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Rhythm disorders are common complications in diabetic patients, due to their enhanced sensitivity to ischaemia. However, experimental studies are inconsistent, and both higher and lower vulnerability to injury has been reported. Our objectives were to compare susceptibility to ventricular arrhythmias in rats with prolonged duration of diabetes induced by streptozotocin (45 mg/kg, i.v.), utilising two different models. Following 8 weeks, either anaesthetised open-chest rats in vivo or isolated Langendorff-perfused hearts were subjected to 30 min regional zero-flow ischaemia induced by occlusion of LAD coronary artery. In addition, cardiac glycogenolysis and lactate production were measured. In open-chest rats, 90 % of the controls exhibited ventricular tachycardia (VT) which represented 55.4 % of total arrhythmias, whereby only 19.9 % of arrhythmias occurred as VT in 44 % of the diabetic rats (P < 0.05 vs controls). Duration of VT and ventricular fibrillation (VF) was reduced from 35.5 +/- 11.1 and 224.8 +/- 153.9 s in the controls to 4.8 +/- 2.5 and 2.2 +/- 0.2 s in the diabetics, respectively (P < 0.05). Accordingly, severity of arrhythmias (arrhythmia score, AS) was also lower in the diabetics (2.0 +/- 0.38 vs 3.3 +/- 0.3 in the controls; P < 0.05). In the isolated hearts, high incidence of VF was decreased in the diabetic hearts, and although VT occurred in almost all of the diabetic hearts, the duration of VT and VF was substantially shorter (61.5 +/- 14.5 and 5.5 +/- 0.5 s vs 221.5 +/- 37 and 398.5 +/- 55 s in the controls, respectively; P < 0.05). AS was reduced to 2.9 +/- 0.12 from 4.1 +/- 0.3 in the controls (P < 0.05). Postischaemic accumulation of lactate was lower in the diabetic than in the non-diabetic myocardium (20.4 +/- 1.9 vs 29.5 +/- 2.9 micromol/l/g w.wt.; P < 0.05). These results suggest that rat hearts with chronic diabetes, despite some differences in the arrhythmia profiles between the in vivo model and isolated heart preparation, are less sensitive to ischaemic injury and exhibit lower susceptibility to ventricular arrhythmias and reduced accumulation ofglycolytic metabolites.

The fine structural alteration and histochemical changes of the cardiac conduction system were studied in dogs and rats using various models of ischemic and reperfusion injury. The role of Ca2+ overload and reactive oxygen species (ROS) per se were also investigated. In all models of injury the activity of glycogen phosphorylase (histochemical indicator of the early ischemic changes) was present in nodal and conducting cells, although it was markedly diminished or absent in surrounding contractile muscle. Fine structural ischemic alterations progressed more slowly in conducting cells in comparison with working myocardial cells. Changes induced by Ca2+ paradox or ROS were reversible in conducting tissue in contrast to working myocardial tissue. The observations support the concept that conducting cells are more resistant to ischemia and also to reperfusion related injury than contractile myocardial cells.

The capability of cyclohexylphenol exaprolol of protecting the ischaemic myocardium during ischaemic cardiac arrest was assessed in the isolated working rat heart. Exaprolol added to the perfusion medium in a dose of 10(-7) mol.l-1 only minimally influenced the left ventricular function (reduced the stroke volume by 18.84% and cardiac output by 14.63%). The hearts were subjected to global ischaemia for 75 min at 26 degrees C and subsequently reperfused for 60 min at 37 degrees C. The recovery of left ventricular function following reperfusion, expressed as a percentage of preischaemic functional performance was used as an indicator of the ischaemic tolerance of the heart. The effect of exaprolol on sarcolemmal (Na+ + K+)-, Mg2+- and Ca2+-ATPase activities was also examined. Exaprolol-pretreated hearts revealed better postischaemic recovery of the left ventricular dP/dt max and stroke volume as well as improved efficiency in the transformation of chemical energy to mechanical work. Exaprolol in 10(-4) mol.l-1 concentration significantly stimulated the specific activity of sarcolemmal (Na+ + K+)-ATPase. Possible mechanisms of the salutary effect of exaprolol on the ischaemic heart are discussed.

Sex-related differences in mortality from ischaemic heart disease are attributed chiefly to difference in the incidence of atherosclerosis. Little attention has been paid to the influence of sex hormones on resistance of the myocardium itself to acute ischaemia. Experiments on rats showed that isolated female hearts were more resistant than male hearts. A period of eight weeks spent at an altitude of 1,350 m raised heart resistance only in males. Conversely, gonadectomy abruptly reduced the resistance of the male heart to ischaemia, especially under conditions of mild altitude hypoxia. The administration of oestradiol to gonadectomized male rats largely abolished the disturbance caused by isolated gonadectomy. Since coronary vasoconstriction and vasospasm lead to temporary ischaemia and even to infarction, the above effect of the sex hormones may play a role in the increased incidence of heart attacks after the gonads have ceased to function.

Statins, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are most frequently used drugs in the prevention of coronary artery disease due to their cholesterol-lowering activity. However, it is not exactly known whether these effects of statins or those independent of cholesterol decrease account for the protection against myocardial ischemia-reperfusion (I/R) injury. In this study, we investigated the effect of 5-day treatment with simvastatin (10 mg/kg) in Langendorff-perfused hearts of healthy control (C) and diabetic-hypercholesterolemic (D-H; streptozotocin + high fat-cholesterol diet, 5 days) rats subjected to 30-min global ischemia followed by 40-min reperfusion for the examination of postischemic contractile dysfunction and reperfusion-induced ventricular arrhythmias or to 30-min (left anterior descending) coronary artery occlusion and 2-h reperfusion for the infarct size determination (IS; tetrazolium staining). Postischemic recovery of left ventricular developed pressure (LVDP) in animals with D-H was improved by simvastatin therapy (62.7±18.2 % of preischemic values vs. 30.3±5.7 % in the untreated D-H; P<0.05), similar to the values in the simvastatin-treated C group, which were 2.5-fold higher than those in the untreated C group. No ventricular fibrillation occurred in the simvastatin-treated C and D-H animals during reperfusion. Likewise, simvastatin shortened the duration of ventricular tachycardia (10.2±8.1 s and 57.8±29.3 s in C and D-H vs. 143.6±28.6 s and 159.3±44.3 s in untreated C and D-H, respectively, both P<0.05). The decreased arrhythmogenesis in the simvastatin-treated groups correlated with the limitation of IS (in % of risk area) by 66 % and 62 % in C and D-H groups, respectively. However, simvastatin treatment decreased plasma cholesterol levels neither in the D-H animals nor in C. The results indicate that other effects of statins (independent of cholesterol lowering) are involved in the improvement of contractile recovery and attenuation of lethal I/R injury in both, healthy and diseased individuals. [ABSTRACT FROM AUTHOR]