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Preconditioning improves myocardial function and reflow, but not vasodilator reactivity, after ischaemia and
1Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Insights
Ischaemic preconditioning improves myocardial reflow and contractility after prolonged ischemia. However, it does not preserve vasodilator function, potentially limiting adequate myocardial perfusion during increased oxygen demand.
Area of Science:
- Cardiovascular Physiology
- Ischemic Heart Disease Research
Background:
- Prolonged ischemia impairs myocardial reflow and vasodilator function.
- Ischemic preconditioning (PC) involves brief cycles of ischemia and reperfusion.
- The protective effects of PC against ischemia-reperfusion injury are well-documented.
Purpose of the Study:
- To investigate if ischemic preconditioning (PC) can prevent vasodilator dysfunction and impaired myocardial reflow caused by prolonged ischemia.
- To assess the impact of PC on cardiac contractility and infarct size following ischemia-reperfusion.
Main Methods:
- Open-chest anesthetized dogs underwent 60-minute left circumflex coronary artery occlusion and 60-minute reperfusion (ISC/REP).
- One group received three cycles of PC before ISC/REP; a control group received only ISC/REP.
- Measurements included coronary blood flow (CBF), left ventricular dP/dt, systemic arterial blood pressure, and heart rate.
Main Results:
- ISC/REP significantly reduced resting CBF and increased coronary vascular resistance (CVR).
- PC prevented the reduction in CBF and increase in CVR caused by ISC/REP, indicating preserved myocardial reflow.
- While PC improved cardiac contractility (left ventricular dP/dt) and reduced infarct size, it did not improve coronary dilator responses to acetylcholine or glyceryl trinitrate.
Conclusions:
- Ischemic preconditioning effectively improves myocardial reperfusion and preserves cardiac contractility following prolonged ischemia.
- PC does not prevent the impairment of coronary vasodilator function induced by ischemia and reperfusion.
- The inability to preserve vasodilator reserve may limit adequate myocardial perfusion in preconditioned hearts under conditions of increased oxygen demand.
Abstract:
1. The present study examines whether three cycles of brief coronary artery occlusion and reperfusion (i.e. ischaemic preconditioning; PC) can prevent vasodilator dysfunction and the impairment of myocardial reflow caused by prolonged ischaemia. Coronary blood flow, left ventricular dP/dt, systemic arterial blood pressure and heart rate were measured in open-chest anaesthetized dogs. 2. Sixty minute occlusion of the left circumflex coronary artery (LCx) and 60 min LCx reperfusion (ISC/REP; group 1) significantly reduced resting coronary blood flow (CBF, initial 29 +/- 3 mL/min; ISC/REP 20 +/- 3 mL/min, P < 0.05 vs initial) and increased coronary vascular resistance (CVR, initial 4.1 +/- 0.6 mmHg/min per mL; ISC/REP 5.8 +/- 1.0 mmHg/min per mL, P < 0.05 vs initial). By contrast CBF and CVR were not affected in dogs subjected to preconditioning before ischaemia (group 2: CBF, initial 24 +/- 4 mL/min; PC+ISC/REP 23 +/- 4 mL/min; CVR, initial 4.7 +/- 0.6 mmHg/min per mL; PC+ ISC/REP 5.3 +/- 1.0 mmHg/min per mL). These data suggest that ischaemic preconditioning prevents the ischaemia-induced impairment of myocardial reflow. 3. Ischaemia and reperfusion impaired coronary dilator responses to the endothelium-dependent dilator acetylcholine (delta CBF, after ISC/REP: 50 +/- 6% of initial) and the endothelium-independent dilator glyceryl trinitrate (delta CBF, ISC/REP: 46 +/- 6% of initial). Despite the improvement in reperfusion in the preconditioned group, there was no significant improvement in responses to acetylcholine (PC+ISC/REP 52 +/- 6% of initial) or glyceryl trinitrate (PC+ISC/REP 59 +/- 6% of initial) after ischaemia and reperfusion. 4. The reduction in left ventricular dP/dt after ischaemia and reperfusion was significantly smaller in the preconditioned group indicating a lower level of impairment of cardiac contractility. In addition, we confirmed that preconditioning caused a significant reduction in infarct size and a reduction in the release of lactate dehydrogenase indicating less cardiac injury. 5. These results suggest that although ischaemic preconditioning was able to improve both myocardial reperfusion and contractility, it was not able to preserve vasodilator function. Such a reduction in vasodilator reserve could prevent adequate myocardial perfusion under conditions of elevated oxygen demand.