Modulation of catecholamine cardiomyopathy by allopurinol.
It has been suggested that cardiac injury by catecholamines may be the result of coronary constriction leading to ischemic damage. Allopurinol (ALLO) has been shown to reduce the extent of myocardial necrosis in various systems. Hence the possibility that ALLO might limit norepinephrine (NE) injury was tested. Rabbit hearts were infused with NE (3 micrograms/min/kg) for 90 minutes, with or without ALLO (50 micrograms/min/kg). Control specimens infused with saline solution plus ALLO were also prepared. Hearts were excised 48 hours later and studied as isovolumic isolated heart preparations. Peak systolic pressure, coronary flow, and myocardial oxygen consumption were significantly reduced in the hearts infused with NE but not in the NE + ALLO hearts. Myocardial adenosine triphosphate and glycogen concentrations were 29% and 26% lower in the NE hearts compared with control hearts. These reductions were absent in the NE + ALLO group. Moreover, rates of creatine phosphokinase and lactic dehydrogenase release were sharply elevated in the NE hearts but not in those also given ALLO. These findings are consistent with the changes observed histologically. The amount of myocardial damage was less in the ALLO + NE group compared with the NE group (p less than 0.02). This appears to be the first report to demonstrate that ALLO reduces myocyte damage by NE. Possible mechanisms include decreased free radical production, scavenging of free radicals, and preservation of the adenine nucleotide pool. Because xanthine oxidase activity is absent in the rabbit, the latter two mechanisms are more likely explanations for the findings.
Jiang
J P
JP
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
Chen
V
V
Downing
S E
SE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000188:drug therapy*; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits
D000493:Allopurinol; D000255:Adenosine Triphosphate; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D009638:Norepinephrine