ULTRASTRUCTURAL BASIS OF THE FREE-RADICAL SCAVENGING EFFECT OF INDAPAMIDE IN EXPERIMENTAL MYOCARDIAL-ISCHEMIA AND REPERFUSION

Reperfusion of acutely ischemic cardiac tissue is associated with seve ral characteristic pathophysiological changes that are generally refer red to as ''reperfusion injury.'' It has been hypothesized that some o f these changes are mediated by oxygen-derived free radicals. Indapami de, a nonthiazide diuretic, has been shown to exert free-radical scave nging properties comparable to that of alpha-tocopherol. The purpose o f the present work was to investigate whether indapamide (IDP) may lim it ultrastructural signs of reperfusion injury in an experimental mode l of myocardial ischemia and reperfusion in isolated rat hearts. Rats received a chronic oral administration of IDP (7 days at 3 mg/kg body weight/day) before excision of the heart. IDP was also added to the pe rfusion fluid at a final concentration of 10(-4) M. Isolated hearts we re perfused under control conditions for 20 min and then submitted to 15 min of global no-flow ischemia, before being reperfused for 15 min. Hearts were fixed by glutaraldehyde perfusion fixation and left ventr icular ultrastructure was studied on ultra-thin sections by electron m icroscopy. Micrographs were taken following a random procedure to obta in a representative overview of the whole section. In the untreated gr oup, marked ultrastructural alterations were observed including contra ction bands, disrupted membranes, and swollen mitochondria. In the ind apamide-treated group, the degree of morphological injury was signific antly lessened. It is concluded that indapamide protects the ultrastru cture of ventricular myocytes against reperfusion injury. This effect might be related to the oxygen free-radical scavenging property of the drug.