INFLUENCE OF ACETYLCYSTEINE ON AGGRAVATION OF ISCHEMIC DAMAGE IN EX-VIVO HEARTS OF RATS EXPOSED TO HYPERBARIC-OXYGEN

Rats were exposed to hyperbaric oxygen (HBO = 100 % oxygen; 2.5 atmosp heres absolute pressure) for 6 h. Isovolumic left heart preparations f rom these animals were subjected to global low flow-ischemia (perfusio n rate from 12 ml/min to 2 ml/min for 40 min) and reperfusion. Hearts from rats not exposed to HBO underwent the same ischemic-reperfusion p rocedure (controls). As compared to control, HBO treatment caused in e x vivo hearts a significant aggravation of cardiac ischemic picture as indicated by a marked increase in left ventricular end diastolic pres sure (LVEDP) and reduced post ischemic left ventricular developed pres sure (LVDP). At the end of the ischemic and reperfusion periods LVEDP values were 6.8 (p < 0.001) and 8 (p < 0.001) times higher than the co rresponding control values. Moreover, LVDP and coronary perfusion pres sure (CPP) values were decreased (2.8 times; p < 0.001) and increased (56 %; p < 0.001), respectively, as compared to control preparations. These events were also associated with a considerable impairment of th e cardiac tissue to generate 6-keto-PGF(1 alpha). Treatments of rats w ith different doses of acetylcysteine (N-acetylcysteine, CAS 616-91-1, NAC; 0.25-0.5-1 g/kg p.o.) before HBO displayed a clear-cut and dose- related protective activity in hearts subjected to ischemia-reperfusio n. Also the generating capacity of 6-keto-PGF(1 alpha) from these hear ts were restored according to the dose of NAC employed. When aortic ri ngs from rats exposed to HBO were considered, they showed a reduced ca pacity to release 6-keto-PGF(1 alpha) and an increased sensitivity to endothelin-1. At the same time, the relaxant activity of acetylcholine in these tissues was almost lost. Again, NAC treatment of the animals before HBO restored in a dose-dependent way the capacity of the aorti c rings to generate 6-keto-PGF(1 alpha). This event was paralleled by normalized responses of the preparations to endothelin-1 and acetylcho line. Taken together these results clearly indicate that acute HBO tre atment of the rats markedly aggravates the ischemic-reperfusion damage in ex vivo hearts. This event is coupled with a compromised integrity of cardiac and extracardiac endothelial cell functions. The protectiv e activity of NAC observed in this study once more emphasises its ther apeutic role in increasing antioxidant defence mechanisms.