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 several characteristic pathophysiological changes that are generally referred to as "reperfusion injury." It has been hypothesized that some of these changes are mediated by oxygen-derived free radicals. Indapamide, a nonthiazide diuretic, has been shown to exert free-radical scavenging properties comparable to that of alpha-tocopherol. The purpose of the present work was to investigate whether indapamide (IDP) may limit ultrastructural signs of reperfusion injury in an experimental model 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 perfusion fluid at a final concentration of 10(-4) M. Isolated hearts were 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 ventricular ultrastructure was studied on ultra-thin sections by electron microscopy. Micrographs were taken following a random procedure to obtain a representative overview of the whole section. In the untreated group, marked ultrastructural alterations were observed including contraction bands, disrupted membranes, and swollen mitochondria. In the indapamide-treated group, the degree of morphological injury was significantly lessened. It is concluded that indapamide protects the ultrastructure of ventricular myocytes against reperfusion injury. This effect might be related to the oxygen free-radical scavenging property of the drug.
Mouhieddine
S
S
Laboratorie de Physiologie Cellulaire Cardiaque, Université Joseph Fourier, Grenoble, France.
Tresallet
N
N
Boucher
F
F
de Leiris
J
J
D000818:Animals; D016166:Free Radical Scavengers; D007190:Indapamide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D007190:Indapamide