Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction.

Abstract

BACKGROUND The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size. METHODS AND RESULTS Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P < .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P < .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P < .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was < 1% of normal myocardial blood flow. CONCLUSIONS We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart.

Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1

“…Previous studies investigating the extent of ischaemic injury in diabetic myocardium have been controversial despite overwhelming clinical evidence that the diabetic heart is highly sensitive to such injury [14,15,16,17]. Differences in the severity (degree of hyperglycaemia) and chronicity of the diabetic state [18], as well as the experimental condition and model used [17], could explain the disparity in experimental findings.…”

Expressão do precondicionamento isquêmico em pacientes com diabetes mellitus tipo 2 e doença arterial coronariana

“…Há trabalhos que sugerem que o diabetes interfere negativamente sobre o PI (37,(42)(43)(44)50,51) , enquanto outros indicam a preservação deste mecanismo cardioprotetor em modelos com diabetes (39,40,43,52,53) .…”

“…Trabalhos como o de Tsang (37) propõem (40) em camundongos com diabetes induzido por estreptozotocina mostra que o dano miocárdico após isquemia grave foi menor no grupo de animais com diabetes comparados aos sem diabetes e o que o estímulo precondicionante prévio a injúria isquêmica protegeu de forma bastante proeminente o miocárdio dos animais com diabetes.…”

“…Desta forma, estudos com cães com diabetes tendem a mostrar maiores áreas de infarto quando comparados a cães sem diabetes após estímulo precondicionante (54) . Por outro lado, estudos com camundongos (40) e coelhos (55) tendem a identificar menor dano miocárdico nos modelos com diabetes.…”

“…Ainda que alguns trabalhos experimentais demonstrem que o diabetes pode alterar algumas vias intracelulares do PI, como as vias da quinase 3 do fosfatidil-inositol (37) ou a função dos canais de potássio dependentes de ATP (38) , prejudicando a expressão do PI, o conjunto destes estudos experimentais tem demonstrado resultados conflitantes (39) . Mesmo que alguns trabalhos demonstrem que o diabetes não interfere substancialmente no PI (40,41) , muitos sugerem influência negativa (42)(43)(44) . (17,18,45) .…”