Effects of oxygen supply on ischemia/reperfusion damage and endothelial nitric oxide.

The aim of this study was to evaluate the possible relationship between endothelial nitric oxide (NO) and ischemia-reperfusion damage in rat hearts submitted to chronic changes of pO2 by means of exposure to hypoxia (13 days) or hyperoxia (72 hours). Wistar rat (250-300 gr. body weight) were used and subdivided into 3 groups: A) Control hearts; B) Hypoxic hearts; C) Hyperoxic hearts. After hypoxia or hyperoxia, hearts were excised, mounted on working heart apparatus and submitted to 15 min. global ischemia. Haemodynamic parameters, CPK and purine release in coronary effluent, heart weight changes (myocardial edema), myocytic and interstitial rearrangement (mitochondrial score, cell swelling) and NO production by means of NADPH-diaphorase (total NO production) and Anti-NOS-3 Ab Immunoperoxidase (endothelial NO) were evaluated. Quantitative analysis of histological changes and NO was performed by a computerized image analysis system. In hearts subjected to chronic hypoxia, after ischemia ventricular function was well preserved in absence of significant enzymatic and purine release. Reperfusion edema was significantly reduced (p<0.01 vs A and p<0.001 vs C). At ultrastructural level ventricular morphometry did not evidence significant signs of cell damage. In addition a significant (p<0.001 vs A) increase of endothelial NO was detected. In chronic hyperoxic hearts submitted to global ischemia we observed evident signs of cellular and mitochondrial damage associated to a significant reperfusion edema (p<0.02 vs A); NO production (endothelial and total NO) was significantly (p<0.01 vs A) reduced. Data show that NO is able to modulate ischemia-reperfusion damage probably by reducing ischemia-induced endothelial permeability alterations.