Effect of acute hyperglycaemia and diabetes mellitus with and without short-term insulin treatment on myocardial ischaemic late preconditioning in the rabbit heart in vivo

Abstract

Diabetes mellitus (DM) and the resulting hyperglycaemia may interfere with the cardioprotective effect of ischaemic late preconditioning (LPC). Therefore, we investigated the effect of acute hyperglycaemia (part 1) and the effect of alloxan-induced DM with or without short-term insulin treatment (part 2) on LPC. Rabbits, chronically instrumented with a coronary artery occluder, were subjected to 30 min coronary artery occlusion and 2 h reperfusion (I/R) and infarct size (IS) was assessed. In part 1, four groups were studied. Controls were not treated further. LPC induced by a 5-min period of myocardial ischaemia 24 h before I/R reduced IS from 42+/-14 (controls) to 22+/-8% of the area at risk. Hyperglycaemia (600 mg dl(-1) by dextrose infusion, H(600)) before and during the 30 min ischaemia tended to increase IS (57+/-16%, P=0.14 vs. controls) and blocked cardioprotection by LPC (H(600)+LPC, 59+/-19%, P=1.0 vs. H(600), P=0.0003 vs. LPC). In part 2, LPC reduced infarct size from 43+/-13% (control) to 23+/-10% ( P=0.003). In diabetic animals, IS was 39+/-11%, and cardioprotection by LPC could not be elicited (DM+LPC, 41+/-16%, P=0.02 vs. LPC). Short-term insulin treatment (I, 90 min before I/R, blood glucose <150 mg dl(-1)) did not restore the cardioprotective effects of LPC (DM+I, 42+/-15%; DM+LPC+I, 40+/-10%, P=0.03 vs. LPC). It is concluded that acute hyperglycaemia and DM block the cardioprotection induced by LPC in rabbits and that the cardioprotection is not restored by short-term insulin treatment.

Ischaemic preconditioning does not protect the heart in obese and lean animal models of Type 2 diabetes

“…Nevertheless, the present results consistently demonstrate that diabetes abolishes the effects of IPC in two different models of Type 2 diabetes. Our data are in accordance with those reported by Ebel and coworkers, who found that late IPC (after 24 hours) in the alloxan model of Type 1 diabetes did not have any cardioprotective effect [20]. The mechanism responsible for the lack of protection afforded by IPC in Type 2 diabetic subjects has yet to be clarified.…”

Glimepiride Treatment Facilitates Ischemic Preconditioning in the Diabetic Heart

“…The majority of previous experimental studies have demonstrated the diabetic heart to be resistant to the cardioprotection elicited by IPC, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] attributing the inability to precondition the diabetic myocardium to hyperglycemia, 19 impaired mitochondrial function, 32 and sarcolemmal K ATP function. 23,28 In the current study, we too find that the diabetic heart is resistant to IPC, but that this can be overcome by increasing the IPC stimulus or treating with glimepiride.…”

“…[12][13][14][15][16] However, the vast majority of studies find that the diabetic heart is resistant to the cardioprotection elicited by IPC. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] The fact that the diabetic heart may be resistant to IPC may impact on the translation of novel cardioprotective strategies into the clinical setting where about 15% to 20% of the patients with CHD are also diabetic. [34][35][36] Studies from our laboratory have also found that the diabetic heart is resistant to IPC, but this resistance can be overcome when a stronger IPC stimulus is used to elicit cardioprotection.…”

The Insulin Sensitizer Pioglitazone Improves the Deterioration of Ischemic Preconditioning in Type 2 Diabetes Mellitus Rats

“…48) The difference in the type of diabetes may be the reason for these differences. [49][50][51] Therefore, the effect of IP may be decreased in type 2 diabetes mellitus with hyperinsulinemia, although it has not yet been clarified in type 1 diabetes mellitus without hyperinsulinemia.…”