© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Protection afforded by preconditioning to the diabetic heart against ischaemic injury
Faculty of Pharmacy, University of Montreal, C.P. 6128, Succursal Centre-ville, Montreal, Québec, Canada, H3C 3J7
* Corresponding author. Tel. (+1-514) 343 5909; Fax (+1-514) 343 2102; E-mail: lamontad@ere.umontreal.ca
Objective: The aim of this study was to assess whether the cardioprotective effect of ischaemic preconditioning (IPC) on endothelial function in coronary arteries and myocardial function is affected in the streptozotocin-induced diabetic rat heart. Methods: Isolated hearts, perfused under constant flow conditions, were exposed to 30 min of partial ischaemia (flow rate 1 ml min–1) followed by 20 min of reperfusion. Results: In the diabetic group (without ischaemia or IPC), infusion of 10 µM serotonin (5-HT), an endothelium-dependent, and 3 µM sodium nitroprusside (SNP), an endothelium-independent vasodilator, in the coronary bed preconstricted with 0.1 µM U-46619 induced a marked vasodilation. Ischaemia, either without or with preconditioning with a single 5 min ischaemia and 10 min reperfusion (IPC1) before ischaemia, was accompanied by a reduced 5-HT-induced vasodilation in diabetic hearts. In contrast, IPC1 preserved the response to 5-HT in non-diabetic hearts. A more extensive IPC with 3 periods of 5 min ischaemia followed by 5 min reperfusion (IPC3) preserved the vasodilation produced by 5-HT in both diabetic and non-diabetic hearts. IPC3 increased the recovery of dP/dtmax and dP/dtmin during the 30 min ischaemic period and during reperfusion in all hearts. In contrast, IPC1 had no effect on myocardial recovery in either groups. Adenosine pre-treatment started 30 min before ischaemia mimicked IPC3, preserving the vasodilation to 5-HT and improving myocardium recovery in both groups. When adenosine was started 15 min before ischaemia, vasodilation to 5-HT was preserved in non-diabetic hearts only. Conclusions: These results suggest that IPC affords protection to endothelial function in resistance coronary arteries of diabetic hearts. To achieve this protection, a more extensive IPC is needed, which may be related to a longer exposure to adenosine.
KEYWORDS Coronary circulation; Diabetes; Endothelium; Heart; Ischaemic preconditioning; Rat
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