Sensitivity to Ischemic Injury in the Diabetic Heart: a Dichotomy between Susceptibility to Ventricular Arrhythmias and the Size of Myocardial Infarction

Abstract

Different from clinical studies of diabetes mellitus (DM), experimental data reveal both, higher and lower vulnerability of the heart to ischemic injury. We have previously demonstrated an enhanced resistance to ischemia-induced arrhythmias in isolated rat hearts in the acute phase of DM. Our objectives were thus to extend our knowledge to the effects of DM of different duration on ischemic tolerance in the in vivo rat model. DM was induced by streptozotocin (45mg/kg, i.v.) and after 1 week (acute phase) and 8 weeks (chronic phase), anesthetized open-chest diabetic and age-matched control rats were subjected to 30-min regional ischemia (occlusion of LAD coronary artery) followed by 4-h reperfusion. The size of myocardial infarction (evaluated by tetrazolium staining), in conjunction with susceptibility to arrhythmias, served as end-points of injury. In the acute phase of DM, arrhythmia profile was similar to that in the control animals, and the incidence and severity of arrhythmias were not enhanced. On the other hand, the size of infarct area normalized to the size of area at risk was significantly smaller in the diabetics than in the controls (47.2 ± 2.8% vs 70.2 ± 2.1%, respectively; P < 0.05). In the chronic phase, only 17.7% of arrhythmias occurred as VT in 44% of the diabetics (vs 45.4% in 90% of non-diabetic animals; P < 0.05). Severity of arrhythmias was also lower (arrhythmia score: 2.1 ± 0.3 vs 2.9 ± 0.3 in the controls, respectively; P < 0.05). This effect was not due to a smaller infarct size, since the latter did not differ from that in the controls. In conclusion: diabetic rat hearts exhibit rather lower, than higher sensitivity to ischemia. In acute phase of DM, diabetic hearts are more resistant to irreversible cell damage, whereas in the chronic phase they exhibit reduced susceptibility to arrhythmias; these discrepancies might reflect different pathogenesis of arrhythmias and myocardial infarction.