Diabetic animals appear to need a more intense ischaemic preconditioning stimulus for cardioprotection, possibly as a consequence of their endothelial dysfunction and insulin resistance. ESMIRO transgenic mice express non-functional insulin receptors in the endothelium, and consequently have vascular endothelial dysfunction similarly to diabetic animals, although they retain normal glucose metabolism. We evaluated the effect of impaired endothelial function and absent vascular insulin signalling on ischaemic preconditioning using ESMIRO mice.Methods
ESMIRO mice and wild type littermates (WT) were subjected to preconditioning via 2 cycles of 5 min ischaemia and 5 min reperfusion (IPC) prior to 35 min ischaemia and 30 min reperfusion (IR). These were compared with ESMIRO and WT control groups which had no IPC prior to IR. Infarct sizes were measured using 2,3,5-Triphenyltetrazolium chloride staining and planimetry analysis.Results
There was a significant 27% reduction in the mean infarct size in the WT preconditioned hearts as compared with WT control group (23±3%, n=8 vs 32±4%, n=9; p=0.04). There was a non-significant 17% reduction in mean infarct size in the preconditioned ESMIRO mice as compared with the ESMIRO control group (27±4%, n=8 vs 34±4%, n=7; p=0.16).Conclusion
Preconditioning was less effective in protecting the myocardium in ESMIRO mice compared to WT. This suggests that vascular endothelium and/or vascular insulin signalling may play a role in myocardial protection offered by preconditioning.