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 atmospheres absolute pressure) for 6 h. Isovolumic left heart preparations from these animals were subjected to global low flow-ischemia (perfusion 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 procedure (controls). As compared to control, HBO treatment caused in ex vivo hearts a significant aggravation of cardiac ischemic picture as indicated by a marked increase in left ventricular end diastolic pressure (LVEDP) and reduced post ischemic left ventricular developed pressure (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 corresponding control values. Moreover, LVDP and coronary perfusion pressure (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 the cardiac tissue to generate 6-keto-PGF1 alpha. Treatments of rats with 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-reperfusion. Also the generating capacity of 6-keto-PGF1 alpha from these hearts were restored according to the dose of NAC employed. When aortic rings from rats exposed to HBO were considered, they showed a reduced capacity to release 6-keto-PGF1 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 aortic rings to generate 6-keto-PGF1 alpha. This event was paralleled by normalized responses of the preparations to endothelin-1 and acetylcholine. Taken together these results clearly indicate that acute HBO treatment 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 protective activity of NAC observed in this study once more emphasises its therapeutic role in increasing antioxidant defence mechanisms.
Rossoni
G
G
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Radice
S
S
Bernareggi
M
M
Polvani
G
G
Oriani
G
G
Chiesara
E
E
Berti
F
F
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects; D015237:Dinoprost / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017725:Ventricular Pressure / Q000187:drug effects
C078129:6-keto-prostaglandin F2alpha; D019332:Endothelin-1; D016166:Free Radical Scavengers; D015237:Dinoprost; D000111:Acetylcysteine