979-33 Ischemia-Reperfusion Injury Impairs Endothelium-Dependent Relaxations Acutely, but not Chronically, and does not Affect Endothelial Pertussis Toxin-Sensitive G Protein Function in Canine Coronary Arteries

While the acute endothelial dysfunction after ischemia-reperfusion injury (IRI) has been studied extensively, little is known about the chronic status of the reperfused coronary endothelium. Also, the effect of IRI on endothelial pertussis toxin-sensitive G protein function is unknown. Using heartworm-free mongrel dogs, percutaneous balloon catheters were used to occlude the left anterior descending coronary artery for 1 hr. The arteries were then reperfused slowly over 15–20 min to mimick the gradual reperfusion seen with thrombolytic therapy. This is in contrast to previous studies where reperfusion was sudden due to the use of clamps or snares to occlude the artery. After 1 hr (n = 6) or 4 weeks (n = 7) of reperfusion, the coronary arteries were dissected and suspended in organ chambers. Left circumflex coronary arteries, not exposed to IRI, from the same dogs were studied in parallel as controls. Endothelium-independent relaxations to the direct vascular smooth muscle dilators SIN-l and lemakalim were unaffected by IRI. The endothelium-dependent relaxations to serotonin, thrombin, and ADP were significantly impaired 1 hr, but not 4 weeks, after IRI. The endothelium-dependent relaxation to serotonin was significantly inhibited by pertussis toxin (100 ng/ml). The endothelium-dependent relaxations to acetylcholine, bradykinin, and A23187 were unaffected by IRI either acutely or chronically. The endothelium-dependent relaxation to UK14304, which was nearly abolflow ished by pertussis toxin, was not significantly impaired by IRI. These findings demonstrate that the early endothelial dysfunction after IRI is transient and not evident 4 weeks after reperfusion, and in contrast to the regenerated endothelium of porcine coronary arteries, the endothelial pertussis toxinsensitive G protein function is not impaired by IRI.