Anti-oxidant therapy improves microvascular ultrastructure and perfusion in postischemic myocardium.
To determine the contribution of oxygen-derived free radicals to the changes in microvascular structure and function which follow reperfusion of ischemic myocardium, isolated perfused rat hearts were subjected to 15 or 45 min of global ischemia followed by 5 min of oxygenated reperfusion. Hearts were then fixed by perfusion with glutaraldehyde and perfused with nuclear track photographic emulsion to identify competent capillaries in scanning and transmission electron micrographs. Reperfusion after 15 min caused a significant reduction in the density of competent capillaries in the subendocardial third of the left ventricle, but this reduction was lessened but not eliminated by the addition of 0.61 mmole/liter desferrioxamine, but not by 60,000 U/liter superoxide dismutase plus 60,000 U/liter catalase, to the perfusate. After 45 min of ischemia both interventions prevented the myocyte swelling, endothelial cell changes, bleb formation, and reduction in microvascular lumina characteristic of unprotected reperfusion, but only desferrioxamine significantly improved microvascular competence. This suggests that the hydroxyl radical rather than superoxide and/or hydrogen peroxide has a pathogenic role, although desferrioxamine may have other effects as nonspecific chelator. Postischemic reductions in capillary function also occur in reversibly injured myocardium in the absence of structural abnormality. Preventing postischemic microvascular incompetence has the potential to minimize ischemic cell injury and to enhance repair following myocardial infarction, but it also may increase the risk of hemorrhage from venules.
Maxwell
L
L
Department of Pathology, University of Auckland School of Medicine, New Zealand.
Gavin
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005609:Free Radicals; D066298:In Vitro Techniques; D008833:Microcirculation / Q000187:drug effects / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009206:Myocardium / Q000648:ultrastructure; D051381:Rats
D000975:Antioxidants; D005609:Free Radicals