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At least 19 recordsLinked to original sources
PubMed2006

Alterations in ion channel physiology in diabetic cardiomyopathy.

Diabetes mellitus is one of the most common chronic illnesses worldwide. This article focuses on a subgroup of diabetic patients with a specific cardiac complication of this disease--diabetic cardiomyopathy. This article initially gives some general background on diabetic cardiomyopathy and ion channels. Next the focus is on how diabetic cardiomyopathy alters calcium homeostasis in cardiac myocytes and highlights the specific alterations in ion channel function that are characteristic of this type of cardiomyopathy. Finally, the importance of the renin-angiotensin system in diabetic cardiomyopathy is reviewed.

Animals↗
PubMed2003

Effects of MCC-135 on Ca2+ uptake by sarcoplasmic reticulum and myofilament sensitivity to Ca2+ in isolated ventricular muscles of rats with diabetic cardiomyopathy.

Diabetic cardiomyopathy is characterized by delayed cardiac relaxation. Delayed relaxation is suggested to be associated with sarcoplasmic reticulum (SR) dysfunction and/or increase in myofilament sensitivity to Ca2+. Although MCC-135, an intracellular Ca2+-handling modulator, accelerates the delayed relaxation without inotropic effect in the ventricular muscle isolated from rats with diabetic cardiomyopathy, the underlying mechanism has not been fully understood. We tested the hypotheses that MCC-135 modulates Ca2+ uptake by SR and myofilament sensitivity to Ca2+. Wistar rats were made diabetic by a single injection of streptozotocin (40 mg/kg i.v.). Seven months later, the left ventricular papillary muscle was isolated and skinned fibers with and without functional SR were prepared by treatment of the papillary muscle with saponin to study SR Ca2+ uptake and myofilament sensitivity to Ca2+, respectively. In diabetic rats, SR Ca2+ uptake was decreased, which was related to decrease in protein level of SR Ca2+-ATPase determined by western blot analysis. MCC-135 enhanced SR Ca2+ uptake in diabetic rats, but not in normal rats. In diabetic rats, maximum force was decreased but force at diastolic level of Ca2+ was increased, without significant change in myofilament sensitivity to Ca2+ compared with normal rats. MCC-135 decreased force at any pCa tested (pCa 7.0-4.4), but had no significant effect on myofilament sensitivity to Ca2+ in diabetic rats. These results suggest that MCC-135 enhances SR Ca2+ uptake and shifts force-pCa curve downward without modulating myofilament sensitivity to Ca2+. These effects may contribute to positive lusitropic effect without inotropic effect of MCC-135 observed in the ventricular muscle of diabetic cardiomyopathy.

Actin Cytoskeleton↗
PubMed2002

Overexpression of the sarcoplasmic reticulum Ca(2+)-ATPase improves myocardial contractility in diabetic cardiomyopathy.

Diabetic cardiomyopathy is characterized by reduced cardiac contractility due to direct changes in heart muscle function independent of vascular disease. An important contributor to contractile dysfunction in the diabetic state is an impaired sarcoplasmic reticulum (SR) function, leading to disturbed intracellular calcium handling. We investigated whether overexpression of the SR calcium pump (SERCA2a) in transgenic mice could reduce the impact of diabetes on the development of cardiomyopathy. Diabetes was induced by streptozotocin injection (200 mg/kg), and left ventricular (LV) function was analyzed in isolated hearts 3 weeks later. In diabetic hearts systolic LV pressure was decreased by 15% and maximum speed of relaxation (-dP/dt) by 34%. Functional changes were also assessed in isolated papillary muscles. Active force was reduced by 61% and maximum speed of relaxation by 65% in the diabetic state. The contractile impairment was accompanied by a 30% decrease in SERCA2a protein in diabetic mice. We investigated whether increased SERCA2a expression in transgenic SERCA2a-overexpressing mice could compensate for the diabetes-induced decrease in cardiac function. Under normal conditions, SERCA2a overexpressors show improved contractile performance relative to wild-type (WT) mice (-dP/dt: 3,169 vs. 2,559 mmHg/s, respectively). Measurement of LV function in hearts from diabetic SERCA2a mice revealed systolic and diastolic functions that were similar to WT control mice and markedly improved relative to diabetic WT mice (-dP/dt: 2,534 vs. 1,690 mmHg/s in diabetic SERCA2a vs. diabetic WT mice, respectively). Similarly, the contractile behavior of isolated papillary muscles from diabetic SERCA2a mice was not different from that of control mice. SERCA2a protein expression was higher (60%) in diabetic SERCA2a mice than WT diabetic mice. These results indicate that overexpression of SERCA2a can protect diabetic hearts from severe contractile dysfunction, presumably by improving the calcium sequestration of the SR.

Animals↗
PubMed2001

Diabetic Cardiomyopathy.

Diabetes mellitus is a major risk factor for the development of congestive heart failure (CHF). Diabetic cardiomyopathy has been acknowledged as a distinct disease entity that is an additional risk for diabetic patients to develop CHF, especially when they are affected by hypertension or epicardial coronary artery disease. Moreover, diabetic cardiomyopathy has been documented to lead to CHF even in the absence of other risk factors. As the combination of hypertension and diabetes has shown to be particularly detrimental, aggressive blood pressure control with a goal of less than 130/85 mm Hg is of critical importance. The first choice for pharmacologic treatment is angiotensin-converting enzyme inhibitors. Double- or triple-drug therapy is frequently required for good control. The increased risk of epicardial coronary artery disease in patients with diabetes warrants stringent treatment of dyslipidemia. If dilated cardiomyopathy with low ejection fraction is present, therapy with angiotensin-converting enzyme inhibitors, digoxin, diuretics, beta-blockers, and spironolactone (for patients with New York Heart Association class III to IV functional status) is indicated. If cardiac dysfunction consists predominantly of impaired diastolic function, heart rate control with a beta-blocker or a calcium antagonist is of particular importance. Control of blood glucose should be achieved, with hemoglobin A(1c) levels of less than 7%. Hyperinsulinemia should be avoided when possible; therefore, insulin-sensitizing agents are preferred over insulin-secretion-enhancing agents. Symptoms of CHF and acutely decompensated CHF should be treated no differently than nondiabetic patients. Care for patients with diabetes always includes lifestyle changes consisting of smoking cessation, decreasing obesity, regular exercise, and a heart-healthy diabetic diet.

Journal Article↗
PubMed2006

The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy.

Diabetes has emerged as a major threat to worldwide health. The increasing incidence of diabetes in young individuals is particularly worrisome given that the disease is likely to evolve over a period of years. In 1972, the existence of a diabetic cardiomyopathy was proposed based on the experience with four adult diabetic patients who suffered from congestive heart failure in the absence of discernible coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholism. The exact mechanisms underlying the disease are unknown; however, an important component of the pathological alterations observed in these hearts includes the accumulation of extracellular matrix (ECM) proteins, in particular collagens. The excess deposition of ECM in the heart mirrors what occurs in other organs such as the kidney and peritoneum of diabetics. Mechanisms responsible for these alterations may include the excess production, reduced degradation, and/or chemical modification of ECM proteins. These effects may be the result of direct or indirect actions of high glucose concentrations. This article reviews our state of knowledge on the effects that diabetes-like conditions exert on the cells responsible for ECM production as well as relevant experimental and clinical data.

Animals↗
PubMed1994

Diabetic cardiomyopathy.

Diabetic cardiomyopathy as a distinct entity was first recognized by Rubler et al. in diabetics with congestive heart failure (CHF), who had no evidence of coronary atherosclerosis. The Framingham study showed a 2.4-fold increased incidence of CHF in diabetic men and a 5.1-fold increase in diabetic women over 18 years. Pathological studies show left ventricular hypertrophy and fibrosis with varying degrees of small vessel disease, the functional significance of which is uncertain. Hypertension was recognized as an important cofactor in the development of fatal congestive heart failure in diabetics. On cardiac catheterization, in patients symptomatic of heart failure, either congestive or restrictive patterns have been observed. In contrast, asymptomatic diabetics had decreased left ventricular compliance but normal systolic function on hemodynamic study. Noninvasive studies show alterations in systolic and especially diastolic function, particularly in diabetics with microvascular complications and/or coexistent hypertension. Using load-independent measures of contractility, however, systolic function was generally found to be normal in asymptomatic normotensive diabetics. Experimental studies have focused on the mildly diabetic dog and the severely diabetic rat. Decreased left ventricular compliance and increased interstitial connective tissue were observed in chronically diabetic dogs. In contrast, ventricular myocardium from diabetic rats exhibits a reversible decrease in the speed of contraction, prolongation of contraction, and a delay in relaxation. These mechanical changes are associated with a decreased myosin ATPase, a shift in myosin isoenzyme distribution, alterations in a variety of Ca2+ fluxes, and changes in responses to alpha- and beta-adrenergic and cholinergic stimulation. These biochemical changes may be secondary to alterations in carbohydrate, lipid, and adenine nucleotide metabolism in the diabetic heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Diabetic cardiomyopathy.

Diabetes mellitus is associated with an excessive cardiovascular morbidity and mortality. Although one frequently associates cardiac dysfunction with enhanced coronary atherosclerosis in diabetic patients, evidence has accumulated for the existence of a specific "diabetic" cardiomyopathy. Abundant literature evidence supports the concept of myocardial dysfunction separate from epicardial coronary disease in diabetic individuals. The relationship of myocardial dysfunction to the type, duration, and treatment of diabetes awaits further delineation. The relative pathogenic significance of the multiple factors that may alter myocardial performance in diabetic patients similarly awaits further elucidation.

Animals↗
PubMed2004

G-protein signaling participates in the development of diabetic cardiomyopathy.

Diabetic patients develop a cardiomyopathy that consists of ventricular hypertrophy and diastolic dysfunction. Although the pathogenesis of this condition is poorly understood, previous studies implicated abnormal G-protein activation. In this work, mice with cardiac overexpression of the transcription factor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) were examined as a model of diabetic cardiomyopathy. PPAR-alpha transgenic mice develop spontaneous cardiac hypertrophy, contractile dysfunction, and "fetal" gene induction. We examined the role of abnormal G-protein activation in the pathogenesis of cardiac dysfunction by crossing PPAR-alpha mice with transgenic mice with cardiac-specific overexpression of regulator of G-protein signaling subtype 4 (RGS4), a GTPase activating protein for Gq and Gi. Generation of compound transgenic mice demonstrated that cardiac RGS4 overexpression ameliorated the cardiomyopathic phenotype that occurred as a result of PPAR-alpha overexpression without affecting the metabolic abnormalities seen in these hearts. Next, transgenic mice with increased or decreased cardiac Gq signaling were made diabetic by injection with streptozotocin (STZ). RGS4 transgenic mice were resistant to STZ-induced cardiac fetal gene induction. Transgenic mice with cardiac-specific expression of mutant Galphaq, Galphaq-G188S, that is resistant to RGS protein action were sensitized to the development of STZ-induced cardiac fetal gene induction and bradycardia. These results establish that Gq-mediated signaling plays a critical role in the pathogenesis of diabetic cardiomyopathy.

Animals↗
PubMedDate not supplied

Diabetic cardiomyopathy.

Diabetes mellitus is associated with a specific cardiomyopathy. This is evident from the clinical-pathological work and the epidemiologic data from the Framingham study. Noninvasive studies of diabetics have shown alterations in systolic and diastolic function that may ultimately lead to clinical heart failure. The relationship of these cardiac changes to the type of diabetes, its duration, and its severity is not settled. However, a correlation between changes in heart function and other complications of diabetes has been demonstrated. Insufficient prospective data is available from noninvasive studies to establish the frequency of progression from subclinical cardiac dysfunction to overt congestive failure. The pathogenesis of this disorder is still uncertain. Pathological studies have shown changes in the intramural arteries, arterioles, and capillaries but their functional significance is uncertain. Experimental studies have shown interstitial changes leading to an apparently less compliant left ventricle in the diabetic dog and monkey. In the diabetic rat reversible changes were found in myocardial function, related to changes in contractile proteins and intracellular calcium metabolism. In both species, the response to anoxia or ischemia was altered in the presence of diabetes. However, irreversible depression of the contractile element was not found in most animal studies of isolated diabetes. In contrast, the combination of hypertension and diabetes leads to substantial cardiac damage and circulatory congestion, both in clinical and experimental investigations. Clearly much more work must be carried out to understand the pathogenesis, treatment, and ultimately the prevention of diabetic cardiomyopathy.

Adult↗
PubMed1996

Role of elevated lipids in diabetic cardiomyopathy.

Diabetic cardiac dysfunction appears to be associated with an increase in plasma lipids especially triglycerides. Drugs that lower plasma lipids will usually improve cardiac performance in diabetic rats. More recently, an association between decreased cardiac glucose metabolism resulting from increased utilization of fatty acid metabolism in the diabetic myocardium has been suggested. Of the drugs tested, those drugs that decreased plasma lipids and improved cardiac glucose metabolism also improved cardiac performance. Drugs, such as clofibrate, which decreased triglyceride levels and did not enhance cardiac performance in diabetic rats will be examined in the near future in order to test the hypothesis.

Animals↗
PubMed1991

Altered inotropic responses in diabetic cardiomyopathy and hypertensive-diabetic cardiomyopathy.

To understand the mechanisms of diabetic cardiomyopathy and the consequences of combined hypertension and diabetes, cardiac tissue responses to various inotropic agents were measured in experimental diabetes. Streptozotocin was injected into Wistar rats, spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs). Six weeks after the injection diabetic rats showed a subsensitivity to beta adrenergic stimulation in ventricular tissue and a supersensitivity and hyper-responsiveness to Ca++ and alpha adrenergic stimulation (except in WKYs) in ventricular tissues and left atria. A supersensitivity to BAY K 8644 in SHR left atria and a hyper-responsiveness to verapamil in ventricular strips were also noted. These alterations may be due to a change in receptor number or to postreceptor alterations. Diabetic SHRs exhibited greater changes in several of the drug responses (responses to isoproterenol, phenylephrine and BAK 8644) were more hyperlipidemic and had a high mortality as compared with Wistar rats and WKY diabetics. These findings confirm that the combination of hypertension and diabetes results in greater cardiac pathology than is seen with either disease alone.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Oxidative stress and diabetic cardiomyopathy: a brief review.

Diabetes is a serious public health problem. Improvements in the treatment of noncardiac complications from diabetes have resulted in heart disease becoming a leading cause of death in diabetic patients. Several cardiovascular pathological consequences of diabetes such as hypertension affect the heart to varying degrees. However, hyperglycemia, as an independent risk factor, directly causes cardiac damage and leads to diabetic cardiomyopathy. Diabetic cardiomyopathy can occur independent of vascular disease, although the mechanisms are largely unknown. Previous studies have paid little attention to the direct effects of hyperglycemia on cardiac myocytes, and most studies, especially in vitro, have mainly focused on the molecular mechanisms underlying pathogenic alterations in vascular smooth-muscle cells and endothelial cells. Thus, a comprehensive understanding of the mechanisms of diabetic cardiomyopathy is urgently needed to develop approaches for the prevention and treatment of diabetic cardiac complications. This review provides a survey of current understanding of diabetic cardiomyopathy. Current consensus is that hyperglycemia results in the production of reactive oxygen and nitrogen species, which leads to oxidative myocardial injury. Alterations in myocardial structure and function occur in the late stage of diabetes. These chronic alterations are believed to result from acute cardiac responses to suddenly increased glucose levels at the early stage of diabetes. Oxidative stress, induced by reactive oxygen and nitrogen species derived from hyperglycemia, causes abnormal gene expression, altered signal transduction, and the activation of pathways leading to programmed myocardial cell deaths. The resulting myocardial cell loss thus plays a critical role in the development of diabetic cardiomyopathy. Advances in the application of various strategies for targeting the prevention of hyperglycemia-induced oxidative myocardial injury may be fruitful.

Cardiomyopathies↗
PubMed2005

Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy: restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor.

BACKGROUND: Diabetic cardiomyopathy (DCM) is characterized by microvascular pathology and interstitial fibrosis, which leads to progressive heart failure; however, the pathogenesis of DCM remains uncertain. METHODS AND RESULTS: Using the streptozotocin-induced diabetic rat model, we evaluated the natural course of DCM over a period of 1 year by serial echocardiography, Western blot analysis for vascular endothelial growth factor (VEGF), endothelial progenitor cell assays, myocardial blood flow measurements, and histopathologic analysis that included terminal dUTP nick end-labeling (TUNEL), capillary and cardiomyocyte density, and fibrosis area. Downregulation of myocardial VEGF expression preceded all other features of DCM and was followed by increased apoptosis of endothelial cells, decreased numbers of circulating endothelial progenitor cells, decreased capillary density, and impaired myocardial perfusion. Apoptosis and necrosis of cardiomyocytes ensued, along with fibrosis and progressive diastolic and then systolic dysfunction. To provide further evidence of the central role of VEGF in the pathophysiology of DCM, we replenished myocardial VEGF expression using naked DNA gene therapy via direct intramyocardial injection of plasmid DNA encoding VEGF (phVEGF165). VEGF-replenished rats showed increased capillary density, decreased endothelial cell and cardiomyocyte apoptosis, and in situ differentiation of bone marrow-derived endothelial progenitor cells into endothelial cells. These anatomic findings were accompanied by significant improvements in cardiac function. CONCLUSIONS: These findings suggest that downregulation of VEGF may compromise microvascular homeostasis in the myocardium and thereby play a central role in the pathogenesis of DCM.

Animals↗
PubMed2002

Overexpression of metallothionein reduces diabetic cardiomyopathy.

Many diabetic patients suffer from cardiomyopathy, even in the absence of vascular disease. This diabetic cardiomyopathy predisposes patients to heart failure and mortality from myocardial infarction. Evidence from animal models suggests that reactive oxygen species play an important role in the development of diabetic cardiomyopathy. Our laboratory previously developed a transgenic mouse model with targeted overexpression of the antioxidant protein metallothionein (MT) in the heart. In this study we used MT-transgenic mice to test whether an antioxidant protein can reduce cardiomyopathy in the OVE26 transgenic model of diabetes. OVE26 diabetic mice exhibited cardiomyopathy characterized by significantly altered mRNA expression, clear morphological abnormalities, and reduced contractility under ischemic conditions. Diabetic hearts appeared to be under oxidative stress because they had significantly elevated oxidized glutathione (GSSG). Diabetic mice with elevated cardiac MT (called OVE26MT mice) were obtained by crossing OVE26 transgenic mice with MT transgenic mice. Hyperglycemia in OVE26MT mice was indistinguishable from hyperglycemia in OVE26 mice. Despite this, the MT transgene significantly reduced cardiomyopathy in diabetic mice: OVE26MT hearts showed more normal levels of mRNA and GSSG. Typically, OVE26MT hearts were found to be morphologically normal, and elevated MT improved the impaired ischemic contractility seen in diabetic hearts. These results demonstrate that cardiomyocyte-specific expression of an antioxidant protein reduces damage to the diabetic heart.

Actins↗
PubMed1986

[Diabetic cardiomyopathy in mild diabetics: evaluation by thallium-201 scintigraphy and exercise radionuclide ventriculography].

Forty mildly diabetic men, with a mean age of 49 +/- 9.7 years, and without clinical or exercise electrocardiographic evidence of ischemic cardiac disease, participated in a study consisting of exercise thallium-201 myocardial scintigraphy and exercise radionuclide ventriculography. 1. Among the 40 patients, 16 (40%) showed no filling defect (negative cases). Mild defects (mild cases) and moderate defects (moderate cases) were observed in 12 and 12 cases, respectively. 2. The percent washout ratio was decreased in none of the 16 negative cases, in three of the 12 mild cases, and in 11 of the 12 moderate cases. 3. There were no significant statistical differences in age, duration of diabetes, fasting blood sugar, HbA1c, serum cholesterol, smoking or blood pressure. Percent of ideal body weight was greater in moderate cases (121 +/- 15%) compared to negative or mild cases (103 +/- 9%, 108 +/- 9%) (p less than 0.01). 4. The percent fractional shortening was decreased in mild cases and in moderate cases (34.6 +/- 6.3%, 32.6 +/- 8.4%) compared to negative cases (41.7 +/- 4.9%) (p less than 0.01). Weissler's index (PEP/ET) was higher in moderate cases (0.42 +/- 0.09) compared to negative or mild cases (0.35 +/- 0.05, 0.36 +/- 0.06) (p less than 0.05). 5. Left ventricular wall motion was abnormal on echocardiography in none of the 16 negative cases, in three of the 12 mild cases and in seven of the moderate cases. The site of echocardiographically abnormal wall motion coincided with the defect area on myocardial scintigraphy in six cases, but not in four cases. 6. Radionuclide ventriculographic studies statistically showed no significant differences in ejection fraction (EF), 1/3EF, time to peak ejection (TPE), ejection time (ET), peak ejection rate (PER), 1/3 filling fraction (FF), 1/3 peak filling rate (PFR) and time to peak filling (TPF). The peak filling rate (PFR) at rest was significantly lower in mild cases (2.4 +/- 0.5 EDV/sec, p less than 0.025). Although the PFR at rest in moderate cases was lower than in negative cases (2.9 +/- 0.6 EDV/sec, 3.2 +/- 0.7 EDV/sec), no significant difference was shown between them. The rate of increase in cardiac output was significantly lower in moderate cases compared to mild cases and negative cases (59 +/- 28%, 96 +/- 49%, 97 +/- 31%, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2001

Downregulation of K(+) channel genes expression in type I diabetic cardiomyopathy.

Type I diabetic cardiomyopathy has consistently been shown to be associated with decrease of repolarising K(+) currents, but the mechanisms responsible for the decrease are not well defined. We investigated the streptozotocin (STZ) rat model of type I diabetes. We utilized RNase protection assay and Western blot analysis to investigate the message expression and protein density of key cardiac K(+) channel genes in the diabetic rat left ventricular (LV) myocytes. Our results show that message and protein density of Kv2.1, Kv4.2, and Kv4.3 are significantly decreased as early as 14 days following induction of type I diabetes in the rat. The results demonstrate, for the first time, that insulin-deficient type I diabetes is associated with early downregulation of the expression of key cardiac K(+) channel genes that could account for the depression of cardiac K(+) currents, I(to-f) and I(to-s). These represent the main electrophysiological abnormality in diabetic cardiomyopathy and is known to enhance the arrhythmogenecity of the diabetic heart. The findings also extend the extensive list of gene expression regulation by insulin.

Animals↗
PubMed2004

Diabetic cardiomyopathy: electromechanical cellular alterations.

Diabetic patients show a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. However, although diabetic cardiomyopathy is a frequent and important complication of diabetes mellitus, its physiological basis is not completely known. The electrocardiogram of diabetic patients shows several alterations from normal patterns, most of them related to the QT interval and T wave. Recently, different alterations in cardiac ionic currents have been described in myocytes isolated from diabetic hearts, mainly a reduction in potassium repolarizing currents. Three different mechanisms could be involved in these alterations. First, direct metabolic alterations of the cardiac myocyte, such as impaired activity of protein kinases and phosphatases, intracellular pH regulation, intracellular calcium handling, and others. Second, impaired support of extra cardiac factors regulating cardiac activity, such as sympathetic regulation of heart rate and contractility. Thus, diabetic autonomic neuropathy leads to diminished noradrenaline release in cardiac ventricle in response to standing, exercise or cold stress. Besides, diabetic cardiomyopathy reduces cardiac myocyte response to acute noradrenaline exposure and finally, impairs support of different trophic factors responsible for the regulation of ionic channel expression. Thus, basal noradrenaline release in the ventricles, necessary to maintain adequate potassium channel expression, is reduced by sympathetic neuropathy. Moreover, the levels of insulin and other trophic factors required for the maintenance of adequate ionic channel expression are also altered in diabetic patients. Therefore, different physiopathological mechanisms are involved in diabetic cardiomyopathy. Thus, further research is needed in order to prevent the development of this long-term complication, and to improve the pharmacological management of diabetic patients.

Calcium↗
PubMed1995

Beneficial effects of beraprost sodium, a stable prostacyclin analogue, in diabetic cardiomyopathy.

We examined whether beraprost sodium (beraprost), a stable prostacyclin analogue, prevented cardiomyopathy in diabetic rats in vivo. Diabetes was induced by a bolus injection of streptozotocin in rat-tail vein. Four weeks after the induction of diabetes, the animals were treated with beraprost (30 micrograms/kg/day, p.o.) for 4 weeks until they were used for the measurement of hemodynamics, electrocardiogram (ECG), and plasma creatine phosphokinase (CK) activity. Nontreated diabetic rats have lower mean blood pressure, heart rate, left ventricular systolic pressure, and peak positive dP/dt at basal levels compared to age-matched normal rats. All of these changes were not improved in beraprost-treated rats. The left ventricular end-diastolic pressure and ST/R ratio in the ECG were significantly increased in diabetic rats. These parameters were significantly improved by beraprost compared with nontreated diabetic rats. Additionally, beraprost significantly suppressed the elevation of plasma CK activity as compared with that in non-treated diabetic rats. Changes in peak positive dP/dt in response to isoproterenol were attenuated in nontreated diabetic rats as compared with age-matched normal rats and beraprost-treated diabetic rats. These results suggest that beraprost is capable of preventing diabetic cardiomyopathy without affecting hyperglycemic condition.

Administration, Oral↗