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R E Beamish

Publications and source records attributed to R E Beamish.

84 records · Page 5Linked to original sources
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Cardiac alpha- and beta-adrenergic receptor alterations in diabetic cardiomyopathy.

The effect of chronic experimental diabetes on the adrenergic receptors in the rat heart was investigated. Diabetes was induced by streptozotocin (65 mg/kg; i.v.) administration, animals were sacrificed 8 weeks later, and positive as well as negative dF/dt values were determined in isolated papillary muscle preparations. Stimulation of the contractile force generation by isoproterenol and methoxamine was attenuated in diabetic preparations. Beta- and alpha-adrenergic receptor bindings were determined in cardiac membranes by employing 3H-dihydroalprenolol and 3H-dihydroergocryptine respectively. Reduced number of beta- and alpha-receptor binding sites without changes in the affinity constants were observed in diabetic myocardium. Such a decrease in alpha- and beta-receptor density in the heart may account for the depressed contractile responsiveness to adrenergic stimuli in diabetic cardiomyopathy.

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Alterations of sarcolemmal Na+-Ca2+ exchange in catecholamine-induced cardiomyopathy.

Rats were injected intraperitoneally with 40 mg/kg body weight isoproterenol and the heart sarcolemma was isolated 3, 9 and 24 hours later. The heart/body weight ratio increased and varying degrees of change in cardiac ultrastructure were apparent at 9 and 24 hours after isoproterenol injection. Na+-dependent Ca2+ uptake activities of heart sarcolemma were depressed at 3, 9 and 24 hours; such alterations in 24 hour preparations were evident at different times of incubation and at different concentrations of Ca2+. No differences in Na+-induced Ca2+ release or Na+-K+ ATPase activities were observed between the control and experimental membranes. The control and isoproterenol-treated heart sarcolemmal preparations were minimally but equally contaminated by other subcellular organelles. Although there was no significant change in the phospholipid composition, the protein pattern as determined by gel electrophoresis was altered in sarcolemma at 24 hours of isoproterenol treatment. These results indicate an abnormality of heart sarcolemmal Na+-dependent Ca+ uptake during the development of catecholamine-induced cardiotoxicity. It is suggested that a depression in the ability of the cell to remove Ca2+ through the Na+-Ca2+ exchange in sarcolemma may contribute to the development of intracellular Ca2+ overload in catecholamine induced cardiomyopathy.

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Effect of adrenochrome on adenine nucleotides and mitochondrial oxidative phosphorylation in rat heart.

Effects of adrenochrome, an oxidation product of epinephrine, on myocardial energy production were investigated by studying changes in adenine nucleotide content and mitochondrial oxidative phosphorylation activities in the isolated rat heart. Perfusion of the heart with 50 mg/L adrenochrome induced a marked decline in contractile force within 5 min and this was associated with a rapid decline in the myocardial ATP/AMP ratio. A significant decrease in ATP and ATP/ADP ratio as well as a significant increase in ADP and AMP content was observed at 10 min of perfusion with adrenochrome. Furthermore, mitochondrial oxidative phosphorylation activities were unchanged except that an increase in state 4 respiration and a decrease in RCI value were seen in the heart perfused with adrenochrome for 10 min. Autoradiography of the sections from hearts perfused with 14C-adrenochrome revealed the localization of a significant amount of radioactivity on mitochondria. Adrenochrome at concentrations of 20 mg/L or higher was found to inhibit the oxidative phosphorylation activities of heart mitochondria under in vitro conditions. The depressant effects of adrenochrome on mitochondrial oxidative phosphorylation were additive to those seen with calcium. These data suggest that adrenochrome in the presence of excess calcium in the myocardial cell may impair the process of energy production in mitochondria and this may result in contractile failure of hearts exposed to this cardiotoxic metabolite of epinephrine.

Adenosine Diphosphate↗
PubMedDate not supplied

Pathogenesis of cardiac dysfunction in diabetes mellitus.

The use of insulin by diabetics has largely removed the threat of death from ketotic coma but cardiovascular dysfunction remains a major cause of death in patients with diabetes. Recent research has indicated a generalized membrane defect, which may cause abnormalities of calcium metabolism in nerves, cardiac and smooth muscle as well as endothelial cells and thus may lead respectively to the development of neuropathy, primary cardiomyopathy, microangiopathy and atherosclerosis in the diabetic population. Each of these pathogenic processes, which are associated with insulin deficiency, alone or in combination with others, may result in cardiac dysfunction in chronic diabetes. Activation of the sympathetic nervous system and abnormalities in catecholamine metabolism have been identified in diabetes; their involvement in the genesis of cardiac pump failure as well as large and small vessel disease is likely. The membrane defects as indicated by changes in both plasma membrane and glycocalyx in diabetic cardiomyopathy appear to be complex and may involve alterations in the metabolism of lipids and pyrimidine nucleotides. It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy; however, a concentrated research effort is required to understand the primary biochemical lesion in the pathogenesis of cardiac dysfunction in diabetes. In the meantime, a heightened awareness on the part of clinicians concerning the susceptibility of diabetic patients to cardiovascular problems may help in reducing mortality and morbidity in the diabetic population.

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