Cardioprotective effect of L-carnitine in rats submitted to permanent left coronary artery ligation.

Several studies have suggested that L-carnitine may limit the cellular alterations induced by myocardial hypoxia or ischemia. In the present study, rats were subjected to chronic treatment with L-carnitine (0, 25, 50 or 200 mg/kg/day i.p.) for 9 days prior to being submitted to permanent regional myocardial ischemia by left coronary artery ligation in situ. Following 48 hours of coronary occlusion, infarct size was measured using planimetry of transverse sections of the hearts, which had been stained with nitro-blue tetrazolium. Various functional and metabolic parameters have also been measured in isolated perfused hearts. Treatment with L-carnitine at 200 mg/kg/day i.p. for 9 days led to a significant reduction in infarct size and a better preservation of residual cardiac function. However, none of the metabolic parameters measured were modified. In conclusion, we suggest that the preservation of cardiac contractile function observed with L-carnitine pretreatment is secondary to carnitine-induced infarct size limitation.

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.

Effects of adriamycin on chronic cardiotoxicity in selenium-deficient rats.

Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers; however, its chronic use is unfortunately accompanied by cardiotoxicity. This toxicity can be reduced by antioxidant agents such as selenium, and it is particularly interesting that cancer patients are usually deficient in this trace element, which suggests that its supplementation could contribute to beneficial treatment. We have examined the effect of adriamycin on chronic cardiotoxicity in 6-week selenium deficiency in rats. Selenium-deficient rats showed a considerable reduction of selenium levels and of selenium-containing glutathione peroxidase. Cardiac lipid peroxides increased slightly in the deficient rats, whereas plasma and heart lipid peroxides increased markedly in adriamycin-treated rats. This increase was greatly accentuated in selenium deficiency. These results suggest that free radical mechanism may be contributing to adriamycin toxicity, and above all show the importance of balancing the selenium levels in adriamycin-treated subjects to limit its harmful myocardial action. A decrease in adriamycin cardiotoxicity with no concomitant decrease in its antineoplastic activity would be of considerable value by improving the therapeutic benefit of the drug.