Oxidative injury in reoxygenated and reperfused hearts.
In this study, we separated the effects of low oxygen supply and low coronary flow in isolated perfused rat hearts to focus on the genesis of free radicals-induced reperfusion injury. Hearts were exposed to either hypoxemia/reoxygenation or ischemia/reperfusion in various sequences, with hypoxemia and ischemia matched for duration (20 min), temperature (37 degrees C), and oxygen supply (10% of baseline). Hypoxemia/reoxygenation (n = 7) resulted in lower (developed pressure) x (heart rate) (p < 0.001) and higher end-diastolic pressure (p < 0.001) than ischemia/reperfusion (n = 9). The presence of 40 IU/ml superoxide dismutase and 104 IU/ml catalase nearly blunted the rise of the end-diastolic pressure (p = 0.02 vs. baseline), but could only partially prevent the depression of myocardial contractility (p < 0.001 vs. baseline, n = 7). Similar patterns were observed when hearts were made ischemic after hypoxemia, eliminating the intermediate reoxygenation step. We conclude that the major determinant of the reperfusion injury is associated with low oxygen supply rather than low coronary flow. Part of the injury is mediated by oxygen-derived free radicals, but a substantial portion of it is associated with energetic processes.
Samaja
M
M
Department of Biomedical Sciences and Technologies, Scientific Institute San Raffaele, Milano, Italy.
Motterlini
R
R
Santoro
F
F
Dell' Antonio
G
G
Corno
A
A
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002245:Carbon Dioxide / Q000097:blood; D002374:Catalase / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D005609:Free Radicals / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D000860:Hypoxia; D066298:In Vitro Techniques; D007511:Ischemia; D008297:Male; D008854:Microscopy, Electron; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D010100:Oxygen / Q000097:blood / Q000494:pharmacology*; D010101:Oxygen Consumption; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology*
D005609:Free Radicals; D002245:Carbon Dioxide; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen