PRECONDITIONING PROTECTS CORONARY ARTERIOLAR ENDOTHELIUM FROM ISCHEMIA-REPERFUSION INJURY

The objectives of this study were to test the hypotheses that 1) endot helium-dependent regulation of coronary arteriolar reactivity is impai red after ischemia and reperfusion, and 2) preconditioning protects th e arteriolar endothelium from reperfusion injury. In anesthetized open -chest dogs, coronary arteriolar diameters (30-110 mum) were measured in the beating heart using intravital microscopy during fluorescent st roboscopic epi-illumination in three groups: 1) control, 2) ischemia a nd reperfusion: 60-min occlusion and 120-min reperfusion of the left c ircumflex coronary artery, and 3) preconditioning: 10-min occlusion an d reperfusion preceding ischemia-reperfusion. To evaluate endothelial reactivity, the diameter responses of coronary arterioles to the endot helium-dependent vasodilators, acetylcholine and serotonin, were asses sed. Ischemia and reperfusion significantly reduced the increase in di ameter by serotonin (0 +/- 2 vs. 11 +/- 3% change in controls; P < 0.0 5) and acetylcholine (7 +/- 2 vs. 20 +/- 2% in controls; P < 0.05). In contrast, preconditioning preserved the dilation to both serotonin (6 +/- 1 %) and acetylcholine (24 +/- 3 %; both NS vs. control; P < 0.05 vs. ischemia and reperfusion). Dilation by the endothelium-independen t vasodilator, papaverine, was similar in the three groups, indicating similar levels of vasodilatory reserve and suggesting that the impair ed dilation to acetylcholine and serotonin after ischemia and reperfus ion was not due to nonspecific damage to vascular smooth muscle. These data demonstrate that ischemia-reperfusion significantly attenuates e ndothelium-dependent vasodilation of coronary arterioles in the intact beating heart. Furthermore, preconditioning reduces the endothelial d ysfunction of coronary arterioles after ischemia-reperfusion.