T2D or T1D (RR 2.25, 95% CI 1.91–2.65. RR 2.68, 95% CI 1.34–5.36). According to different grades of DR in patients with T2D, RR for all-cause mortality varied, the risk of nonproliferative diabetic retinopathy (NPDR) was 1.38 (1.11–1.70), while the risk of proliferative diabetic retinopathy (PDR) was 2.32 (1.75–3.06). There was no evidence of significant heterogeneity (Cochran Q test P = 0.29 vs 0.26, I2 = 19.6% vs 22.6%, respectively). Data from 5 studies in relation to DR and the risk of stroke showed that DR was significantly associated with increased risk of stroke (RR = 1.74, 95%CI: 1.35–2.24), compared with patients without DR. Furthermore, DR (as compared with individuals without DR) was associated with a marginal increased risk of HF in patients with diabetes mellitus (DM) (n = 3 studies; RR 2.24, 95% CI 0.98–5.14, P = 0.056). Our results showed that DR increased the risk of all-cause mortality, regardless of the different stages, compared with the diabetic individuals without DR. DR predicted

  13. Heart Disease Risk Factors

    Science.gov (United States)

    ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke Heart Disease Risk Factors Recommend ... Hearts® WISEWOMAN Program Other Chronic Disease Topics Diabetes Nutrition Obesity Physical Activity Stroke File Formats Help: How do ...

  14. Risk factors for mortality and ischemic heart disease in patients with long-term type 1 diabetes

    DEFF Research Database (Denmark)

    Grauslund, Jakob; Mejnert Jørgensen, Trine; Nybo, Mads;

    2010-01-01

    AIMS: The purpose of this study is to evaluate the effect of glycemic regulation, dyslipidemia, and renal dysfunction on mortality (all-cause and cardiovascular) and ischemic heart disease (IHD) in a long-term follow-up of a population-based cohort of Danish type 1 diabetic patients with at least...

  15. Congenital Heart Disease With and Without Cyanotic Potential and the Long-term Risk of Diabetes Mellitus

    DEFF Research Database (Denmark)

    Madsen, Nicolas L; Marino, Bradley S; Woo, Jessica G

    2016-01-01

    BACKGROUND: Long-term survival for persons born with congenital heart disease (CHD) is improved, but limited knowledge exists of this growing population's acquired cardiovascular risk profile. This study's purpose was to assess CHD survivors' risk for type 2 diabetes mellitus (T2DM) with attention...

  16. Use of fluorquinolones is associated with a reduced risk of coronary heart disease in diabetes mellitus type 2 patients

    NARCIS (Netherlands)

    Erkens, JA; Klungel, OH; Herings, RMC; Stolk, RP; Spoelstra, JA; Grobbee, DE; Leufkens, HGM

    2002-01-01

    Aims The aim of the present study was to investigate whether use of specific antibiotic drugs decreases the risk of coronary heart disease in diabetes mellitus type 2 patients. Methods and Results Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and

  17. Lifestyle intervention improves heart rate recovery from exercise in adults with type 2 diabetes: Results from the Look AHEAD study

    Science.gov (United States)

    The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT), and (2) to determine the independent and combined...

  18. Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease

    NARCIS (Netherlands)

    Liu, Licette C. Y.; Schutte, Elise; Gansevoort, Ron T.; van der Meer, Peter; Voors, Adriaan A.

    2015-01-01

    Introduction: The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limi

  19. Long-term impact of diabetes in patients hospitalized with ischemic and non-ischemic heart failure

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Weeke, Peter; Pecini, Redi

    2010-01-01

    Abstract Objectives. Diabetes mellitus (DM) in combination with heart failure (HF) is associated with a high risk of death, but it is uncertain whether the prognosis differs in ischemic and non-ischemic HF groups. Design. One thousand, three hundred and six patients with ischemic HF and 1315...

  20. METHYLENE BLUE IMPROVES MITOCHONDRIAL RESPIRATION AND DECREASES OXIDATIVE STRESS IN A SUBSTRATE-DEPENDENT MANNER IN DIABETIC RAT HEARTS.

    Science.gov (United States)

    Duicu, Oana M; Privistirescu, Andreea; Wolf, Adrian; Petrus, Alexandra; Dănilă, Maria D; Ratiu, Corina; Muntean, Danina M; Sturza, Adrian

    2017-07-24

    Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox-drug with reported protective effects mainly on brain mitochondria. The present study was purported to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H2O2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. Hydrogen peroxide production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μM) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H2O2 release in the presence of CI substrates (glutamate-malate), but had an opposite effect in mitochondria energized with CII substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and non-diabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

  1. Body mass index is closely correlated to incident diabetes in patients with heart failure or myocardial infarction

    DEFF Research Database (Denmark)

    Schmiegelow, Michelle; Andersson, Charlotte; Olesen, Jonas Bjerring;

    2011-01-01

    ¿=¿3472) or MI (n¿=¿5723) was followed in the period 1995-2006. Methods: Multivariable Cox proportional-hazard models were used to estimate the risk of developing diabetes according to the World Health Organization body mass index (BMI) classification. Normal weight patients (BMI 18.5-24.9¿kg/m(2)) were......Background: Diabetes in patients with heart failure or myocardial infarction (MI) increases morbidity and mortality, but little is known about the impact of obesity on the risk of developing diabetes in these populations. Design: A cohort of patients consecutively hospitalized with heart failure (n...... used as the reference. Results: In both populations, more than half of the patients with a BMI above 34.9¿kg/m(2) developed diabetes. In heart failure patients, a BMI above 24.9¿kg/m(2) was associated with an increased risk of diabetes for the three BMI groups, i.e. 25.0-29.9¿kg/m(2), 30.9-34.9¿kg/m(2...

  2. WEIGHTS or RABBITS

    African Journals Online (AJOL)

    heart and spleen from_male and femalerabbits were made, in rabbits fed graded levels (0, 4, 8, 12%) of oil palm indiets. ..... aeetyl CoA derived mainly from carbohydrate wasdepressed ... an integral part in the synthesis and metabolism of.

  3. Nitric oxide mediates the vagal protective effect on ventricular fibrillation via effects on action potential duration restitution in the rabbit heart.

    Science.gov (United States)

    Brack, Kieran E; Patel, Vanlata H; Coote, John H; Ng, G André

    2007-09-01

    We have previously shown that direct vagus nerve stimulation (VNS) reduces the slope of action potential duration (APD) restitution while simultaneously protecting the heart against induction of ventricular fibrillation (VF) in the absence of any sympathetic activity or tone. In the current study we have examined the role of nitric oxide (NO) in the effect of VNS. Monophasic action potentials were recorded from a left ventricular epicardial site on innervated, isolated rabbit hearts (n = 7). Standard restitution, effective refractory period (ERP) and VF threshold (VFT) were measured at baseline and during VNS in the presence of the NO synthase inhibitor N(G)-nitro-L-arginine (L-NA, 200 microm) and during reversing NO blockade with L-arginine (L-Arg, 1 mm). Data represent the mean +/- S.E.M. The restitution curve was shifted upwards and became less steep with VNS when compared to baseline. L-NA blocked the effect of VNS whereas L-Arg restored the effect of VNS. The maximum slope of restitution was reduced from 1.17 +/- 0.14 to 0.60 +/- 0.09 (50 +/- 5%, P < 0.0001) during control, from 0.98 +/- 0.14 to 0.93 +/- 0.12 (2 +/- 10%, P = NS) in the presence of L-NA and from 1.16 +/- 0.17 to 0.50 +/- 0.10 (41 +/- 9%, P = 0.003) with L-Arg plus L-NA. ERP was increased by VNS in control from 119 +/- 6 ms to 130 +/- 6 ms (10 +/- 5%, P = 0.045) and this increase was not affected by L-NA (120 +/- 4 to 133 +/- 4 ms, 11 +/- 3%, P = 0.0019) or L-Arg with L-NA (114 +/- 4 to 123 +/- 4 ms, 8 +/- 2%, P = 0.006). VFT was increased from 3.0 +/- 0.3 to 5.8 +/- 0.5 mA (98 +/- 12%, P = 0.0017) in control, 3.4 +/- 0.4 to 3.8 +/- 0.5 mA (13 +/- 12%, P = 0.6) during perfusion with L-NA and 2.5 +/- 0.4 to 6.0 +/- 0.7 mA (175 +/- 50%, P = 0.0017) during perfusion with L-Arg plus L-NA. Direct VNS increased VFT and flattened the slope of APD restitution curve in this isolated rabbit heart preparation with intact autonomic nerves. These effects were blocked using L-NA and reversed by replenishing

  4. Inhibition of mammalian target of rapamycin protects against reperfusion injury in diabetic heart through STAT3 signaling.

    Science.gov (United States)

    Das, Anindita; Salloum, Fadi N; Filippone, Scott M; Durrant, David E; Rokosh, Gregg; Bolli, Roberto; Kukreja, Rakesh C

    2015-05-01

    Diabetic patients suffer augmented severity of myocardial infarction. Excessive activation of the mammalian target of rapamycin (mTOR) and decreased activation of STAT3 are implicated in diabetic complications. Considering the potent cardioprotective effect of mTOR inhibitor, rapamycin, we hypothesized that reperfusion therapy with rapamycin would reduce infarct size in the diabetic hearts through STAT3 signaling. Hearts from adult male db/db or wild type (WT) C57 mice were isolated and subjected to 30 min of normothermic global ischemia and 60 min of reperfusion in Langendorff mode. Rapamycin (100 nM) was infused at the onset of reperfusion. Myocardial infarct size (IS) was significantly reduced in rapamycin-treated mice (13.3 ± 2.4 %) compared to DMSO vehicle control (35.9 ± 0.9 %) or WT mice (27.7 ± 1.1 %). Rapamycin treatment restored phosphorylation of STAT3 and enhanced AKT phosphorylation (target of mTORC2), but significantly reduced ribosomal protein S6 phosphorylation (target of mTORC1) in the diabetic heart. To determine the cause and effect relationship of STAT3 in cardioprotection, inducible cardiac-specific STAT3-deficient (MCM TG:STAT3(flox/flox)) and WT mice (MCM TG:STAT3(flox/flox)) were made diabetic by feeding high fat diet (HFD). Rapamycin given at reperfusion reduced IS in WT mice but not in STAT3-deficient mice following I/R. Moreover, cardiomyocytes isolated from HFD-fed WT mice showed resistance against necrosis (trypan blue staining) and apoptosis (TUNEL assay) when treated with rapamycin during reoxygenation following simulated ischemia. Such protection was absent in cardiomyocytes from HFD-fed STAT3-deficient mice. STAT3 signaling plays critical role in reducing IS and attenuates cardiomyocyte death following reperfusion therapy with rapamycin in diabetic heart.

  5. Attenuated ventricular β-adrenergic response and reduced repolarization reserve in a rabbit model of chronic heart failure

    DEFF Research Database (Denmark)

    Nissen, Jakob Dahl; Thomsen, Morten Bækgaard; Bentzen, Bo Hjorth

    2012-01-01

    mortality but profound structural, functional, and electrical remodeling and compare with nonpaced controls. Pacing increased heart weight/body weight ratio and decreased left ventricular fractional shortening in tachypaced only. Electrocardiogram recordings during sinus rhythm revealed QTc prolongation...... remodeling but very low mortality. Isokalemic and hyperkalemic responses indicate downregulation of functional IKs. Increased short-term variability during hypokalemia unmasks a reduced repolarization reserve....

  6. Hypersensitivity of myofilament response to Ca2+ in association with maladaptation of estrogen-deficient heart under diabetes complication.

    Science.gov (United States)

    Thawornkaiwong, Ariyaporn; Pantharanontaga, Jantarima; Wattanapermpool, Jonggonnee

    2007-02-01

    The amelioration of cardioprotective effect of estrogen in diabetes suggests potential interactive action of estrogen and insulin on myofilament activation. We compared Ca2+-dependent Mg2+-ATPase activity of isolated myofibrillar preparations from hearts of sham and 10-wk ovariectomized rats with or without simultaneous 8 wk-induction of diabetes and from diabetic-ovariectomized rats with estrogen and/or insulin supplementation. Similar magnitude of suppressed maximum myofibrillar ATPase activity was demonstrated in ovariectomized, diabetic, and diabetic-ovariectomized rat hearts. Such suppressed activity and the relative suppression in alpha-myosin heavy chain level in ovariectomy combined with diabetes could be completely restored by estrogen and insulin supplementation. Conversely, the myofilament Ca2+ hypersensitivity detected only in the ovariectomized but not diabetic group was also observed in diabetic-ovariectomized rats, which was restored upon estrogen supplementation. Binding kinetics of beta1-adrenergic receptors and immunoblots of beta1-adrenoceptors as well as heat shock 72 (HSP72) were analyzed to determine the association of changes in receptors and HSP72 to that of the myofilament response to Ca2+. The amount of beta1-adrenoceptors significantly increased concomitant with Ca2+ hypersensitivity of the myofilament, without differences in the receptor binding affinity among the groups. In contrast, changes in HSP72 paralleled that of maximum myofibrillar ATPase activity. These results indicate that hypersensitivity of cardiac myofilament to Ca2+ is specifically induced in ovariectomized rats even under diabetes complication and that alterations in the expression of beta1-adrenoceptors may, in part, play a mechanistic role underlying the cardioprotective effects of estrogen that act together with Ca2+ hypersensitivity of the myofilament in determining the gender difference in cardiac activation.

  7. Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes-induced apoptosis.

    Science.gov (United States)

    Amin, Ali H; El-Missiry, Mohamed A; Othman, Azza I

    2015-01-15

    The present study investigated the ability of melatonin in reducing metabolic risk factors and cardiac apoptosis induced by diabetes. Streptozotocin (60 mg/kg, i.p.) was injected into male rats, and after diabetic induction melatonin (10mg/kg i.g.) was administered orally for 21 days. Diabetic hearts showed increased number of apoptotic cells with downregulation of Bcl-2 and activation of p53 and CD95 as well as the caspases 9, 8 and 3. In addition, there was a significant decrease in insulin level, hyperglycemia, elevated HOMA-IR, glycosylated hemoglobin (HbA1c), total lipids, triglycerides, total cholesterol, low and very low-density lipoprotein and decreased high-density lipoprotein. These changes were coupled with a significant increase in the activities of creatin kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum of the diabetic rats indicating myocardium injury. Oral administration of melatonin for 3 weeks after diabetes induction ameliorated the levels of hyperglycemia, insulin, HbA1c, lipids profile and HOMA-IR. The oral melatonin treatment of diabetic rats significantly decreased the number of apoptotic cells in the heart compared to diabetic rats. It enhanced Bcl-2 expression and blocked the activation of CD95 as well as caspases 9, 8 and 3. These changes were accompanied with significant improvement of CK-MB and LDH in the serum indicating the ameliorative effect of melatonin on myocardium injury. Melatonin effectively ameliorated diabetic myocardium injury, apoptosis, reduced the metabolic risk factors and modulated important steps in both extrinsic and intrinsic pathways of apoptosis. Thus, melatonin may be a promising pharmacological agent for ameliorating potential cardiomyopathy associated with diabetes.

  8. Autonomic nervous system function in type 2 diabetes using conventional clinical autonomic tests, heart rate and blood pressure variability measures

    Directory of Open Access Journals (Sweden)

    S Sucharita

    2011-01-01

    Full Text Available Background: There are currently approximately 40.9 million patients with diabetes mellitus in India and this number is expected to rise to about 69.9 million by the year 2025. This high burden of diabetes is likely to be associated with an increase in associated complications. Materials and Methods: A total of 23 (15 male and 8 female patients with type 2 diabetes of 10-15 years duration and their age and gender matched controls (n=23 were recruited. All subjects underwent detailed clinical proforma, questionnaire related to autonomic symptoms, anthropometry, peripheral neural examination and tests of autonomic nervous system including both conventional and newer methods (heart rate and blood pressure variability. Results: Conventional tests of cardiac parasympathetic and sympathetic activity were significantly lower in patients with diabetes compared to the controls (P<0.05. The diabetic patients group had significantly lower high frequency and low-frequency HRV when expressed in absolute units (P<0.05 and total power (P<0.01 compared to the controls. Conclusion: Data from the current study demonstrated that diabetics had both cardiac sympathetic and cardiac parasympathetic nervous system involvement. The presence of symptoms and involvement of both components of the autonomic nervous system suggest that dysfunction has been present for a while in these diabetics. There is a strong need for earlier and regular evaluation of autonomic nervous system in type 2 diabetics to prevent further complications.

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

    Science.gov (United States)

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

    2015-08-01

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

  10. Identifying diabetic patients with cardiac autonomic neuropathy by heart rate complexity analysis

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    Palaniswami Marimuthu

    2009-01-01

    Full Text Available Abstract Background Cardiac autonomic neuropathy (CAN in diabetes has been called a "silent killer", because so few patients realize that they suffer from it, and yet its effect can be lethal. Early sub clinical detection of CAN and intervention are of prime importance for risk stratification in preventing sudden death due to silent myocardial infarction. This study presents the usefulness of heart rate variability (HRV and complexity analyses from short term ECG recordings as a screening tool for CAN. Methods A total of 17 sets of ECG recordings during supine rest were acquired from diabetic subjects with CAN (CAN+ and without CAN (CAN- and analyzed. Poincaré plot indexes as well as traditional time and frequency, and the sample entropy (SampEn measure were used for analyzing variability (short and long term and complexity of HRV respectively. Results Reduced (p > 0.05_Poincaré plot patterns and lower (p Conclusion Our results demonstrate the potential utility of SampEn (a complexity based estimator of HRV in identifying asymptomatic CAN.

  11. Relationships between Diet, Alcohol Preference, and Heart Disease and Type 2 Diabetes among Americans.

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    Michael K Adjemian

    Full Text Available Although excessive alcohol consumption is a recognized cause of morbidity and mortality, many studies have linked moderate alcohol consumption to improved cardiovascular health and a lower risk of Type 2 Diabetes (T2D. Self-reported alcohol and diet data used to generate these results suffer from measurement error due to recall bias. We estimate the effects of diet, alcohol, and lifestyle choices on the prevalence and incidence of cardiovascular disease and T2D among U.S. adults using a nationally representative cohort of households with scanner data representing their food-at-home, alcohol, and tobacco purchases from 2007-2010, and self-reported health surveys for the same study participants from 2010-2012. Multivariate regression models were used to identify significant associations among purchase data and lifestyle/demographic factors with disease prevalence in 2010, and with incidence of new disease from 2011-2012. After controlling for important confounders, respondents who purchased moderate levels of wine were 25% less likely than non-drinkers to report heart disease in 2010. However, no alcohol-related expenditure variables significantly affected the likelihood of reporting incident heart disease from 2011-2012. In contrast, many types of alcohol-related purchases were associated with a lower prevalence of T2D, and respondents who purchased the greatest volumes of wine or beer--but not liquor--were less likely to report being diagnosed with T2D in 2011-2012 than non-drinkers.

  12. Heart Rate Dynamics after Exercise in Cardiac Patients with and without Type 2 Diabetes.

    Science.gov (United States)

    Neves, Victor R; Kiviniemi, Antti M; Hautala, Arto J; Karjalainen, Jaana; Piira, Olli-Pekka; Catai, Aparecida M; Mäkikallio, Timo H; Huikuri, Heikki Veli; Tulppo, Mikko P

    2011-01-01

    The incidence of cardiovascular events is higher in coronary artery disease patients with type 2 diabetes (CAD + T2D) than in CAD patients without T2D. There is increasing evidence that the recovery phase after exercise is a vulnerable phase for various cardiovascular events. We hypothesized that autonomic regulation differs in CAD patients with and without T2D during post-exercise condition. A symptom-limited maximal exercise test on a bicycle ergometer was performed for 68 CAD + T2D patients (age 61 ± 5 years, 78% males, ejection fraction (EF) 67 ± 8, 100% on β-blockade), and 64 CAD patients (age 62 ± 5 years, 80% males, EF 64 ± 8, 100% on β-blockade). Heart rate (HR) recovery after exercise was calculated as the slope of HR during the first 60 s after cessation of exercise (HRR(slope)). R-R intervals were measured before (5 min) and after exercise from 3 to 8 min, both in a supine position. R-R intervals were analyzed using time and frequency methods and a detrended fluctuation method (α(1)). BMI was 30 ± 4 vs. 27 ± 3 kg m(2) (p exercise capacity, 6.5 ± 1.7 vs. 7.7 ± 1.9 METs (p exercise condition. HR recovery is delayed in CAD + T2D patients, suggesting impairment of vagal activity and/or augmented sympathetic activity after exercise. Blunted HR recovery after exercise in diabetic patients compared with non-diabetic patients is more closely related to low exercise capacity and obesity than to T2D itself.

  13. Determinants of heart rate recovery in coronary artery disease patients with and without type 2 diabetes.

    Science.gov (United States)

    Karjalainen, Jaana J; Kiviniemi, Antti M; Hautala, Arto J; Piira, Olli-Pekka; Lepojärvi, E Samuli; Mäkikallio, Timo H; Huikuri, Heikki V; Tulppo, Mikko P

    2012-11-02

    Cardiovascular autonomic dysfunction, which is a common complication of diabetes, is associated with increased mortality in patients with coronary artery disease (CAD). However, the reasons of autonomic dysfunction in CAD patients with or without diabetes are not well known. We examine the association between heart rate recovery (HRR) and other potential factors among CAD patients with and without type 2 diabetes (T2D). Correlations between HRR 60s after exercise (HRR(60)), characteristics, laboratory and echocardiographic variables, exercise capacity and physical activity were assessed in 50 CAD patients with T2D and 55 patients with CAD alone. HRR(60) had the closest univariate correlation with physical activity and exercise capacity in patients with T2D (r=0.38, p=0.006 and r=0.37, p=0.008, respectively). Age, exercise capacity and high-density lipoprotein cholesterol level explained 30% of the HRR(60) in patients with T2D (p=0.001), while the high intensity physical activity was the only predictor of HRR(60) in CAD patients (12%, p=0.010). HRR(60) was reduced in patients with T2D as compared with those without (34±9 vs. 39±9bpm, p=0.005), but the difference was no longer significant after adjustments for physical activity, exercise capacity, body mass index and the use of calcium antagonists and nitrates (p=0.273). In conclusion, blunted HRR is more common among CAD patients with T2D than in those without, and this is more closely related to physical activity and obesity than to the duration of T2D or associated co-morbidities. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes.

    Science.gov (United States)

    Qi, Lu; Qi, Qibin; Prudente, Sabrina; Mendonca, Christine; Andreozzi, Francesco; di Pietro, Natalia; Sturma, Mariella; Novelli, Valeria; Mannino, Gaia Chiara; Formoso, Gloria; Gervino, Ernest V; Hauser, Thomas H; Muehlschlegel, Jochen D; Niewczas, Monika A; Krolewski, Andrzej S; Biolo, Gianni; Pandolfi, Assunta; Rimm, Eric; Sesti, Giorgio; Trischitta, Vincenzo; Hu, Frank; Doria, Alessandro

    2013-08-28

    Diabetes is associated with an elevated risk of coronary heart disease (CHD). Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and nondiabetic individuals. To identify genetic determinants of CHD that are specific to patients with diabetes. We studied 5 independent sets of CHD cases and CHD-negative controls from the Nurses' Health Study (enrolled in 1976 and followed up through 2008), Health Professionals Follow-up Study (enrolled in 1986 and followed up through 2008), Joslin Heart Study (enrolled in 2001-2008), Gargano Heart Study (enrolled in 2001-2008), and Catanzaro Study (enrolled in 2004-2010). Included were a total of 1517 CHD cases and 2671 CHD-negative controls, all with type 2 diabetes. Results in diabetic patients were compared with those in 737 nondiabetic CHD cases and 1637 nondiabetic CHD-negative controls from the Nurses' Health Study and Health Professionals Follow-up Study cohorts. Exposures included 2,543,016 common genetic variants occurring throughout the genome. Coronary heart disease--defined as fatal or nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or angiographic evidence of significant stenosis of the coronary arteries. A variant on chromosome 1q25 (rs10911021) was consistently associated with CHD risk among diabetic participants, with risk allele frequencies of 0.733 in cases vs 0.679 in controls (odds ratio, 1.36 [95% CI, 1.22-1.51]; P = 2 × 10(-8)). No association between this variant and CHD was detected among nondiabetic participants, with risk allele frequencies of 0.697 in cases vs 0.696 in controls (odds ratio, 0.99 [95% CI, 0.87-1.13]; P = .89), consistent with a significant gene × diabetes interaction on CHD risk (P = 2 × 10(-4)). Compared with protective allele homozygotes, rs10911021 risk allele homozygotes were characterized by a 32% decrease in the

  15. Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease.

    Science.gov (United States)

    Drechsler, Christiane; Kalim, Sahir; Wenger, Julia B; Suntharalingam, Pirianthini; Hod, Tammy; Thadhani, Ravi I; Karumanchi, S Ananth; Wanner, Christoph; Berg, Anders H

    2015-06-01

    Serum carbamylated albumin (C-Alb) levels are associated with excess mortality in patients with diabetic end-stage renal disease. To gain insight into the pathophysiology of carbamylation, we determined associations between C-Alb and causes of death in patients on chronic hemodialysis. The Die Deutsche Diabetes Dialyse Studie (4D study) was a randomized controlled trial testing the effects of atorvastatin on survival in diabetic patients on dialysis during a median follow-up of 4 years. We stratified 1161 patients by C-Alb to see whether differences in carbamylation altered the effects of atorvastatin on survival. Baseline C-Alb significantly correlated with serum cardiac stress markers troponin T and N-terminal pro-B-type-natriuretic peptide and was associated with a history of heart failure and arrhythmia. C-Alb was strongly associated with 1-year adjusted risk of cardiovascular mortality, sudden cardiac death, and the 4-year risk of death from congestive heart failure (hazard ratios of 3.06, 3.78, and 4.64, respectively) but not with myocardial infarction or stroke. Patients with low C-Alb, treated with atorvastatin, experienced a significant improvement in their 4-year survival (hazard ratio 0.692). High C-Alb levels are associated with ongoing cardiac damage, risk of congestive heart failure, and sudden cardiac death. Thus, carbamylation and uremic cardiomyopathy are associated in patients with diabetes mellitus and kidney disease. In addition, statins were specifically beneficial to hemodialysis patients with low C-Alb.

  16. Effects of 12 weeks combined aerobic and resistance exercise on heart rate variability in type 2 diabetes mellitus patients.

    Science.gov (United States)

    Kang, Seol-Jung; Ko, Kwang-Jun; Baek, Un-Hyo

    2016-07-01

    [Purpose] This study evaluated the effects of 12 weeks combined aerobic and resistance exercise on heart rate variability in patients with Type 2 diabetes mellitus. [Subjects and Methods] The subjects were 16 female patients with Type 2 diabetes mellitus selected among the participants of a chronic disease management exercise class at C Region Public Health Center in South Korea. Subjects were randomly assigned to the exercise group (n=8; age, 55.97 ± 7.37) or the control group (n=8; age, 57.53 ± 4.63) The exercise group performed aerobic and resistance exercises for 60 minutes per day, 3 times per week for 12 weeks. Anthropometric measurements, biochemical markers, physical fitness, and heart rate variability were examined. [Results] After 12 weeks of exercise, weight, body fat percentage, waist circumference, blood glucose, insulin resistance, glycated hemoglobin level, systolic blood pressure, and diastolic blood pressure significantly decreased and cardiorespiratory fitness and muscular strength significantly increased in the exercise group. Although heart rate variability measures showed favorable changes with the exercise program, none were significant. [Conclusion] Although the exercise program did not show notable changes in heart rate variability in patients with Type 2 diabetes within the timeframe of the study, exercise may contribute to the prevention and control of cardiovascular autonomic neuropathy.

  17. Comparison of tegaserod (HTF 919) and its main human metabolite with cisapride and erythromycin on cardiac repolarization in the isolated rabbit heart.

    Science.gov (United States)

    Drici, M D; Ebert, S N; Wang, W X; Rodriguez, I; Liu, X K; Whitfield, B H; Woosley, R L

    1999-07-01

    Tegaserod (HTF 919) is a new drug being developed for gastrointestinal motility disorders. Because other gastrointestinal prokinetic agents, such as cisapride and erythromycin, cause slowing of cardiac repolarization and have been implicated in the development of the potentially fatal ventricular arrhythmia, torsades de pointes, a study was initiated to determine whether tegaserod and its main human metabolite adversely influence cardiac repolarization. By using isolated Langendorff-perfused rabbit hearts, we show that QT intervals remain unchanged at concentrations of tegaserod from 0.5 to 10 microM. It was not until the tegaserod concentration was increased to 50 microM (roughly 500-5,000 times more concentrated than those typically found in human plasma after administration of recommended clinical dosages), that a small, but significant increase in the QT interval (12+/-4%; p 70%, respectively; p < 0.01; n = 4). Erythromycin also caused significant lengthening of QT intervals (11+/-2%; p < 0.001; n = 4), although 100 microM concentrations of this drug were required to achieve this effect. These results demonstrate that both cisapride and erythromycin can slow cardiac repolarization at therapeutic doses and that tegaserod's lack of QT prolongation at therapeutic doses suggests that it has the potential to be a safer alternative to cisapride as a gastrointestinal prokinetic agent.

  18. Ⅱ型糖尿病兔大脑皮质和海马神经元的神经丝蛋白表达%THE EXPRESSION OF NEUROFILAMENT PROTEINS IN CEREBRAL CORTEX AND HIPPOCAMPUS IN TYPE Ⅱ DIABETES IN RABBITS

    Institute of Scientific and Technical Information of China (English)

    马志健; 刘正清; 张秋菊; 蔡维君; 李明波; 刘小丹; 陈二云

    2002-01-01

    Objective:To investigate the morphological changes of the neuronal neurites in diabetic rabbit brain. Methods: Twenty- four New Zealand White rabbits were divided into 2 groups: control group and type Ⅱ diabetic group induced by high - carbohydrate and high- fat diet. The levels of blood sugar and insulin were detected at week 0(w0), w4, w8, w13, w18, w23 and w28. Brain tissue was stained by Nissl staining and immunolistochemistry with a specific antibody to neurofilament proteins. Result: In diabetic rabbits, the amount of large pyramidal neuron was significantly reduced, and neuronal neurites became swollen, whorled, disrupted and changed in caliber. In hippocampus CA1 region neurofilament staining was very weak. Conclusion: Neurotoxicity of chronic hyperglycemia might be relevant to vascular chronic complications, which affected the expression of NF and led to neurophysiological and structural changes in the brain of rabbits with type Ⅱ diabetes.

  19. Disposable rabbit

    Science.gov (United States)

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  20. Disposal rabbit

    Science.gov (United States)

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  1. The Relationship Between Daytime, Nighttime and 24-Hour Heart Rate with Urinary Albumin and Protein Excretion in Patients with Newly Diagnosed Type 2 Diabetes

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    Barış AFŞAR

    2012-05-01

    Full Text Available OBJECTIVE: Autonomic nervous system dysfunction (ASD has been widely observed in patients with type 2 diabetes. 24-hour ambulatory blood pressure (ABP and heart rate measurements have been found to associate with ASD in patient with Type 2 diabetes. Since albumin excretion is also related with ASD in type 2 diabetes; in the current study, the relationships between daytime, nighttime and 24- hour heart rates with 24 hour urinary albumin excretion (UAE and 24-hour urinary protein excretion (UPE were analyzed in patients with newly diagnosed type 2 diabetes. MATERIAL and METHODS: All patients underwent following procedures: history taking, physical examination, BP measurement, 12 lead electrocardiographic evaluations, routine urine analysis, biochemical analysis, 24-hour urine collection to measure UAE, UPE and creatinine clearance. 24-hour ABP and heart rate monitoring were performed for all patients. RESULTS: In total 80 patients with newly diagnosed type 2 diabetes were included. Stepwise linear regression revealed that logarithmically converted 24-hour UAE were independently related with 24- hour ambulatory SBP, (P:0.001 and heart rate (night (P<0.0001. Stepwise linear regression revealed that logarithmically converted 24-hour UPE were independently related with age (P:0.032, with averaged fasting blood glucose (P:0.023, with 24-hour ambulatory SBP, (P:0.002 and with heart rate (night (P:0.001. CONCLUSION: Nighttime heart rate, but not daytime and 24-hour heart rate was related with both 24-hour UAE and UPE in patients with Type 2 diabetes.

  2. Heart rate variability and increased risk for developing type 2 diabetes mellitus

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    Penčić-Popović Biljana

    2014-01-01

    Full Text Available Background/Aim. To our knowledge there are no data about the relationship between elevated risk for developing type 2 diabetes mellitus (DM2 and altered cardiac autonomic function. The aim of this study was to evaluate the association between heart rate variability (HRV and slightly increased risk for DM2. Methods. We evaluated 69 subjects (50.0 ± 14.4 years; 30 male without DM2, coronary artery disease and arrhythmias. The subjects were divided into two groups according to the Finnish Diabetes Risk Score (FINDRISC: group I (n = 39 included subjects with 12 > FINDRISC ≥ 7; group II (n = 30 subjects with FINDRISC < 7. HRV was derived from 24-h electrocardiogram. We used time domain variables and frequency domain analysis performed over the entire 24-h period, during the day (06-22 h and overnight (22-06 h. Results. Standard deviation of the average normal RR intervals was significantly lower in the group with increased risk for DM2 compared to the group II (127.1 ± 26.6 ms vs 149.6 ± 57.6 ms; p = 0.035. Other time domain measures were similar in both groups. The group I demonstrated significantly reduced frequency domain measures, total power - TP (7.2 ± 0.3 ln/ms2 vs 7.3 ± 0.3 ln/ms2; p = 0.029, and low frequency - LF (5.9 ± 0.4 ln/ms2 vs 6.3 ± 0.6 ln/ms2; p = 0.006, over entire 24 h, as well as TP (7.1 ± 0.3 ln/ms2 vs 7.3 ± 0.3 ln/ms2; p = 0.004, very low frequency (6.2 ± 0.2 ln/ms2 vs 6.3 ± 0.2 ln/ms2; p = 0.030, LF (5.9 ± 0.4 ln/ms2 vs 6.2 ± 0.3 ln/ms2; p = 0.000 and high frequency (5.7 ± 0.4 ln/ms2 vs 5.9 ± 0.4 ln/ms2; p = 0.011 during the daytime compared to the group II. Nocturnal frequency domain analysis was similar between the groups. The low diurnal frequency was independently related to elevated risk for diabetes mellitus (beta = -0,331; p = 0.006. Conclusion. The obtained results suggest that even slightly elevated risk for developing diabetes mellitus may be related to impaired HRV.

  3. Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats.

    Science.gov (United States)

    El-Seweidy, Mohamed M; Sadik, Nermin A H; Shaker, Olfat G

    2011-02-01

    This study examined the downstream signaling whereby hyperglycemia may lead to myocardial fibrosis and apoptosis in the left ventricle of diabetic rats. The effects of sulfurous mineral water or sodium hydrosulfide (NaHS) as possible modulators were also examined. Sulfurous mineral water (as drinking water) and NaHS (14μmol/kg/day, IP) were administered for 7 week to rats with streptozotocin (STZ)-induced diabetes. Hyperglycemia, overproduction of glycated hemoglobin (HbA1C) and serum decline in insulin, C-peptide and insulin like growth factor-I (IGF-I) were observed in diabetic rats. Up-regulation of gene expressions of nuclear factor (NF-κB), profibrogenic growth factor such as transforming growth factor-β1 (TGF-β1), matrix metalloproteniase-2 (MMP-2), procollagen-1 and Fas ligand (Fas-L) were observed in the left ventricle of diabetic rats. A linear positive correlation between TGF-β1 and MMP-2 was also detected in diabetic group. An increase in hydroxyproline level and a disturbance in oxidative balance were detected in heart of diabetic rats. Sulfurous mineral water and NaHS treatment possibly, by improving cardiac GSH level, counteracted the enhanced expression of NF-κB, the profibrogenic and apoptotic parameters. Histopathological examination was in accordance with the biochemical and molecular findings of this study. We suggest a novel therapeutic approach of sulfurous mineral water and exogenous supplementation of H(2)S in diabetic cardiomyopathy.

  4. Heart attack

    Science.gov (United States)

    ... Saunders; 2014:chap 51. Read More Arrhythmias Cardiogenic shock Diabetes Hardening of the arteries Heart failure - overview High blood pressure Implantable cardioverter-defibrillator Lipoprotein- ...

  5. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

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    Yang Wu

    2017-01-01

    Full Text Available Background. Histone deacetylases (HDACs play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R. Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA. TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP, and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim.

  6. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

    Science.gov (United States)

    Wu, Yang; Leng, Yan; Meng, Qingtao; Xue, Rui; Zhao, Bo; Zhan, Liying

    2017-01-01

    Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim. PMID:28191472

  7. Efficacy and safety of modified Yale insulin infusion protocol in Japanese diabetic patients after open-heart surgery.

    Science.gov (United States)

    Tamaki, Motoyuki; Shimizu, Tomoaki; Kanazawa, Akio; Tamura, Yoshifumi; Hanzawa, Ayame; Ebato, Chie; Itou, Chiharu; Yasunari, Eisuke; Sanke, Haruna; Abe, Hiroko; Kawai, Junko; Okayama, Kaede; Matsumoto, Kazuhisa; Komiya, Koji; Kawaguchi, Minako; Inagaki, Noriko; Watanabe, Takahiro; Kanazawa, Yoshie; Hirose, Takahisa; Kawamori, Ryuzo; Watada, Hirotaka

    2008-09-01

    To our knowledge, there is currently no insulin infusion protocol for critically ill patients especially designed for Asian diabetics although many such protocols are used in Western countries. In this study, we modified the Yale insulin infusion protocol taking into consideration the characteristics of Japanese diabetics and hospital environment. We tested the modified protocol in 40 type 2 diabetic patients after elective open-heart surgery (MY group) comparing with 35 type 2 diabetic patients under empirical blood glucose control (EC group). Analyses of 1656 blood glucose measurements during insulin infusion revealed that percentage of samples that showed achievement of target blood glucose level (80-140 mg/dl) was higher under MY (78+/-15%, n=870) than EC (57+/-23%, n=786, p<0.0001). On the other hand, the percentage of samples in which blood glucose was less than 60 mg/dl was comparable in the two groups (MY: 0.5+/-5.9 per thousand, EC: 5.1+/-18.5 per thousand). None of the patients with hypoglycemia showed significant clinical adverse effects. In conclusion, our modified Yale insulin infusion protocol is effective and safe for tight blood glucose control in Japanese diabetic patients after open-heart surgery.

  8. Impaired cytosolic NADH shuttling and elevated UCP3 contribute to inefficient citric acid cycle flux support of postischemic cardiac work in diabetic hearts.

    Science.gov (United States)

    Banke, Natasha H; Lewandowski, E Douglas

    2015-02-01

    Diabetic hearts are subject to more extensive ischemia/reperfusion (ISC/REP) damage. This study examined the efficiency of citric acid cycle (CAC) flux and the transfer of cytosolic reducing equivalents into the mitochondria for oxidative support of cardiac work following ISC/REP in hearts of c57bl/6 (NORM) and type 2 diabetic, db/db mouse hearts. Flux through the CAC and malate-aspartate shuttle (MA) were monitored via dynamic (13)C NMR of isolated hearts perfused with (13)C palmitate+glucose. MA flux was lower in db/db than NORM. Oxoglutarate malate carrier (OMC) was elevated in the db/db heart, suggesting a compensatory response to low NADHc. Baseline CAC flux per unit work (rate-pressure-product, RPP) was similar between NORM and db/db, but ISC/REP reduced the efficiency of CAC flux/RPP by 20% in db/db. ISC/REP also increased UCP3 transcription, indicating potential for greater uncoupling. Therefore, ISC/REP induces inefficient carbon utilization through the CAC in hearts of diabetic mice due to the combined inefficiencies in NADHc transfer per OMC content and increased uncoupling via UCP3. Ischemia and reperfusion exacerbated pre-existing mitochondrial defects and metabolic limitations in the cytosol of diabetic hearts. These limitations and defects render diabetic hearts more susceptible to inefficient carbon fuel utilization for oxidative energy metabolism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Metformin in patients with ischemic heart disease and type 2 diabetes mellitus: mechanism of action and clinical efficiency

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    E N Kravchuk

    2013-03-01

    Full Text Available Diabetes mellitus is one of the leading causes of death in modern society, primarily due to its cardiovascular complications. This factor drives search for novel pharmacologic agents to affect not only glycemic levels, but also the cardiovascular prognosis in diabetic patients with ischemic heart disease. Recent studies demonstrate that aside from basic blood glucose lowering action, metformin shows beneficial influence on blood rheology and vascular tone, hemostasis, oxidative stress, lipid spectrum and delivers and an ant-ischemic effect. Here we review clinical and experimental evidence on cardio- and vasoprotective effects of metformin, highlighting their molecular mechanisms.

  10. Monoamine Oxidases as Potential Contributors to Oxidative Stress in Diabetes: Time for a Study in Patients Undergoing Heart Surgery

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    Oana M. Duicu

    2015-01-01

    Full Text Available Oxidative stress is a pathomechanism causally linked to the progression of chronic cardiovascular diseases and diabetes. Mitochondria have emerged as the most relevant source of reactive oxygen species, the major culprit being classically considered the respiratory chain at the inner mitochondrial membrane. In the past decade, several experimental studies unequivocally demonstrated the contribution of monoamine oxidases (MAOs at the outer mitochondrial membrane to the maladaptative ventricular hypertrophy and endothelial dysfunction. This paper addresses the contribution of mitochondrial dysfunction to the pathogenesis of heart failure and diabetes together with the mounting evidence for an emerging role of MAO inhibition as putative cardioprotective strategy in both conditions.

  11. S100A8 and S100A9 are Associated with Doxorubicin-induced Cardiotoxicity in the Heart of Diabetic Mice

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    Xiao Pei

    2016-08-01

    Full Text Available Cardiomyopathy is a clinical problem that occurs in the hearts of type 2 diabetic patients as well as cancer patients undergoing doxorubicin chemotherapy. The number of diabetic cancer patients is increasing but surprisingly the cardiac damaging effects of doxorubicin, a commonly used chemotherapeutic drug, on diabetic hearts have not been well-examined. As the signaling mechanisms of the doxorubicin-induced cardiomyopathy in type 2 diabetic heart are largely unknown, this study examined the molecular signaling pathways that are responsible for the doxorubicin-induced cardiotoxicity in type 2 diabetic hearts. Male 14- to 18-week-old db/db mice were used as the type 2 diabetic model, and age-matched non-diabetic db/+ mice served as controls. The db/+ non-diabetic and db/db diabetic mice were randomly assigned to the following groups: db/+CON, db/+DOX-5d, db/+DOX-7d, db/dbCON, db/dbDOX-5d, and db/dbDOX-7d. Mice assigned to doxorubicin (DOX group were exposed to an intraperitoneal (i.p. injection of DOX at a dose of 15 mg/kg to induce cardiomyopathy. Mice in control (CON groups were i.p. injected with the same volume of saline instead of DOX. Mice were euthanized by overdose of ketamine and xylazine 5 days or 7 days after the DOX injection. Microarray analysis was adopted to examine the changes of the whole transcriptional profile in response to doxorubicin exposure in diabetic hearts. Ventricular fractional shortening was examined as an indicator of cardiac function by transthoracic echocardiography. The presence of diabetic cardiomyopathy in db/db mice was evident by the reduction of fractional shortening. There was a further impairment of cardiac contractile function 7 days after the DOX administration in db/db diabetic mice. According to our microarray analysis, we identified a panel of regulatory genes associated with cardiac remodeling, inflammatory response, oxidative stress, and metabolism in the DOX-induced cardiac injury in diabetic heart

  12. Association of serum calcium and heart failure with preserved ejection fraction in patients with type 2 diabetes

    OpenAIRE

    Li, Junfeng; Wu, Nan; Dai, Wenling; Jiang, Liu; Li, Yintao; Li, Shibao; WEN, ZHONGYUAN

    2016-01-01

    Background Type 2 diabetes mellitus (T2DM) is a recognized trigger factor for heart failure with preserved ejection fraction (HFpEF). Recent studies show that higher serum calcium level is associated with greater risk of both T2DM and heart failure. We speculate that increased serum calcium is related to HFpEF prevalence in patients with T2DM. Methods In this cross-sectional echocardiographic study, 807 normocalcemia and normophosphatemia patients with T2DM participated, of whom 106 had HFpEF...

  13. Retinol Binding Protein-4 Is Associated with TNF-α and Not Insulin Resistance in Subjects with Type 2 Diabetes Mellitus and Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Nasser M. Al-Daghri

    2009-01-01

    Full Text Available We studied the association between RBP4 and various markers related to insulin resistance and diabetic complications as well as inflammatory markers in Saudi population suffering from type 2 diabetes and coronary heart disease. Patients with type 2 diabetes were divided into 3 groups according to the type of treatment and involvement of coronary artery disease. Serum RBP4, TNF-α, insulin, CRP, resistin, leptin and adiponectin were analysed in all samples. RBP4 levels increased significantly in the group of diabetic subjects treated with oral hypoglycemic agents and diabetic patients with coronary heart disease (30.2 ± 11.8; 33.4 ± 13.6 respectively, while there was no significant change in the other group for diabetic subjects on low-carbohydrate diet (25.1 ± 10.9 compared to control group (22.6 ± 9.5. RPB4 levels were positively correlated with TNF-α in the group of diabetic subjects on oral hypoglycemic agents and diabetic patients with coronary heart disease (r = 0.52, P < 0.05; r = 0.58, P < 0.05 respectively. No correlations were found between RBP4 levels and insulin resistance in all studied groups. Our findings suggest that serum RBP4 levels is associated with pro-inflammatory cytokine (TNF-α and is not associated with insulin resistance among patients with type 2 diabetes and coronary heart disease.

  14. MORTALITY FROM DIABETES MELLITUS (TYPE 2) AND ISCHEMIC HEART DISEASE IN FOUR U.S. WHEAT-PRODUCING STATES: A HYPOTHESIS

    Science.gov (United States)

    In this ecologic study we examined ischemic heart disease (IHD) and diabetes mortality in rural agricultural counties of Minnesota, Montana, North Dakota, and South Dakota, in association with environmental exposure to chlorophenoxy herbicides, using wheat acreage as a surrogate ...

  15. Faster heart rate and muscular oxygen uptake kinetics in type 2 diabetes patients following endurance training.

    Science.gov (United States)

    Koschate, Jessica; Drescher, Uwe; Brinkmann, Christian; Baum, Klaus; Schiffer, Thorsten; Latsch, Joachim; Brixius, Klara; Hoffmann, Uwe

    2016-11-01

    Cardiorespiratory kinetics were analyzed in type 2 diabetes patients before and after a 12-week endurance exercise-training intervention. It was hypothesized that muscular oxygen uptake and heart rate (HR) kinetics would be faster after the training intervention and that this would be detectable using a standardized work rate protocol with pseudo-random binary sequences. The cardiorespiratory kinetics of 13 male sedentary, middle-aged, overweight type 2 diabetes patients (age, 60 ± 8 years; body mass index, 33 ± 4 kg·m(-2)) were tested before and after the 12-week exercise intervention. Subjects performed endurance training 3 times a week on nonconsecutive days. Pseudo-random binary sequences exercise protocols in combination with time series analysis were used to estimate kinetics. Greater maxima in cross-correlation functions (CCFmax) represent faster kinetics of the respective parameter. CCFmax of muscular oxygen uptake (pre-training: 0.31 ± 0.03; post-training: 0.37 ± 0.1, P = 0.024) and CCFmax of HR (pre-training: 0.25 ± 0.04; post-training: 0.29 ± 0.06, P = 0.007) as well as peak oxygen uptake (pre-training: 24.4 ± 4.7 mL·kg(-1)·min(-1); post-training: 29.3 ± 6.5 mL·kg(-1)·min(-1), P = 0.004) increased significantly over the course of the exercise intervention. In conclusion, kinetic responses to changing work rates in the moderate-intensity range are similar to metabolic demands occurring in everyday habitual activities. Moderate endurance training accelerated the kinetic responses of HR and muscular oxygen uptake. Furthermore, the applicability of the used method to detect these accelerations was demonstrated.

  16. Modulation by endothelin-1 of spontaneous activity and membrane currents of atrioventricular node myocytes from the rabbit heart.

    Directory of Open Access Journals (Sweden)

    Stéphanie C Choisy

    Full Text Available BACKGROUND: The atrioventricular node (AVN is a key component of the cardiac pacemaker-conduction system. Although it is known that receptors for the peptide hormone endothelin-1 (ET-1 are expressed in the AVN, there is very little information available on the modulatory effects of ET-1 on AVN electrophysiology. This study characterises for the first time acute modulatory effects of ET-1 on AVN cellular electrophysiology. METHODS: Electrophysiological experiments were conducted in which recordings were made from rabbit isolated AVN cells at 35-37°C using the whole-cell patch clamp recording technique. RESULTS: Application of ET-1 (10 nM to spontaneously active AVN cells led rapidly (within ~13 s to membrane potential hyperpolarisation and cessation of spontaneous action potentials (APs. This effect was prevented by pre-application of the ET(A receptor inhibitor BQ-123 (1 µM and was not mimicked by the ET(B receptor agonist IRL-1620 (300 nM. In whole-cell voltage-clamp experiments, ET-1 partially inhibited L-type calcium current (I(Ca,L and rapid delayed rectifier K(+ current (I(Kr, whilst it transiently activated the hyperpolarisation-activated current (I(f at voltages negative to the pacemaking range, and activated an inwardly rectifying current that was inhibited by both tertiapin-Q (300 nM and Ba(2+ ions (2 mM; each of these effects was sensitive to ET(A receptor inhibition. In cells exposed to tertiapin-Q, ET-1 application did not produce membrane potential hyperpolarisation or immediate cessation of spontaneous activity; instead, there was a progressive decline in AP amplitude and depolarisation of maximum diastolic potential. CONCLUSIONS: Acutely applied ET-1 exerts a direct modulatory effect on AVN cell electrophysiology. The dominant effect of ET-1 in this study was activation of a tertiapin-Q sensitive inwardly rectifying K(+ current via ET(A receptors, which led rapidly to cell quiescence.

  17. The Effects of Electroacupuncture at the Heart Meridian on Myocardial Contractile Function in Rabbits with Myocardial Ischemia

    Institute of Scientific and Technical Information of China (English)

    方志斌; 周逸平; 王月兰

    2002-01-01

    @@ Acute myocardial ischemia was induced by intravenous injection of pituitrin, and electroacupuncture (EA) was applied at the Heart and Lung Meridians (HM and LM), 3 points on each meridian. The changes in the left intraventricular pressure (LVP), the maximum rise rate of intraventricular pressure (LVP dp/dtmax), the area of cardiac force loop (ACFL), and the maximum shortening velocity of myocardial contractile element (Vmax) were observed. As a result, there were significant differences in the improvement of LVP, LVP dp/dtmax, ACFL and Vmax between EA at HM and LM. The regulatory action of EA at HM on the myocardial contractile function was significantly better than that of EA at LM, indicating that HM has a close relationship with the myocardial contractile function.

  18. Resting heart rate variability and exercise capacity in Type 1 diabetes.

    Science.gov (United States)

    Wilson, Luke C; Peebles, Karen C; Hoye, Neil A; Manning, Patrick; Sheat, Catherine; Williams, Michael J A; Wilkins, Gerard T; Wilson, Genevieve A; Baldi, James C

    2017-04-01

    People with type 1 diabetes (T1D) have lower exercise capacity (V̇O2max) than their age-matched nondiabetic counterparts (CON), which might be related to cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV; indicator of cardiac autonomic modulation) was associated with exercise capacity in those with and without T1D. Twenty-three participants with uncomplicated T1D and 17 matched CON were recruited. Heart rate (HR; ECG), blood pressure (BP; finger photo-plethysmography), and respiratory rate (respiratory belt) were measured during baseline, paced-breathing and clinical autonomic reflex tests (CARTs); deep breathing, lying-to-stand, and Valsalva maneuver. Baseline and paced-breathing ECG were analyzed for HRV (frequency-domain). Exercise capacity was determined during an incremental cycle ergometer test while V̇O2, 12-lead ECG, and BP were measured. In uncomplicated T1D, resting HR was elevated and resting HRV metrics were reduced, indicative of altered cardiac parasympathetic modulation; this was generally undetected by the CARTs. However, BP and plasma catecholamines were not different between groups. In T1D, V̇O2max tended to be lower (P = 0.07) and HR reserve was lower (P exercise (R(2 )= 0.042-0.3) in both T1D and CON Alterations in cardiac autonomic modulation are an early manifestation of uncomplicated T1D. Total Power was associated with reduced exercise capacity regardless of group, and these associations were generally stronger than traditional indicators. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  19. The clinical course and outcomes of post-transplantation diabetes mellitus after heart transplantation.

    Science.gov (United States)

    Cho, Min Soo; Choi, Hyo-In; Kim, In-Ok; Jung, Sung-Ho; Yun, Tae-Jin; Lee, Jae-Won; Kim, Min-Seok; Kim, Jae-Joong

    2012-12-01

    The aim of this study was to describe in more detail the predisposition, natural course, and clinical impact of post-transplantation diabetes mellitus (PTDM) after heart transplantation (HT). The characteristics and clinical outcomes of 54 patients with PTDM were compared with those of 140 patients without PTDM. The mean age of PTDM patients was significantly higher than controls (48.9 ± 9.3 vs 38.6 ± 13.3 yr, respectively, P = 0.001), and ischemic heart disease was a more common indication of HT (20.4% [11/54] vs 7.1% [10/140], respectively, P = 0.008). In multivariate analysis, only recipient age (odds ratio, 1.80; 95% confidence interval, 1.35-2.40; P = 0.001) was associated with PTDM development. In 18 patients (33%), PTDM was reversed during the follow-up period, and the reversal of PTDM was critically dependent on the time taken to develop PTDM (1.9 ± 1.0 months in the reversed group vs 14.5 ± 25.3 months in the maintained group, P = 0.005). The 5-yr incidence of late infection (after 6 months) was higher in the PTDM group than in the control group (30.4% ± 7.1% vs 15.4% ± 3.3%, respectively, P = 0.031). However, the 5-yr overall survival rate was not different (92.9% ± 4.1% vs 85.8% ± 3.2%, respectively, P = 0.220). In conclusion, PTDM after HT is reversible in one-third of patients and is not a critical factor in patient survival after HT.

  20. Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice.

    Science.gov (United States)

    Zhang, Jingjing; Cheng, Yanli; Gu, Junlian; Wang, Shudong; Zhou, Shanshan; Wang, Yuehui; Tan, Yi; Feng, Wenke; Fu, Yaowen; Mellen, Nicholas; Cheng, Rui; Ma, Jianxing; Zhang, Chi; Li, Zhanquan; Cai, Lu

    2016-04-01

    Fenofibrate (FF), as a peroxisome-proliferator-activated receptor α (PPARα) agonist, has been used clinically for decades to lower lipid levels. In the present study, we examined whether FF can be repurposed to prevent the pathogenesi of the heart in Type 1 diabetes and to describe the underlying mechanism of its action. Streptozotocin (STZ)-induced diabetic mice and their age-matched control mice were treated with vehicle or FF by gavage every other day for 3 or 6 months. FF prevented diabetes-induced cardiac dysfunction (e.g. decreased ejection fraction and hypertrophy), inflammation and remodelling. FF also increased cardiac expression of fibroblast growth factor 21 (FGF21) and sirtuin 1 (Sirt1) in non-diabetic and diabetic conditions. Deletion of FGF21 gene (FGF21-KO) worsened diabetes-induced pathogenic effects in the heart. FF treatment prevented heart deterioration in the wild-type diabetic mice, but could not do so in the FGF21-KO diabetic mice although the systemic lipid profile was lowered in both wild-type and FGF21-KO diabetic mice. Mechanistically, FF treatment prevented diabetes-impaired autophagy, reflected by increased microtubule-associated protein 1A/1B-light chain 3, in the wild-type diabetic mice but not in the FGF21-KO diabetic mice. Studies with H9C2 cells in vitro demonstrated that exposure to high glucose (HG) significantly increased inflammatory response, oxidative stress and pro-fibrotic response and also significantly inhibited autophagy. These effects of HG were prevented by FF treatment. Inhibition of either autophagy by 3-methyladenine (3MA) or Sirt1 by sirtinol (SI) abolished FF's prevention of HG-induced effects. These results suggested that FF could prevent Type 1 diabetes-induced pathological and functional abnormalities of the heart by increasing FGF21 that may up-regulate Sirt1-mediated autophagy.

  1. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats.

    Science.gov (United States)

    Huisamen, Barbara; Genis, Amanda; Marais, Erna; Lochner, Amanda

    2011-02-01

    Cardiovascular risk is closely associated with insulin resistance and type 2 diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel approach to treat this disease. The aims of this study was therefore to use an animal model to determine whether (i) pre-treatment of obese, insulin resistant but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10 mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject hearts to ischaemia/reperfusion to determine infarct size, functional recovery and post-ischaemic activation of proteins associated with cardiac protection. Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity. Other assessments included body weight, intra-peritoneal fat weight, insulin and GLP-1 levels as well as histological evaluation of the pancreata. Results showed that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed animals. They presented with elevated plasma insulin levels and lower GLP-1 levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size development in hearts from DIO rats after ischaemia/reperfusion accompanied by activation of cardioprotective kinases. GLP-1 levels were elevated and plasma insulin levels lower after treatment. In addition, the beta-cell to alpha-cell ratio of the pancreas was improved. We conclude that treatment with PFK275-055 for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

  2. Hospitalization for heart disease, stroke, and diabetes mellitus among Indian-born persons: a small area analysis

    Directory of Open Access Journals (Sweden)

    Khan Kamran

    2004-10-01

    Full Text Available Abstract Background We set out to describe the risk of hospitalization from heart disease, stroke, and diabetes among persons born in India, all foreign-born persons, and U.S.-born persons residing in New York City. Methods We examined billing records of 1,083,817 persons hospitalized in New York City during the year 2000. The zip code of each patient's residence was linked to corresponding data from the 2000 U.S. Census to obtain covariates not present in the billing records. Using logistic models, we evaluated the risk of hospitalization for heart disease, stroke and diabetes by country of origin. Results After controlling for covariates, Indian-born persons are at similar risk of hospitalization for heart disease (RR = 1.02, 95% confidence interval 1.02, 1.03, stroke (RR = 1.00, 95% confidence interval, 0.99, 1.01, and diabetes mellitus (RR = 0.96 95% confidence interval 0.94, 0.97 as native-born persons. However, Indian-born persons are more likely to be hospitalized for these diseases than other foreign-born persons. For instance, the risk of hospitalization for heart disease among foreign-born persons is 0.70 (95% confidence interval 0.67, 0.72 and the risk of hospitalization for diabetes is 0.39 (95% confidence interval 0.37, 0.42 relative to native-born persons. Conclusions South Asians have considerably lower rates of hospitalization in New York than reported in countries with national health systems. Access may play a role. Clinicians working in immigrant settings should nonetheless maintain a higher vigilance for these conditions among Indian-born persons than among other foreign-born populations.

  3. A longitudinal analysis of the risk factors for diabetes and coronary heart disease in the Framingham Offspring Study

    Directory of Open Access Journals (Sweden)

    Bhargava Alok

    2003-04-01

    Full Text Available Abstract Background The recent trends in sedentary life-styles and weight gain are likely to contribute to chronic conditions such as hypertension, diabetes, and cardiovascular diseases. The temporal sequence and pathways underlying these conditions can be modeled using the knowledge from the biomedical and social sciences. Methods The Framingham Offspring Study in the U.S. collected information on 5124 subjects at baseline, and 8, 12, 16, and 20 years after the baseline. Dynamic random effects models were estimated for the subjects' weight, LDL and HDL cholesterol, and blood pressure using 4 time observations. Logistic and probit models were estimated for the probability of diabetes and coronary heart disease (CHD events. Results The subjects' age, physical activity, alcohol consumption, and cigarettes smoked were important predictors of the risk factors. Moreover, weight and height were found to differentially affect the probabilities of diabetes and CHD events; body weight was positively associated with the risk of diabetes while taller individuals had lower risk of CHD events. Conclusion The results showed the importance of joint modeling of body weight, LDL and HDL cholesterol, and blood pressure that are risk factors for diabetes and CHD events. Lower body weight and LDL concentrations and higher HDL levels achieved via physical exercise are likely to reduce diabetes and CHD events.

  4. Effect of gender and type 2 diabetes mellitus on heart rate recovery in patients with coronary artery disease after cardiac rehabilitation

    NARCIS (Netherlands)

    Soleimani, A.; Abbasi, K.; Nejatian, M.; Movahhedi, N.; Hajizaynali, M. Ali; Salehiomran, A.; Abbasi, S. Hesameddin; Alidoosti, M.; Sheikhfathollahi, M.; Abbasi, A.

    2010-01-01

    Aim. The purpose of this study was to clarify whether type 2 diabetic patients with coronary disease are subject to similar benefits on heart rate recovery (HRR) as non-diabetic coronary individuals after cardiac rehabilitation, assessing separately male and female subjects separately. Methods. Data

  5. The association of alcohol and alcohol metabolizing gene variants with diabetes and coronary heart disease risk factors in a white population

    DEFF Research Database (Denmark)

    Husemoen, Lise Lotte N; Jørgensen, Torben; Borch-Johnsen, Knut

    2010-01-01

    Epidemiological studies have shown a J- or U-shaped relation between alcohol and type 2 diabetes and coronary heart disease (CHD). The underlying mechanisms are not clear. The aim was to examine the association between alcohol intake and diabetes and intermediate CHD risk factors in relation...

  6. Effect of gender and type 2 diabetes mellitus on heart rate recovery in patients with coronary artery disease after cardiac rehabilitation

    NARCIS (Netherlands)

    Soleimani, Abbas; Nejatian, Mostafa; Hajizaynali, Mohammad Ali; Abbasi, Seyed Hesameddin; Alidoosti, Mohammad; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Introduction: The purpose of this study was to clarify whether type 2 diabetic patients with coronary disease are subject to similar benefits in heart rate recovery (HRR) as non-diabetic counterpatrs after cardiac rehabilitation, assessing men and women subjects separately. Material and methods: The

  7. Effect of gender and type 2 diabetes mellitus on heart rate recovery in patients with coronary artery disease after cardiac rehabilitation

    NARCIS (Netherlands)

    Soleimani, A.; Abbasi, K.; Nejatian, M.; Movahhedi, N.; Hajizaynali, M. Ali; Salehiomran, A.; Abbasi, S. Hesameddin; Alidoosti, M.; Sheikhfathollahi, M.; Abbasi, A.

    Aim. The purpose of this study was to clarify whether type 2 diabetic patients with coronary disease are subject to similar benefits on heart rate recovery (HRR) as non-diabetic coronary individuals after cardiac rehabilitation, assessing separately male and female subjects separately. Methods. Data

  8. Effect of gender and type 2 diabetes mellitus on heart rate recovery in patients with coronary artery disease after cardiac rehabilitation

    NARCIS (Netherlands)

    Soleimani, Abbas; Nejatian, Mostafa; Hajizaynali, Mohammad Ali; Abbasi, Seyed Hesameddin; Alidoosti, Mohammad; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Introduction: The purpose of this study was to clarify whether type 2 diabetic patients with coronary disease are subject to similar benefits in heart rate recovery (HRR) as non-diabetic counterpatrs after cardiac rehabilitation, assessing men and women subjects separately. Material and methods: The

  9. Heart failure severity, as determined by loop diuretic dosages, predicts the risk of developing diabetes after myocardial infarction: a nationwide cohort study

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Norgaard, Mette Lykke; Hansen, Peter R;

    2010-01-01

    Heart failure (HF) is associated with increased insulin resistance, but the consequences of HF for development of diabetes are not well studied. The aim of the present study was to investigate the relationship between HF severity and risk of developing diabetes in a nationwide cohort of patients ...

  10. Effect of gender and type 2 diabetes mellitus on heart rate recovery in patients with coronary artery disease after cardiac rehabilitation

    NARCIS (Netherlands)

    Soleimani, A.; Abbasi, K.; Nejatian, M.; Movahhedi, N.; Hajizaynali, M. Ali; Salehiomran, A.; Abbasi, S. Hesameddin; Alidoosti, M.; Sheikhfathollahi, M.; Abbasi, A.

    2010-01-01

    Aim. The purpose of this study was to clarify whether type 2 diabetic patients with coronary disease are subject to similar benefits on heart rate recovery (HRR) as non-diabetic coronary individuals after cardiac rehabilitation, assessing separately male and female subjects separately. Methods. Data

  11. Cardiac structure and function, remodeling, and clinical outcomes among patients with diabetes after myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both

    DEFF Research Database (Denmark)

    Shah, Amil M; Hung, Chung-Lieh; Shin, Sung Hee

    2011-01-01

    The mechanisms responsible for the increased risk of heart failure (HF) post-myocardial infarction (MI) may differ between patients with versus without diabetes. We hypothesized that after high-risk MI, patients with diabetes would demonstrate patterns of remodeling that are suggestive of reduced...

  12. The Additive Effects of Type-2 Diabetes on Cognitive Function in Older Adults with Heart Failure

    Directory of Open Access Journals (Sweden)

    Michael L. Alosco

    2012-01-01

    Full Text Available Background. Medical comorbidity has been theorized to contribute to cognitive impairment in heart failure (HF patients. Specifically, type-2 diabetes mellitus (T2DM, a common coexisting condition among HF patients, may be an independent predictor of cognitive impairment. Nonetheless, the relationships between T2DM and other risk factors for cognitive impairment among persons with HF are unclear. Methods. Persons with HF (N=169, 34.3% women, age 68.57±10.28 years completed neuropsychological testing within a framework of an ongoing study. History of T2DM, along with other medical characteristics, was ascertained through a review of participants’ medical charts and self-report. Results. Many participants (34.9% had a comorbid T2DM diagnosis. After adjustment for demographic and medical characteristics, HF patients with T2DM evidenced significantly greater impairments across multiple cognitive domains than HF patients without T2DM: λ=.92, F(5,156=2.82, P=.018. Post hoc tests revealed significant associations between T2DM and attention (P=.003, executive function (P=.032, and motor functioning (P=.008. Conclusion. The findings suggest additive contributions of T2DM and HF to impairments in attention, executive function, and motor function. Future work is needed to elucidate the mechanisms by which T2DM exacerbates cognitive impairment in HF.

  13. Metabolic alterations induce oxidative stress in diabetic and failing hearts: different pathways, same outcome.

    Science.gov (United States)

    Roul, David; Recchia, Fabio A

    2015-06-10

    Several authors have proposed a link between altered cardiac energy substrate metabolism and reactive oxygen species (ROS) generation. A cogent evidence of this association has been found in diabetic cardiomyopathy (dCM); however, experimental findings in animal models of heart failure (HF) and in human myocardium also seem to support the coexistence of the two alterations in HF. Two important questions remain open: whether pathological changes in metabolism play an important role in enhancing oxidative stress and whether there is a common pathway linking altered substrate utilization and activation of ROS-generating enzymes, independently of the underlying cardiac pathology. In this regard, the comparison between dCM and HF is intriguing, in that these pathological conditions display very different cardiac metabolic phenotypes. Our literature review on this topic indicates that a vast body of knowledge is now available documenting the relationship between the metabolism of energy substrates and ROS generation in dCM. In some cases, biochemical mechanisms have been identified. On the other hand, only a few and relatively recent studies have explored this phenomenon in HF and their conclusions are not consistent. Better methods of investigation, especially in vivo, will be necessary to test whether the metabolic fate of certain substrates is causally linked to ROS production. If successful, these studies will place a new emphasis on the potential clinical relevance of metabolic modulators, which might indirectly mitigate cardiac oxidative stress in dCM, HF, and, possibly, in other pathological conditions.

  14. Combined Heart Rate- and Accelerometer-Assessed Physical Activity Energy Expenditure and Associations With Glucose Homeostasis Markers in a Population at High Risk of Developing Diabetes

    DEFF Research Database (Denmark)

    Hansen, Anne-Louise Smidt; Carstensen, Bendix; Helge, Jørn Wulff

    2013-01-01

    energy expenditure (PAEE) with detailed measures of glucose homeostasis. RESEARCH DESIGN AND METHODS: In 1,531 men and women, with low to high risk of developing type 2 diabetes, we measured 7 days of PAEE using a combined accelerometry and heart rate monitor (ActiHeart). Measures and indices of glucose...

  15. Marital Status, Hypertension, Coronary Heart Disease, Diabetes, and Death among African American Women and Men: Incidence and Prevalence in the Atherosclerosis Risk in Communities (ARIC) Study Participants

    Science.gov (United States)

    Schwandt, Hilary M.; Coresh, Josef; Hindin, Michelle J.

    2010-01-01

    Heart disease is the leading cause of death in the United States, and African Americans disproportionately experience more cardiovascular disease, including coronary heart disease (CHD), hypertension, and diabetes. The literature documents a complex relationship between marital status and health, which varies by gender. We prospectively examine…

  16. Marital Status, Hypertension, Coronary Heart Disease, Diabetes, and Death among African American Women and Men: Incidence and Prevalence in the Atherosclerosis Risk in Communities (ARIC) Study Participants

    Science.gov (United States)

    Schwandt, Hilary M.; Coresh, Josef; Hindin, Michelle J.

    2010-01-01

    Heart disease is the leading cause of death in the United States, and African Americans disproportionately experience more cardiovascular disease, including coronary heart disease (CHD), hypertension, and diabetes. The literature documents a complex relationship between marital status and health, which varies by gender. We prospectively examine…

  17. Heart rate variability modifications following exercise training in type 2 diabetic patients with definite cardiac autonomic neuropathy.

    Science.gov (United States)

    Pagkalos, M; Koutlianos, N; Kouidi, E; Pagkalos, E; Mandroukas, K; Deligiannis, A

    2008-01-01

    Cardiac autonomic neuropathy (CAN) as a result of diabetic autonomic neuropathy is positively related to a poor prognosis in diabetic patients. The measurement of heart rate variability (HRV) is a remarkable index of cardiac autonomic dysfunction. The aim of this study was to examine the effects of long-term exercise training on HRV in type 2 diabetic patients with definite CAN. Seventeen type 2 diabetic patients with definite CAN (group A: 56.2 years (SD 5.8)) and 15 without CAN (group B: 55.8 years (SD 5.6)) participated in the study. All patients followed an aerobic exercise training programme three times a week for 6 months; the intensity of the session was 70% to 85% of heart rate reserve. At the beginning and end of the study all subjects underwent graded maximal exercise testing with spiroergometry for the evaluation of their aerobic capacity (VO(2)peak). Moreover, time and frequency domain indices of HRV were obtained from 24 h ambulatory continuous ECG Holter recordings. At baseline, all measurements of HRV indices were significantly reduced in group A compared with group B (pexercise training programme, the SD of all normal-to-normal RR intervals in the entire recording (SDNN) was increased by 18.8% (pexercise training programme, SDNN, rMSSd and low frequency power (LF) were significantly lower (24.3% (pexercise training programme had significant effects on blood lipid and glucose levels and glycosylated haemoglobin (HbA(1c)) in both groups. The results indicate that 6-month aerobic exercise training improves the cardiac autonomic nervous system function in type 2 diabetic patients. However, more favourable effects are found in type 2 diabetic patients with definite CAN.

  18. The transplantation of Akt-overexpressing amniotic fluid-derived mesenchymal stem cells protects the heart against ischemia-reperfusion injury in rabbits.

    Science.gov (United States)

    Wang, Yan; Li, Yigang; Song, Lei; Li, Yanyan; Jiang, Shan; Zhang, Song

    2016-07-01

    Amniotic fluid-derived mesenchymal stem cells (AFMSCs) are an attractive cell source for applications in regenerative medicine, due to characteristics such as proliferative capacity and multipotency. In addition, Akt, a serine‑threonine kinase, maintains stem cells by promoting viability and proliferation. Whether the transplantation of Akt-overexpressing AFMSCs protects the heart against ischemia‑reperfusion (I/R) injury has yet to be elucidated. Accordingly, the Akt gene was overexpressed in AFMSCs using lentiviral transduction, and Akt‑AFMSCs were transplanted into the ischemic myocardium of rabbits prior to reperfusion. Any protective effects resulting from this procedure were subsequently sought after three weeks later. A histological examination revealed that there was a decrease in intramyocardial inflammation and ultrastructural damage, and an increase in capillary density and in the levels of GATA binding protein 4, connexin 43 and cardiac troponin T in the Akt‑AFMSC group compared with the control group. A significant decrease in cardiomyocyte apoptosis, accompanying an increase in phosphorylated Akt and B‑cell lymphoma 2 (Bcl-2) and a decrease in caspase‑3, was also observed. Furthermore, the left ventricular function was markedly augmented in the Akt‑AFMSC group compared with the control group. These observations suggested that the protective effect of AFMSCs may be due to the delivery of secreted cytokines, promotion of neoangiogenesis, prevention of cardiomyocyte apoptosis, transdifferentiation into cardiomyocytes and promotion of the viability of AFMSCs, which are assisted by Akt gene modification. Taken together, the results of the present study have indicated that transplantation of Akt-AFMSCs is able to alleviate myocardial I/R injury and improve cardiac function.

  19. 姜黄素对心力衰竭兔肌浆网钙泵表达的影响%Effects of curcumin on sarcoplasmic reticulum Ca~(2+) -ATPase in rabbits with heart failure

    Institute of Scientific and Technical Information of China (English)

    张艳; 林国生; 包明威; 武欣迎; 王澈; 杨波

    2010-01-01

    目的 探讨姜黄素对心力衰竭(心衰)兔肌浆网钙泵表达的影响.方法 采用主动脉瓣反流联合腹主动脉缩窄制作慢性心衰家兔模型.随机分为心衰姜黄素组、心衰安慰剂组、对照姜黄素组、对照安慰剂组.8周后计算心脏重量与体重比值,观察超微结构,检测肌浆网钙泵mRNA和蛋白的表达水平及活性.结果 心衰姜黄素组和心衰安慰剂组心脏重量与体重比值均大于对照组(P<0.05);且心衰姜黄素组比值小于心衰安慰剂组(P<0.05).电子显微镜显示心衰姜黄素组的心脏超微结构有所改善.心衰姜黄素组和心衰安慰剂组肌浆网钙泵mRNA、蛋白表达及活性均小于对照组(P<0.05),但心衰姜黄素组均显著高于心衰安慰剂组(P<0.05).结论 姜黄素能在mRNA水平和蛋白水平提高心衰家兔肌浆网钙泵的表达,提高肌浆网钙泵的活性,这可能是姜黄素改善心衰的机制之一.%Objective To investigate the effects of curcumin on sarcoplasmic reticulum Ca~(2+)-ATPase in heart failure rabbits.Methods Rabbit heart failure model was made with aortic regurgitation and abdominal aorta constriction and 40 rabbits were randomly divided into 4 groups including:(1) heart failure treated with curcumin;(2) heart failure treated with placebo;(3) healthy control treated with curcumin and (4) healthy control treated with placebo.All rabbits were administrated with curcumin capsules or placebo capsules 100 mg·kg~(-1)·d~(-1),respectively.All groups were sacrificed after eight weeks.Myocardial ultrastructural organization was detected by transmission electron microscope.RT-PCR and Western blot were used to measure the expression of sarcoplasmic reticulum Ca~(2+)-ATPase in mRNA and protein levels,respectively.Malachite green colorimetric assay was used to evaluate the activity of sarcoplasmic reticulum Ca~(2+) -ATPase.Results All detected parameters were similar between control curcumin group and control placebo

  20. Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death: Outcomes at 4 Years From the Reduction of Atherothrombosis for Continued Health (REACH) Registry.

    Science.gov (United States)

    Cavender, Matthew A; Steg, Ph Gabriel; Smith, Sidney C; Eagle, Kim; Ohman, E Magnus; Goto, Shinya; Kuder, Julia; Im, Kyungah; Wilson, Peter W F; Bhatt, Deepak L

    2015-09-08

    Despite the known association of diabetes mellitus with cardiovascular events, there are few contemporary data on the long-term outcomes from international cohorts of patients with diabetes mellitus. We sought to describe cardiovascular outcomes at 4 years and to identify predictors of these events in patients with diabetes mellitus. The Reduction of Atherothrombosis for Continued Health (REACH) registry is an international registry of patients at high risk of atherothrombosis or established atherothrombosis. Four-year event rates in patients with diabetes mellitus were determined with the corrected group prognosis method. Of the 45 227 patients in the REACH registry who had follow-up at 4 years, 43.6% (n=19 699) had diabetes mellitus at baseline. The overall risk and hazard ratio (HR) of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke were greater in patients with diabetes compared with patients without diabetes (16.5% versus 13.1%; adjusted HR, 1.27; 95% confidence interval [CI] 1.19-1.35). There was also an increase in both cardiovascular death (8.9% versus 6.0%; adjusted HR, 1.38; 95% CI, 1.26-1.52) and overall death (14.3% versus 9.9%; adjusted HR, 1.40; 95% CI, 1.30-1.51). Diabetes mellitus was associated with a 33% greater risk of hospitalization for heart failure (9.4% versus 5.9%; adjusted odds ratio, 1.33; 95% CI, 1.18-1.50). In patients with diabetes mellitus, heart failure at baseline was independently associated with cardiovascular death (adjusted HR, 2.45; 95% CI, 2.17-2.77; PDiabetes mellitus substantially increases the risk of death, ischemic events, and heart failure. Patients with both diabetes mellitus and heart failure are at particularly elevated risk of cardiovascular death, highlighting the need for additional therapies in this high-risk population. © 2015 American Heart Association, Inc.

  1. Metabolic factors and genetic risk mediate familial type 2 diabetes risk in the Framingham Heart Study

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    Raghavan, Sridharan; Porneala, Bianca; McKeown, Nicola; Fox, Caroline S.; Dupuis, Josée; Meigs, James B.

    2015-01-01

    Aims/hypothesis Type 2 diabetes mellitus in parents is a strong determinant of diabetes risk in their offspring. We hypothesise that offspring diabetes risk associated with parental diabetes is mediated by metabolic risk factors. Methods We studied initially non-diabetic participants of the Framingham Offspring Study. Metabolic risk was estimated using beta cell corrected insulin response (CIR), HOMA-IR or a count of metabolic syndrome components (metabolic syndrome score [MSS]). Dietary risk and physical activity were estimated using questionnaire responses. Genetic risk score (GRS) was estimated as the count of 62 type 2 diabetes risk alleles. The outcome of incident diabetes in offspring was examined across levels of parental diabetes exposure, accounting for sibling correlation and adjusting for age, sex and putative mediators. The proportion mediated was estimated by comparing regression coefficients for parental diabetes with (βadj) and without (βunadj) adjustments for CIR, HOMA-IR, MSS and GRS (percentage mediated = 1 – βadj / βunadj). Results Metabolic factors mediated 11% of offspring diabetes risk associated with parental diabetes, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.96. GRS mediated 9% of risk, corresponding to a reduction in OR per diabetic parent from 2.13 to 1.99. Conclusions/interpretation Metabolic risk factors partially mediated offspring type 2 diabetes risk conferred by parental diabetes to a similar magnitude as genetic risk. However, a substantial proportion of offspring diabetes risk associated with parental diabetes remains unexplained by metabolic factors, genetic risk, diet and physical activity, suggesting that important familial influences on diabetes risk remain undiscovered. PMID:25619168

  2. Influences of autonomic nervous system on atrial arrhythmogenic substrates and the incidence of atrial fibrillation in diabetic heart.

    Science.gov (United States)

    Otake, Hideki; Suzuki, Hitoshi; Honda, Takashi; Maruyama, Yukio

    2009-09-01

    Diabetes mellitus (DM) is clinically associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism remains unclear. We hypothesized that neural remodeling enhances AF vulnerability in diabetic hearts. Eight weeks after creating streptozotocin-induced diabetic rats (DM rats) or control rats, the hearts were perfused according to the Langendorff method. Inducibility of AF was evaluated by 5 times burst pacing from the right atrium and the atrial effective refractory period (AERP) was measured. The protocol was repeated during sympathetic nerve stimulation (SNS) or parasympathetic nerve stimulation (PNS). In tissue samples taken from the right atrium, the density of nerves positive for tyrosine hydroxylase (TH) and acetylcholinesterase (AChE) were determined. SNS significantly increased the incidence of AF in DM rats (14 +/- 6 to 30 +/- 8%, P < 0.01), but not in control rats (11 +/- 4 to 14 +/- 6%, NS). Although AERP was significantly decreased by SNS in both rats (each P < 0.01), increased heterogeneity of AERP by SNS was seen only in DM rats. PNS significantly decreased AERP and increased the incidence of AF (9 +/- 5 to 30 +/- 5% in control rats, 12 +/- 6 to 27 +/- 6% in DM rats, each P < 0.01) in both rats. The density of TH-positive nerves was heterogeneous in DM rats compared with control rats, whereas the heterogeneity of AChE-positive nerves was not different in the rats. The prevalence of AF was enhanced by adrenergic activation in diabetic hearts, in which heterogeneous sympathetic innervation was evident. These results suggest that neural remodeling may play a crucial role for increased AF vulnerability in DM.

  3. Relative hypoglycemia of rectal insulin suppositories containing deoxycholic acid, sodium taurocholate, polycarbophil, and their combinations in diabetic rabbits.

    Science.gov (United States)

    Hosny, E A

    1999-06-01

    In this study, insulin suppositories containing 50 U insulin incorporated with 50 mg of deoxycholic acid, sodium taurocholate, or both were placed in the rectum of alloxan-induced hyperglycemic rabbits. A large decrease in plasma glucose concentrations was observed, and the relative hypoglycemias were calculated to be 38.0%, 34.9%, and 44.4%, respectively, compared with insulin subcutaneous (s.c.) injection (40 U). Insulin suppositories containing 50 mg polycarbophil alone or mixed with 50 mg deoxycholic acid produced relative hypoglycemia of 43.1% and 42.2%, respectively. The most pronounced effect was observed with the addition of polycarbophil to the suppository formulation containing a combination of deoxycholic acid and sodium taurocholate, which produced a 56% relative hypoglycemia compared with subcutaneous injection. These suppository formulations could be very promising alternatives to the current insulin injections, being roughly half as efficacious as subcutaneous injection.

  4. Heart rate dynamics after exercise in cardiac patients with and without type 2 diabetes

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    Antti M Kiviniemi

    2011-09-01

    Full Text Available Purpose: The incidence of cardiovascular events is higher in coronary artery disease patients with type 2 diabetes (CAD+T2D than in CAD patients without T2D. There is increasing evidence that the recovery phase after exercise is a vulnerable phase for various cardiovascular events. We hypothesized that autonomic regulation differs in CAD patients with and without T2D during post-exercise condition. Methods: A symptom-limited maximal exercise test on a bicycle ergometer was performed for 68 CAD+T2D patients (age 61 ± 5 years, 78% males, ejection fraction 67 ± 8, 100% on β-blockade and 64 CAD patients (age 62 ± 5 years, 80% males, ejection fraction 64 ± 8, 100% on β-blockade. Heart rate (HR recovery after exercise was calculated as the slope of HR during the first 60 sec after cessation of exercise (HRRslope. R-R intervals were measured before (5 min and after exercise from 3 to 8 min, both in a supine position. R-R intervals were analyzed using time and frequency methods and a detrended fluctuation method (α1. Results: BMI was 30 ± 4 vs. 27 ± 3 kg•m2 (p < 0.001; maximal exercise capacity, 6.5 ± 1.7 vs. 7.7 ± 1.9 METs (p < 0.001; maximal HR, 128 ± 19 vs. 132 ± 18 bpm (p = ns; and HRRslope, -0.53 ± 0.17 vs. -0.62 ± 0.15 beats/sec (p = 0.004, for CAD patients with and without T2D, respectively. There was no differences between the groups in HRRslope after adjustment for METs, BMI and medication (ANCOVA, p = 0.228 for T2D and e.g. p = 0.030 for METs. CAD+T2D patients had a higher HR at rest than nondiabetic patients (57 ± 10 vs. 54 ± 6 bpm, p = 0.030, but no other differences were observed in HR dynamics at rest or in post-exercise condition. Conclusion: HR recovery is delayed in CAD+T2D patients, suggesting impairment of vagal activity and/or augmented sympathetic activity after exercise. Blunted HR recovery after exercise in diabetic patients compared with nondiabetic patients is more closely related to low exercise capacity and

  5. [THE INFLUENCE OF MONO- AND MULTIVASCULAR LESIONS OF CORONARY ARTERIES ON THE COURSE OF CORONARY HEART DISEASE IN PATIENTS WITH DIABETES MELLITUS TYPE 2].

    Science.gov (United States)

    Sypalo, A; Kravchun, P; Kadykova, O

    2017-03-01

    The article assesses the influence of mono- and multivascular lesions of coronary arteries on the course of coronary heart disease at patients with diabetes mellitus type 2. For this purpose, a comprehensive survey of 75 patients with coronary heart disease and diabetes mellitus type 2 was arranged. Depending on the number of vascular lesions of the coronary arteries, according to the data of coronary arteries computer tomography, all patients were divided into two subgroups. The first subgroup included 27 patients with coronary heart disease and diabetes mellitus type 2 with monovascular lesions of coronary arteries. To the second subgroup were included 48 patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries. During the analysis of carbohydrate metabolism in cases of coronary heart disease and diabetes mellitus type 2 the HOMA index increase by 25.40% and insulin level increase by 17.05% were revealed at patients with multivascular lesions of coronary arteries in comparison with patients with monovascular lesions of coronary arteries, respectively. The combination of coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries was associated with an increase of sortilin level (233,47±47,85 ng/l). A significant increase in triglycerides, lipoprotein cholesterol of very low density influences greatly on the progression of coronary atherosclerosis with lesions of greater number of coronary arteries at patients surveyed. At patients with coronary heart disease and diabetes mellitus type 2 with multivascular lesions of coronary arteries the left ventricle myocardial re-modeling occurred through the increase of left ventricle's size and cavity.

  6. The role of autonomic cardiovascular neuropathy in pathogenesis of ischemic heart disease in patients with diabetes mellitus

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    Popović-Pejičić Snježana

    2006-01-01

    Full Text Available Introduction. Diabetes is strongly associated with macrovascular complications, among which ischemic heart disease is the major cause of mortality. Autonomic neuropathy increases the risk of complications, which calls for an early diagnosis. The aim of this study was to determine both presence and extent of cardiac autonomic neuropathy, in regard to the type of diabetes mellitus, as well as its correlation with coronary disease and major cardiovascular risk factors. Material and methods. We have examined 90 subjects, classified into three groups, with 30 patients each: those with type 1 diabetes, type 2 diabetes and control group of healthy subjects. All patients underwent cardiovascular tests (Valsalva maneuver, deep breathing test, response to standing, blood pressure response to standing sustained, handgrip test, electrocardiogram, treadmill exercise test and filled out a questionnaire referring to major cardiovascular risk factors: smoking, obesity, hypertension, and dyslipidemia. Results. Our results showed that cardiovascular autonomic neuropathy was more frequent in type 2 diabetes, manifesting as autonomic neuropathy. In patients with autonomic neuropathy, regardless of the type of diabetes, the treadmill test was positive, i.e. strongly correlating with coronary disease. In regard to coronary disease risk factors, the most frequent correlation was found for obesity and hypertension. Discussion Cardiovascular autonomic neuropathy is considered to be the principal cause of arteriosclerosis and coronary disease. Our results showed that the occurrence of cardiovascular autonomic neuropathy increases the risk of coronary disease due to dysfunction of autonomic nervous system. Conclusions. Cardiovascular autonomic neuropathy is a common complication of diabetes that significantly correlates with coronary disease. Early diagnosis of cardiovascular autonomic neuropathy points to increased cardiovascular risk, providing a basis for preventive

  7. Association between type-2 diabetes mellitus and post-discharge outcomes in heart failure patients: findings from the RICA registry.

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    Carrasco-Sánchez, Francisco Javier; Gomez-Huelgas, Ricardo; Formiga, Francesc; Conde-Martel, Alicia; Trullàs, Joan Carles; Bettencourt, Paulo; Arévalo-Lorido, José Carlos; Pérez-Barquero, Manuel Montero

    2014-06-01

    Heart failure (HF) and diabetes are common clinical conditions that may coexist. The main objective was to analyze the association of type-2 diabetes mellitus (T2DM) on prognosis in hospitalized patients with HF. We evaluated the association between T2DM with all-cause mortality and readmissions in the Spanish National Registry on Heart Failure-"Registro Nacional de Insuficiencia Cardiaca" (RICA). This is a multi-center and prospective cohort study that includes patients admitted for decompensated HF from 2008 to 2011. Study endpoints were all-cause mortality and hospital readmission. We determined the adjusted hazard ratio (HR) by a multivariable Cox regression model. A total of 1082 patients (mean age 77.6±8.5) were included of whom 490 (45.3%) had diabetes and 592 patients (54.7%) had preserved left ventricular ejection fraction (LVEF). During one-year follow-up, 287 patients died (151 patients with diabetes) and 383 patients were readmitted (197 patients with diabetes). After adjusting for baseline characteristics T2DM was significantly associated with all-cause mortality (HR 1.54; 95%CI 1.20-1.97, p=0.001) and readmissions (HR 1.46; 95%CI 1.18-1.80, prenal insufficiency, hyponatremia and anemia were also independently associated with outcomes. There were no differences in mortality (p=0.415) and readmissions (p=0.514) according to preserved or reduced LVEF. T2DM is very common in patients hospitalized for HF. This condition is a strong and independent co-morbidity of all-cause mortality and readmission for both HF with preserved and reduced LVEF. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. 乙酰胆碱诱导的离体兔心房颤动模型的建立%Establishment of acetylcholine-induced atrial fibrillation model in isolated rabbit heart

    Institute of Scientific and Technical Information of China (English)

    潘磊; 李俊

    2012-01-01

    Objective To establish an acetylcholine-induced atrial fibrillation (AF) model in the isolated rabbit heart. Methods Forty healthy male New Zealand rabbits (2.2-2.5 kg) were used in the study. The isolated rabbit hearts were randomly assigned to normal perfusion (group A), normal perfusion with burst high-frequency electric stimulation (group B), acetylcholine perfusion (group C) and acetylcholine perfusion with burst electric stimulation (group D) (n = 10 in each group). The isolated hearts were perfused with Langendorff perfusion system. Results The AF incidence in group D ( acetylcholine perfusion combined with burst electric stimulation) was 50% ; while no AF was induced in other three groups. Conclusion A simple and stable acetylcholine-induced atrial fibrillation model has been established in isolated rabbit heart with Langendorff perfusion system.%目的 建立乙酰胆碱诱导的离体Langendorff灌流的兔的心房颤动模型.方法 健康雄性的新西兰兔40只,2.2 ~2.5 kg,分为4组,分别为正常灌流组、正常灌流+burst刺激组、正常灌流+乙酰胆碱灌注组和正常灌流+乙酰胆碱灌注+ burst刺激组,每组各10只.在Langendorff灌流装置下行主动脉逆行灌流,通过乙酰胆碱灌注和burst刺激诱发心房颤动.结果 正常灌流组、正常灌流+burst刺激组和正常灌流+乙酰胆碱灌注组均没有发生心房颤动,而正常灌流+乙酰胆碱灌注+ burst刺激组心房颤动的发生率为50%.结论 在Langendorff心脏灌流时,给予乙酰胆碱灌注模拟胆碱能激活,并给予burst刺激模拟应激事件,可以稳定地诱导心房颤动的发生.

  9. Lipoprotein lipase and angiopoietin-like 4 - Cardiomyocyte secretory proteins that regulate metabolism during diabetic heart disease.

    Science.gov (United States)

    Puthanveetil, Prasanth; Wan, Andrea; Rodrigues, Brian

    2015-01-01

    Cardiac diseases have been extensively studied following diabetes and altered metabolism has been implicated in its initiation. In this context, there is a shift from glucose utilization to predominantly fatty acid metabolism. We have focused on the micro- and macro-environments that the heart uses to provide fatty acids to the cardiomyocyte. Specifically, we will discuss the cross talk between endothelial cells, smooth muscles and cardiomyocytes, and their respective secretory products that allows for this shift in metabolism. These changes will then be linked to alterations in the cardiovascular system and the augmented heart disease observed during diabetes. Traditionally, the heart was only thought of as an organ that supplies oxygen and nutrients to the body through its function as a pump. However, the heart as an endocrine organ has also been suggested. Secreted products from the cardiomyocytes include the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Both have been shown to have vasodilatory, diuretic and antihypertensive effects. These peptides have been extensively studied and their deficiency is considered to be a major cause for the initiation of cardiovascular and cardiometabolic disorders. Another secretory enzyme, lipoprotein lipase (LPL), has been implicated in diabetic heart disease. LPL is a triglyceride-hydrolyzing enzyme that is synthesized within the cardiomyocyte and secreted towards the lumen under various conditions. For example, moderate or short-term hyperglycemia stimulates the release of LPL from the cardiomyocytes towards the endothelial cells. This process allows LPL to contact lipoprotein triglycerides, initiating their break down, with the product of lipolysis (free fatty acids, FA) translocating towards the cardiomyocytes for energy consumption. This mechanism compensates for the lack of glucose availability following diabetes. Under prolonged, chronic conditions of hyperglycemia, there is

  10. CLINICAL EFFICACY OF GLYCOSAMINOGLYCANS IN PATIENTS WITH DIABETES MELLITUS AND ISCHEMIC HEART DISEASE

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    L. V. Kozlova

    2011-01-01

    Full Text Available Aim. To study sulodexide clinical efficacy in patients with type 2 diabetes mellitus (DM and ischemic heart disease (IHD in prevention of contrast induced nephropathy (CIN. Material and мethods. Patients with type 2 DM and IHD who undergone X-Ray contrast intervention. The patients were randomized into 2 groups: 56 patients of the main group were i/v administered sulodexide (Vessel Due F , “Alfa Wassermann”, Italy according to standard procedure; 56 patients of the control group were treated with unfractionated heparin. Results. The incidence of CIN in the main and control groups was, respectively , 16% and 42% (p<0.01. Reduction of microalbuminuria (MAU was found in 89.3% of the sulodexide group patients. MAU dynamics in patients of control group was not observed. There were no deteriorations in echocardiography characteristics in patients of both groups. The reduction in  low density cholesterol and triglyceride plasma levels was observed in the main group. Sulodexide induced a lengthening of the activated partial thromboplastin time (from 30±0.6 to 34±0.5 s, without altering fibrinogen level. There were no thrombotic and hemorrhagic complications of endovascular intervention in sulodexide group. No one case of thrombocytopenia was observed. Higher risk of CIN in patients without sulodexide treatment compared with this in sulodexide treated patients was associated with multiple lesions of coronary arteries, diuretic intake in periprocedural period, contrast agent dose, duration of hospitalization, seriousness of intervention. Conclusion. Sulodexide therapy in patients with 2 type DM and IHD undergone X-Ray contrast intervention prevents renal dysfunction, providing antiproteinuric effect and correcting lipid metabolism and coagulation system disturbances.

  11. DIAGNOSTIC VALUE OF GALECTIN-3 LEVEL IN PATIENTS WITH CHRONIC HEART FAILURE AND TYPE 2 DIABETES

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    A. A. Snetkova

    2015-01-01

    Full Text Available Currently, a greater emphasis is placed on the search for additional biomarkers of chronic heart failure (CHF. Galectin-3, a marker of fibrosis and inflammation, has shown himself as a biomarker of CHF in many studies, but the dynamics of its levels in patients with concomitant diabetes mellitus (DM type 2 is not well-studied.Aim. To identify diagnostic significance of galectin-3 plasma level evaluation and its correlations with echocardiographic criteria for patients with CHF and DM type 2.Material and methods. The study included 33 patients with ischemic CHF (all patients had a history of myocardial infarction and DM type 2. The patients were divided into two groups according to the left ventricle (LV ejection fraction (EF: a group with CHF and preserved ejection fraction (PEF (EF≥50% and with CHF and reduced ejection fraction (EF<50%. Patients underwent clinical laboratory tests and Doppler echocardiography; moreover, the levels of brain natriuretic peptide (BNP and galeсtin-3 were measured.Results. The mean level of galectin-3 in blood plasma in the group with CHF and PEF was significantly higher than in the group with CHF and reduced EF (p=0.007. In the group with CHF and PEF a positive correlation between the level of galectin-3 and diastolic LV function E/E' was found (r=0.620, p=0.01. A significant correlation between galectin-3 level and LV systolic function was stated in the group with reduced EF (r=0.53; p<0.05, while in the group with PEF, the correlation was not significant (p=0.225. In the group of patients with reduced EF a negative correlation between galectin-3 and the volume of left atrium was revealed (r=-0.53; p<0.05.Conclusion. Galectin-3 can be used as a diagnostic biomarker primarily in patients with CHF and PEF.

  12. DIAGNOSTIC VALUE OF GALECTIN-3 LEVEL IN PATIENTS WITH CHRONIC HEART FAILURE AND TYPE 2 DIABETES

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    A. A. Snetkova

    2015-09-01

    Full Text Available Currently, a greater emphasis is placed on the search for additional biomarkers of chronic heart failure (CHF. Galectin-3, a marker of fibrosis and inflammation, has shown himself as a biomarker of CHF in many studies, but the dynamics of its levels in patients with concomitant diabetes mellitus (DM type 2 is not well-studied.Aim. To identify diagnostic significance of galectin-3 plasma level evaluation and its correlations with echocardiographic criteria for patients with CHF and DM type 2.Material and methods. The study included 33 patients with ischemic CHF (all patients had a history of myocardial infarction and DM type 2. The patients were divided into two groups according to the left ventricle (LV ejection fraction (EF: a group with CHF and preserved ejection fraction (PEF (EF≥50% and with CHF and reduced ejection fraction (EF<50%. Patients underwent clinical laboratory tests and Doppler echocardiography; moreover, the levels of brain natriuretic peptide (BNP and galeсtin-3 were measured.Results. The mean level of galectin-3 in blood plasma in the group with CHF and PEF was significantly higher than in the group with CHF and reduced EF (p=0.007. In the group with CHF and PEF a positive correlation between the level of galectin-3 and diastolic LV function E/E' was found (r=0.620, p=0.01. A significant correlation between galectin-3 level and LV systolic function was stated in the group with reduced EF (r=0.53; p<0.05, while in the group with PEF, the correlation was not significant (p=0.225. In the group of patients with reduced EF a negative correlation between galectin-3 and the volume of left atrium was revealed (r=-0.53; p<0.05.Conclusion. Galectin-3 can be used as a diagnostic biomarker primarily in patients with CHF and PEF.

  13. Preparation of Preproinsulin Gene Construct Containing the Metallothionein2A (pBINDMTChIns and Its Expression in NIH3T3 Cell Line and Muscle Tissue of Alloxan Diabetic Rabbits

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    Piri

    2014-08-01

    Full Text Available Background Diabetes mellitus type 1, formerly called insulin-dependent diabetes, is one of the autoimmune diseases where insulin-producing cells are destroyed by autoimmune response via T cells. The new approaches in treatment of diabetes are using the stem cells, cell transplantation of islet β cell, gene transfer by virus based plasmids, and non-viral gene constructs. Objectives The purpose of this study was to construct glucose inducible insulin gene plasmid and use it in the muscle tissue of the rabbit. Materials and Methods To achieve this goal, the preproinsulin, metallothionein2A promoter and the response element to carbohydrate genes were cloned into pBIND plasmid by standard cloning methods, to construct pBINDMTChIns. The gene cloning products were confirmed by the polymerase chain reaction (PCR and restriction enzyme digestion template. The recombinant plasmid, containing the preproinsulin gene, was transferred into NIH3T3 cells and insulin gene expression was evaluated by reverse transcriptase PCR and western blotting techniques. Plasmid naked DNA containing the preproinsulin gene was injected into the rabbits’ thigh muscles, and its expression was confirmed by western blotting method. Results This study shows the prepared gene construct is inducible by glucose. Gene expression of preproinsulin was observed in muscle tissue of rabbits. Conclusions These finding indicated that research in diabetes mellitus gene therapy could be performed on larger animals.

  14. Estimation of 10-Year Risk of Coronary Heart Disease in Nepalese Patients with Type 2 Diabetes: Framingham Versus United Kingdom Prospective Diabetes Study.

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    Pokharel, Daya Ram; Khadka, Dipendra; Sigdel, Manoj; Yadav, Naval Kishor; Sapkota, Lokendra Bahadur; Kafle, Ramchandra; Nepal, Sarthak; Sapkota, Ravindra Mohan; Choudhary, Niraj

    2015-08-01

    Predicting future coronary heart disease (CHD) risk with the help of a validated risk prediction function helps clinicians identify diabetic patients at high risk and provide them with appropriate preventive medicine. The aim of this study is to estimate and compare 10-year CHD risks of Nepalese diabetic patients using two most common risk prediction functions: The Framingham risk equation and United Kingdom Prospective Diabetes Study (UKPDS) risk engine that are yet to be validated for Nepalese population. We conducted a hospital-based, cross-sectional study on 524 patients with type 2 diabetes. Baseline and biochemical variables of individual patients were recorded and CHD risks were estimated by the Framingham and UKPDS risk prediction functions. Estimated risks were categorized as low, medium, and high. The estimated CHD risks were compared using kappa statistics, Pearson's bivariate correlation, Bland-Altman plots, and multiple regression analysis. The mean 10-year CHD risks estimated by the Framingham and UKPDS risk functions were 17.7 ± 12.1 and 16.8 ± 15 (bias: 0.88, P > 0.05), respectively, and were always higher in males and older age groups (P < 0.001). The two risk functions showed moderate convergent validity in predicting CHD risks, but differed in stratifying them and explaining the patients' risk profile. The Framingham equation predicted higher risk for patients usually below 70 years and showed better association with their current risk profile than the UKPDS risk engine. Based on the predicted risk, Nepalese diabetic patients, particularly those associated with increased numbers of risk factors, bear higher risk of future CHDs. Since this study is a cross-sectional one and uses externally validated risk functions, Nepalese clinicians should use them with caution, and preferably in combination with other guidelines, while making important medical decisions in preventive therapy of CHD.

  15. Estimation of 10-year risk of coronary heart disease in nepalese patients with type 2 diabetes: Framingham versus United Kingdom prospective diabetes study

    Directory of Open Access Journals (Sweden)

    Daya Ram Pokharel

    2015-01-01

    Full Text Available Background: Predicting future coronary heart disease (CHD risk with the help of a validated risk prediction function helps clinicians identify diabetic patients at high risk and provide them with appropriate preventive medicine. Aim: The aim of this study is to estimate and compare 10-year CHD risks of Nepalese diabetic patients using two most common risk prediction functions: The Framingham risk equation and United Kingdom Prospective Diabetes Study (UKPDS risk engine that are yet to be validated for Nepalese population. Patients and Methods: We conducted a hospital-based, cross-sectional study on 524 patients with type 2 diabetes. Baseline and biochemical variables of individual patients were recorded and CHD risks were estimated by the Framingham and UKPDS risk prediction functions. Estimated risks were categorized as low, medium, and high. The estimated CHD risks were compared using kappa statistics, Pearson′s bivariate correlation, Bland-Altman plots, and multiple regression analysis. Results: The mean 10-year CHD risks estimated by the Framingham and UKPDS risk functions were 17.7 ± 12.1 and 16.8 ± 15 (bias: 0.88, P > 0.05, respectively, and were always higher in males and older age groups (P < 0.001. The two risk functions showed moderate convergent validity in predicting CHD risks, but differed in stratifying them and explaining the patients′ risk profile. The Framingham equation predicted higher risk for patients usually below 70 years and showed better association with their current risk profile than the UKPDS risk engine. Conclusions: Based on the predicted risk, Nepalese diabetic patients, particularly those associated with increased numbers of risk factors, bear higher risk of future CHDs. Since this study is a cross-sectional one and uses externally validated risk functions, Nepalese clinicians should use them with caution, and preferably in combination with other guidelines, while making important medical decisions in

  16. Cardiac-specific overexpression of catalase prevents diabetes-induced pathological changes by inhibiting NF-κB signaling activation in the heart.

    Science.gov (United States)

    Cong, Weitao; Ruan, Dandan; Xuan, Yuanhu; Niu, Chao; Tao, Youli; Wang, Yang; Zhan, Kungao; Cai, Lu; Jin, Litai; Tan, Yi

    2015-12-01

    Catalase is an antioxidant enzyme that specifically catabolizes hydrogen peroxide (H2O2). Overexpression of catalase via a heart-specific promoter (CAT-TG) was reported to reduce diabetes-induced accumulation of reactive oxygen species (ROS) and further prevent diabetes-induced pathological abnormalities, including cardiac structural derangement and left ventricular abnormity in mice. However, the mechanism by which catalase overexpression protects heart function remains unclear. This study found that activation of a ROS-dependent NF-κB signaling pathway was downregulated in hearts of diabetic mice overexpressing catalase. In addition, catalase overexpression inhibited the significant increase in nitration levels of key enzymes involved in energy metabolism, including α-oxoglutarate dehydrogenase E1 component (α-KGD) and ATP synthase α and β subunits (ATP-α and ATP-β). To assess the effects of the NF-κB pathway activation on heart function, Bay11-7082, an inhibitor of the NF-κB signaling pathway, was injected into diabetic mice, protecting mice against the development of cardiac damage and increased nitrative modifications of key enzymes involved in energy metabolism. In conclusion, these findings demonstrated that catalase protects mouse hearts against diabetic cardiomyopathy, partially by suppressing NF-κB-dependent inflammatory responses and associated protein nitration.

  17. [Oxidation of [1-14C]palmitoyl-CoA, [1-14C]acetyl-CoA and [2-14C]pyruvate in rabbit adrenal, liver and heart mitochondria under normal conditions and in acute stress].

    Science.gov (United States)

    Mandrik, K A; Doroshkevich, N A; Vinogradov, V V

    1986-01-01

    The acute immobilized stress was studied for its effect on oxidation rate of [1-14C]palmitoyl-CoA, [1-14C]acetyl-CoA and [2-14C]pyruvate in mitochondria of the adrenals, liver and heart of rabbits. The stress effect on the energy metabolism of adrenals is associated with an increase of the rate of CO2 formation from pyruvate and with a decrease of the rate of CO2 formation from palmitoyl-CoA. Intensified oxidation of all substrates is observed in the heart mitochondria. The processes of beta-oxidation are more active in the liver. The data obtained evidence for differences in the mechanisms of energy metabolism reconstruction under acute stress in tissues with different functional specialization.

  18. Phosphorylated heat shock protein 27 is involved in enhanced heart tolerance to ischemia in short-term type 1 diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Hong CHEN; King-jun WU; Xi-yuan LU; Liang ZHU; Li-ping WANG; Huang-tian YANG; Hong-zhuan CHEN; Wen-jun YUAN

    2005-01-01

    Aim: To examine the tolerance of type 1 diabetic hearts to ischemia and reperfusion injury.Myocardial contents of 27-kDa and 70-kDa heat shock proteins (hsp) as well as phosphorylated hsp27 were also determined.Methods: Hearts from hyperglycemic rats 3 weeks after streptozocin injection and age-matched normal rats were subjected to ischemia and reperfusion in vitro.Cardiac function and electrocardiogram were recorded throughout experiments.Myocardial heat shock proteins were detected with Western blot.Results: Despite depressed systolic function at the baseline, diabetic hearts exhibited considerable enhancement in postischemic heart function, manifested by an increase in the maximal rate of left ventricular pressure rise and fall (post-ischemic dp/dtmax and dp/dtmin were 560± 117and -313±68 mmHg/s in control, n=7, 1249±57 and -1204±36 mmHg/s in diabetes,n=10, P<0.01).Reperfusion ventricular fibrillation in the diabetic group were attenuated compared with controls (1.5±0.3 vs 7.2±2.1 min in control, P<0.01).The increased heart resistance to ischemia in diabetes was associated with hyperglycemia and accompanied by enhanced expression of myocardial phosphorylated hsp27 with normal aortic vessel relaxation.Cardioprotection was abrogated by metabolic correction with insulin and accompanied by phospho-hsp27 reduction.Conclusion: Heart resistance to ischemia is increased in type 1 diabetes, and hyperglycemia may present a mild yet stressful stimulus leading to upregulation of endogenous stress protein, which may play a potential role in cardioprotection and compensate for detrimental effects of hyperglycemia in diabetes.

  19. Association between glycated haemoglobin and the risk of congestive heart failure in diabetes mellitus: systematic review and meta-analysis.

    Science.gov (United States)

    Erqou, Sebhat; Lee, Chee-Tin Christine; Suffoletto, Matthew; Echouffo-Tcheugui, Justin B; de Boer, Rudolf A; van Melle, Joost P; Adler, Amanda I

    2013-02-01

    Clinical trials to date have not provided definitive evidence regarding the effects of glucose lowering on the incidence of congestive heart failure (CHF). We synthesized available prospective epidemiological data on the association between glycaemia measured by haemoglobin A(1c) (HbA(1c)) and incident CHF in individuals with diabetes. We searched electronic databases and reference lists of selected articles for relevant prospective epidemiological studies. We abstracted data from relevant studies using standardized forms and obtained additional data from investigators when required. We pooled study-specific relative risk estimates using random-effects model meta-analysis. Of the 1044 citations identified, we included 10 studies comprising 178 929 participants with diabetes and 14 176 incident CHF cases. Five studies included only patients with type 2 diabetes, four studies had predominantly patients with type 2 diabetes, and one study included only patients with type 1 diabetes. All studies except one showed an increased risk of CHF with higher HbA(1c). The overall adjusted risk ratio (RR) for CHF was 1.15 [95% confidence interval (CI) 1.10-1.21] for each percentage point higher HbA(1c). There was substantial heterogeneity across the 10 studies (I(2): 83%; 95% CI 69-91%; P level characteristics such as study design or average HbA(1c) level. In seven studies reporting RRs with more than one degree of adjustment, the association was minimally altered after adjustment for several cardiovascular risk factors. In observational studies of individuals with diabetes, a higher HbA(1c) level was associated with a significantly increased incidence of CHF.

  20. Effects of acculturation and socioeconomic status on obesity and diabetes in Mexican Americans. The San Antonio Heart Study.

    Science.gov (United States)

    Hazuda, H P; Haffner, S M; Stern, M P; Eifler, C W

    1988-12-01

    The authors hypothesized that increased socioeconomic status and acculturation of Mexican Americans to mainstream US society would be accompanied by a progressive lessening of obesity and non-insulin-dependent diabetes mellitus. This hypothesis was tested in 1979-1982 in the San Antonio Heart Study, a population-based study of 1,288 Mexican Americans and 929 non-Hispanic whites, aged 25-64 years, randomly selected from three San Antonio neighborhoods: a low-income barrio, a middle-income transitional neighborhood, and a high-income suburb. Socioeconomic status was assessed by the Duncan Socioeconomic Index, a global measure of socioeconomic status based on occupational prestige. Acculturation was assessed by three scales which measure functional integration with mainstream society, value placed on preserving Mexican cultural origin, and attitude toward traditional family structure and sex-role organization. In Mexican-American men, increased acculturation was accompanied by a statistically significant, linear decline in both obesity and diabetes, while socioeconomic status had no significant effect on either outcome. In Mexican-American women, on the other hand, increased acculturation and increased socioeconomic status were accompanied by statistically significant, linear declines in both outcomes. However, the effects of acculturation on obesity and diabetes prevalence in women were stronger than the effects of socioeconomic status. In women, obesity also appeared to be a more important mediator of the relation between socioeconomic status and diabetes than of the relation between acculturation and diabetes. The results of this study suggest that culturally mediated factors exert a more pervasive influence on obesity and diabetes in Mexican Americans than do socioeconomically mediated factors. The influence of socioeconomic status in women, however, cannot be ignored, particularly with regard to obesity.

  1. Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Ramesh B; Karuna R; Sreenivasa Reddy S; Haritha K; Sai Mangala D; Sasi Bhusana Rao B; Saralakumari D

    2012-01-01

    Objective: To study the antioxidant efficacy of Commiphora mukul (C. mukul) gum resin ethanolic extract in streptozotocin (STZ) induced diabetic rats. Methods: The male Wistar albino rats were randomly divided into four groups of eight animals each: Control group (C), CM-treated control group (C+CMEE), Diabetic control group (D), CM- treated diabetic group (D+CMEE). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg/ bwt). After being confirmed the diabetic rats were treated with C. mukul gum resin ethanolic extract (CMEE) for 60 days. The biochemical estimations like antioxidant, oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed. Results: The diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) in liver and kidney and oxidative markers like lipid peroxidation (LPO) and protein oxidation (PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group. Administration of CMEE (200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy. Conclusions: In conclusion, our data indicate the preventive role of C. mukul against STZ-induced diabetic oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status.

  2. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

    Science.gov (United States)

    2012-01-01

    Background Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1) in aorta in type 2 diabetic rats. Methods Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4), monocyte chemoattractant protein-1(MCP-1) and connective tissue growth factor (CTGF)in the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-κB) in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d) by gavage for 12 weeks. Results Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P Telmisartan treatment significantly attenuated these changes in diabetic rats (P telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-κB in the abdominal aorta in diabetic rats. PMID:22873349

  3. TIME AND FREQUENCY DOMAIN ANALYSIS OF HEART RATE VARIABILITY SIGNAL IN PROGNOSIS OF TYPE 2 DIABETIC AUTONOMIC NEUROPATHY

    Directory of Open Access Journals (Sweden)

    SARIKA TALE,

    2011-04-01

    Full Text Available Heart disease occurs eventually in majority of patients with diabetes mellitus and to be the outstanding factor in over all diabetes morbidity and mortality rates. Thus the timely detection of diabetic autonomic neuropathy and the use of effective means to improve autonomic nervous system function become of almost significance. In this work Electrocardiogram (ECG data of 20 Diabetes Mellitus (DM and 20 normal control volunteers were recorded and autonomic nervous system activities are quantified by means of frequency and time domainanalysis. Time domain measure ,Standard deviation of successive NN intervals (SDNN,NN intervals differing more than 50 msec.( NN50 count,Percentage value of NN50 count( pNN50 count, HRV triangular index, show a lower variation in the DM patient group compared to normal subjects and p value <0.01. The frequency domain measures indicate significant differences in very low frequency (VLF, low frequency (LF power and high frequency (HF power. Value generated from the ratio of low frequency to high frequency, (LF/HF ispretty high, with not much significance between both groups.

  4. 高压脉冲电流对家兔心脏功能与结构的影响%Effect Of high-voltage impulse current on the structure and function of rabbit heart

    Institute of Scientific and Technical Information of China (English)

    徐新萍; 左红艳; 王少霞; 李杨; 王晓民; 彭瑞云; 王德文

    2011-01-01

    目的 探讨高压脉冲电流对家兔心脏功能与结构的影响.方法 健康雄性家兔60只,分别采用0、50、100、150、250、500mA的高压脉冲电流进行电击,脉宽100μs,持续电击5s.于电击前,电击后即刻及1、3、7、14、28d检测家兔心率和心电图变化,并在电击后即刻和28d取心肌组织观察心脏组织病理学改变.结果 50~500mA电击后即刻,家兔心率呈不同程度增加,心电图呈心律不齐、心肌缺血、心房纤颤、房室传导阻滞等改变,1d后逐渐恢复.病理学观察显示,50~500mA电击后即刻家兔心肌细胞见肿胀、肌原纤维分离、蒲肯野纤维肌浆凝聚等改变,28d后上述病变基本恢复.随电流强度增大,心脏的损伤效应呈加重趋势,尤其在150mA以上时明显加重,且恢复时间延长.结论 一定强度的高压脉冲电流可对心脏结构及功能造成可恢复性的损伤,且此损伤效应与电流强度有关.%Objective To explore the effect of high-voltage impulse current (HVIC) on the structure and function of rabbit heart.Methods Sixty healthy male rabbits were involved in present study and divided into 6 groups randomly ( n=10) . The rabbits were then shocked using a high-voltage pulse generator with current intensity of 0.50, 100, 150, 250 and 500mA (pulse width 1OOμs, duration 5s)respectively. The heart rate and electrocardiogram (ECG) of rabbits were detected before and 0.1, 3, 7, 14 and 28 days after the electric shock. Moreover, the myocardial tissue of rabbits was obtained immediately and 28 days after shock to observe the pathological changes.Results Immediately after electric shock of 50 to 500mA, the heart rate of rabbit increased by different degree, and the ECG showed arrhythmia, myocardial ischemia, atrial fibrillation and atrioventricular block, and the changes recovered gradually one day later. The pathological observation showed cell swelling, separation of myofibril and sarcoplasmic condensation of Purkinje

  5. Heart failure

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009170 Curcumin attenuates left ventricular dysfunction and remodeling in rabbits with chronic heart failure. TANG Yanhong(唐艳红),et al.Dept Cardiol,Renmin Hosp,Wuhan Univ,Wuhan 430060.Chin J Cardiol,2009;37(3):262-267.

  6. Clinical and socio-demographic determinants of self-care behaviours in patients with heart failure and diabetes mellitus: A multicentre cross-sectional study.

    Science.gov (United States)

    Ausili, Davide; Rebora, Paola; Di Mauro, Stefania; Riegel, Barbara; Valsecchi, Maria Grazia; Paturzo, Marco; Alvaro, Rosaria; Vellone, Ercole

    2016-11-01

    Self-care is vital for patients with heart failure to maintain health and quality of life, and it is even more vital for those who are also affected by diabetes mellitus, since they are at higher risk of worse outcomes. The literature is unclear on the influence of diabetes on heart failure self-care as well as on the influence of socio-demographic and clinical factors on self-care. (1) To compare self-care maintenance, self-care management and self-care confidence of patients with heart failure and diabetes versus those heart failure patients without diabetes; (2) to estimate if the presence of diabetes influences self-care maintenance, self-care management and self-care confidence of heart failure patients; (3) to identify socio-demographic and clinical determinants of self-care maintenance, self-care management and self-care confidence in patients with heart failure and diabetes. Secondary analysis of data from a multicentre cross-sectional study. Outpatient clinics from 29 Italian provinces. 1192 adults with confirmed diagnosis of heart failure. Socio-demographic and clinical data were abstracted from patients' medical records. Self-care maintenance, self-care management and self-care confidence were measured with the Self-Care of Heart Failure Index Version 6.2; each scale has a standardized score from 0 to 100, where a score <70 indicates inadequate self-care. Multiple linear regression analyses were performed. Of 1192 heart failure patients, 379 (31.8%) had diabetes. In these 379, heart failure self-care behaviours were suboptimal (means range from 53.2 to 55.6). No statistically significant differences were found in any of the three self-care measures in heart failure patients with and without diabetes. The presence of diabetes did not influence self-care maintenance (p=0.12), self-care management (p=0.21) or self-care confidence (p=0.51). Age (p=0.04), number of medications (p=0.01), presence of a caregiver (p=0.04), family income (p=0.009) and self

  7. Family history and body mass index predict perceived risks of diabetes and heart attack among community-dwelling Caucasian, Filipino, Korean, and Latino Americans--DiLH Survey.

    Science.gov (United States)

    Fukuoka, Yoshimi; Choi, JiWon; S Bender, Melinda; Gonzalez, Prisila; Arai, Shoshana

    2015-07-01

    The purpose of the study was to explore the perceived risk for diabetes and heart attack and associated health status of Caucasian, Filipino, Korean, and Latino Americans without diabetes. A cross-sectional survey was conducted with 904 urban adults (mean age 44.3±16.1 years; 64.3% female) in English, Spanish or Korean between August and December 2013. Perceived risk for developing diabetes was indicated by 46.5% (n=421), and 14.3% (n=129) perceived themselves to be at risk for having a heart attack in their lifetime. Significant predictors of pessimistic diabetes risk perceptions: Filipino (adjusted odds ratio [AOR]=1.7; 95% CI: 1.04-2.86) and Korean (AOR=2.4; 1.33-4.48) ethnicity, family history of diabetes (AOR=1.4; 1.00-1.84), female gender (AOR=1.4; 1.04-1.96), high cholesterol (AOR= 1.6; 1.09-2.37) and higher body mass index (BMI) (AOR=1.1; 1.08-1.15). Predictors of pessimistic heart attack risk perceptions were family history of an early heart attack (AOR=2.9; 1.69-5.02), high blood pressure (AOR=2.4; 1.45-3.84), and higher BMI (AOR=1.1; 1.04-1.12) after controlling for socio-demographic factors. Older age, physical inactivity, smoking, and low HDL levels were not associated with risk perceptions. Multiple risk factors were predictive of greater perceived diabetes risk, whereas, only family history of heart attack, high blood pressure and increases in BMI significantly contributed to perceived risk of heart attack among ethnically diverse at risk middle-aged adults. It is important that healthcare providers address the discordance between an individual's risk perceptions and the presence of actual risk factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Loss of Intralipid®- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling.

    Directory of Open Access Journals (Sweden)

    Phing-How Lou

    Full Text Available Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury.Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1% was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-% served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained.Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3.Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection.

  9. Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

    Directory of Open Access Journals (Sweden)

    Guo Zhixin

    2012-08-01

    Full Text Available Abstract Background Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2 and nicotinamide adenine dinucleotide phosphate (NADPH oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1 in aorta in type 2 diabetic rats. Methods Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ. Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4, monocyte chemoattractant protein-1(MCP-1 and connective tissue growth factor (CTGFin the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-κB in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d by gavage for 12 weeks. Results Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P Conclusions Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-κB in the abdominal aorta in diabetic rats.

  10. Early Cardiac Dysfunction in the Type 1 Diabetic Heart Using Speckle-Tracking Based Strain Imaging

    Science.gov (United States)

    Shepherd, Danielle L.; Nichols, Cody E.; Croston, Tara L.; McLaughlin, Sarah L.; Petrone, Ashley B.; Lewis, Sara E.; Thapa, Dharendra; Long, Dustin M.; Dick, Gregory M.; Hollander, John M.

    2016-01-01

    Enhanced sensitivity in echocardiographic analyses may allow for early detection of changes in cardiac function beyond the detection limits of conventional echocardiographic analyses, particularly in a small animal model. The goal of this study was to compare conventional echocardiographic measurements and speckle-tracking based strain imaging analyses in a small animal model of type 1 diabetes mellitus. Conventional analyses revealed differences in ejection fraction, fractional shortening, cardiac output, and stroke volume in diabetic animals relative to controls at 6-weeks post-diabetic onset. In contrast, when assessing short- and long-axis speckle-tracking based strain analyses, diabetic mice showed changes in average systolic radial strain, radial strain rate, radial displacement, and radial velocity, as well as decreased circumferential and longitudinal strain rate, as early as 1-week post-diabetic onset and persisting throughout the diabetic study. Further, we performed regional analyses for the LV and found that the free wall region was affected in both the short- and long-axis when assessing radial dimension parameters. These changes began 1-week post-diabetic onset and remained throughout the progression of the disease. These findings demonstrate the use of speckle-tracking based strain as an approach to elucidate cardiac dysfunction from a global perspective, identifying left ventricular cardiac regions affected during the progression of type 1 diabetes mellitus earlier than contractile changes detected by conventional echocardiographic measurements. PMID:26654913

  11. Impact of glycemic control, disease duration, and exercise on heart rate variability in children with type 1 diabetes mellitus.

    Science.gov (United States)

    Chen, Su-Ru; Lee, Yann-Jinn; Chiu, Hung-Wen; Jeng, Chii

    2007-11-01

    Type 1 diabetes is commonly associated with autonomic neuropathy. The present study investigated the influences of glycemic control, disease duration (DD), and exercise on autonomic nervous function in children with type 1 diabetes by analysis of their heart rate variability (HRV). Seventy-nine type 1 diabetic children were recruited and categorized into four groups by HbA1c of 8% and DD of 4.5 years. HRV parameters as determined by separate frequency domain components (low frequency: LnLF, 0.04-0.15 Hz; high frequency: LnHF, 0.15-0.5 Hz; total power: LnTP, 0.04-0.5 Hz) were measured both at rest and during exercise. Pearson's correlation, one-way ANOVA, and multiple regressions with stepwise method were used for statistical analysis. While at rest, HbA1c and DD were negatively correlated with all HRV parameters. Both HbA1c and DD were significant predictors in LnTP. However, only HbA1c was a significant predictor in LnLF and LnHF. Type 1 diabetes patients with HbA1c > 8% and DD > 4.5 years had a significantly lower HRV than the other patients. During exercise, HRV reduced significantly and no significant correlation between HbA1c and HRV or between DD and HRV was observed. Also, a significant difference in HRV among the four groups was not demonstrated. The smallest decrement in HRV from resting to exercise were in subjects with HbA1c > 8% and DD > 4.5 years. HbA1c was a more dominant predictor for LnTP, LnHF and LnLF than DD in children with type 1 diabetes at rest. HRV reduced significantly from resting to exercise. However, the responses of HRV during exercise differ from the responses of HRV at rest.

  12. Effects of Aerobic Exercise Based upon Heart Rate at Aerobic Threshold in Obese Elderly Subjects with Type 2 Diabetes.

    Science.gov (United States)

    Emerenziani, Gian Pietro; Gallotta, Maria Chiara; Meucci, Marco; Di Luigi, Luigi; Migliaccio, Silvia; Donini, Lorenzo Maria; Strollo, Felice; Guidetti, Laura

    2015-01-01

    In obese diabetic subjects, a correct life style, including diet and physical activity, is part of a correct intervention protocol. Thus, the aim of this study was to evaluate the effects of aerobic training intervention, based on heart rate at aerobic gas exchange threshold (AerTge), on clinical and physiological parameters in obese elderly subjects with type 2 diabetes (OT2DM). Thirty OT2DM subjects were randomly assigned to an intervention (IG) or control group (CG). The IG performed a supervised aerobic exercise training based on heart rate at AerTge whereas CG maintained their usual lifestyle. Anthropometric measures, blood analysis, peak oxygen consumption ([Formula: see text]), metabolic equivalent (METpeak), work rate (WRpeak), and WRAerTge were assessed at baseline and after intervention. After training, patients enrolled in the IG had significantly higher (P exercise prescription based upon HR at AerTge could be a valuable physical intervention tool to improve the fitness level and metabolic equilibrium in OT2DM patients.

  13. Effects of Aerobic Exercise Based upon Heart Rate at Aerobic Threshold in Obese Elderly Subjects with Type 2 Diabetes

    Science.gov (United States)

    Donini, Lorenzo Maria

    2015-01-01

    In obese diabetic subjects, a correct life style, including diet and physical activity, is part of a correct intervention protocol. Thus, the aim of this study was to evaluate the effects of aerobic training intervention, based on heart rate at aerobic gas exchange threshold (AerTge), on clinical and physiological parameters in obese elderly subjects with type 2 diabetes (OT2DM). Thirty OT2DM subjects were randomly assigned to an intervention (IG) or control group (CG). The IG performed a supervised aerobic exercise training based on heart rate at AerTge whereas CG maintained their usual lifestyle. Anthropometric measures, blood analysis, peak oxygen consumption (V˙O2peak), metabolic equivalent (METpeak), work rate (WRpeak), and WRAerTge were assessed at baseline and after intervention. After training, patients enrolled in the IG had significantly higher (P < 0.001) V˙O2peak, METpeak, WRpeak, and WRAerTge and significantly lower (P < 0.005) weight, BMI, %FM, and waist circumference than before intervention. Both IG and CG subjects had lower glycated haemoglobin levels after intervention period. No significant differences were found for all the other parameters between pre- and posttraining and between groups. Aerobic exercise prescription based upon HR at AerTge could be a valuable physical intervention tool to improve the fitness level and metabolic equilibrium in OT2DM patients. PMID:26089890

  14. Disease management 360 degrees: a scorecard approach to evaluating TRICARE's programs for asthma, congestive heart failure, and diabetes.

    Science.gov (United States)

    Yang, Wenya; Dall, Timothy M; Zhang, Yiduo; Hogan, Paul F; Arday, David R; Gantt, Cynthia J

    2010-08-01

    To assess the effect of TRICARE's asthma, congestive heart failure, and diabetes disease management programs using a scorecard approach. EVALUATION MEASURES: Patient healthcare utilization, financial, clinical, and humanistic outcomes. Absolute measures were translated into effect size and incorporated into a scorecard. Actual outcomes for program participants were compared with outcomes predicted in the absence of disease management. The predictive equations were established from regression models based on historical control groups (n = 39,217). Z scores were calculated for the humanistic measures obtained through a mailed survey. Administrative records containing medical claims, patient demographics and characteristics, and program participation status were linked using an encrypted patient identifier (n = 57,489). The study time frame is 1 year prior to program inception through 2 years afterward (October 2005-September 2008). A historical control group was identified with the baseline year starting October 2003 and a 1-year follow-up period starting October 2004. A survey was administered to a subset of participants 6 months after baseline assessment (39% response rate). Within the observation window--24 months for asthma and congestive heart failure, and 15 months for the diabetes program--we observed modest reductions in hospital days and healthcare cost for all 3 programs and reductions in emergency visits for 2 programs. Most clinical outcomes moved in the direction anticipated. The scorecard provided a useful tool to track performance of 3 regional contractors for each of 3 diseases and over time.

  15. Heart Rate and Systolic Blood Pressure Variability in the Time Domain in Patients with Recent and Long-Standing Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Ana Leonor Rivera

    Full Text Available Diabetes Mellitus (DM affects the cardiovascular response of patients. To study this effect, interbeat intervals (IBI and beat-to-beat systolic blood pressure (SBP variability of patients during supine, standing and controlled breathing tests were analyzed in the time domain. Simultaneous noninvasive measurements of IBI and SBP for 30 recently diagnosed and 15 long-standing DM patients were compared with the results for 30 rigorously screened healthy subjects (control. A statistically significant distinction between control and diabetic subjects was provided by the standard deviation and the higher moments of the distributions (skewness, and kurtosis with respect to the median. To compare IBI and SBP for different populations, we define a parameter, α, that combines the variability of the heart rate and the blood pressure, as the ratio of the radius of the moments for IBI and the same radius for SBP. As diabetes evolves, α decreases, standard deviation of the IBI detrended signal diminishes (heart rate signal becomes more "rigid", skewness with respect to the median approaches zero (signal fluctuations gain symmetry, and kurtosis increases (fluctuations concentrate around the median. Diabetes produces not only a rigid heart rate, but also increases symmetry and has leptokurtic distributions. SBP time series exhibit the most variable behavior for recently diagnosed DM with platykurtic distributions. Under controlled breathing, SBP has symmetric distributions for DM patients, while control subjects have non-zero skewness. This may be due to a progressive decrease of parasympathetic and sympathetic activity to the heart and blood vessels as diabetes evolves.

  16. Impact of Hypertension, Diabetes and Dyslipidemia on Ischemic Heart Disease among Japanese: A Case-Control Study Based on National Health Insurance Medical Claims

    OpenAIRE

    Huang, Hairong; Ye, Zhaojia; Nagahama, Iyoko; Tazoe, Hideaki; Abe, Yasuyo; Aoyagi, Kiyoshi

    2012-01-01

    Aim Although the important role of conventional risk factors (cigarette smoking, hypertension, diabetes and dyslipidemia) in the pathogenesis of ischemic heart disease (IHD) has been established, how frequently IHD is preceded by exposure to conventional risk factors remains controversial. The present study aimed to identify the prevalence of hypertension, diabetes and dyslipidemia among patients with IHD and examine associations between each of them with IHD in a Japanese population...

  17. Heart rate variability analysis of patients with coronary heart disease and type 2 diabetes%冠心病伴发2型糖尿病患者心率变异性分析

    Institute of Scientific and Technical Information of China (English)

    陈序

    2011-01-01

    目的 观察冠心病合并2型糖尿病患者自主神经功能状态.方法 选择2005~2011年在我院行24h动态心电图检查的冠心病及糖尿病患者各30人,冠心病伴发2型糖尿病者30人,健康体检者40人,由计算机自动测出心率变异性时城各项指标.结果 冠心病患者或2型糖尿病患者心率变异性指标均低于健康对照组(P<0.05),冠心病合并2型糖尿病患者心率变异性指标低于单一疾病者(P<0.05).结论 冠心病合并2型搪尿病患者自主神经功能损害较重,发生恶性心血管事件几率较大.%Objective To observe the autonomic nerve activity of patients with coronary heart disease and type 2 diabetes. Methods The observed object include 30 cases with coronary heart disease, 30 cases with diabetes, 30 cases with coronary heart disease and type 2 diabetes? 40 healthy cases. The heart rate variability in time domain indexes were measured automatically By the computer. Results The heart rate variability indexes of cases with coronary heart disease or type 2 diabetes were lower than healthy persons(P<0. 05). The heart rate variability indexes of cases with coronary heart disease and type 2 diabetes were lower than single disease(P<0. 05). Conclusion The autonomic nerve activity damage of patients with coronary heart disease and type 2 diabetes is heavier, the occurrence of cardiovascular events are more likely.

  18. C1q/TNF-Related Protein 9 Protects Diabetic Rat Heart against Ischemia Reperfusion Injury: Role of Endoplasmic Reticulum Stress

    Science.gov (United States)

    Bai, Sanxing; Cheng, Liang; Yang, Yang; Fan, Chongxi; Zhao, Dajun; Qin, Zhigang; Feng, Xiao; Zhao, Lin; Ma, Jipeng; Wang, Xiaowu; Yang, Jian; Xu, Xuezeng

    2016-01-01

    As a newly identified adiponectin paralog, C1q/TNF-related protein 9 (CTRP9) reduces myocardial ischemia reperfusion (IR) injury through partially understood mechanisms. In the present study, we sought to identify the role of endoplasmic reticulum stress (ERS) in CTRP9 induced cardioprotection in diabetic heart. Isolated hearts from high-fat-diet (HFD) induced type 2 diabetic Sprague-Dawley rats were subjected to ex vivo IR protocol via a Langendorff apparatus at the presence of globular CTRP9. CTRP9 significantly improved post-IR heart function and reduced cardiac infarction, cardiomyocytes apoptosis, Caspase-3, Caspase-9, Caspase-12, TNF-α expression, and lactate dehydrogenase activity. The cardioprotective effect of CTRP9 was associated with reduced ERS and increased expression of disulfide-bond A oxidoreductase-like protein (DsbA-L) in diabetic heart. CTRP9 reduced ERS in thapsigargin (TG) treated cardiomyocytes and protected endoplasmic reticulum (ER) stressed H9c2 cells against simulated ischemia reperfusion (SIR) injury, concurrent with increased expression of DsbA-L. Knockdown of DsbA-L increased ERS and attenuated CTRP9 induced protection against SIR injury in H9c2 cells. Our findings demonstrated for the first time that CTRP9 exerts cardioprotection by reducing ERS in diabetic heart through increasing DsbA-L.

  19. Effects of Acute Cold Exposure on Rabbit Heart, Liver and Renal Function%急性低温暴露对家兔心肝肾功能的影响

    Institute of Scientific and Technical Information of China (English)

    吴丽珍; 杜兴华; 雷艳; 蔡颖; 董兆君

    2013-01-01

    目的 探讨急性低温暴露对家兔心、肝、肾功能的影响.方法 15只家兔随机分为3组,20℃组、-20℃组、2℃组,每组5只.动物经腹腔注射麻醉后行左侧颈总动脉插管术,按分组分别置于20℃室温、2℃和-20 ℃实验冰柜中.各组在置于实验温度后0、30、60、90、120 min时间点经颈动脉插管采血并分离血浆,采用生化方法测定肝功能指标包括门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)、L-γ谷氨酰基转移酶(GGT);肾功能指标尿素(BU)、肌酐(CREA)、尿酸(UA);心肌酶谱指标包括门冬氨酸氨基转移酶(AST)、肌酸激酶(CK)及同工酶(CKMB)、乳酸脱氢酶(LDH)和α一羟丁酸脱氢酶(a-HBDH)的含量.结果 急性低温暴露能显著影响家兔心、肝、肾功能血生化指标,-20℃暴露组更明显.结论 急性低温暴露可对家兔心、肝、肾功能造成损伤,低温暴露强度越强损伤越明显.%Objective To explore the effects of acute cold exposure on the rabbits heart,liver and renal function.Methods 15 rabbits were randomly divided into 3 groups,20℃ group,-20℃ group and 2℃ group,with 5 rabbits in each group.Animals were anesthetized by intraperitoneal injection,then were treated with the left common carotid artery intubation.According to the grouping,they were exposed to freezer at 20℃,2 ℃ and-20 ℃,respectively.At 0,30,60,90 and 120 min after exposure,the blood was collected by the way of carotid intubation,and plasma was separated.Then,the biochemical method was used to determine the contents of liver function indexes including aspartate aminotransferase (AST),alanine aminotransferase (ALT),alkaline phosphatase (ALP) and L-γ-glutamyl transferase (GGT) ; of renal function indexes including urea (BU),creatinine (CREA),uric acid (UA) ; and of heart function indexes including aspartate aminotransferase myocardial enzyme (AST),creatine kinase (CK) and isoenzyme (CKMB

  20. Calpain-Calcineurin-Nuclear Factor Signaling and the Development of Atrial Fibrillation in Patients with Valvular Heart Disease and Diabetes

    Directory of Open Access Journals (Sweden)

    Yong Zhao

    2016-01-01

    Full Text Available Calpain, calcineurin (CaN, and nuclear factor of activated T cell (NFAT play a key role in the development of atrial fibrillation. Patients with valvular heart disease (VHD are prone to develop atrial fibrillation (AF. Thus, our current study was aimed at investigating whether activation of calpain-CaN-NFAT pathway is associated with the incidence of AF in the patients with VHD and diabetes. The expressions of calpain 2 and alpha- and beta-isoforms of CaN catalytic subunit (CnA as well as NFAT-c3 and NFAT-c4 were quantified by quantitative reverse transcription-polymerase chain reaction in atrial tissues from 77 hospitalized patients with VHD and diabetes. The relevant protein content was measured by Western blot and calpain 2 in human atrium was localized by immunohistochemistry. We found that the expressions of calpain 2, CnA alpha and CnA beta, and NFAT-c3 but not NFAT-c4 were significantly elevated in the samples from patients with AF compared to those with sinus rhythm (SR. Elevated protein levels of calpain 2 and CnA were observed in patients with AF, and so was the enhanced localization of calpain 2. We thereby concluded that CaN together with its upstream molecule, calpain 2, and its downstream effector, NFAT-c3, might contribute to the development of AF in patients with VHD and diabetes.

  1. Influence of Diabetes Mellitus and Hyperglycemia on Prognosis in Patients >= 70 Years Old With Heart Failure and Effects of Nebivolol (Data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure [SENIORS])

    NARCIS (Netherlands)

    de Boer, Rudolf A.; Doehner, Wolfram; van der Horst, Iwan C. C.; Anker, Stefan D.; Babalis, Daphne; Roughton, Michael; Coats, Andrew J.; Flather, Marcus D.; van Veldhuisen, Dirk J.

    2010-01-01

    The beneficial effects of beta blockers in younger patients with heart failure (HF) due to systolic dysfunction are well established. However, data from patients >= 70 years old with diabetes mellitus and HF are lacking. The Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalizatio

  2. Changes associated with Na,K-ATPase in brain, kidney, heart and liver of the spontaneously diabetic Goto-Kakizaki rat

    OpenAIRE

    2014-01-01

    Alterations in Na,K-ATPase activity, in isoenzyme expression and/or number of units of the pump present in the plasma membrane have been associated with diabetes. These changes were described in different organs and tissues such as brain, heart, kidney, among others, and may result from altered insulin levels. However, the vast majority of studies were conducted in animal models of chemically induced diabetes, which are not consensual models for type 2 diabetes (T2D). The major goal of this w...

  3. Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2

    Directory of Open Access Journals (Sweden)

    de Wit G Ardine

    2009-12-01

    Full Text Available Abstract Background We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat, natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely. Primary objectives - To assess the prevalence of (previously unrecognised heart failure in primary care patients with diabetes type 2. - To establish the most cost-effective diagnostic strategy to detect unrecognised heart failure in these patients. Secondary objectives - To assess the impact of heart failure, and the combination of a new diagnosis with accordingly treatment in patients with diabetes type 2 on health status. Methods/Design Design: A prospective diagnostic efficiency study. Patient population: Patients aged 60 years and older with diabetes type 2 from primary care, enlisted with the diabetes service of the Diagnostic Center in Etten-Leur (SHL All participants will be investigated at the cardiology out-patient department of the regional hospital (Oosterschelde Hospital in Goes, Zeeland, the Netherlands during a single 1.5 hour standardised diagnostic assessment, including history taking, physical examination, electrocardiography, echocardiography, blood tests, and Health status questionnaires. Patients will be asked if we can contact them afterwards for follow-up and for repeating the questionnaires after

  4. How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

    2010-01-01

    An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...

  5. How should we manage heart failure developing in patients already treated with angiotensin-converting enzyme inhibitors and beta-blockers for hypertension, diabetes or coronary disease?

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Segura, Julian; Ruilope, Luis M

    2010-01-01

    An increasing number of patients in the community are being treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and beta-blockers for hypertension, coronary disease or diabetic renal and vascular complications. Some of these patients will develop heart...... failure despite such treatment. Based on data from hypertension trials it can be estimated that approximately 5% of treated patients will develop heart failure over 5 years. It is unclear whether patients developing heart failure on and off ACE-inhibitors or beta-blockers, respectively, at the time...

  6. Long-term insulin treatment restores cardioprotection induced by sufentanil postconditioning in diabetic rat heart.

    Science.gov (United States)

    Zhang, Yuwen; Zhang, Lei; Gu, Erwei; Zhu, Bingqing; Zhao, Xianya; Chen, Jingjing

    2016-03-01

    Sufentanil, a commonly used opioid analgesic, could mimic ischemia postconditioning to attenuate ischemia reperfusion injury, but this effect might be hindered in diabetic animals by inhibition of glycogen synthase kinase-3β phosphorylation. Also, diabetes can abrogate the cardioprotection of sevoflurane (an inhaled anesthetic) against ischemia reperfusion injury, and short-term insulin treatment does not restore protection by sevoflurane postconditioning. We hypothesized that long-term insulin treatment might restore the cardioprotective effect of sufentanil postconditioning in diabetic rats via phosphorylation of glycogen synthase kinase-3β. Streptozotocin (55 mg/kg)-induced diabetic rats received insulin (Novolin N, 6-8 u/d) for two days or two weeks, then were exposed to 30-min ischemia and 120-min reperfusion. Sufentanil postconditioning was performed 5 min before the onset of reperfusion. Controls included non-diabetic rats, sham surgery for ischemia/reperfusion, and sufentanil vehicle. Infarct size, cardiac troponin I, and phosphorylated glycogen synthase kinase-3β were examined. Sufentanil postconditioning reduced infarct size by 46% in non-diabetic rats (P insulin treatment was not effective, but two-week treatment reduced infarct size by 45% (P insulin treatment. The underlying mechanism may be increased phosphorylation of glycogen synthase kinase-3β.

  7. Influence of high-voltage electric burn on the microcirculation of heart in rabbit%高压电烧伤对兔心脏微循环的影响

    Institute of Scientific and Technical Information of China (English)

    张庆富; 周慧敏; 王车江; 邵洪波

    2012-01-01

    Objective To study the influence of high-voltage electric burn on the microcirculation of heart in rabbit. Methods One-hundred and twenty New Zealand rabbits of clean grade were divided into control group (C) and electric burn group (EB) according to the random number table,with 60 rabbits in each group.Rabbits in EB group were subjected to high-vohage electric burn ( the electrical current flow into the left foreleg at the lateral side of proximal end and out from the corresponding site of the right hind leg) with voltage regulator and experimental transformer.Rabbits in C group were sham injured with the same devices without electrification.At 15 minutes before injury,and 5 minutes,1,2,4,8 hour (s) post injury ( PIM or PIH ),ten rabbits in each group were chosen to examine the cardiac apex microcirculation hemoperfusion (CAMH) with laser Doppler hemoperfusion image instrument.The morphologic changes of microvessels of left ventricular wall tissues of 2 rabbits from each of the 10 rabbits collected at above-mentioned time points were observed with light microscope and transmission electron microscope.Auricular vein blood of rabbit was harvested at above-mentioned time points for the determination of aspartate amino transferase ( AST),lactate dehydrogenase ( LDH ),hydroxybutyrate dehydrogenase ( HBDH ),creatine kinase ( CK),and creatine kinase isozyme MB (CK-MB) by full-automatic biochemical analyzer.Data were processed with two-factor analysis of variance and LSD test. Results ( 1 ) The differences between C group and EB group in detection results were statistically significant,with F values from 425.991 to 3046.834,P values all below 0.01.Only the data within EB group were comparable.(2) At PIM 5,the CAMH value of rabbits in EB group was (1.96 ±0.09) V,which was lower than that at 15 minutes before injury [(4.34±0.35) V,P < 0.01 ].The CAMH value of rabbits in EB group was increased at PIH 1 [ (3.43 ± 0.30) V ],and then it showed a tendency of decrease.(3

  8. Chocolate Consumption and Risk of Coronary Heart Disease, Stroke, and Diabetes: A Meta-Analysis of Prospective Studies.

    Science.gov (United States)

    Yuan, Sheng; Li, Xia; Jin, Yalei; Lu, Jinping

    2017-07-02

    Although epidemiological studies have examined the role of chocolate in preventing cardiometabolic disease, the results remain inconsistent. Herein, we conducted a meta-analysis of prospective studies to determine the association between chocolate intake and risk of coronary heart disease (CHD), stroke, and diabetes. A systematical search in PubMed and Embase through March 2017, together with reference scrutiny of relevant literatures, was performed to identify eligible studies. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled using random effect models. Fourteen prospective studies of primary prevention with 508,705 participants were finally included, with follow-up durations ranging from 5 to 16 years. The summary RRs for the highest versus lowest chocolate consumption were 0.90 (95% CI: 0.82-0.97; n = 6) for CHD, 0.84 (95% CI: 0.78-0.90; n = 7) for stroke, and 0.82 (95% CI: 0.70-0.96; n = 5) for diabetes. Dose-response meta-analysis suggested a nonlinear association of chocolate consumption with all outcomes. For both CHD and stroke, there was little additional risk reduction when consuming chocolate ≥3 servings/week (one serving was defined as 30 g of chocolate). For diabetes, the peak protective effect of chocolate emerged at 2 servings/week (RR: 0.75, 95% CI: 0.63-0.89), with no benefit observed when increasing consumption above 6 servings/week. In conclusion, chocolate intake is associated with decreased risks of CHD, stroke, and diabetes. Consuming chocolate in moderation (≤6 servings/week) may be optimal for preventing these disorders.

  9. Chocolate Consumption and Risk of Coronary Heart Disease, Stroke, and Diabetes: A Meta-Analysis of Prospective Studies

    Directory of Open Access Journals (Sweden)

    Sheng Yuan

    2017-07-01

    Full Text Available Although epidemiological studies have examined the role of chocolate in preventing cardiometabolic disease, the results remain inconsistent. Herein, we conducted a meta-analysis of prospective studies to determine the association between chocolate intake and risk of coronary heart disease (CHD, stroke, and diabetes. A systematical search in PubMed and Embase through March 2017, together with reference scrutiny of relevant literatures, was performed to identify eligible studies. Relative risks (RRs and 95% confidence intervals (CIs were pooled using random effect models. Fourteen prospective studies of primary prevention with 508,705 participants were finally included, with follow-up durations ranging from 5 to 16 years. The summary RRs for the highest versus lowest chocolate consumption were 0.90 (95% CI: 0.82–0.97; n = 6 for CHD, 0.84 (95% CI: 0.78–0.90; n = 7 for stroke, and 0.82 (95% CI: 0.70–0.96; n = 5 for diabetes. Dose–response meta-analysis suggested a nonlinear association of chocolate consumption with all outcomes. For both CHD and stroke, there was little additional risk reduction when consuming chocolate ≥3 servings/week (one serving was defined as 30 g of chocolate. For diabetes, the peak protective effect of chocolate emerged at 2 servings/week (RR: 0.75, 95% CI: 0.63–0.89, with no benefit observed when increasing consumption above 6 servings/week. In conclusion, chocolate intake is associated with decreased risks of CHD, stroke, and diabetes. Consuming chocolate in moderation (≤6 servings/week may be optimal for preventing these disorders.

  10. Association of antidiabetic medications targeting the glucagon-like peptide 1 pathway and heart failure events in patients with diabetes.

    Science.gov (United States)

    Velez, Mauricio; Peterson, Edward L; Wells, Karen; Swadia, Tanmay; Sabbah, Hani N; Williams, L Keoki; Lanfear, David E

    2015-01-01

    Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors (GLP-1 agents) may be protective in heart failure (HF). We set out to determine whether GLP-1 agent use is associated with HF risk in diabetics. In this retrospective cohort study of members of a large health system, we identified >19,000 adult diabetics from January 1, 2000, to July 1, 2012. GLP-1 agent users were matched 1:2 to control subjects with the use of propensity matching based on age, race, sex, coronary disease, HF, diabetes duration, and number of antidiabetic medications. The association of GLP-1 agents with time to HF hospitalization was tested with multivariable Cox regression. All-cause hospitalization and mortality were secondary end points. We identified 1,426 users of GLP-1 agents and 2,798 control subjects. Both were similar except for angiotensin-converting enzyme inhibitors/angiotensin receptor blocker use, number of antidiabetic medications, and age. There were 199 hospitalizations, of which 128 were for HF, and 114 deaths. GLP-1 agents were associated with reduced risk of HF hospitalization (adjusted hazard ratio [aHR] 0.51, 95% confidence interval [CI] 0.34-0.77; P = .002), all-cause hospitalization (aHR 0.54, 95% CI 0.38-0.74; P = .001), and death (aHR 0.31, 95% CI 0.18-0.53; P = .001). GLP-1 agents may reduce the risk of HF events in diabetics. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. The Effect of Resting Heart Rate on the New Onset of Microalbuminuria in Patients With Type 2 Diabetes: A Subanalysis of the ROADMAP Study.

    Science.gov (United States)

    Schmieder, Roland E; Bramlage, Peter; Haller, Hermann; Ruilope, Luis M; Böhm, Michael

    2016-04-01

    The association between resting heart rate and new-onset microalbuminuria in patients with type 2 diabetes is not clear. The objective of the current analysis was to assess the relationship between heart rate and incidence of microalbuminuria in patients with type 2 diabetes. Data from the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study were retrospectively analyzed. New-onset microalbuminuria was documented and related to heart rate as recorded at baseline and last assessment, and the mean of the measurements taken during the double-blind part of the ROADMAP trial. Patients (n = 4299) had a mean age of 57.8 ± 8.7 years and 46.3% were male. Characteristics were not different between the olmesartan and the placebo groups, except for a higher systolic blood pressure (136.7 vs 135.7 mm Hg; P = 0.04) and albumin creatinine ratio (5.9 vs 5.5; P = 0.03). Increased risk of microalbuminuria was found with increasing heart rate, independent of whether baseline [highest vs lowest quartile odds ratio (OR) 1.39; 95% confidence interval (95% CI) 1.03-1.87; P = 0.032], last assessment (OR 1.71; 95% CI 1.26-2.31; P = 0.001), or mean heart rate was considered (OR: 1.77; 95% CI: 1.30-2.41; P = 0.0003). The greater risk of new-onset microalbuminuria with a high baseline heart rate was also found when data were adjusted for mean systolic blood pressure (OR: 1.35; 95% CI: 1.00-1.82; P = 0.0496; interaction P microalbuminuria was less frequent in patients receiving olmesartan in the low heart rate quartiles (P = 0.002 for trend). A low heart rate reduces the risk of patients with type 2 diabetes developing microalbuminuria, independent of blood pressure. The data demonstrate potential benefits of reducing the heart rate of type 2 diabetes patients, and indicate that olmesartan could, in particular, reduce the risk of microalbuminuria in patients with low heart rate.

  12. The Long-Term Effect of the Periconception Period on the Embryo's Epigenetic Profile and Phenotype: The Role of Maternal Disease Such as Diabetes and How the Effect Is Mediated (Example from a Rabbit Model).

    Science.gov (United States)

    Fischer, Bernd; Schindler, Maria; Mareike Pendzialek, S; Gürke, Jacqueline; Haucke, Elisa; Grybel, Katarzyna Joanna; Thieme, René; Santos, Anne Navarrete

    2017-01-01

    Maternal metabolic diseases such as diabetes mellitus with diabetogenic hypoinsulinemia and hyperglycemia change periconceptional developmental conditions in utero. In preimplantation rabbit embryos, all major metabolic pathways are affected. Alterations in protein, lipid and glucose metabolism, adipokines, advanced glycation end products (AGEs) and reactive oxygen species (ROS) are described in this review. The embryonic metabolism is characterized by a high plasticity which enables survival of most preimplantation embryos under the non-physiological developmental conditions in diabetic mothers. Adiponectin, for example, compensates for the missing insulin-driven glucose supply and stimulates intracellular lipid accumulation in embryonic cells. AGEs and ROS are clear indicators of metabolic stress. The price paid for survival, however, needs to be taken into consideration. It is an increase in lipogenesis and proteinogenesis, leading to metabolic stress and with potentially negative long-term health effects.

  13. Effect of tighter glycemic control on cardiac function, exercise capacity, and muscle strength in heart failure patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Bent Roni Ranghøj; Wiggers, Henrik; Thomsen, Henrik Holm;

    2016-01-01

    OBJECTIVES: In patients with type 2 diabetes (T2D) and heart failure (HF), the optimal glycemic target is uncertain, and evidence-based data are lacking. Therefore, we performed a randomized study on the effect of optimized glycemic control on left ventricular function, exercise capacity, muscle...

  14. Reply: “Comment on: Chocolate Consumption and Risk of Coronary Heart Disease, Stroke, and Diabetes: A Meta-Analysis of Prospective Studies, Nutrients 2017, 9, 688”

    Directory of Open Access Journals (Sweden)

    Sheng Yuan

    2017-08-01

    Full Text Available To the editor, We would like to thank Dr. Hurtado-Torres for his valuable comments on our article entitled “Chocolate Consumption and Risk of Coronary Heart Disease, Stroke, and Diabetes: A Meta-Analysis of Prospective Studies”, which was published in Nutrients in July 2017 [1]. [...

  15. Soluble urokinase plasminogen activator receptor, C-reactive protein and triglyceride are associated with heart rate variability in non-diabetic Danes

    DEFF Research Database (Denmark)

    Intzilakis, Theodoros; Hartmann, Gro; Mouridsen, Mette R

    2013-01-01

    Heart rate variability (HRV) is associated with an increased risk of cardiovascular morbidity and mortality. HRV is in part a function of the activity of the autonomic nervous system and has been associated with low-grade inflammation. In patients with type 2 diabetes, HRV is decreased and is a p...

  16. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease

    DEFF Research Database (Denmark)

    Filippatos, Gerasimos; Anker, Stefan D; Böhm, Michael;

    2016-01-01

    AIMS: To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. METHODS AND RESULTS: Miner Alocorticoid Receptor antagon...

  17. Automatic identification of type 2 diabetes, hypertension, ischaemic heart disease, heart failure and their levels of severity from Italian General Practitioners' electronic medical records: a validation study

    Science.gov (United States)

    Schuemie, Martijn J; Mazzaglia, Giampiero; Lapi, Francesco; Francesconi, Paolo; Pasqua, Alessandro; Bianchini, Elisa; Montalbano, Carmelo; Roberto, Giuseppe; Barletta, Valentina; Cricelli, Iacopo; Cricelli, Claudio; Dal Co, Giulia; Bellentani, Mariadonata; Sturkenboom, Miriam; Klazinga, Niek

    2016-01-01

    Objectives The Italian project MATRICE aimed to assess how well cases of type 2 diabetes (T2DM), hypertension, ischaemic heart disease (IHD) and heart failure (HF) and their levels of severity can be automatically extracted from the Health Search/CSD Longitudinal Patient Database (HSD). From the medical records of the general practitioners (GP) who volunteered to participate, cases were extracted by algorithms based on diagnosis codes, keywords, drug prescriptions and results of diagnostic tests. A random sample of identified cases was validated by interviewing their GPs. Setting HSD is a database of primary care medical records. A panel of 12 GPs participated in this validation study. Participants 300 patients were sampled for each disease, except for HF, where 243 patients were assessed. Outcome measures The positive predictive value (PPV) was assessed for the presence/absence of each condition against the GP's response to the questionnaire, and Cohen's κ was calculated for agreement on the severity level. Results The PPV was 100% (99% to 100%) for T2DM and hypertension, 98% (96% to 100%) for IHD and 55% (49% to 61%) for HF. Cohen's kappa for agreement on the severity level was 0.70 for T2DM and 0.69 for hypertension and IHD. Conclusions This study shows that individuals with T2DM, hypertension or IHD can be validly identified in HSD by automated identification algorithms. Automatic queries for levels of severity of the same diseases compare well with the corresponding clinical definitions, but some misclassification occurs. For HF, further research is needed to refine the current algorithm. PMID:27940627

  18. Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

    Science.gov (United States)

    Maggioni, Aldo P.; Greene, Stephen J.; Fonarow, Gregg C.; Böhm, Michael; Zannad, Faiez; Solomon, Scott D.; Lewis, Eldrin F.; Baschiera, Fabio; Hua, Tsushung A.; Gimpelewicz, Claudio R.; Lesogor, Anastasia; Gheorghiade, Mihai; Ramos, Silvina; Luna, Alejandra; Miriuka, Santiago; Diez, Mirta; Perna, Eduardo; Luquez, Hugo; Pinna, Jorge Garcia; Castagnino, Jorge; Alvarenga, Pablo; Ibañez, Julio; Blumberg, Eduardo Salmon; Dizeo, Claudio; Guerrero, Rodolfo Ahuad; Schygiel, Pablo; Milesi, Rodolfo; Sosa, Carlos; Hominal, Miguel; Marquez, Lilia Lobo; Poy, Carlos; Hasbani, Eduardo; Vico, Marisa; Fernandez, Alberto; Vita, Nestor; Vanhaecke, Johan; De Keulenaer, Gilles; Striekwold, Harry; Vervoort, Geert; Vrolix, Mathias; Henry, Philippe; Dendale, Paul; Smolders, Walter; Marechal, Patrick; Vandekerckhove, Hans; Oliveira, Mucio; Neuenschwande, Fernando; Reis, Gilmar; Saraiva, Jose; Bodanese, Luiz; Canesin, Manoel; Greco, Oswaldo; Bassan, Roberto; Marino, Roberto Luis; Giannetti, Nadia; Moe, Gordon; Sussex, Bruce; Sheppard, Richard; Huynh, Thao; Stewart, Robert; Haddad, Haissam; Echeverria, Luis; Quintero, Adalberto; Torres, Adriana; Jaramillo, Mónica; Lopez, Mónica; Mendoza, Fernan; Florez, Noel; Cotes, Carlos; Garcia, Magali; Belohlavek, Jan; Hradec, Jaromir; Peterka, Martin; Gregor, Pavel; Monhart, Zdenek; Jansky, Petr; Kettner, Jiri; Reichert, Petr; Spinar, Jindrich; Brabec, Tomas; Hutyra, Martin; Solar, Miroslav; Pietilä, Mikko; Nyman, Kai; Pajari, Risto; Cohen, Ariel; Galinier, Michel; Gosse, Philippe; Livarek, Bernard; Neuder, Yannick; Jourdain, Patrick; Picard, François; Isnard, Richard; Hoppe, Uta; Kaeaeb, Stefan; Rosocha, Stefan; Prondzinsky, Roland; Felix, Stephan; Duengen, Hans-Dirk; Figulla, Hans-Reiner; Fischer, Sven; Behrens, Steffen; Stawowy, Philipp; Kruells-Muench, Juergen; Knebel, Fabian; Nienaber, Christoph; Werner, Dierk; Aron, Wilma; Remppis, Bjoern; Hambrecht, Rainer; Kisters, Klaus; Werner, Nikos; Hoffmann, Stefan; Rossol, Siegbert; Geiss, Ernst; Graf, Kristof; Hamann, Frank; von Scheidt, Wolfgang; Schwinger, Robert; Tebbe, Ulrich; Costard-Jaeckle, Angelika; Lueders, Stephan; Heitzer, Thomas; Leutermann-Oei, Marie-Louise; Braun-Dullaeus, Ruediger; Roehnisch, Jens-Uwe; Muth, Gerhard; Goette, Andreas; Rotter, Achim; Ebelt, Henning; Olbrich, Hans-Georg; Mitrovic, Veselin; Hengstenberg, Christian; Schellong, Sebastian; Zamolyi, Karoly; Vertes, Andras; Matoltsy, Andras; Palinkas, Attila; Herczeg, Bela; Apro, Dezso; Lupkovics, Geza; Tomcsanyi, Janos; Toth, Kalman; Mathur, Atul; Banker, Darshan; Bharani, Anil; Arneja, Jaspal; Khan, Aziz; Gadkari, Milind; Hiremath, Jagdish; Patki, Nitin; Kumbla, Makund; Santosh, M.J.; Ravikishore, A.G.; Abhaichand, Rajpal; Maniyal, Vijayakukmar; Nanjappa, Manjunath; Reddy, P. Naveen; Chockalingam, Kulasekaran; Premchand, Rajendra; Mahajan, Vijay; Lewis, Basil; Wexler, Dov; Shochat, Michael; Keren, Andre; Omary, Muhamad; Katz, Amos; Marmor, Alon; Lembo, Giuseppe; Di Somma, Salvatore; Boccanelli, Alessandro; Barbiero, Mario; Pajes, Giuseppe; De Servi, Stefano; Greco, Dott Cosimo; De Santis, Fernando; Floresta, Agata; Visconti, Luigi Oltrona; Piovaccari, Giancarlo; Cavallini, Claudio; Di Biase, Matteo; Masini, Dott Franco; Vassanelli, Corrado; Viecca, Maurizio; Cangemi, Dott Francesco; Pirelli, Salvatore; Borghi, Claudio; Volpe, Massimo; Branzi, Angelo; Percoco, Dott Giovanni; Severi, Silvia; Santini, Alberto; De Lorenzi, Ettore; Metra, Marco; Zacà, Valerio; Mortara, Andrea; Tranquilino, Francisco P.; Babilonia, Noe A.; Ferrolino, Arthur M.; Manlutac, Benjamin; Dluzniewski, Miroslaw; Dzielinska, Zofia; Nowalany-Kozie, Ewa; Mazurek, Walentyna; Wierzchowiecki, Jerzy; Wysokinski, Andrzej; Szachniewicz, Joanna; Romanowski, Witold; Krauze-Wielicka, Magdalena; Jankowski, Piotr; Berkowski, Piotr; Szelemej, Roman; Kleinrok, Andrzej; Kornacewicz-Jac, Zdzislawa; Vintila, Marius; Vladoianu, Mircea; Militaru, Constantin; Dan, Gheorghe; Dorobantu, Maria; Dragulescu, Stefan; Kostenko, Victor; Vishnevsky, Alexandr; Goloschekin, Boris; Tyrenko, Vadim; Gordienko, Alexander; Kislyak, Oxana; Martsevich, Sergey; Kuchmin, Alexey; Karpov, Yurii; Fomin, Igor; Shvarts, Yury; Orlikova, Olga; Ershova, Olga; Berkovich, Olga; Sitnikova, Maria; Pakhomova, Inna; Boldueva, Svetlana; Tyurina, Tatiana; Simanenkov, Vladimir; Boyarkin, Mikhail; Novikova, Nina; Tereschenko, Sergey; Zadionchenko, Vladimir; Shogenov, Zaur; Gordeev, Ivan; Moiseev, Valentin; Wong, Raymond; Ong, Hean Yee; Le Tan, Ju; Goncalvesova, Eva; Kovar, Frantisek; Skalina, Ivan; Kasperova, Viera; Hojerova, Silvia; Szentivanyi, Miroslav; Stancak, Branislav; Babcak, Marian; Kycina, Peter; Poliacik, Pavol; Toth, Peter; Sirotiakova, Jana; de Sa, Esteban Lopez; Bueno, Manuel Gomez; Selles, Manuel Martinez; Cabrera, Jose Angel; Freire, Ramon Bover; Gonzalez Juanatey, Jose Ramon; Comin, Josep; Soriano, FranciscoRidocci; Lopez, Alejandro; Vicho, Raul; Lama, Manuel Geraldia; Schaufelberger, Maria; Brunotte, Richard; Ullman, Bengt; Hagerman, Inger; Cizinsky, Stella; Cherng, Wen-Jin; Yu, Wen-Chung; Kuo, Chi-Tai; Chang, Kuan-Cheng; Lai, Wen-Ter; Kuo, Jen-Yuan; Ural, Dilek; Badak, Ozer; Akin, Mustafa; Yigit, Zerrin; Yokusoglu, Mehmet; Yilmaz, Mehmet; Abaci, Adnan; Ebinc, Haksun; Perlman, Richard; Parish, David; Bergin, James; Burnham, Kenneth; Brown, Christopher; Lundbye, Justin; Williams, Celeste; Eisen, Howard; Juneman, Elizabeth; Joseph, Susan; Peberdy, Mary Ann; Peura, Jennifer; Gupta, Vishal; Habet, Kalim; French, William; Mody, Freny; Graham, Susan; Hazelrigg, Monica; Chung, Eugene; Dunlap, Stephanie; Nikolaidis, Lazaros; Najjar, Samer; Katz, Richard; Murali, Srinivas; Izzo, Joseph L.; Callister, Tracy; Phillips, Roland; Lippolis, Nicholas; Winterton, John; Meymandi, Sheba; Heilman, Karl; Oren, Ron; Zolty, Ronald; Brottman, Michael; Gunawardena, D.R.; Adams, Kirkwood; Barnard, Denise; Klapholz, Marc; Fulmer, James

    2013-01-01

    Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64–0.99; DM: HR: 1.16, 95% CI: 0.91–1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50–0.94; DM: HR: 1.64, 95% CI: 1.15–2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71–1.93; DM: HR: 2.39, 95% CI: 1.30

  19. Molecular mechanisms of AGE/RAGE-mediated fibrosis in the diabetic heart

    Science.gov (United States)

    Zhao, Jia; Randive, Rushil; Stewart, James A

    2014-01-01

    Chronic hyperglycemia is one of the main characteristics of diabetes. Persistent exposure to elevated glucose levels has been recognized as one of the major causal factors of diabetic complications. In pathologies, like type 2 diabetes mellitus (T2DM), mechanical and biochemical stimuli activate profibrotic signaling cascades resulting in myocardial fibrosis and subsequent impaired cardiac performance due to ventricular stiffness. High levels of glucose nonenzymatically react with long-lived proteins, such as collagen, to form advanced glycation end products (AGEs). AGE-modified collagen increase matrix stiffness making it resistant to hydrolytic turnover, resulting in an accumulation of extracellular matrix (ECM) proteins. AGEs account for many of the diabetic cardiovascular complications through their engagement of the receptor for AGE (RAGE). AGE/RAGE activation stimulates the secretion of numerous profibrotic growth factors, promotes increased collagen deposition leading to tissue fibrosis, as well as increased RAGE expression. To date, the AGE/RAGE cascade is not fully understood. In this review, we will discuss one of the major fibrotic signaling pathways, the AGE/RAGE signaling cascade, as well as propose an alternate pathway via Rap1a that may offer insight into cardiovascular ECM remodeling in T2DM. In a series of studies, we demonstrate a role for Rap1a in the regulation of fibrosis and myofibroblast differentiation in isolated diabetic and non-diabetic fibroblasts. While these studies are still in a preliminary stage, inhibiting Rap1a protein expression appears to down-regulate the molecular switch used to activate the ζ isotype of protein kinase C thereby promote AGE/RAGE-mediated fibrosis. PMID:25512788

  20. Molecular mechanisms of AGE/RAGE-mediated fibrosis in the diabetic heart

    Institute of Scientific and Technical Information of China (English)

    Jia; Zhao; Rushil; Randive; James; A; Stewart

    2014-01-01

    Chronic hyperglycemia is one of the main characteristics of diabetes. Persistent exposure to elevated glucose levels has been recognized as one of the major causal factors of diabetic complications. In pathologies, like type 2 diabetes mellitus(T2DM), mechanical and biochemical stimuli activate profibrotic signaling cascades resulting in myocardial fibrosis and subsequent impaired cardiac performance due to ventricular stiffness. High levels of glucose nonenzymatically react with long-lived proteins, such as collagen, to form advanced glycation end products(AGEs). AGE-modified collagen increase matrix stiffness making it resistant to hydrolytic turnover, resulting in an accumulation of extracellular matrix(ECM) proteins. AGEs account for many of the diabetic cardiovascular complications through their engagement of the receptor for AGE(RAGE). AGE/RAGE activation stimulates the secretion of numerous profibrotic growth factors, promotes increased collagen deposition leading to tissue fibrosis, as well as increased RAGE expression. To date, the AGE/RAGE cascade is not fully understood. In this review, we willdiscuss one of the major fibrotic signaling pathways, the AGE/RAGE signaling cascade, as well as propose an alternate pathway via Rap1 a that may offer insight into cardiovascular ECM remodeling in T2 DM. In a series of studies, we demonstrate a role for Rap1 a in the regulation of fibrosis and myofibroblast differentiation in isolated diabetic and non-diabetic fibroblasts. While these studies are still in a preliminary stage, inhibiting Rap1 a protein expression appears to down-regulate the molecular switch used to activate the ζ isotype of protein kinase C thereby promote AGE/RAGE-mediated fibrosis.

  1. Effects of Percutaneous Coronary Intervention on Viable Myocardium and Heart Function of Diabetic Patients With Chronic Total Occlusion.

    Science.gov (United States)

    Zhou, Guowei; Yang, Wenyi; Li, Liang

    The aim of this study was to compare the effects of percutaneous coronary intervention (PCI) on coronary chronic total occlusion patients with (DM) or without (NDM) diabetes mellitus. A total of 78 patients were divided into DM group and NDM group according to whether the patient has DM. The results of PCI were analyzed using quantitative coronary analysis. In addition, all the patients underwent Tc-MIBI (methoxyisobutylisonitrile) single-photon emission computed tomography (SPECT) and ultrasonic cardiogram in the first week and the sixth month after PCI to evaluate PCI results. During the 6-month follow-up, major adverse cardiac event (MACE) was recorded and analyzed as well. The first and second classes of collateral circulation between the 2 groups have significant differences (P coronary intervention has beneficial effects on heart functions and MACE when performed on chronic total occlusion patients with and without DM.

  2. Readmission patterns in patients with chronic obstructive pulmonary disease, chronic heart failure and diabetes mellitus: an administrative dataset analysis.

    Science.gov (United States)

    Brand, C; Sundararajan, V; Jones, C; Hutchinson, A; Campbell, D

    2005-05-01

    Comprehensive disease management programmes for chronic disease aim to improve patient outcomes and reduce health-care utilization. Readmission rates are often used as an outcome measure of effectiveness. This study aimed to document readmission rates, and risk for early and late readmission, for patients discharged from the Royal Melbourne Hospital with a disease diagnosis of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes mellitus compared to those with other general medical conditions. Eighty five (8.6%) of patients were readmitted within 28 days and 183 (20.8%) were readmitted between 29 and 180 days. No risk factors for early readmission were identified. Patients with a primary disease diagnosis of CHF and COPD are at increased risk of late readmissions (29-180 days).

  3. Comparative Analysis of Changes of Myocardial Angiogenesis and Energy Metabolism in Postinfarction and Diabetic Damage of Rat Heart

    Directory of Open Access Journals (Sweden)

    Sergey A. Afanasiev

    2014-01-01

    Full Text Available Comparative study of changes in myocardial activity of lactate dehydrogenase (LDH, succinate dehydrogenase (SDH, and capillary density distribution in the experimental models of diabetic and postinfarction damage of rat heart was performed. Data showed that decrease in LDH and SDH activities was observed in both pathologies which can suggest abnormal processes of glycolysis and oxidative phosphorylation in cardiac mitochondria. Activity of LDH and SDH in combined pathologies was comparative with the corresponding values of these parameters in control group. The authors hypothesize that these differences can be caused by specifics of myocardial vascularization. The results of the study showed that an increase in capillary density was found in all groups of rats with pathologies compared with control group. However, no significant differences in the intensity of angiogenesis processes were found between groups with pathologies.

  4. In vivo evaluation of a conjugated poly(lactide-ethylene glycol nanoparticle depot formulation for prolonged insulin delivery in the diabetic rabbit model

    Directory of Open Access Journals (Sweden)

    Tomar L

    2013-02-01

    Full Text Available Lomas Tomar,1,2 Charu Tyagi,1,3 Manoj Kumar,2 Pradeep Kumar,1 Harpal Singh,2 Yahya E Choonara,1 Viness Pillay11University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, Johannesburg, Gauteng, South Africa; 2Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, India; 3VSPG College, Chaudhary Charan Singh University, Meerut, IndiaAbstract: Poly(ethylene glycol (PEG and polylactic acid (PLA-based copolymeric nanoparticles were synthesized and investigated as a carrier for prolonged delivery of insulin via the parenteral route. Insulin loading was simultaneously achieved with particle synthesis using a double emulsion solvent evaporation technique, and the effect of varied PEG chain lengths on particle size and insulin loading efficiency was determined. The synthesized copolymer and nanoparticles were analyzed by standard polymer characterization techniques of gel permeation chromatography, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. In vitro insulin release studies performed under simulated conditions provided a near zero-order release pattern up to 10 days. In vivo animal studies were undertaken with varied insulin loads of nanoparticles administered subcutaneously to fed diabetic rabbits and, of all doses administered, nanoparticles containing 50 IU of insulin load per kg body weight controlled the blood glucose level within the physiologically normal range of 90–140 mg/dL, and had a prolonged effect for more than 7 days. Histopathological evaluation of tissue samples from the site of injection showed no signs of inflammation or aggregation, and established the nontoxic nature of the prepared copolymeric nanoparticles. Further, the reaction profiles for PLA-COOH and NH2-PEGDA-NH2 were elucidated using molecular mechanics energy relationships in vacuum and in a solvated system by exploring the spatial disposition of various

  5. Clinical Effects of Home Telemonitoring in the Context of Diabetes, Asthma, Heart Failure and Hypertension: A Systematic Review

    Science.gov (United States)

    Moqadem, Khalil; Pineau, Gilles; St-Hilaire, Carole

    2010-01-01

    Background Home telemonitoring figures among the various solutions that could help attenuate some of the problems associated with aging populations, rates of chronic illness, and shortages of health professionals. Objective The primary aim of this study was to further our understanding of the clinical effects associated with home telemonitoring programs in the context of chronic diseases. Methods We conducted a systematic review which covered studies published between January 1966 and December 2008. MEDLINE, The Cochrane Library, and the INAHTA (International Network of Agencies for Health Technology Assessment) database were consulted. Our inclusion criteria consisted of: (1) English language publications in peer-reviewed journals or conference proceedings and (2) studies involving patients with diabetes, asthma, heart failure, or hypertension, and presenting results on the clinical effects of home telemonitoring. Results In all, 62 empirical studies were analyzed. The results from studies involving patients with diabetes indicated a trend toward patients with home telemonitoring achieving better glycemic control. In most trials in which patients with asthma were enrolled, results showed significant improvements in patients’ peak expiratory flows, significant reductions in the symptoms associated with this illness, and improvements in perceived quality of life. Virtually all studies involving patients with hypertension demonstrated the ability of home telemonitoring to reduce systolic and/or diastolic blood pressure. Lastly, due to the equivocal nature of current findings of home telemonitoring involving patients with heart failure, larger trials are still needed to confirm the clinical effects of this technology for these patients. Conclusions Although home telemonitoring appears to be a promising approach to patient management, designers of future studies should consider ways to make this technology more effective as well as controlling possible mediating

  6. Plasticity of heart rate signalling and complexity with exercise training in obese individuals with and without type 2 diabetes.

    Science.gov (United States)

    Kanaley, J A; Goulopoulou, S; Franklin, R M; Baynard, T; Holmstrup, M E; Carhart, R; Weinstock, R S; Fernhall, B

    2009-10-01

    To examine the responsiveness of cardiac autonomic function and baroreflex sensitivity (BRS) to exercise training in obese individuals without (OB) and with type 2 diabetes (ObT2D). Subjects were tested in the supine position and in response to a sympathetic challenge before and after a 16-week aerobic training program. All testing was conducted in the morning following a 12-h fast. A total of 34 OB and 22 ObT2D men and women (40-60 years of age) were studied. Heart rate variability (HRV) was measured at rest via continuous ECG (spectral analysis with the autoregressive approach) and in response to upright tilt. The dynamics of heart rate complexity were analyzed with sample entropy and Lempel-Ziv entropy, and BRS was determined via the sequence technique. Subjects were aerobically trained 4 times per week for 30-45 min for 16 weeks. Resting HR decreased and total power (lnTP, ms(2)) of HRV increased in response to exercise training (Pchanges occurred in ln low frequency/HF power with training. Upright tilt decreased lnTP and lnHF and increased LF/HF (Pchanges nor were they altered with training in either group. Tilt also decreased complexity (sample entropy and Lempel-Ziv entropy; Pchange with training. Compared to OB subjects the ObT2D had less tilt-induced changes in BRS. Exercise training improved HRV and parasympathetic modulation (lnHF) in OB subjects but not in ObT2D, indicating plasticity in the autonomic nervous system in response to this weight-neutral exercise program only in the absence of diabetes. HR complexity and BRS were not altered by 16 weeks of training in either OB or ObT2D individuals.

  7. 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.

  8. Associations between plasma fibulin-1, pulse wave velocity and diabetes in patients with coronary heart disease

    DEFF Research Database (Denmark)

    Hansen, Maria Lyck; Rasmussen, Lars Melholt

    2015-01-01

    BACKGROUND: Diabetes is related to increased risk of cardiovascular disease, and arterial stiffness and its consequences may be the factor connecting the two. Arterial stiffness is often measured by carotid-femoral pulse wave velocity (cf-PWV), but no plasma biomarker reflecting arterial stiffnes...

  9. Exercise mediated protection of diabetic heart through modulation of microRNA mediated molecular pathways

    OpenAIRE

    Lew, Jason Kar Sheng; Pearson, James T; Schwenke, Daryl O.; Katare, Rajesh

    2017-01-01

    Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfun...

  10. Impact of Orlistat-Induced Weight Loss on Diastolic Function and Heart Rate Variability in Severely Obese Subjects with Diabetes

    Directory of Open Access Journals (Sweden)

    Julie Martin

    2011-01-01

    Full Text Available Objective. Determine the impact of Orlistat-induced weight loss on metabolic profile and cardiovascular function in severely obese patients with type 2 diabetes. Methods. Twenty-nine patients were randomized either to a nonplacebo control group or to a treatment group with Orlistat thrice a day. Metabolic profile, anthropometric parameters, heart rate variability indices, and echocardiographic variables were measured before and after a 12-week treatment period. Results. Treatment with Orlistat induced a modest but significant weight loss compared to controls (3.7 ± 3.0 versus 0.5 ± 2.2 kg, resp.; P=.003. There was significant decrease in fasting glycemia (7.9 ± 3.0 versus 6.7 ± 2.2 mmol/L; P=.03 and significant improvements in left ventricular diastolic function (P=.03 and in the sympathovagal balance (LF/HF ratio (P=.04 in the Orlistat group. Conclusion. These results suggest that a modest weight loss improves fasting glycemia, left ventricular diastolic function, and sympathovagal balance in severely obese patients with type 2 diabetes.

  11. Fibroblast Growth Factor-9 Activates c-Kit Progenitor Cells and Enhances Angiogenesis in the Infarcted Diabetic Heart

    Directory of Open Access Journals (Sweden)

    Dinender Singla

    2016-01-01

    Full Text Available We hypothesized that fibroblast growth factor-9 (FGF-9 would enhance angiogenesis via activating c-kit positive stem cells in the infarcted nondiabetic and diabetic heart. In brief, animals were divided into three groups: Sham, MI, and MI+FGF-9. Two weeks following MI or sham surgery, our data suggest that treatment with FGF-9 significantly diminished vascular apoptosis compared to the MI group in both C57BL/6 and db/db mice (p<0.05. Additionally, the number of c-kit+ve/SM α-actin+ve cells and c-kit+ve/CD31+ve cells were greatly enhanced in the MI+FGF-9 groups relative to the MI suggesting FGF-9 enhances c-Kit cell activation and their differentiation into vascular smooth muscle cells and endothelial cells, respectively (p<0.05. Histology shows that the total number of vessels were quantified for all groups and our data suggest that the FGF-9 treated groups had significantly more vessels than their MI counterparts (p<0.05. Finally, echocardiographic data suggests a significant improvement in left ventricular output, as indicated by fractional shortening and ejection fraction in both nondiabetic and diabetic animals treated with FGF-9 (p<0.05. Overall, our data suggests FGF-9 has the potential to attenuate vascular cell apoptosis, activate c-Kit progenitor cells, and enhance angiogenesis and neovascularization in C57BL/6 and db/db mice leading to improved cardiac function.

  12. Diabetes

    OpenAIRE

    Smith, Paul

    2003-01-01

    Derbyshire general practitioner Stuart Bootle has had diabetes for 20 years. He speaks to Paul Smith, who has type 1 diabetes himself, about the trials and tribulations of being on the receiving end of NHS care

  13. Lifestyle intervention improves heart rate recovery from exercise in adults with type 2 diabetes: results from the Look AHEAD study.

    Science.gov (United States)

    Ribisl, Paul M; Gaussoin, Sarah A; Lang, Wei; Bahnson, Judy; Connelly, Stephanie A; Horton, Edward S; Jakicic, John M; Killean, Tina; Kitzman, Dalane W; Knowler, William C; Stewart, Kerry J

    2012-01-01

    The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT) and (2) to determine the independent and combined effects of weight loss and fitness changes upon HRR. In 4503 participants (45-76 years) who completed 1 year of intervention, HRR was measured after a submaximal GXT to compare the influence of (ILI) with (DSE) upon HRR. Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (P exercise and HRR variables in ILI improved (P heart rate (HR) at rest was lower (72.8 ± 11.4 versus 77.7 ± 11.7 b/min), HR range was greater (57.7 ± 12.1 versus 53.1 ± 12.4 b/min), HR at 2 minutes was lower (89.3 ± 21.8 versus 93.0 ± 12.1 b/min), and HRR was greater (41.25 ± 22.0 versus 37.8 ± 12.5 b/min). Weight loss and fitness gain produced significant separate and independent improvements in HRR.

  14. β-Blockers in hypertension, diabetes, heart failure and acute myocardial infarction: a review of the literature.

    Science.gov (United States)

    DiNicolantonio, James J; Fares, Hassan; Niazi, Asfandyar K; Chatterjee, Saurav; D'Ascenzo, Fabrizio; Cerrato, Enrico; Biondi-Zoccai, Giuseppe; Lavie, Carl J; Bell, David S; O'Keefe, James H

    2015-01-01

    β-Blockers (BBs) are an essential class of cardiovascular medications for reducing morbidity and mortality in patients with heart failure (HF). However, a large body of data indicates that BBs should not be used as first-line therapy for hypertension (HTN). Additionally, new data have questioned the role of BBs in the treatment of stable coronary heart disease (CHD). However, these trials mainly tested the non-vasodilating β1 selective BBs (atenolol and metoprolol) which are still the most commonly prescribed BBs in the USA. Newer generation BBs, such as the vasodilating BBs carvedilol and nebivolol, have been shown not only to be better tolerated than non-vasodilating BBs, but also these agents do not increase the risk of diabetes mellitus (DM), atherogenic dyslipidaemia or weight gain. Moreover, carvedilol has the most evidence for reducing morbidity and mortality in patients with HF and those who have experienced an acute myocardial infarction (AMI). This review discusses the cornerstone clinical trials that have tested BBs in the settings of HTN, HF and AMI. Large randomised trials in the settings of HTN, DM and stable CHD are still needed to establish the role of BBs in these diseases, as well as to determine whether vasodilating BBs are exempt from the disadvantages of non-vasodilating BBs.

  15. Omega-3 Polyunsaturated Fatty Acids in Treatment of Patients with Coronary Heart Disease and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Aisulu T. Mussagalieva, MD, PhD

    2012-03-01

    Full Text Available Increased platelet aggregation is one of the major risk factors for cardiovascular events. However, recent studies have demonstrated the inhibition of platelet aggregation by omega-3 PUFAs. The aim of this work was to study the effect of the addition of omega-3 PUFAs to the combination of aspirin and clopidogrel on the platelet aggregation in patients with coronary heart disease. In all, 40 patients with coronary heart disease and diabetes mellitus type 2 undergoing PCI with stent implantation were included in the study. Clopidogrel in a 300 mg loading dose was given after drawing blood for baselinemeasurement of ADP-induced platelet aggregation. Patients were randomized into two groups. The first group included 20 patients who received 75 mg clopidogrel once daily, 100 mg aspirin once daily and 1000 mg omega-3 PUFAs daily. The second group included 20 patients who received 75 mg clopidogrel once daily and 100 mg aspirin daily. The ADP– induced platelet aggregation was performed twice, once before clopidogrel administration and once after one month. All the patients were genotyped for CYP2C19 polymorphism. No significant differences were noted among the genotype and allele frequencies of the cytochrome CYP2C19 gene between the two groups. The addition of omega-3 PUFAs to the standard dual antiplatelet therapy of aspirin and clopidogrel significantly decreased the ADP-induced platelet aggregation.

  16. The effects of crocin, insulin and their co-administration on the heart function and pathology in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Amir Farshid

    2016-11-01

    Full Text Available Objective: Crocinisa saffron constituent with a potent anti-oxidant activity. The present study investigated the effects of crocin and insulin treatments (alone or in combination on cardiac function and pathology in diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (i.p. injection of streptozotocin (STZ, 50 mg/kg. Thereafter, crocin (5, 10 and 20 mg/kg, i.p., subcutaneous (s.c. injection of insulin (4 IU/kg and their combination were administeredfor eight weeks. Blood glucose level andwhole heart and body weights were measured. Electrocardiography (ECG was carried out using the lead II. Serum concentrations of lactate dehydrogenase (LDH, creatine kinase-MB isoenzyme (CK-MB, and the heart tissue malodialdehyde (MDA and superoxide dismutase (SOD contents were determined. The heart lesions were evaluated by light microscopy. Results: STZ decreased body weight and increased whole heart weight/body weight ratio. It also decreased heart rate, and increased RR and QT intervals and T wave amplitude. STZ increased blood glucose, serum LDH andCK-MB levels, augmentedheart tissue MDA content, decreased SOD content of heart tissue, and produced hemorrhages, degeneration, interstitial edema, and fibroblastic proliferation in the heart tissue. Crocin (10 and 20 mg/kg, i.p., insulin (4 IU/kg, s.c. and their combination (5 mg/kg of crocin with 4 IU/kg of insulin treatments recovered the ECG, biochemical and histopathological changes induced by STZ. Conclusion: The results showed cardioprotective  effects of crocin and insulin in STZ-induced diabetic rats. The antioxidant and anti-hyperglycemic properties of crocin and insulin may be involved in their cardioprotective actions.

  17. Importance of the 31-p-nmr-spectroscopy for prediction and early detection of coronary heart disease in patients with diabetes mellitus type I

    CERN Document Server

    Steinboeck, P

    2001-01-01

    Microvascular abnormalities and dysfunction via thickening of the basement membrane are known to occur in diabetic patients. Myocardial high energy phosphates have been shown to be reduced by ischemia and alterations of the cardiac metabolism are the primary consequence of myocardial ischemia. The present study involved 30 male patients with diabetes mellitus type I and 36 healthy male volunteers as age-matched controls. Phosphorus-31-P-nuclear-magnetic-resonance-spectroscopic-imaging of the heart was performed in all subjects using a 1.5 Tesla whole-body-magnetic-resonance-scanner. The ratios of phosphocreatinine (PCr) to adenosine-triphosphate (ATP) were calculated. Moreover, echocardiographic evaluation and stress tests were performed in all individuals. The myocardium of patients with diabetes mellitus type I showed significantly decreased ratios of PCr/ATP compared with healthy controls. This study demonstrates for the first time a decreased ratio of PCr/ATP in the myocardium of patients with diabetes me...

  18. Impact of sex and age at onset of diabetes on mortality from ischemic heart disease in patients with type 1 diabetes.

    Science.gov (United States)

    Harjutsalo, Valma; Maric-Bilkan, Christine; Forsblom, Carol; Groop, Per-Henrik

    2014-01-01

    OBJECTIVE To study whether ischemic heart disease (IHD) mortality among patients with type 1 diabetes (T1D) depends on the age at onset of diabetes and whether this effect is sex specific. RESEARCH DESIGN AND METHODS The study examined long-term IHD-specific mortality in a Finnish population-based cohort of patients with early-onset (0-14 years) and late-onset (15-29 years) T1D (n = 17,306). RESULTS During 433,782 person-years of follow-up, 478 deaths from IHD were observed. Within the early-onset cohort, the average crude mortality rate in women was 33.3% lower than in men, whereas in the late-onset cohort, mortality was only one-half that in men. In contrast, the standardized mortality ratio (SMR) was higher in women than in men (21.6 [95% CI 17.2-27.0] vs. 5.8 [5.1-6.6]). The difference in SMR between sexes was more striking in the early-onset cohort (women 52.8 [36.3-74.5], men 12.1 [9.2-15.8]). The SMR was also greater in women in the late-onset cohort (15.8 [11.8-20.7]) compared with men (5.0 [4.3-5.8]). The relative risk of dying from IHD was greatest in women aged early- and late-onset cohorts, respectively. CONCLUSIONS The risk of mortality from IHD is exceptionally high in women with early-onset T1D compared with women in the background population. These observations underscore the importance of identifying risk factors early in women and delivering more-aggressive treatment after diagnosis.

  19. Acute effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate responses to intraduodenal glucose infusion in type 2 diabetes.

    Science.gov (United States)

    Thazhath, Sony S; Marathe, Chinmay S; Wu, Tongzhi; Chang, Jessica; Khoo, Joan; Kuo, Paul; Checklin, Helen L; Bound, Michelle J; Rigda, Rachael S; Horowitz, Michael; Jones, Karen L; Rayner, Christopher K

    2017-01-01

    To evaluate the effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate during an intraduodenal glucose infusion in type 2 diabetes. Nine subjects with type 2 diabetes were randomised to receive intravenous exenatide or saline control in a crossover design. Glucose (3 kcal min(-1)) was infused via an intraduodenal manometry catheter for 60 min. Blood pressure, heart rate, and the frequency and amplitude of duodenal pressure waves were measured at regular intervals. Gastrointestinal symptoms were monitored using 100 mm visual analogue scales. During intraduodenal glucose infusion (0-60 min), diastolic (p(0-60) = 0.03) and mean arterial (p(0-60) = 0.03) blood pressures and heart rate (p(0-60) = 0.06; p(0-120) = 0.03)) were higher with exenatide compared to placebo. The increase in the area under the curve for diastolic blood pressure and mean arterial blood pressure was related directly to the suppression of the duodenal motility index with exenatide compared to control (p = 0.007 and 0.04, respectively). In type 2 diabetes, intravenous exenatide increases mean arterial blood pressure and heart rate during an intraduodenal glucose infusion, supporting the need for further research with exenatide for its potential use in postprandial hypotension. © The Author(s) 2016.

  20. Renal and vascular studies of aqueous extract of Urtica dioica in rats and rabbits

    Directory of Open Access Journals (Sweden)

    K.F. Dizaye

    2013-06-01

    Full Text Available Urtica dioica has a variety of uses in traditional medicine for genitourinary ailments kidney disorders, allergies, diabetes, anemia, gastrointestinal tract ailments, musculoskeletal aches and alopecia. However, only a few of these uses have scientific bases that support their clinical uses. This study was done to evaluate some of the in vivo and in vitro pharmacological actions of this plant. Eighteen local domestic rabbits (Oryctolagus cuniculus were used for in vitro studies (effect of the plant extract on isolated pulmonary arteries and isolated urinary bladder smooth muscle and in vivo studies (effect of the extract on renal function. Six male albino rats were used for studying the effects of the plant extract on blood pressure and heart rate. Urtica dioica extract produced a significant increase in urine volume and urinary Na+ excretion without significant changes in K+ excretion rates in experimental rabbits. No changes occurred in Glomerular filtration rate and %Na+ reabsorption of filtered load. Neither vasodilatation nor vasoconstriction of isolated pulmonary arteries of the rabbit was seen after applying the aqueous extract of U. dioica. Besides it could not reverse the vasoconstrictor effect of phenylephrine. Urtica dioica has no detectable effects on the isolated bladder; moreover it did not reverse the contraction that was produced by pilocarpine. In experimental rats, the plant extract produced a profound drop in blood pressure associated with decreased heart rate. In conclusion the aqueous extract of U. dioica produced diuretic and natriuretic effects with out significant effect on the K+ excretion rate in rabbits. Moreover it produced a profound drop in blood pressure and heart rate.

  1. 糖尿病合并心力衰竭研究进展%Diabetes mellitus combined with heart failure: research progress

    Institute of Scientific and Technical Information of China (English)

    陈树; 李秀钧

    2012-01-01

    随着糖尿病发病率的逐年增高,糖尿病合并心力衰竭的患者也在逐渐增多,糖尿病是心力衰竭一个重要且独立的危险因素,可进一步恶化心力衰竭的预后,显著增加心力衰竭患者的住院率及死亡率,两者往往伴发出现,预后极差.糖尿病并发心力衰竭已成为目前老年糖尿病患者最主要的心脏事件之一.本文从糖尿病合并心力衰竭的发病机制、病理改变、临床表现及管理治疗等几个方面展开讨论,从而做到积极预防、延缓病情发展,提高患者的生存质量.%With the increase of diabetes incidence rate, diabetes patients with heart failure are also gradually increased year by year. Diabetes is an important and independent risk factor for heart failure, which worsens the prognosis and causes significant increase in hospitalization rate and mortality of patients with heart failure. These two diseases often occur concomitantly with poor prognosis, which has become one of the major cardiac events in the elderly with diabetes. In this paper, we reviewed the pathogenesis, pathological changes, clinical manifestations and the management of diabetes patients with heart failure, so as to actively prevent, retard the progression, and improve the patients' quality of life.

  2. Heart Rate and Systolic Blood Pressure Variability in the Time Domain in Patients with Recent and Long-Standing Diabetes Mellitus

    Science.gov (United States)

    Rivera, Ana Leonor; Estañol, Bruno; Sentíes-Madrid, Horacio; Fossion, Ruben; Toledo-Roy, Juan C.; Mendoza-Temis, Joel; Morales, Irving O.; Landa, Emmanuel; Robles-Cabrera, Adriana; Moreno, Rene; Frank, Alejandro

    2016-01-01

    Diabetes Mellitus (DM) affects the cardiovascular response of patients. To study this effect, interbeat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) variability of patients during supine, standing and controlled breathing tests were analyzed in the time domain. Simultaneous noninvasive measurements of IBI and SBP for 30 recently diagnosed and 15 long-standing DM patients were compared with the results for 30 rigorously screened healthy subjects (control). A statistically significant distinction between control and diabetic subjects was provided by the standard deviation and the higher moments of the distributions (skewness, and kurtosis) with respect to the median. To compare IBI and SBP for different populations, we define a parameter, α, that combines the variability of the heart rate and the blood pressure, as the ratio of the radius of the moments for IBI and the same radius for SBP. As diabetes evolves, α decreases, standard deviation of the IBI detrended signal diminishes (heart rate signal becomes more “rigid”), skewness with respect to the median approaches zero (signal fluctuations gain symmetry), and kurtosis increases (fluctuations concentrate around the median). Diabetes produces not only a rigid heart rate, but also increases symmetry and has leptokurtic distributions. SBP time series exhibit the most variable behavior for recently diagnosed DM with platykurtic distributions. Under controlled breathing, SBP has symmetric distributions for DM patients, while control subjects have non-zero skewness. This may be due to a progressive decrease of parasympathetic and sympathetic activity to the heart and blood vessels as diabetes evolves. PMID:26849653

  3. New-onset diabetes mellitus after heart transplantation in children - Incidence and risk factors.

    Science.gov (United States)

    Sehgal, Swati; Bock, Matthew J; Louks Palac, Hannah; Brickman, Wendy J; Gossett, Jeffrey G; Marino, Bradley S; Backer, Carl L; Pahl, Elfriede

    2016-11-01

    Diabetes mellitus is a recognized complication of SOT in adults and is associated with decreased graft and patient survival. Little is known about NOD in pediatric HT recipients. We aimed to characterize the incidence and describe risk factors for development of NOD after HT in children. Children who developed diabetes after HT were identified from the OPTN database. Demographic and clinical data before and after transplant were compared between patients with and without NOD. A total of 2056 children were included, 56% were male, 54% were Caucasian, and 62% had cardiomyopathy prior to HT. NOD developed in 219 children (11%) after HT. The incidence of NOD was 2.4, 9.0, and 10.4% at one, five, and 10 yr after HT, respectively. Obesity (HR: 4.32), dialysis prior to transplant (HR: 2.38), African American race (HR: 1.86), transplant before year 2000 (HR: 1.82), female gender (HR: 1.68), and older age at transplant (HR: 1.28) were independent predictors of NOD. The major modifiable risk factor for NOD is obesity, imparting the maximum hazard. Improved surveillance for diabetes in high-risk patients and specific prevention and intervention strategies are imperative in this population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Rabbit hematology.

    Science.gov (United States)

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  5. Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin

    Directory of Open Access Journals (Sweden)

    Schaan B.D.

    1997-01-01

    Full Text Available Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP variability in rats (164.5 ± 1.7 g 7, 14, 30 and 120 days after streptozotocin (STZ injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN and root mean square of successive difference of RR intervals (RMSSD. MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1 - (MAPn] x density. The indices represent the maximum concentration of points (P1, the longitudinal axis (P2, and the transversal axis (P3 and MN represents P1 x P2 x P3 x 10-3. STZ induced increased urinary glucose in diabetic (D rats compared to controls (C. Seven days after STZ, diabetes reduced resting HR from 380.6 ± 12.9 to 319.2 ± 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 ± 1.67 to 19.87 ± 2.60 ms, did not change MAP, and reduced P1 from 61.0 ± 5.3 to 51.5 ± 1.8 arbitrary units (AU, P2 from 41.3 ± 0.3 to 29.0 ± 1.8 AU, and MN from 171.1 ± 30.2 to 77.2 ± 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r = -0.76, P = 0.03 as well as with the MN index (r = -0.83, P = 0.01. We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The

  6. A propensity‐matched study of the effect of diabetes on the natural history of heart failure: variations by sex and age

    Science.gov (United States)

    Ahmed, Ali; Aban, Inmaculada B; Vaccarino, Viola; Lloyd‐Jones, Donald M; Goff, David C; Zhao, Jiannan; Love, Thomas E; Ritchie, Christine; Ovalle, Fernando; Gambassi, Giovanni; Dell'Italia, Louis J

    2007-01-01

    Background Poor prognosis in heart failure (HF) patients with diabetes is often attributed to increased co‐morbidity and advanced disease. Further, this effect may be worse in women. Objective To determine whether the effect of diabetes on outcomes and the sex‐related variation persisted in a propensity score‐matched HF population, and whether the sex‐related variation was a function of age. Methods Of the 7788 HF patients in the Digitalis Investigation Group trial, 2218 had a history of diabetes. Propensity score for diabetes was calculated for each patient using a non‐parsimonious logistic regression model incorporating all measured baseline covariates, and was used to match 2056 (93%) diabetic patients with 2056 non‐diabetic patients. Results All‐cause mortality occurred in 135 (25%) and 216 (39%) women without and with diabetes (adjusted HR = 1.67; 95% CI = 1.34 to 2.08; p<0.001). Among men, 535 (36%) and 609 (41%) patients without and with diabetes died from all causes (adjusted HR = 1.21; 95% CI = 1.07 to 1.36; p = 0.002). Sex–diabetes interaction (overall adjusted p<0.001) was only significant in patients ⩾65 years (15% absolute risk increase in women; multivariable p for interaction = 0.005), but not in younger patients (2% increase in women; p for interaction = 0.173). Risk‐adjusted HR (95% CI) for all‐cause hospitalisation for women and men were 1.49 (1.28 to 1.72) and 1.21 (1.11 to 1.32), respectively, also with significant sex–diabetes interaction (p = 0.011). Conclusions Diabetes‐associated increases in morbidity and mortality in chronic HF were more pronounced in women, and theses sex‐related differences in outcomes were primarily observed in elderly patients. PMID:17488764

  7. Reduced capacity of heart rate regulation in response to mild hypoglycemia induced by glibenclamide and physical exercise in type 2 diabetes.

    Science.gov (United States)

    Soydan, Nedim; Bretzel, Reinhard G; Fischer, Britta; Wagenlehner, Florian; Pilatz, Adrian; Linn, Thomas

    2013-05-01

    Decreased heart rate variability (HRV) is associated with enhanced mortality due to abnormal cardiac rhythm. While hypoglycemic events are increasingly common in the treatment of type 2 diabetes, HRV is part of the counter-regulation against low blood glucose levels. We hypothesized that HRV was impaired in mild hypoglycemia in diabetic individuals. Hyperinsulinemic-hypoglycemic clamps were performed in twelve type 2 diabetic patients without cardiovascular disease and in non-diabetic subjects matched for age, sex, and weight. In an additional study, hypoglycemic events, induced by either a single morning dose of glibenclamide or physical exercise, were recorded for the subsequent 24h. Blood glucose concentrations and electrocardiograms were continuously monitored. Serum hormone levels, hypoglycemic symptoms, and forearm blood flow were measured at defined time points. Occurrence of a symptomatic hypoglycemic episode (mean blood glucose 3.1±0.4 mmol/l) attenuated most of the time and frequency domain measurements in both healthy and diabetic individuals. The magnitude of reduction of HRV parameters was significantly lower in diabetic compared to healthy subjects. Glibenclamide taken in the morning enhanced the daily number of mild hypoglycemic events compared with placebo or moderate exercise. Concordantly, 24-h mean HRV measurements were decreased. HRV response to hypoglycemia is impaired in type 2 diabetic subjects resulting in a higher than expected risk for sudden arrhythmia following mild hypoglycemic episodes. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Circadian Variations in Blood Pressure, Heart Rate, and HR-BP Cross-Correlation Coefficient during Progression of Diabetes Mellitus in Rat.

    Science.gov (United States)

    Anigbogu, Chikodi N; Williams, Daniel T; Brown, David R; Silcox, Dennis L; Speakman, Richard O; Brown, Laura C; Karounos, Dennis G; Randall, David C

    2011-01-01

    Circadian changes in cardiovascular function during the progression of diabetes mellitus in the diabetes prone rat (BBDP) (n = 8) were studied. Age-matched diabetes-resistant rats (BBDR) served as controls. BP was recorded via telemetry in contiguous 4 hr time periods over 24 hours starting with 12 midnight to 4 am as period zero (P0). Prior to onset of diabetes BP was high at P0, peaked at P2, and then fell again at P3; BP and heart rate (HR) then increased gradually at P4 and leveled off at P5, thereby exhibiting a bipodal rhythm. These patterns changed during long-term diabetes. The cross-correlation coefficient of BP and HR was not significantly different across groups at onset, but it fell significantly at 9 months of duration of diabetes (BBDP: 0.39 ± 0.06; BBDR: 0.65 ± 0.03; P < .05). These results show that changes in circadian cardiovascular rhythms in diabetes mellitus became significant at the late stage of the disease.

  9. Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes.

    Science.gov (United States)

    Korkmaz-Icöz, Sevil; Lehner, Alice; Li, Shiliang; Vater, Adrian; Radovits, Tamás; Hegedűs, Péter; Ruppert, Mihály; Brlecic, Paige; Zorn, Markus; Karck, Matthias; Szabó, Gábor

    2015-01-01

    Despite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and type 2 diabetic Goto-Kakizaki (GK) rats (16-week-old) underwent 45 min occlusion of the left anterior descending coronary artery and 24 h reperfusion. The plasma glucose level was significantly higher in diabetic rats compared to the nondiabetics. Diabetes mellitus was associated with ventricular hypertrophy and increased interstitial fibrosis. Inducing myocardial infarction increased the glucose levels in diabetic compared to nondiabetic rats. Furthermore, the infarct size was smaller in GK rats than in the control group. Systolic and diastolic functions were impaired in W + MI and did not reach statistical significance in GK + MI animals compared to the corresponding controls. Among the 125 genes surveyed, 35 genes showed a significant change in expression in GK + MI compared to W + MI rats. Short-term diabetes promotes compensatory mechanisms that may provide cardioprotection against ischemia/reperfusion injury, at least in part, by increased antioxidants and the upregulation of the prosurvival PI3K/Akt pathway, by the downregulation of apoptotic genes, proinflammatory cytokine TNF-α, profibrogenic TGF-β, and hypertrophic marker α-actin-1.

  10. Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability

    Energy Technology Data Exchange (ETDEWEB)

    Scholte, Arthur J.H.A.; Schuijf, Joanne D.; Delgado, Victoria; Kok, Jurriaan A.; Bus, Mieke T.J.; Maan, Arie C.; Wall, Ernst E. van der; Bax, Jeroen J. [Leiden University Medical Center, Department of Cardiology, Albinusdreef 2, PO Box 9600, Leiden (Netherlands); Stokkel, Marcel P.; Dibbets-Schneider, Petra [Leiden University Medical Center, Nuclear Medicine, Leiden (Netherlands); Kharagitsingh, Antje V. [Medisch Centrum Haaglanden, Department of Internal Medicine, The Hague (Netherlands)

    2010-09-15

    The purpose of this study was to evaluate the prevalence of cardiac autonomic neuropathy (CAN) in a cohort of patients with type 2 diabetes, truly asymptomatic for coronary artery disease (CAD), using heart rate variability (HRV) and {sup 123}I-metaiodobenzylguanidine ({sup 123}I-mIBG) myocardial scintigraphy. The study group comprised 88 patients with type 2 diabetes prospectively recruited from an outpatient diabetes clinic. In all patients myocardial perfusion scintigraphy, CAN by HRV and {sup 123}I-mIBG myocardial scintigraphy were performed. Two or more abnormal tests were defined as CAN-positive (ECG-based CAN) and one or fewer as CAN-negative. CAN assessed by {sup 123}I-mIBG scintigraphy was defined as abnormal if the heart-to-mediastinum ratio was <1.8, the washout rate was >25%, or the total defect score was >13. The prevalence of CAN in patients asymptomatic for CAD with type 2 diabetes and normal myocardial perfusion assessed by HRV and {sup 123}I-mIBG scintigraphy was respectively, 27% and 58%. Furthermore, in almost half of patients with normal HRV, {sup 123}I-mIBG scintigraphy showed CAN. The current study revealed a high prevalence of CAN in patients with type 2 diabetes. Secondly, disagreement between HRV and {sup 123}I-mIBG scintigraphy for the assessment of CAN was observed. (orig.)

  11. Coexistence of beta 1- and beta 2-adrenoceptors in the rabbit heart: quantitative analysis of the regional distribution by (-)-/sup 3/H-dihydroalprenolol binding

    Energy Technology Data Exchange (ETDEWEB)

    Brodde, O.E.; Leifert, F.J.; Krehl, H.J.

    1982-01-01

    We determined the amount of beta 1- and beta 2-adrenoceptors in right and left atria and ventricles of rabbits. For this purpose inhibition of specific (-)-/sup 3/H-dihydroalprenolol ((-)-/sup 3/H-DHA) binding (5 nM) by beta 1-selective (practolol, metoprolol) and beta 2-selective (zinterol, IPS 339) adrenergic drugs was determined and analyzed by pseudo-Scatchard (Hofstee) plots. For both atria, inhibition of binding by the four selective beta-adrenergic drugs resulted in non-linear Hofstee plots, suggesting the coexistence of both beta-adrenoceptor subtypes. From these plots we calculated a beta 1:beta 2-adrenoceptor ratio of 72:28 for the right atrium and of 82:18 for the left. In contrast, only a very small amount of beta 2-adrenoceptors (approximately 5-7% of the total beta-adrenoceptor population) could be detected in the ventricles. For comparison we analyzed the inhibition of specific (-)-/sup 3/H-DHA binding in tissues with homogeneous population of beta-adrenoceptors (beta 1:guinea pig left ventricle; beta 2: cerebellum of mature rats). For both tissues the four selective beta-adrenergic drugs showed linear Hofstee plots, demonstrating that in tissues with homogeneous beta-receptor population interaction of each drug with the receptor followed simple mass-action kinetics. We conclude that beta 1- and beta 2-adrenoceptors coexist in rabbit atria while the ventricles are predominantly endowed the beta 1-adrenoceptors.

  12. National Diabetes Statistics Report, 2014

    Science.gov (United States)

    ... I ndirect costs $ 69 billion (disability, work loss, premature death). 8 General Information What is diabetes? Diabetes is ... as heart disease, stroke, kidney failure, blindness, and premature death. Types of diabetes Type 1 diabetes was previously ...

  13. Reduction of n-3 PUFAs, specifically DHA and EPA, and enhancement of peroxisomal beta-oxidation in type 2 diabetic rat heart

    Directory of Open Access Journals (Sweden)

    Hou Lianguo

    2012-10-01

    Full Text Available Abstract Background There is overwhelming evidence that dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs, mainly EPA (C20:5n-3 and DHA (C22:6n-3, has cardiovascular protective effects on patients with type 2 diabetes mellitus (T2DM but not on healthy people. Because the T2DM heart increases fatty acid oxidation (FAO to compensate for the diminished utilization of glucose, we hypothesize that T2DM hearts consume more n-3 PUFAs and, therefore, need more n-3 PUFAs. In the present study, we investigated the changes in cardiac n-3 PUFAs and peroxisomal beta-oxidation, which are responsible for the degradation of PUFAs in a high-fat diet (HFD and low-dose streptozotocin- (STZ induced type 2 diabetic rat model. Methods and results The capillary gas chromatography results showed that all the n-3 (or omega-3 PUFAs, especially DHA (~50% and EPA (~100%, were significantly decreased, and the n-6/n-3 ratio (~115% was significantly increased in the hearts of diabetic rats. The activity of peroxisomal beta-oxidation, which is crucial to very-long-chain and unsaturated FA metabolism (including DHA, was significantly elevated in DM hearts. Additionally, the real-time PCR results showed that the mRNA expression of most peroxisomal beta-oxidation key enzymes were up-regulated in T2DM rat hearts, which might contribute to the reduction of n-3 (or omega-3 PUFAs. Conclusion In conclusion, our results indicate that T2DM hearts consume more n-3 PUFAs, especially DHA and EPA, due to exaggerated peroxisomal beta-oxidation.

  14. Preventing Diabetes Problems

    Science.gov (United States)

    ... Other Dental Problems Diabetes & Sexual & Urologic Problems Preventing Diabetes Problems View or Print All Sections Heart Disease & ... prevent or delay sexual and urologic problems. Depression & Diabetes Depression is common among people with a chronic, ...

  15. Patterns of Heart Attacks

    Science.gov (United States)

    2010-06-01

    Hypertension (high blood pressure), smoking, family history of heart disease, and diabetes mellitus (both types 1 and 2) are also factors that increase the risk...breath 16% 19% Hyperlipidemia 2% Asthma 23% Coronary Artery Disease 15% Chest Pain 4% Pneumonia 24% 38% Diabetes 7% Congestive Heart Failure 9% 6...Pain Diabetes Congestive Heart Failure Hypertension Asthma Table 5.7: Diagnoses that distinguish cluster 8 from the cost bucket 2 population average. The

  16. [Heart rate variability is significantly reduced in non-diabetic patients with hypertension].

    Science.gov (United States)

    Nagy, Krisztina; Sipos, Evelin; El Hadj Othmane, Taha

    2014-06-01

    Bevezetés: A szívfrekvencia-variabilitás csökken hypertoniában vagy diabetes mellitusban szenvedők körében. A hypertonia és a diabetes mellitus egymással gyakori komorbiditást mutatnak. Nincs elegendő adat arról, hogy a kontrollhoz képest diabetes mellitusban nem szenvedő hypertoniás betegek körében hogyan változik a szívfrekvencia-variabilitás. Célkitűzés: A szerzők hypertoniában szenvedő diabeteses és nem diabeteses betegekben, valamint kontrollegyénekben a szívfrekvencia-variabilitás vizsgálatát tűzték ki célul. Módszer: 130 hypertoniában, 48 hypertoniában és 2-es típusú diabetes mellitusban szenvedő beteget, valamint 87 kontrollszemélyt vontak be a vizsgálatba. A minimális, átlagos és maximális szívfrekvenciát, valamint az egymást követő RR-intervallumok időtartamának és 5 perces szegmensekben mért átlagának szórását határozták meg. Eredmények: Az átlagos minimális szívfrekvencia szignifikánsan nem különbözött a csoportok között. A kontrollhoz képest a többi paraméter szignifikánsan csökkent mind a hypertoniában, mind a hypertoniában és diabetesben szenvedő betegek csoportjában. A hypertoniás csoporthoz képest a hypertoniában és diabetesben szenvedő csoportban a paraméterek nem különböztek szignifikánsan. Következtetések: Diabetes mellitusban nem szenvedő hypertoniás betegek körében a szívfrekvencia-variabilitás jelentősen beszűkül. Úgy tűnik, hogy hypertoniás betegek körében a 2-es típusú diabetes mellitus szignifikánsan már nem csökkenti tovább a szívfrekvencia-variabilitást. Orv. Hetil., 2014, 155(22), 865–870.

  17. Longitudinal analysis of arterial blood pressure and heart rate response to acute behavioral stress in rats with type 1 diabetes mellitus and in age-matched controls

    Directory of Open Access Journals (Sweden)

    David C. Randall

    2011-08-01

    Full Text Available We recorded via telemetry the arterial blood pressure (BP and heart rate (HR response to classical conditioning following the spontaneous onset of autoimmune diabetes in BBDP/Wor rats versus age-matched, diabetes resistant control (BBDR/Wor rats. Our purpose was to evaluate the autonomic regulatory responses to an acute stress in a diabetic state of up to 12 months duration. The stress was a 15 sec. pulsed tone (CS+ followed by a 0.5 sec. tail shock. The initial, transient increase in BP (i.e., the ‘first component’, or C1, known to be derived from an orienting response and produced by a sympathetic increase in peripheral resistance, was similar in diabetic and control rats through ~9 months of diabetes; it was smaller in diabetic rats 10 months after diabetes onset. Weakening of the C1 BP increase in rats that were diabetic for > 10 months is consistent with the effects of sympathetic neuropathy. A longer-latency, smaller, but sustained ‘second component’ (C2 conditional increase in BP, that is acquired as a rat learns the association between CS+ and the shock, and which results from an increase in cardiac output, was smaller in the diabetic vs. control rats starting from the first month of diabetes. A concomitant HR slowing was also smaller in diabetic rats. The difference in the C2 BP increase, as observed already during the first month of diabetes, is probably secondary to the effects of hyperglycemia upon myocardial metabolism and contractile function, but it may also result from effects on cognition. The small HR slowing concomitant with the C2 pressor event is probably secondary to differences in baroreflex activation or function, though parasympathetic dysfunction may contribute later in the duration of diabetes. The nearly immediate deficit after disease onset in the C2 response indicates that diabetes alters BP and HR responses to external challenges prior to the development of structural changes in the vasculature or autonomic

  18. Impact of disease control and co-existing risk factors on heart rate variability in Gujarati type 2 diabetics: An observational study.

    Science.gov (United States)

    Solanki, Jayesh Dalpatbhai; Basida, Sanket D; Mehta, Hemant B; Panjwani, Sunil J; Gadhavi, Bhakti P; Patel, Pathik

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a proven threat of cardiac dysautonomia with paucity of studies from India. Poor disease control makes it further worse with co-existence of hypertension in majority. Heart rate variability (HRV) is a validated noninvasive tool to assess cardiac autonomic status. We studied HRV parameters of type 2 diabetics looking for effects of disease control and other co-existing risk factors. Ninety-eight hypertensive and forty normotensive under-treatment, Gujarati type 2 diabetics were evaluated for disease control and risk stratification. Five minutes resting, HRV was measured by Variowin HR, software-based instrument, using standard protocols to record time domain, frequency domain, and Poincare plot HRV parameters. They were compared between subgroups for the difference with P < 0.05 defining statistical significance. All HRV parameters were reduced in type 2 diabetics, having mean age 56 years, mean duration 6 years with poor glycemic but comparatively better pressure control. HRV parameters were significantly not different in good compared to poor glycemics or in subjects with optimum pressure control than those without it. Results did not differ significantly, by the presence of individual cardiovascular risk factor in diabetics except resting heart rate. Our findings of HRV suggest that type 2 diabetics with poor glycemic control do not have a significant difference of cardiac dysautonomia by pressure control, glycemic control, and absence of risk cardiovascular factor. It suggests diabetes as a major cause for cardiac dysautonomia, residual risk despite treatment and need for HRV screening, strict glycemic control, and further studies.

  19. Impact of disease control and co-existing risk factors on heart rate variability in Gujarati type 2 diabetics: An observational study

    Directory of Open Access Journals (Sweden)

    Jayesh Dalpatbhai Solanki

    2016-01-01

    Full Text Available Background: Type 2 diabetes mellitus (T2DM is a proven threat of cardiac dysautonomia with paucity of studies from India. Poor disease control makes it further worse with co-existence of hypertension in majority. Heart rate variability (HRV is a validated noninvasive tool to assess cardiac autonomic status. Aim: We studied HRV parameters of type 2 diabetics looking for effects of disease control and other co-existing risk factors. Materials and Methods: Ninety-eight hypertensive and forty normotensive under–treatment, Gujarati type 2 diabetics were evaluated for disease control and risk stratification. Five minutes resting, HRV was measured by Variowin HR, software-based instrument, using standard protocols to record time domain, frequency domain, and Poincare plot HRV parameters. They were compared between subgroups for the difference with P< 0.05 defining statistical significance. Results: All HRV parameters were reduced in type 2 diabetics, having mean age 56 years, mean duration 6 years with poor glycemic but comparatively better pressure control. HRV parameters were significantly not different in good compared to poor glycemics or in subjects with optimum pressure control than those without it. Results did not differ significantly, by the presence of individual cardiovascular risk factor in diabetics except resting heart rate. Conclusion: Our findings of HRV suggest that type 2 diabetics with poor glycemic control do not have a significant difference of cardiac dysautonomia by pressure control, glycemic control, and absence of risk cardiovascular factor. It suggests diabetes as a major cause for cardiac dysautonomia, residual risk despite treatment and need for HRV screening, strict glycemic control, and further studies.

  20. Cardiovascular autonomic neuropathy in insulin-dependent diabetes mellitus: prevalence and estimated risk of coronary heart disease in the general population

    DEFF Research Database (Denmark)

    May, O; Arildsen, H; Damsgaard, E M

    2000-01-01

    OBJECTIVES: The aim of the study was to estimate the prevalence of cardiovascular autonomic neuropathy (CAN) in Type 1 diabetes mellitus in the general population and to assess the relationship between CAN and risk of future coronary heart disease (CHD). METHODS: The Type 1 diabetes mellitus......-R interval in expiration divided by the shortest in inspiration during deep breathing at 6 breaths min(-1) and taken to express the degree of CAN. A maximal symptom-limited exercise test was carried out and the VA Prognostic Score, indicating risk of cardiovascular death or non-fatal myocardial infarction...... = 0.001). Exercise capacity, rise in systolic blood pressure and heart rate were positively correlated with the E/I ratio. A high VA Prognostic Score was correlated with a low E/I ratio (r = - 0.58, P

  1. Genetic evidence for a link between favorable adiposity and lower risk of type 2 diabetes, hypertension and heart disease

    Science.gov (United States)

    Yaghootkar, Hanieh; Lotta, Luca A.; Tyrrell, Jessica; Smit, Roelof A. J.; Jones, Sam E.; Donnelly, Louise; Beaumont, Robin; Campbell, Archie; Tuke, Marcus A.; Hayward, Caroline; Ruth, Katherine S.; Padmanabhan, Sandosh; Jukema, J. Wouter; Palmer, Colin C.; Hattersley, Andrew; Freathy, Rachel M.; Langenberg, Claudia; Wareham, Nicholas J.; Wood, Andrew R.; Murray, Anna; Weedon, Michael N.; Sattar, Naveed; Pearson, Ewan; Scott, Robert A.; Frayling, Timothy M.

    2017-01-01

    Recent genetic studies have identified some alleles associated with higher BMI but lower risk of type 2 diabetes, hypertension and heart disease. These “favorable adiposity” alleles are collectively associated with lower insulin levels and higher subcutaneous-to-visceral adipose tissue ratio and may protect from disease through higher adipose storage capacity. We aimed to use data from 164,609 individuals from the UK Biobank and five other studies to replicate associations between a genetic score of 11 favorable adiposity variants and adiposity and risk of disease, test for interactions between BMI and favorable adiposity genetics and test effects separately in men and women. In the UK Biobank the 50% of individuals carrying the most favorable adiposity alleles had higher BMIs (0.120 Kg/m2 [0.066,0.174]; p=1E-5) and higher body fat percentage (0.301 % [0.230,0.372]; p=1E-16) compared to the 50% of individuals carrying the fewest alleles. For a given BMI, the 50% of individuals carrying the most favourable adiposity alleles were at: 0.837 OR [0.784,0.894] lower risk of type 2 diabetes (p=1E-7), -0.859 mmHg [-1.099,-0.618] lower systolic (p=3E-12) and -0.394 mmHg [-0.534,-0.254] lower diastolic blood pressure (p=4E-8), 0.935 OR [0.911,0.958] lower risk of hypertension (p=1E-7) and 0.921 OR [0.872,0.973] lower risk of heart disease (p=3E-3). In women, these associations could be explained by the observation that the alleles associated with higher BMI but lower risk of disease were also associated with a favourable body fat distribution, with a lower waist-hip ratio (-0.004 [-0.005,-0.003] 50% vs 50%; p=3E-14) but in men, the favourable adiposity alleles were associated with higher waist circumference (0.454 cm [0.267,0.641] 50% vs 50%; p=2E-6) and higher waist-hip ratio (0.0013 [0.0003,0.0024] 50% vs 50%; p=0.01). Results were strengthened when meta-analysing with five additional studies. There was no evidence of interaction between a genetic score consisting of

  2. Lifestyle Intervention Improves Heart Rate Recovery from Exercise in Adults with Type 2 Diabetes: Results from the Look AHEAD Study

    Directory of Open Access Journals (Sweden)

    Paul M. Ribisl

    2012-01-01

    Full Text Available The primary aims of this paper were (1 to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI compared with diabetes support and education (DSE upon Heart Rate Recovery (HRR from graded exercise testing (GXT and (2 to determine the independent and combined effects of weight loss and fitness changes upon HRR. In 4503 participants (45–76 years who completed 1 year of intervention, HRR was measured after a submaximal GXT to compare the influence of (ILI with (DSE upon HRR. Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (P<0.001 while mean fitness increased in ILI by 20.9% versus 5.8% in DSE (P<0.001. At Year 1, all exercise and HRR variables in ILI improved (P<0.0001 versus DSE: heart rate (HR at rest was lower (72.8±11.4 versus 77.7±11.7 b/min, HR range was greater (57.7±12.1 versus 53.1±12.4 b/min, HR at 2 minutes was lower (89.3±21.8 versus 93.0±12.1 b/min, and HRR was greater (41.25±22.0 versus 37.8±12.5 b/min. Weight loss and fitness gain produced significant separate and independent improvements in HRR.

  3. Socioeconomic inequalities in mobility decline in chronic disease groups (asthma/COPD, heart disease, diabetes mellitus, low back pain): only a minor role for disease severity and comorbidity

    OpenAIRE

    2004-01-01

    Objective: This study examined the association between socioeconomic status and mobility decline and whether this could be explained by disease severity and comorbidity in four different chronic disease groups (asthma/COPD, heart disease, diabetes mellitus, and low back pain). It is not clear, whether the adverse course of physical functioning in persons with a low socioeconomic status can be explained by a higher prevalence of more severe disease or comorbidity in these persons.

  4. Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease

    DEFF Research Database (Denmark)

    Thomsen, Stine B; Rathcke, Camilla N; Zerahn, Bo;

    2010-01-01

    Low grade inflammation is of pathogenic importance in atherosclerosis and in the development of cardiovascular disease (CVD) and type 2 diabetes (T2D). Matrix GLA protein (MGP), an inhibitor of medial calcification of arteries, is increased in patients with atherosclerosis. In the present study...... levels of markers of calcification (MGP) and inflammation (YKL-40, hsCRP) were evaluated in patients with T2 D and/or ischemic heart disease (IHD)....

  5. Standardization of an experimental model of parabiotic isolated heart in rabbits Padronização de modelo experimental de coração isolado parabiótico em coelhos

    Directory of Open Access Journals (Sweden)

    Antônio Sérgio Martins

    2000-09-01

    Full Text Available The objective was to standardize an experimental model of parabiotic isolated heart in rabbits, testing their stability and durability for use in cardiovascular research. Sixty-six Norfolk-2000 rabbits were used and divided in 2 groups: donors of the isolated heart and support animals, in a total of 33 preparations. Circulatory support for the isolated heart was established with the aid of peristaltic pumps and the flow was kept constant (16ml/min.. An intraventricular balloon was inserted in the left ventriculum, and was adjusted to produce diastolic pressure of ± 10mmHg. Heart rate was established at 120 beats per minute with the use of a pacemaker. Hemodynamic, laboratory and histopathological parameters were evaluated. Of the 33 preparations, 13 were excluded according to preestablished criteria. Of the 20 remaining preparations, 10 completed the maximum protocol time (180 minutes. There was progressive hemodynamic deterioration with decrease of mean blood pressure (89.30±6.09mmHg->47.50±6.35mmHg in the support animal. There was hemodynamic stability of the isolated heart for the 10 preparations that completed the 180 minutes of the protocol. Laboratory parameters showed progressive decrease of sodium, potassium and hemoglobin, which is compatible with hemodilution. Histopathology showed greater distance among the fibers, compatible with edema. The present model showed 100% stability and activity of the preparations within 60 minutes, and 50% of the active preparations were progressively lost within 180 minutes. The present model is viable for cardiovascular research.O objetivo foi a padronização de modelo experimental de coração isolado parabiótico em coelhos, testando sua estabilidade e durabilidade, para fins de pesquisa cardiovascular. Foram utilizados 66 coelhos raça Norfolk-2000 divididos em grupo doador do coração isolado e animais suporte, totalizando 33 preparações. Mediante auxilio de bombas peristálticas estabeleceu

  6. Relationships between serum MCP-1 and subclinical kidney disease: African American-Diabetes Heart Study

    Directory of Open Access Journals (Sweden)

    Murea Mariana

    2012-11-01

    Full Text Available Abstract Background Monocyte chemoattractant protein-1 (MCP-1 plays important roles in kidney disease susceptibility and atherogenesis in experimental models. Relationships between serum MCP-1 concentration and early nephropathy and subclinical cardiovascular disease (CVD were assessed in African Americans (AAs with type 2 diabetes (T2D. Methods Serum MCP-1 concentration, urine albumin:creatinine ratio (ACR, estimated glomerular filtration rate (eGFR, and atherosclerotic calcified plaque (CP in the coronary and carotid arteries and infrarenal aorta were measured in 479 unrelated AAs with T2D. Generalized linear models were fitted to test for associations between MCP-1 and urine ACR, eGFR, and CP. Results Participants were 57% female, with mean ± SD (median age 55.6±9.5 (55.0 years, diabetes duration 10.3±8.2 (8.0 years, urine ACR 149.7±566.7 (14.0 mg/g, CKD-EPI eGFR 92.4±23.3 (92.0 ml/min/1.73m2, MCP-1 262.9±239.1 (224.4 pg/ml, coronary artery CP 280.1±633.8 (13.5, carotid artery CP 47.1±132.9 (0, and aorta CP 1616.0±2864.0 (319.0. Adjusting for age, sex, smoking, HbA1c, BMI, and LDL, serum MCP-1 was positively associated with albuminuria (parameter estimate 0.0021, P=0.04 and negatively associated with eGFR (parameter estimate −0.0003, P=0.001. MCP-1 remained associated with eGFR after adjustment for urine ACR. MCP-1 levels did not correlate with the extent of CP in any vascular bed, HbA1c or diabetes duration, but were positively associated with BMI. No interaction between BMI and MCP-1 was detected on nephropathy outcomes. Conclusions Serum MCP-1 levels are associated with eGFR and albuminuria in AAs with T2D. MCP-1 was not associated with subclinical CVD in this population. Inflammation appears to play important roles in development and/or progression of kidney disease in AAs.

  7. 不同浓度瑞芬太尼对家兔心肌单相动作电位的影响%Effects of different concentrations of remifentanil on monophasic action potential in isolated rabbit hearts

    Institute of Scientific and Technical Information of China (English)

    刘艳秋; 高鸿; 张凯强; 安丽; 李惠; 熊永红

    2016-01-01

    目的 评价不同浓度瑞芬太尼对家兔心肌单相动作电位的影响.方法 成年家兔,体重2.0~2.5 kg,雌雄不拘,成功制备Langendorff离体心脏灌注模型24个,采用随机数字表法,将其分为4组(n=6):对照组(C组)和不同浓度瑞芬太尼组(R1组、R2组和R3组).平衡灌注15 min时C组继续灌注K-H液60 min;R1组-R3组分别灌注含12、25、50 ng/ml瑞芬太尼的K-H液60 min.记录平衡灌注15 min、继续灌注15、30、60 min时HR、左心室前壁三层心肌单相动作电位0期最大上升速率(Vmax)、振幅(MAPA),计算动作电位复极90%的时程(APD90)和跨室壁复极离散度(TDR).结果 与C组比较,R1组-R3组继续灌注15、30、60 min时HR减慢,APD90和TDR延长(P<0.05);与C组和R1组比较,R2组和R3组继续灌注15、30、60 min时Vmax减慢,MAPA降低(P<0.05).结论 低浓度瑞太芬尼通过增加家兔心肌单相动作电位TDR诱发心脏传导阻滞,而高浓度瑞太芬尼通过抑制家兔心肌单相动作电位去极和增加TDR诱发心脏传导阻滞.%Objective To evaluate the effects of different concentrations of remifentanil on myocardial monophasic action potential (MAP) in isolated rabbit hearts.Methods Adult rabbits of both sexes,weighing 2.0-2.5 kg,were used in the study.Their hearts were excised,and retrogradely perfused with oxygenated K-H solution saturated with 95%O2-5%CO2 at 37 ℃ in a Langendorff apparatus.Twenty-four isolated hearts were randomly divided into 4 groups (n =6 each) using a random number table:control group (group C) and 3 different concentrations of remifentanil groups (group R1-3).After 15 min of stabilization,K-H solution was continuously perfused for 60 min in group C,and K-H solution containing 12,25 and 50 ng/ml remifentanil was continuously perfused for 60 min in R1,R2 and R3 groups,respectively.At 15 min of stabilization,and 15,30 and 60 min of perfusion with K-H solution,the heart rate,and the maximal velocity and amplitude of the

  8. Gap junction modifier rotigaptide decreases the susceptibility to ventricular arrhythmia by enhancing conduction velocity and suppressing discordant alternans during therapeutic hypothermia in isolated rabbit hearts

    DEFF Research Database (Denmark)

    Hsieh, Yu-Cheng; Lin, Jiunn-Cherng; Hung, Chen-Ying

    2016-01-01

    ) and 30°C (P = .042). Rotigaptide did not change connexin43 expressions and distributions during hypothermia. CONCLUSION: Rotigaptide protects the hearts against ventricular arrhythmias by increasing ventricular CV, delaying the onset of SDA, and reducing repolarization heterogeneity during TH. Enhancing...

  9. Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

    Directory of Open Access Journals (Sweden)

    Amy Botta

    Full Text Available PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα and systemic (circulating chemokines and cytokines inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.

  10. Healing the diabetic heart: modulation of cardiometabolic syndrome through peroxisome proliferator activated receptors (PPARs).

    Science.gov (United States)

    Huang, Tom Hsun-Wei; Roufogalis, Basil D

    2012-06-01

    Cardiometabolic syndrome is a mixture of interrelated risk factors predisposing individuals to elevated risk of atherosclerotic cardiovascular disease and type 2 diabetes mellitus. Nuclear receptors, specifically peroxisome proliferator-activated receptors (PPARs), were identified to play a pivotal role in the regulation of metabolic homeostasis. However, with rosiglitazone currently under intense scrutiny great concerns have arisen regarding the safety of the thiazolidinedione PPAR-γ agonist family as a whole. This review discusses the current concern with PPAR-γ agonists by exploring if PPARs can still be considered worth pursuing as a viable target for cardiovascular diseases. We examine current research focusing on identifying ligands that are dual and pan-PPAR agonists, selective PPAR-γ modulators, PPAR-β/δ agonists and that are of natural origin.

  11. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

    2012-01-15

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

  12. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death

    DEFF Research Database (Denmark)

    Almdal, Thomas; Scharling, Henrik; Jensen, Jan Skov

    2004-01-01

    , admission for, or death from ischemic heart disease, acute myocardial infarction, or stroke, as well as total mortality in persons with type 2 DM compared with healthy controls, were estimated. RESULTS: The relative risk of first, incident, and admission for myocardial infarction was increased 1.5- to 4.......5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. The relative risk of first, incident, and admission for stroke was increased 2- to 6.5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. In both women and men the relative risk...... of death was increased 1.5 to 2 times. CONCLUSIONS: In persons with type 2 DM, the risk of having an incident myocardial infarction or stroke is increased 2- to 3-fold and the risk of death is increased 2-fold, independent of other known risk factors for cardiovascular diseases....

  13. [Association of I/D and -786 Polymorphisms of ACE and NOS3 Genes With Features of the Course of Ischemic Heart Disease and Diabetes Mellitus Type 2].

    Science.gov (United States)

    Afanasiev, S A; Muslimova, E F; Rebrov, T Y; Sergienko, T N; Repin, A N

    2016-09-01

    to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

  14. Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study.

    Science.gov (United States)

    Hanley, Anthony J G; Williams, Ken; Gonzalez, Clicerio; D'Agostino, Ralph B; Wagenknecht, Lynne E; Stern, Michael P; Haffner, Steven M

    2003-02-01

    To determine and formally compare the ability of simple indexes of insulin resistance (IR) to predict type 2 diabetes, we used combined prospective data from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study, which include well-characterized cohorts of non-Hispanic white, African-American, Hispanic American, and Mexican subjects with 5-8 years of follow-up. Poisson regression was used to assess the ability of each candidate index to predict incident diabetes at the follow-up examination (343 of 3,574 subjects developed diabetes). The areas under the receiver operator characteristic (AROC) curves for each index were calculated and statistically compared. In pooled analysis, Gutt et al.'s insulin sensitivity index at 0 and 120 min (ISI(0,120)) displayed the largest AROC (78.5%). This index was significantly more predictive (P < 0.0001) than a large group of indexes (including those by Belfiore, Avignon, Katz, and Stumvoll) that had AROC curves between 66 and 74%. These findings were essentially similar both after adjustment for covariates and when analyses were conducted separately by glucose tolerance status and ethnicity/study subgroups. In conclusion, we found substantial differences between published IR indexes in the prediction of diabetes, with ISI(0,120) consistently showing the strongest prediction. This index may reflect other aspects of diabetes pathogenesis in addition to IR, which might explain its strong predictive abilities despite its moderate correlation with direct measures of IR.

  15. Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease.

    Science.gov (United States)

    Rehkopf, David H; Eisen, Ellen A; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F; Slade, Martin D; Cullen, Mark R

    2015-08-01

    We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

  16. Whole grains, type 2 diabetes, coronary heart disease, and hypertension: links to the aleurone preferred over indigestible fiber.

    Science.gov (United States)

    Lillioja, Stephen; Neal, Andrew L; Tapsell, Linda; Jacobs, David R

    2013-01-01

    Higher whole grain cereal intakes are associated with substantially lower risks of type 2 diabetes, coronary heart disease, and hypertension. These reduced risks have been established in large prospective studies that now include millions of person-years of follow-up. We analyze the results of 11 major prospective studies to provide recommendations about whole grain consumption. The following review establishes the amount of whole grains that should ideally be consumed based on prospective evidence; defines the nature of whole grains; identifies that the whole grain evidence is robust and not due to confounding; and provides a detailed assessment of several potential mechanisms for the effect of whole grains on health. We draw the following conclusions. Firstly, to maintain health, 40 grams or more of whole grains should be consumed daily. This is about a bowl of whole grain breakfast cereal daily, but 80% of the population does not achieve this. Secondly, aleurone in bran is a critical grain component generally overlooked in favor of indigestible fiber. Live aleurone cells constitute 50% of millers' bran. They store minerals, protein, and the antioxidant ferulic acid, and are clearly more than just indigestible fiber. Finally, we suggest potential roles for magnesium, zinc, and ferulic acid in the development of chronic disease. If the results of prospective studies were applied to the life-style practices of modern societies there exists the potential for enormous personal health and public financial benefits.

  17. Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: the Kuopio Ischemic Heart Disease Risk Factor study.

    Science.gov (United States)

    Virtanen, Jyrki K; Mursu, Jaakko; Voutilainen, Sari; Uusitupa, Matti; Tuomainen, Tomi-Pekka

    2014-01-01

    OBJECTIVE The relationship between fish or omega-3 polyunsaturated fatty acids (PUFAs) and type 2 diabetes is inconclusive. Even contaminants in fish, such as mercury, may modify the effects. We investigated the associations between serum omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), hair mercury, and risk of incident type 2 diabetes in middle-aged and older Finnish men. RESEARCH DESIGN AND METHODS A total of 2,212 men from the prospective, population-based Kuopio Ischemic Heart Disease Risk Factor study, aged 42-60 years and free of type 2 diabetes at baseline in 1984-1989, were investigated. Serum PUFA and hair mercury were used as biomarkers for exposure. Dietary intakes were assessed with 4-day food recording. Type 2 diabetes was assessed by self-administered questionnaires and fasting and 2-h oral glucose tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 years after the baseline and by record linkage to hospital discharge registry and reimbursement register on diabetes medication expenses. Cox proportional hazards models were used to analyze associations. RESULTS During the average follow-up of 19.3 years, 422 men developed type 2 diabetes. Men in the highest versus the lowest serum EPA + DPA + DHA quartile had 33% lower multivariate-adjusted risk for type 2 diabetes (95% CI 13-49; P trend 0.01). No statistically significant associations were observed with serum or dietary ALA, dietary fish or EPA + DHA, or hair mercury. CONCLUSIONS Serum long-chain omega-3 PUFA concentration, an objective biomarker for fish intake, was associated with long-term lower risk of type 2 diabetes.

  18. Diabetes.

    Science.gov (United States)

    Lomberk, Gwen

    2009-01-01

    Pancreatologists have often divided research of the pancreas based upon the origin of the function or disease, namely the endocrine or exocrine pancreas. In fact, as a result, many of our meetings and conferences have followed separate paths. Interestingly, among patients with chronic pancreatitis and pancreatic cancer, both disorders of the exocrine pancreas, diabetes is common. However, the clinical features of the diabetes associated with these two differ. Peripheral insulin resistance and hyperinsulinemia are the predominant diabetic traits in pancreatic cancer, while reduced islet cell mass and impaired insulin secretion are observed more often in chronic pancreatitis. The causal relationship between diabetes and pancreatic cancer remains an intriguing but unanswered question. Since diabetes often precedes pancreatic cancer, it is regarded as a potential risk factor for malignancy. On the other hand, there remains the possibility that pancreatic cancer secretes diabetogenic factors. Regardless of how the science ultimately illuminates this issue, there is increasing interest in utilizing screening for diabetes to aid early detection of pancreatic tumor lesions. Therefore, in this issue of Pancreatology and the Web, we explore the topic of diabetes to keep us alert to this very important association, even if we study diseases of the exocrine pancreas.

  19. Effect of acute hyperglycemia on left ventricular contractile function in diabetic patients with and without heart failure: two randomized cross-over studies.

    Directory of Open Access Journals (Sweden)

    Roni Nielsen

    Full Text Available It is unknown whether changes in circulating glucose levels due to short-term insulin discontinuation affect left ventricular contractile function in type 2 diabetic patients with (T2D-HF and without (T2D-nonHF heart failure.In two randomized cross-over-designed trials, 18 insulin-treated type 2 diabetic patients with (Ejection Fraction (EF 36 ± 6%, n = 10 (trial 2 and without systolic heart failure (EF 60 ± 3%, n = 8 (trial 1 were subjected to hyper- and normoglycemia for 9-12 hours on two different occasions. Advanced echocardiography, bicycle exercise tests and 6-minute hall walk distance were applied.Plasma glucose levels differed between study arms (6.5 ± 0.8 mM vs 14.1 ± 2.6 mM (T2D-HF, 5.8 ± 0.4 mM vs 9.9 ± 2.1 mM (T2D-nonHF, p<0.001. Hyperglycemia was associated with an increase in several parameters: maximal global systolic tissue velocity (Vmax (p<0.001, maximal mitral annulus velocity (S'max (p<0.001, strain rate (p = 0.02 and strain (p = 0.05. Indices of increased myocardial systolic contractile function were significant in both T2D-HF (Vmax: 14%, p = 0.02; S'max: 10%, p = 0.04, T2D-nonHF (Vmax: 12%, p<0.01; S'max: 9%, p<0.001 and in post exercise S'max (7%, p = 0.049 during hyperglycemia as opposed to normoglycemia. LVEF did not differ between normo- and hyperglycemia (p = 0.17, and neither did peak exercise capacity nor catecholamine levels. Type 2 diabetic heart failure patients' 6-minute hall walk distance improved by 7% (p = 0.02 during hyperglycemia as compared with normoglycemia.Short-term hyperglycemia by insulin discontinuation is associated with an increase in myocardial systolic contractile function in type 2 diabetic patients with and without heart failure and with a slightly prolonged walking distance in type 2 diabetic heart failure patients. (Clinicaltrials.gov identifier NCT00653510.

  20. Diabetes

    DEFF Research Database (Denmark)

    Damm, Peter; Mathiesen, Elisabeth R

    2015-01-01

    For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women with gestat......For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women...... with gestational diabetes mellitus is highly relevant....

  1. Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer.

    Science.gov (United States)

    Roche, T E; Hiromasa, Y

    2007-04-01

    The fraction of pyruvate dehydrogenase complex (PDC) in the active form is reduced by the activities of dedicated PD kinase isozymes (PDK1, PDK2, PDK3 and PDK4). Via binding to the inner lipoyl domain (L2) of the dihydrolipoyl acetyltransferase (E2 60mer), PDK rapidly access their E2-bound PD substrate. The E2-enhanced activity of the widely distributed PDK2 is limited by dissociation of ADP from its C-terminal catalytic domain, and this is further slowed by pyruvate binding to the N-terminal regulatory (R) domain. Via the reverse of the PDC reaction, NADH and acetyl-CoA reductively acetylate lipoyl group of L2, which binds to the R domain and stimulates PDK2 activity by speeding up ADP dissociation. Activation of PDC by synthetic PDK inhibitors binding at the pyruvate or lipoyl binding sites decreased damage during heart ischemia and lowered blood glucose in insulin-resistant animals. PDC activation also triggers apoptosis in cancer cells that selectively convert glucose to lactate.

  2. Differences between left and right ventricular anatomy determine the types of reentrant circuits induced by an external electric shock. A rabbit heart simulation study.

    Science.gov (United States)

    Rodríguez, Blanca; Eason, James C; Trayanova, Natalia

    2006-01-01

    Despite the fact that elucidating the mechanisms of cardiac vulnerability to electric shocks is crucial to understanding why defibrillation shocks fail, important aspects of cardiac vulnerability remain unknown. This research utilizes a novel anatomically based bidomain finite-element model of the rabbit ventricles to investigate the effect of shock polarity reversal on the reentrant activity induced by an external defibrillation-strength shock in the paced ventricles. The specific goal of the study is to examine how differences between left and right ventricular chamber anatomy result in differences in the types of reentrant circuits established by the shock. Truncated exponential monophasic shocks of duration 8 ms were delivered via two external electrodes at various timings. Vulnerability grids were constructed for shocks of reversed polarity (referred to as RV- or LV- when either the RV or the LV electrode is a cathode). Our results demonstrate that reversing electrode polarity from RV- to LV- changes the dominant type of post-shock reentry: it is figure-of-eight for RV- and quatrefoil for LV- shocks. Differences in secondary types of post-shock arrhythmia also occur following shock polarity reversal. These effects of polarity reversal are primarily due to the fact that the LV wall is thicker than the RV, resulting in a post-shock excitable gap that is predominantly within the LV wall for RV- shocks and in the septum for LV- shocks.

  3. Diabetes

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for diabetes. The data is provided by three managed care organizations in Allegheny County (Gateway Health Plan,...

  4. Age, gender, insulin and blood glucose control status alter the risk of ischemic heart disease and stroke among elderly diabetic patients

    Directory of Open Access Journals (Sweden)

    Hattori Yoshiyuki

    2011-10-01

    Full Text Available Abstract Background We analyzed the effects of insulin therapy, age and gender on the risk of ischemic heart disease (IHD and cerebrovascular accident (CVA according to glycemic control. Methods and Results We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study of type 2 diabetes patients (n = 4014 for 2 years. The primary endpoint was the onset of fatal/non-fatal IHD and/or CVA, which occurred at rates of 7.9 and 7.2 per 1000 person-years, respectively. We divided diabetic patients into four groups based on age (≤ 70 and > 70 and hemoglobin A1C levels (≤ 7.0 and > 7.0%. Multiple regression analysis revealed that IHD was associated with high systolic blood pressure and low HDL-C in patients under 70 years of age with fair glycemic control and was associated with low diastolic blood pressure in the older/fair group. Interestingly, insulin use was associated with IHD in the older/poor group (OR = 2.27, 95% CI = 1.11-5.89; p = 0.026 and was associated with CVA in the older/fair group (OR = 2.09, 95% CI = 1.06-4.25; p = 0.028. CVA was associated with lower HDL-C and longer duration of diabetes in younger/poor glycemic control group. Results by stepwise analysis were similar. Next, patients were divided into four groups based on gender and diabetic control(hemoglobinA1C 7.0%. Multiple regression analysis revealed that IHD was associated with high systolic blood pressure in male/fair glycemic control group, age in male/poor control group, and short duration of diabetic history in females in both glycemic control groups. Interestingly, insulin use was associated with IHD in the male/poor group(OR = 4.11, 95% CI = 1.22-8.12; p = 0.018 and with CVA in the female/poor group(OR = 3.26, 95% CI = 1.12-6.24; p = 0.02. CVA was associated with short duration of diabetes in both female groups. Conclusions IHD and CVA risks are affected by specific factors in diabetics, such as treatment, gender and age. Specifically, insulin

  5. Age, gender, insulin and blood glucose control status alter the risk of ischemic heart disease and stroke among elderly diabetic patients

    Science.gov (United States)

    2011-01-01

    Background We analyzed the effects of insulin therapy, age and gender on the risk of ischemic heart disease (IHD) and cerebrovascular accident (CVA) according to glycemic control. Methods and Results We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study) of type 2 diabetes patients (n = 4014) for 2 years. The primary endpoint was the onset of fatal/non-fatal IHD and/or CVA, which occurred at rates of 7.9 and 7.2 per 1000 person-years, respectively. We divided diabetic patients into four groups based on age (≤ 70 and > 70) and hemoglobin A1C levels (≤ 7.0 and > 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure and low HDL-C in patients under 70 years of age with fair glycemic control and was associated with low diastolic blood pressure in the older/fair group. Interestingly, insulin use was associated with IHD in the older/poor group (OR = 2.27, 95% CI = 1.11-5.89; p = 0.026) and was associated with CVA in the older/fair group (OR = 2.09, 95% CI = 1.06-4.25; p = 0.028). CVA was associated with lower HDL-C and longer duration of diabetes in younger/poor glycemic control group. Results by stepwise analysis were similar. Next, patients were divided into four groups based on gender and diabetic control(hemoglobinA1C 7.0%). Multiple regression analysis revealed that IHD was associated with high systolic blood pressure in male/fair glycemic control group, age in male/poor control group, and short duration of diabetic history in females in both glycemic control groups. Interestingly, insulin use was associated with IHD in the male/poor group(OR = 4.11, 95% CI = 1.22-8.12; p = 0.018) and with CVA in the female/poor group(OR = 3.26, 95% CI = 1.12-6.24; p = 0.02). CVA was associated with short duration of diabetes in both female groups. Conclusions IHD and CVA risks are affected by specific factors in diabetics, such as treatment, gender and age. Specifically, insulin use has a potential

  6. Heart Disease, Hypertension, Gestational Diabetes Mellitus, and Preeclampsia/Eclampsia in Mothers With Juvenile Arthritis: A Nested Case-Control Study.

    Science.gov (United States)

    Feldman, Debbie E; Vinet, Évelyne; Bérard, Anick; Duffy, Ciarán; Hazel, Beth; Meshefedjian, Garbis; Sylvestre, Marie-Pierre; Bernatsky, Sasha

    2017-02-01

    To determine whether women with a history of juvenile arthritis are at higher risk for heart disease and hypertension and for developing adverse maternal outcomes: gestational diabetes mellitus, maternal hypertension, and preeclampsia/eclampsia. We designed a nested case-control study from a cohort of first-time mothers with prior physician billing codes suggesting juvenile arthritis, and a matched comparison group without juvenile arthritis. For the nested case-control design, we selected 3 controls for each case for the outcomes of heart disease (n = 403), prepregnancy hypertension (n = 66), gestational diabetes mellitus (n = 285), maternal hypertension (n = 561), and preeclampsia/eclampsia (n = 236). We used conditional logistic regression, adjusting for maternal age and education. Having juvenile arthritis was associated with heart disease (odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.15-5.15]) but not with gestational hypertension, diabetes mellitus, or preeclampsia/eclampsia. All 66 cases of prepregnancy hypertension had juvenile arthritis. Having prepregnancy hypertension was strongly associated with preeclampsia/eclampsia (OR 8.05 [95% CI 2.69-24.07]). Women with a history of juvenile arthritis had a higher risk of heart disease. This risk signals the potential importance of cardiac prevention strategies in juvenile arthritis. As this was a retrospective study, it was not possible to correct for some relevant potential confounders. Further studies should assess the impact of medications, disease severity, and other factors (e.g., obesity) on cardiac outcomes in juvenile arthritis. © 2016, American College of Rheumatology.

  7. Association of the consumption of common food groups and beverages with mortality from cancer, ischaemic heart disease and diabetes mellitus in Serbia, 1991-2010: an ecological study.

    Science.gov (United States)

    Ilic, Milena; Ilic, Irena; Stojanovic, Goran; Zivanovic-Macuzic, Ivana

    2016-01-05

    This paper reports association between mortality rates from cancer, ischaemic heart disease and diabetes mellitus and the consumption of common food groups and beverages in Serbia. In this ecological study, data on both mortality and the average annual consumption of common food groups and beverages per household's member were obtained from official data-collection sources. The multivariate linear regression analysis was used to determine the strength of the associations between consumption of common food groups and beverages and mortality rates. Markedly increasing trends of cancer, ischaemic heart disease and diabetes mellitus mortality rates were observed in Serbia in the period 1991-2010. Mortality rates from cancer were negatively associated with consumption of vegetable oil (p=0.005) and grains (p=0.001), and same was found for ischaemic heart disease (p=0.002 and 0.021, respectively), while consumption of other dairy products showed a significant positive association (pconsumption of poultry (p=0.014 and 0.004, respectively). Consumption of beef and grains showed a significant negative association with cancer mortality rates in both genders (p=0.002 and pconsumption of cheese was negatively associated only in men (pconsumption of animal fat and other dairy products only in women (p=0.003 and 0.046, respectively). Association between unfavourable mortality trends from cancer, ischaemic heart disease and diabetes mellitus, and common food groups and beverages consumption was observed and should be assessed in future analytical epidemiological studies. Promotion of healthy diet is sorely needed in Serbia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  8. Insulin provision therapy and mortality in older adults with diabetes mellitus and stable ischemic heart disease: Insights from BARI-2D trial.

    Science.gov (United States)

    Damluji, Abdulla A; Cohen, Erin R; Moscucci, Mauro; Myerburg, Robert J; Cohen, Mauricio G; Brooks, Maria M; Rich, Michael W; Forman, Daniel E

    2017-08-15

    Optimal strategies for glucose control in very old adults with diabetes and stable ischemic heart disease (SIHD) are unclear. To compare the effects of insulin provision (IP) therapy versus insulin sensitizing (IS) therapy for glycemic control in older (≥75years) and younger (diabetes (DM) and SIHD. Adults enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) were studied. The BARI 2D study population (all with type II DM and SIHD) was randomized twice: (1) between revascularization plus intensive medical therapy versus intensive medical therapy alone, and (2) between IP versus IS therapies. The primary endpoint was all-cause-mortality over five-year follow-up. In this substudy outcomes related to IP vs. IS are assessed in relation to age. Adults aged ≥75years who received IP versus IS are compared to those history of heart failure. Within the older cohort, the IP and IS subgroups were similar in respect to baseline cardiovascular risk factors, medications, and coronary artery disease severity. During follow-up, the older subjects receiving IP therapy had higher cardiovascular mortality compared to those receiving IS therapy (16% vs. 11%, p=0.040). Using Cox proportional hazards analysis, the older IP subjects were at increased risk for all-cause-mortality (hazard ratio 1.89, CI 1.1-3.2, p=0.020). No mortality difference between IP and IS was observed in those diabetes and SIHD aged ≥75years, IP therapy may be associated with increased mortality compared to IS therapy. Additional studies are needed to further refine optimal treatment strategies for diabetes and SIHD in old age. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  9. Effects of hypothermia combined with dexmedetomidine on myocardial monophasic action potentials in isolated rabbit hearts%低温联合右美托咪定对兔心肌单相动作电位的影响

    Institute of Scientific and Technical Information of China (English)

    李惠; 高鸿; 赵艳; 龙娟; 张凯强; 刘艳秋

    2015-01-01

    Objective To investigate the effects of hypothermia combined with dexmedetomidine on myocardial monophasic action potentials (MAPs) in isolated rabbit hearts.Methods Adult rabbits,weighing 2.0-2.5 kg,were heparinized and anesthetized with pentobarbital sodium 30 mg/kg.Their hearts were rapidly removed and retrogradely perfused in a Langendorff apparatus at 37 ℃.Eighteen hearts were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C),hypothermia group (group H),and hypothermia+dexmedetomidine group (group HD).The hearts were continuously perfused for 60 min with 37 ℃ K-H solution in group C,with 32 ℃ K-H solution in group H,or with 32 ℃ K-H solution containing dexmedetomidine 25 ng/ml in group HD.At the end of equilibration (T0) and at 15,30 and 60 min of perfusion with K-H solution,HR and MAPs of left ventricular epicardium,mid-myocardium and endocardium were recorded.MAP duration at 50% repolarization (MAPD50) and at 90% repolarization (MAPD90),monophasic action potential amplitude (MAPA) and maximal velocity (Vmax) were calculated.Results Compared with group C,HR was significantly decreased,and MAPD50 and MAPD90 were prolonged at each time of perfusion with K-H solution in H and HD groups.There was no significant difference in HR,MAPD50 and MAPD90 between H group and HD group.There was no significant difference in MAPA and Vmax between the three groups.Conclusion Hypothermia combined with dexmedetomidine can lead to prolongation of myocardial repolarization,and dexmedetomidine exerts no effect on hypothermia-induced change in MAPs in isolated rabbit hearts.%目的 探讨低温联合右美托咪定对兔心肌单相动作电位的影响.方法 成年家兔,体重2.0~ 2.5 kg,制备Langendorff离体心脏灌注模型,取模型制备成功的心脏18个,采用随机数字表法分为3组(n=6):正常对照组(C组)、低温组(H组)和低温+右美托咪定组(HD组).C组继续灌注37℃K-H液60 min

  10. Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Ferdinand, Keith C; White, William B; Calhoun, David A; Lonn, Eva M; Sager, Philip T; Brunelle, Rocco; Jiang, Honghua H; Threlkeld, Rebecca J; Robertson, Kenneth E; Geiger, Mary Jane

    2014-10-01

    Glucagon-like peptide-1 receptor agonists, used to treat type 2 diabetes mellitus, are associated with small reductions in systolic blood pressure (SBP) and increases in heart rate. However, findings based on clinic measurements do not adequately assess a drug's 24-hour pharmacodynamic profile. The effects of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, on BP and heart rate were investigated using ambulatory BP monitoring. Patients (n=755; 56±10 years; 81% white; 48% women), with type 2 diabetes mellitus, taking ≥1 oral antihyperglycemic medication, with a clinic BP between 90/60 and 140/90 mm Hg were randomized to dulaglutide (1.5 or 0.75 mg) or placebo subcutaneously for 26 weeks. Ambulatory BP monitoring was performed at baseline and at 4, 16, and 26 weeks. The primary end point was change from baseline to week 16 in mean 24-hour SBP, a tree gatekeeping strategy compared the effects of dulaglutide to placebo. Both doses of dulaglutide were noninferior to placebo for changes in 24-hour SBP and diastolic blood pressure, and dulaglutide 1.5 mg significantly reduced SBP (least squares mean difference [95% confidence interval]), -2.8 mm Hg [-4.6, -1.0]; P≤0.001). Dulaglutide 0.75 mg was noninferior to placebo (1.6 bpm; [0.3, 2.9]; P≤0.02) for 24-hour heart rate (least squares mean difference [95% confidence interval]), but dulaglutide 1.5 mg was not (2.8 bpm [1.5, 4.2]). Dulaglutide 1.5 mg was associated with a reduction in 24-hour SBP and an increase in 24-hour heart rate. The mechanisms responsible for the observed effects remain to be clarified. © 2014 American Heart Association, Inc.

  11. Analysis of thrombelastography in type 2 diabetes patients complicated with angina pectoris of coronary heart disease and its correlation with disease severity

    Institute of Scientific and Technical Information of China (English)

    Hong-Hong Liu; Zhao-Chuan Liu; Hong-Tao Liu; Yu-Ji Zhang; Qing-Ling Fu; Jun-Ling Wang

    2016-01-01

    Objective:To analyze the thrombelastography parameters in type 2 diabetes patients complicated with angina pectoris of coronary heart disease and their correlation with disease severity.Methods:30 cases of healthy volunteers, 30 cases of patients with simple angina pectoris of coronary heart disease (CHD) and 30 cases of type 2 diabetes patients complicated with angina pectoris of coronary heart disease were selected for study. Thrombelastography parameters R value, K value, αangle and MA value as well as inflammation-associated molecules YKL-40 and NK-kB expression were detected.Results:R values and K values of simple CHD group and diabetes complicated with CHD group were lower than those of control group, and αangle and MA values were higher than those of control group; R values and K values of diabetes complicated with CHD group were lower than those of simple CHD group, and αangle and MA values were higher than those of simple CHD group; R values and K values of 2 branch lesions group and 3 branch lesions group were lower than those of 1 branch lesion group, and αangle and MA values as well as YKL-40 and NK-kB contents were higher than those of 1 branch lesion group; R values and K values of 3 branch lesions group were lower than those of 2 branch lesions group, and αangle and MA values as well as YKL-40 and NK-kB contents were higher than those of 2 branch lesions group; R value and K value were negatively correlated with YKL-40 and NK-kB contents, and αangle and MA value were positively correlated with YKL-40 and NK-kB contents.Conclusions: Thrombelastography parameters in type 2 diabetes patients complicated with angina pectoris of coronary heart disease are significantly abnormal, and R value, K value, αangle and MA value can reflect disease severity and inflammation degree.

  12. Physical activity and life expectancy with and without diabetes: life table analysis of the Framingham Heart Study

    NARCIS (Netherlands)

    J.T. Jonker; C.E.D. de Laet (Chris); O.H. Franco (Oscar); A. Peeters (Anna); W.J. Nusselder (Wilma); J.P. Mackenbach (Johan)

    2006-01-01

    textabstractOBJECTIVE: Physical activity is associated with a reduced risk of developing diabetes and with reduced mortality among diabetic patients. However, the effects of physical activity on the number of years lived with and without diabetes are unclear. Our aim is to

  13. Heart rate variability and plasma biomarkers in patients with type 1 diabetes mellitus: Effect of a bout of aerobic exercise.

    Science.gov (United States)

    Anaruma, Chadi P; Ferreira, Maycon; Sponton, Carlos H G; Delbin, Maria A; Zanesco, Angelina

    2016-01-01

    The aim of this study was to evaluate: (1) the cardiovascular parameters and plasma biomarkers in people with type 1 diabetes mellitus (T1DM) at baseline; and (2) the heart rate variability (HRV) and blood glucose in response to a session of aerobic exercise (AE) and during recovery period. Adults (18-35 years) were divided into two groups: control (CT, n=10) and T1DM (n=9). Anthropometric, cardiovascular, and biochemical parameters, and aerobic capacity (indirect peak oxygen uptake, VO2peak) were evaluated at baseline. Thirty minutes of AE (40-60% intensity) was performed on a treadmill. Blood glucose and HRV were determined at rest, during AE, and during the recovery period. Anthropometric measurements, cardiovascular parameters, aerobic capacity, and biochemical parameters were similar between the groups at baseline. In the T1DM group, blood glucose, glycated hemoglobin, and thiobarbituric acid reactive substances concentrations were increased while nitrite/nitrate (NOx(-)) levels were reduced. During AE, the magnitude of the reduction of blood glucose was greater than that during the recovery period in the T1DM group. The RR intervals and SDNN were reduced at rest as well as in the recovery period in T1DM subjects, whereas the RMSSD and pNN50 were only reduced during the recovery period. No changes were observed in low frequency (LF), high frequency (HF), and LF/HF ratio. Our study shows that T1DM patients on insulin therapy have poor blood glucose control with greater lipid peroxidation and lower NOx(-) levels, accompanied by an imbalance in autonomic function detected by the challenge of AE. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. (-)-Epicatechin rich cocoa mediated modulation of oxidative stress regulators in skeletal muscle of heart failure and type 2 diabetes patients.

    Science.gov (United States)

    Ramirez-Sanchez, Israel; Taub, Pam R; Ciaraldi, Theodore P; Nogueira, Leonardo; Coe, Taylor; Perkins, Guy; Hogan, Michael; Maisel, Alan S; Henry, Robert R; Ceballos, Guillermo; Villarreal, Francisco

    2013-10-09

    Type 2 diabetes (T2D) and heart failure (HF) are associated with high levels of skeletal muscle (SkM) oxidative stress (OS). Health benefits attributed to flavonoids have been ascribed to antioxidation. However, for flavonoids with similar antioxidant potential, end-biological effects vary widely suggesting other mechanistic venues for reducing OS. Decreases in OS may follow the modulation of key regulatory pathways including antioxidant levels (e.g. glutathione) and enzymes such as mitochondrial superoxide dismutase (SOD2) and catalase. We examined OS-related alterations in SkM in T2D/HF patients (as compared vs. healthy controls) and evaluated the effects of three-month treatment with (-)-epicatechin (Epi) rich cocoa (ERC). To evidence Epi as the mediator of the improved OS profile we examined the effects of pure Epi (vs. water) on SkM OS regulatory systems in a mouse model of insulin resistance and contrasted results vs. normal mice. There were severe alterations in OS regulatory systems in T2D/HF SkM as compared with healthy controls. Treatment with ERC induced recovery in glutathione levels and decreases in the nitrotyrosilation and carbonylation of proteins. With treatment, key transcriptional factors translocate into the nucleus leading to increases in SOD2 and catalase protein expression and activity levels. In insulin resistant mice, there were alterations in muscle OS and pure Epi replicated the beneficial effects of ERC found in humans. Major perturbations in SkM OS can be reversed with ERC in T2D/HF patients. Epi likely mediates such effects and may provide an effective means to treat conditions associated with tissue OS. © 2013.

  15. Saturated fat and cardiometabolic risk factors, coronary heart disease, stroke, and diabetes: a fresh look at the evidence.

    Science.gov (United States)

    Micha, Renata; Mozaffarian, Dariush

    2010-10-01

    Dietary and policy recommendations frequently focus on reducing saturated fatty acid consumption for improving cardiometabolic health, based largely on ecologic and animal studies. Recent advances in nutritional science now allow assessment of critical questions about health effects of saturated fatty acids (SFA). We reviewed the evidence from randomized controlled trials (RCTs) of lipid and non-lipid risk factors, prospective cohort studies of disease endpoints, and RCTs of disease endpoints for cardiometabolic effects of SFA consumption in humans, including whether effects vary depending on specific SFA chain-length; on the replacement nutrient; or on disease outcomes evaluated. Compared with carbohydrate, the TC:HDL-C ratio is nonsignificantly affected by consumption of myristic or palmitic acid, is nonsignificantly decreased by stearic acid, and is significantly decreased by lauric acid. However, insufficient evidence exists for different chain-length-specific effects on other risk pathways or, more importantly, disease endpoints. Based on consistent evidence from human studies, replacing SFA with polyunsaturated fat modestly lowers coronary heart disease risk, with ~10% risk reduction for a 5% energy substitution; whereas replacing SFA with carbohydrate has no benefit and replacing SFA with monounsaturated fat has uncertain effects. Evidence for the effects of SFA consumption on vascular function, insulin resistance, diabetes, and stroke is mixed, with many studies showing no clear effects, highlighting a need for further investigation of these endpoints. Public health emphasis on reducing SFA consumption without considering the replacement nutrient or, more importantly, the many other food-based risk factors for cardiometabolic disease is unlikely to produce substantial intended benefits.

  16. [The role of nitric oxide and superoxide synthesis in protective mechanism of ecdysterone in the heart mitochondria of rats with streptozotocin-induced diabetes].

    Science.gov (United States)

    Korkach, Iu P; Rudyk, O V; Kotsiuruba, A V; Prysiazhna, O D; Sahach, V F

    2007-01-01

    This study evaluated generation of O2*- and NO in