Abstract
Catecholamines have been demonstrated to be cardiotoxic. Besides hemodynamic alterations, oxygen free radicals generated by the auto-oxidation of catecholamines might contribute to their deleterious effects. We examined the influence of exogenous norepinephrine (NE), after inhibiting functional alterations by alpha and beta-adrenoceptor blockade, on acute regional ischemia (MI). Method: We used isolated electrically-driven rabbit hearts with depleted catecholamine stores (reserpine 7.0 mg/kg i.p. 16–24 h before preparation, Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca 2+ 1.8 mmol/l, 37°C, 185–200 beats/min). Repetitive MI, separated by a reperfusion period of 50 min, was induced by coronary artery branch ligature and quantitated from epicardial NADH-fluorescence photography. Starting after a reperfusion period of 20 min, isolated hearts were treated with NE (10−6 M), in the presence of propranolol (10−6 M), phentolamine (10−6 M) and vitamin C (3 × 10−8 M) in the perfusion buffer to prevent the functional effects of NE. The influence of the free radical scavenger superoxide dismutase (SOD) (30 U/ml) or captopril (10−6 M) on MI was also examined. Results: Left ventricular pressure or coronary flow were not significantly affected by either treatment (p>0.05). Epicardial NADH-fluorescence area and intensity were, however, significantly enhanced by NE (+ 22%) (P<0.05), although propranolol, phentolamine and vitamin C had no significant influence on MI (P>0.05). SOD had no significant effect on MI in control hearts (P> 0.05) but completely prevented MI enlargement by NE (P>0.05). Captopril did not significantly affect MI in control hearts and did not inhibit MI enlargement by NE (P<0.05). Conclusion: NE has deleterious effects .on MI in isolated rabbit hearts that are independent of functional alterations. This MI enlargement by NE is mediated by superoxide anion radicals since it could be prevented by SOD. Free radical scavenging properties reported for vitamin C, propranolol or captopril in several in-vitro systems are uneffective in preventing NE cardiotoxicity mediated by oxygen free radicals in isolated rabbit hearts.
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Correspondence to: A.F.E. Rump at the above address
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Rump, A.F.E., Klaus, W. Evidence for norepinephrine cardiotoxicity mediated by superoxide anion radicals in isolated rabbit hearts. Naunyn-Schmiedeberg's Arch Pharmacol 349, 295–300 (1994). https://doi.org/10.1007/BF00169296
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DOI: https://doi.org/10.1007/BF00169296