Reactive hyperemia during early reperfusion as a determinant of improved functional recovery in ischemic preconditioned rat hearts.

Objective: Our study was undertaken to clarify the impact of the shear stress-induced reactive hyperemia (associated with reperfusion) in preconditioning-mediated protection.

Methods: In control rat hearts, a 40-minute preischemic perfusion (constant pressure: 70 mm Hg) period was followed by 25-minute global low-flow ischemia (constant flow: 0.3 mL/min) and 30-minute reperfusion (constant pressure). As preconditioning protocol, hearts underwent 2 cycles of 5-minute no-flow ischemia/5-minute reperfusion.

Results: Although coronary vasodilation in response to shear stress is severely impaired after global low-flow ischemia and reperfusion, it is fully preserved by ischemic preconditioning concomitantly with an improvement of left ventricular developed pressure. Restricting coronary peak flow to 100% of baseline at reperfusion reduced left ventricular recovery to the control level. N(G)-nitro-l-arginine methyl ester affects the restoration of reperfusion-reactive hyperemia and the improvement of contractile recovery afforded by ischemic preconditioning. However, if the time course of hyperemia was restored by forcibly reperfusing to 150% of baseline for 10 minutes and, therefore, by restricting final peak flow to 80% of baseline for 20 minutes, contractile function recovered to a high degree despite the presence of N(G)-nitro-l-arginine methyl ester.

Conclusion: We conclude that wall stretch and shear stress during reperfusion are necessary for the mediation phase of preconditioning.