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Objective: Studies have shown that the diabetic heart exhibits abnormalities in cellular ion transport, which can affect susceptibility to reperfusion-induced ventricular fibrillation (VF), tachycardia (VT) and functional derangements. It has been shown that “preconditioning” renders the heart very resistant to a subsequent prolonged ischemic episode. This phenomenon has been extensively studied in healthy myocardium, but such a study has not been previously done in diseased (hypertrophic or myopathic) hearts. Methods: We studied the incidence of reperfusion-induced VF, VT, cardiac function, and ion shifts (Na+, K+, Ca2+, and Mg2+) induced by ischemia/reperfusion in isolated hearts from rats with streptozotocin-induced diabetes. Following 2, 4, 6, and 8 weeks of diabetes, hearts were isolated and subjected to 30 min global ischemia followed by reperfusion. Results: In the 2-week diabetic group the total incidence of VF and VT was reduced from their non-diabetic age-matched control value of 100 and 100% to 42 ( P < 0.05) and 42% ( P < 0.05), respectively. Such a reduction in the incidence of VF and VT was not observed with progressive diabetes (4, 6, and 8 weeks). In the 2-week diabetics, the reduction in the VF and VT was reflected in the improvement of postischemic function, the reduction of ischemia and reperfusion-induced Na+ and Ca2+ gains, and the prevention in K+ and Mg2+ loss. This diabetes-induced initial protection was not seen in the 4- and 6-week diabetics, and a deterioration of postischemic function was observed in the 8-week diabetics. Four cycles of preconditioning, each consisting of 5 min ischemia followed by 10 min reperfusion, failed to reduce the incidence of VF and VT, improve cardiac function, and prevent ion shifts induced by 30 min ischemia followed by 30 min reperfusion in 4- and 8-week diabetics. Conclusions: In the early phase of diabetes the heart is more resistant to ischemia/reperfusion than the non-diabetic heart. Preconditioning does not afford protection against a prolonged period of ischemia in diabetics, indicating that preconditioning may be a “healthy heart phenomenon”.

Study objective – The aim of the study was to investigate the generation of free oxyradicals as factors in myocardial ischaemia-reperfusion pathology. Design – Isolated perfused rat hearts were subjected to 30 min global ischaemia followed by reperfusion. The spin trap 5,5-dimethyl-l-pyrroline-1-oxide was added to the effluent of the heart to avoid pharmacological interaction with the heart. The effluent was then analysed by electron spin resonance spectroscopy. Materials – Studies were performed on hearts of 51 male Sprague-Dawley rats, weight 300-350 g. Measurements and results – During reperfusion, the formation of hydroxyl radical adducts of the trap was observed, with a maximal value after 3 min. The initial amount of radicals trapped during the first 3 min of reperfusion showed an inverse correlation with the degree of heart function restored within 30 min of reperfusion. Spearman's rank correlation coefficients were calculated to be -0.734 for heart rate, -0.825 for left ventricular developed pressure, -0.787 for the maximum of its first derivative, -0.787 for coronary flow, and -0.796 for aortic flow (p

Isolated guinea pig hearts subjected to global ischaemia were used to investigate whether low extracellular Na+ exerts an anti-arrhythmic action against reperfusion arrhythmias, and the effects of extracellular Na+ manipulation upon myocardial ion contents (Na+, K+ and Ca2+) during ischaemia and reperfusion were studied. Using an optimal concentration of 144 mmol·litre−1 of extracellular Na+, hearts were subjected to 10, 20, 25, 30 or 40 min of global ischaemia followed by 25 min reperfusion. A bell shaped curve was obtained such that with increasing durations of ischaemia from 20 to 30 min there was an increasing incidence of reperfusion arrhythmias. Beyond this optimum (at which 100% exhibited reperfusion induced ventricular fibrillation and tachycardia) there was a decline in the susceptibility of the hearts to arrhythmias. Low extracellular Na+ was given 5 min prior to the global ischaemia and maintained during reperfusion. With extracellular Na+ of 24, 54, 84 and 114 mmol·litre−1, reperfusion induced ventricular fibrillation and tachycardia were reduced from their control incidence of 91% and 100% to 8% (p

Using the isolated perfused rat heart with transient (10 min) regional ischaemia induced by coronary artery ligation, we have shown that slow heart rate can dramatically reduce the vulnerability of the myocardium to reperfusion induced ventricular fibrillation and ventricular tachycardia. In the heart rate range of 200-400 beats.min-1, slower heart rates exerted a frequency dependent protective effect against reperfusion induced arrhythmias. At the optimal rate of 200 beats.min-1, the incidence of total ventricular fibrillation (irreversible plus reversible) and ventricular tachycardia fell to 33% and 50% of their control values (100%). The anti-arrhythmic effect was achieved with only a minor (less than 20%) effect on coronary flow. To ascertain whether or not slow heart rate achieved an absolute reduction in vulnerability to arrhythmias irrespective of the duration of ischaemia, hearts were also subjected to 5, 10, 20, 30 or 40 min of ischaemia followed by 30 min of reperfusion with and without pacing at 200 beats.min-1. A bellshaped time-response profile was obtained in both groups. In unpaced controls (n = 12) this gave a maximal vulnerability to arrhythmias after 10 min of ischaemia. In the paced hearts (n = 12) the curve was shifted to the right, with a peak vulnerability at 20 min. These results show that the action of pacing is to exert a delaying effect which extends the duration of ischaemia that can be tolerated before the heart becomes vulnerable to reperfusion induced arrhythmias. Heart rate can have a substantial effect on reperfusion induced arrhythmias and should be considered when making therapeutic interventions and risk assessments in this setting.