A PROTECTIVE ROLE OF NITRIC-OXIDE IN ISOLATED ISCHEMIC-REPERFUSED RAT-HEART

Objectives: The importance of NO-induced vasodilator tone in maintaini ng adequate coronary flow to sustain hemodynamic function in aerobical ly perfused heart and the role of NO in the injury development in isch aemic/reperfused heart was studied. Methods: Effect of NO synthesis in hibitor (N-omega-nitro-L-arginine, L-NOARG) on isolated working rat he arts subjected to either 90 min of aerobic perfusion or to a global is chaemia (27.5 to 42.5 min) followed by 40 min reperfusion was studied. To overcome coronary flow reducing effect of L-NOARG either perfusion pressure was raised from 75 to 120 cm H2O or adenosine (400 nM) was a dministered. Results: In the hearts perfused at coronary pressure of 7 5 and 120 cm H2O, L-NOARG (10 mu M) reduced coronary flow by 30% and 1 7%, respectively, while cardiac output was not affected. Only a transi ent increase in adenosine and lactate outflow occurred in L-NOARG-trea ted hearts. The post-ischaemic recovery of functions was impaired in L -NOARG-treated hearts, an effect not correlating with L-NOARG-induced reduction in coronary flow. Although the pre-ischaemic coronary flow w as similar in the untreated hearts perfused at 75 cm H2O and in L-NOAR G-treated hearts perfused at 120 cm H2O, the post-ischaemic recovery i n the latter group was still impaired as compared to that in the untre ated hearts. Likewise, coronary flow was similar in the untreated hear ts and in those treated with L-NOARG plus adenosine, nevertheless, the post-ischaemic recovery in the latter group was impaired as compared to that in the untreated hearts. Conclusions: While the inhibition of NO synthesis resulted in coronary flow reduction it did not induce a s tate of permanent ischaemia in isolated rat heart. L-NOARG-induced aug mentation of the ischaemia/reperfusion injury was related to the defic it of NO, itself, rather than to the reduction in myocardial perfusion .