PRECONDITIONING PREVENTS CHRONIC REPERFUSION-INDUCED CORONARY ENDOTHELIAL DYSFUNCTION IN RATS

Experiments were designed to test whether preconditioning protects aga inst chronic endothelial injury after ischemia and reperfusion. Corona ry arteries were isolated from rats subjected to sham surgery or 20 mi n of ischemia followed by 1 h, 1 day, 1 wk, or 1 mo of reperfusion wit hout or with preconditioning. The endothelium-dependent relaxations to acetylcholine (ACh; assessed in vitro) were markedly reduced after is chemia and 1 h of reperfusion (31 +/- 6 vs. 57 +/- 6% in sham; P < 0.0 1) and did not recover after longer durations of reperfusion (1 mo: 32 +/- 5 vs. 56 +/- 2%; P < 0.01). The impaired response to ACh was rest ored by preconditioning at all time points (1 h: 53 +/- 6; 1 mo: 65 +/ - 4%). After 1 mo, the potency of ACh in preconditioned arteries was a lso increased compared with that in sham animals. Electron microscopy showed marked endothelial damage after 1 h of reperfusion and signs of regenerated endothelium after 1 mo of reperfusion. Both acute and chr onic ultrastructural changes were prevented by preconditioning. Thus p reconditioning, in addition to protecting myocardial cells, also prote cts against chronic reperfusion-induced endothelial injury, both in te rms of functional and structural changes.