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Cardiac protection by ischaemic preconditioning is not mediated by myocardial stunning
M Matsuda1, T G Catena, R S Vander Heide
1Department of Pathology, Duke University Medical Center, Durham, NC 27710.
Insights
Ischaemic preconditioning protects the heart, but reduced contractile effort is not required for this effect. Restoring contractile function with dobutamine in preconditioned hearts did not increase infarct size, confirming preconditioning’s protective benefits.
Area of Science:
- Cardiovascular Physiology
- Myocardial Ischemia
- Cardiac Preconditioning
Background:
- Cardiac protection via ischaemic preconditioning (IP) diminishes before contractile function recovery.
- Myocardial stunning alone is insufficient to induce preconditioning.
Purpose of the Study:
- To investigate if reduced contractile effort is essential for the cardioprotective effects of IP.
- To determine the impact of restoring contractile function on infarct size in preconditioned hearts.
Main Methods:
- Dogs underwent IP using repeated coronary artery occlusions and reperfusions.
- Contractile function was assessed, and dobutamine was administered to restore baseline function in some groups.
- Sustained ischemia followed by reperfusion was induced to measure infarct size.
Main Results:
- IP reduced infarct size by 64% compared to controls (4.4% vs. 12.3% of area at risk).
- Dobutamine reversed post-ischemic contractile dysfunction in preconditioned hearts.
- Dobutamine administration did not significantly alter infarct size in either preconditioned or control groups.
Conclusions:
- Restored contractile function with dobutamine did not compromise the infarct-size-limiting effects of IP.
- Reduced contractile effort is not a prerequisite for the cardioprotective benefits of ischaemic preconditioning.
Objective:
Previous studies have shown that cardiac protection by ischaemic preconditioning wanes before contractile function recovers; thus stunning is insufficient to cause preconditioning. To test whether reduced contractile effort is necessary for preconditioning induced protection, the effect on myocardial infarct size of restoring contractile function with dobutamine was examined in preconditioned and control dogs.
Methods:
In two experimental groups (groups P and P+D), preconditioning was produced by four 5 min occlusions of the left anterior descending coronary artery, each separated by 5 min of reperfusion. Contractile function was assessed by sonomicrometry 5 min after completion of the preconditioning protocol. In group P+D, dobutamine (average dose = 5 micrograms.kg-1.min-1) was then infused intravenously to restore systolic shortening to baseline. The artery then was reoccluded for 40 min of sustained ischaemia followed by 4 d of reperfusion. Two additional groups of non-preconditioned control dogs (groups C and C+D) also underwent 40 min of coronary occlusion and 4 d of reperfusion. Group C+D received a dobutamine infusion beginning 15 min before and during the 40 min occlusion to match the dobutamine received in group P+D, whereas group C received normal saline.
Results:
Preconditioning caused mild postischaemic contractile dysfunction (50% decrease in systolic shortening) which was easily reversed by dobutamine treatment. Dobutamine also increased both the rate-pressure product and the left ventricular dP/dt in both treated groups (C+D and P+D). Histological infarct size was 12.3(SEM 2.0)% of the area at risk in the untreated control group (n = 11), and was reduced to 4.4(1.7)% in the untreated preconditioning group (n = 8; p < 0.05). Dobutamine increased non-preconditioned infarct size (group C+D) to 22.1(3.4)% (n = 7; p < 0.05). Infarct size in the dobutamine treated preconditioning group (P+D) was not significantly different from infarct size in group P (n = 8), at 6.1(2.5%).
Conclusions:
In preconditioned hearts, dobutamine restored postischaemic contractile function but did not increase infarct size significantly. Thus reduced contractile effort is not required for the cardioprotective effect on ischaemic preconditioning.