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Calcium-channel blockers preserve coronary endothelial reactivity after ischemia-reperfusion
F Dagenais1, R Cartier, C Hollmann
1Department of Cardiovascular Surgery, Montreal Heart Institute, Quebec, Canada.
Insights
Calcium channel blockers improve coronary artery relaxation after ischemia-reperfusion. Pretreatment with these drugs enhances both endothelium-dependent and -independent vasoregulation, preserving coronary blood flow.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Ischemia-Reperfusion Injury
Background:
- Calcium-channel blockers are known to aid myocardial recovery post-ischemia-reperfusion.
- Their precise impact on coronary blood flow regulation during such events requires further elucidation.
Purpose of the Study:
- To investigate the effects of calcium antagonists on coronary artery vasoregulation following ischemia-reperfusion.
- To evaluate dose- and drug-dependent responses of calcium channel blockers on coronary flow and hemodynamics.
Main Methods:
- Isolated rat hearts were pretreated with diltiazem, verapamil, or nifedipine.
- Hearts underwent 30 minutes of no-flow ischemia followed by 45 minutes of reperfusion.
- Endothelium-dependent and -independent relaxations were assessed using 5-hydroxytryptamine and sodium nitroprusside, respectively.
Main Results:
- All tested calcium antagonists dose-dependently improved endothelium-dependent relaxation post-ischemia, with nifedipine showing higher potency.
- Endothelium-independent relaxation was preserved by calcium antagonists, irrespective of the drug type.
- Nifedipine exhibited the most potent vasodilation and negative inotropic effect, while diltiazem was least effective on hemodynamics and coronary flow.
Conclusions:
- Preischemic administration of calcium antagonists enhances both endothelium-dependent and -independent coronary artery relaxation in a rat heart model.
- These beneficial effects on vasoregulation can be achieved at low doses without compromising left ventricular hemodynamics.
- Calcium antagonists show potential in preserving coronary artery autoregulation following ischemia-reperfusion injury.
Background:
Calcium-channel blockers have been reported to improve myocardial recovery after ischemia-reperfusion, but their effects on coronary blood flow regulation remain to be defined. Experiments were designed to evaluate the effects of calcium antagonists on coronary artery vasoregulation exposed to ischemia-reperfusion.
Methods:
Three groups of hearts (n = 6) were pretreated with a 10-minute infusion of either diltiazem, verapamil, or nifedipine at concentrations of 10(-9) mol/L to 10(-6) mol/L and exposed to 30 minutes of no-flow ischemia and 45 minutes of reperfusion. Another group (n = 6) received no pretreatment and was used as control. Endothelium-dependent and -independent relaxations were tested by assessing coronary flow increase to 5-hydroxytryptamine (10(-6) mol/L) and sodium nitroprusside (10(-5) mol/L) infusion, respectively. Left ventricular pressure, its first derivative, and coronary basal flow were recorded before and after ischemia as well as during calcium antagonist infusion.
Results:
Endothelium-dependent relaxation after ischemia was significantly improved with all three drugs in a dose-dependent fashion; nifedipine was found to be the more potent. Endothelium-independent relaxation was also significantly preserved with calcium antagonists regardless of the type, whereas left ventricular hemodynamics were not. During perfusion, nifedipine was found to have the most negative inotropic effect and to be the most potent vasodilator on the coronary circulation. Diltiazem was the less effective drug on both left ventricular hemodynamics and coronary circulation.
Conclusions:
This study indicates that preischemic infusion of calcium antagonists enhance endothelium-dependent and -independent coronary artery relaxation in the isolated rat heart model in a dose- and drug-dependent fashion. This can be achieved at low doses without affecting left ventricular hemodynamics and should contribute to preserve coronary artery autoregulation.