REPERFUSION INJURY IN THE ENDOTOXIN-TREATED RAT-HEART - REEVALUATION OF THE ROLE OF NITRIC-OXIDE

1 The role of nitric oxide (NO) in ischaemia-reperfusion injury to the heart continues to be debated. 2 The role of NO released during endot oxemia on myocardial reperfusion injury was examined in rats given sal ine or lipopolysaccharide (LPS, 10 mg kg(-1)). 3 Aortic rings from LPS -treated rats showed a markedly decreased contractile response to both noradrenaline (NA) and U46619, and a diminished relaxation response t o acetylcholine, thrombin and aggregating platelets. Treatment of rat aortic rings from LPS-treated rats with the NO synthesis inhibitor N-o mega-nitro-L-arginine (L-NOARG) reversed the diminished contractile re sponse to NE and U46619. 4 Before ischaemia-reperfusion, baseline forc e of cardiac contraction (FCC) and coronary perfusion pressure (CPP) w ere lower and coronary flow was higher in hearts from LPS-treated rats (all P<0.05 vs. saline-treated group). Treatment of hearts from LPS-t reated rats with L-NOARG increased baseline FCC and CPP. 5 After ischa emia-reperfusion, hearts from saline-treated rats showed a 36+/-5% fal l in FCC, a 38+/-6% rise in CPP and a 38+/-5% fall in coronary flow, w hereas hearts from LPS-treated rats revealed only a 16+/-9% fall in FC C, a 10+/-3% rise in CPP and a 20+/-4% fall in coronary how (all P<0.0 5 vs. changes in saline-treated group). Fewer hearts from LPS-treated rats developed reperfusion arrhythmias (6% vs. 60% hearts from saline- treated rats, P<0.02). Myocardial superoxide dismutase activity was hi gher in the LPS-treated group (P<0.05). 6 NO synthesis, measured as fo rmation of nitrite, was higher (P<0.05) in cardiac and aortic tissues from LPS-treated rats. Prostacyclin (PGI(2)) release in coronary efflu ent was greater in LPS-treated rat hearts (P<0.05 vs. saline-treated r ats). 7 Thus LPS-treated hearts demonstrate a basal decrease in FCC an d coronary vascular resistance. These hearts demonstrate a modest prot ection from reperfusion injury. Induction of NO synthesis, and possibl y PGI(2) release, may underlie cardioprotection from ischaemia-reperfu sion.