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

The prevalence of type 2 diabetes mellitus is increasing worldwide with obese diabetic patients constituting the majority of this population. Type 2 diabetes is associated with increased morbidity and mortality after acute myocardial infarction. Previous experimental studies of ischaemia-reperfusion tolerance in diabetes have only been performed in animal models of type 1 diabetes mellitus, yielding conflicting data. The aim of the present study was to characterise and compare the tolerance to ischaemia and effects of ischaemic preconditioning (IPC) in hearts from obese Zucker diabetic fatty (ZDF) and lean Goto-Kakizaki (GK) type 2 diabetic rats, using non-obese Zucker and Wistar rats as respective controls.

The two rat strains were divided into 8 groups. The ZDF study (n=47) consisted of: Control -IPC, Control +IPC, ZDF -IPC and ZDF +IPC. The GK study (n=38) consisted of: Control -IPC, Control +IPC, GK -IPC and GK +IPC. Hearts, which were studied in a Langendorff preparation perfused with Krebs-Henseleit buffer, were subjected or not to IPC (+IPC, -IPC) before 50 minutes of regional ischaemia and 120 minutes reperfusion.

Ischaemic reperfusion injury was smaller in obese (p<0.05) and lean (p<0.05) type 2 diabetic animals than in their respective control animals. IPC reduced ischaemic reperfusion injury during reperfusion in non-diabetic control rats (p<0.01), but failed to protect hearts from both diabetic animal models. Post-ischaemic haemodynamic recovery was impaired in the ZDF rats compared to both control and GK rats (p<0.05).

Ischaemic preconditioning does not protect hearts from obese or lean type 2 diabetic animals. However, the susceptibility of the type 2 diabetic myocardium to ischaemic damage is lower than in non-diabetic hearts. The method described here could be used as a tool to study the pathogenesis of increased cardiovascular morbidity and mortality in type 2 diabetes.