Protection afforded by preconditioning to the diabetic heart against ischaemic injury
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Published on: June 2, 2015
1Faculty of Pharmacy, University of Montreal, Québec, Canada.
Insights
Ischaemic preconditioning (IPC) protects diabetic rat hearts, but requires an extended protocol to preserve endothelial function. A more extensive IPC protocol, potentially involving longer adenosine exposure, is necessary for cardioprotection in diabetes.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus impairs endothelial function and myocardial performance.
- Ischaemic preconditioning (IPC) is a protective phenomenon against ischaemia-reperfusion injury.
- The efficacy of IPC in diabetic hearts requires further investigation.
Purpose of the Study:
- To evaluate the cardioprotective effects of IPC on endothelial and myocardial function in a rat model of streptozotocin-induced diabetes.
- To determine if diabetes alters the response to IPC.
Main Methods:
- Isolated rat hearts were subjected to 30 minutes of partial ischaemia and 20 minutes of reperfusion.
- Hearts underwent different IPC protocols (single or triple cycles) or adenosine pre-treatment.
- Endothelial-dependent (serotonin) and independent (sodium nitroprusside) vasodilation were assessed.
- Myocardial function (dP/dtmax, dP/dtmin) was measured.
Main Results:
- Diabetic hearts showed reduced vasodilation to serotonin, an endothelium-dependent agent.
- A single IPC protocol (IPC1) failed to preserve vasodilation in diabetic hearts, unlike in non-diabetic hearts.
- An extended IPC protocol (IPC3) preserved serotonin-induced vasodilation in both diabetic and non-diabetic hearts.
- IPC3 improved myocardial function recovery during ischaemia and reperfusion, while IPC1 did not.
- Adenosine pre-treatment mimicked IPC3 effects when given 30 minutes prior to ischaemia.
Conclusions:
- IPC can protect endothelial function in the coronary arteries of diabetic rat hearts.
- A more extensive IPC protocol is required for this protective effect in diabetes.
- The protective mechanism may involve prolonged exposure to adenosine.
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 microM serotonin (5-HT), an endothelium-dependent, and 3 microM sodium nitroprusside (SNP), an endothelium-independent vasodilator, in the coronary bed preconstricted with 0.1 microM 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 d P/dtmax and d P/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.
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