title: Cardioprotection by superoxide dismutase: a catecholamine-dependent process?
abstract: Oxygen-derived free radicals may contribute to tissue injury in myocardial ischemia although the mechanism is unclear. Catecholamines possibly could be involved in the genesis of free radicals because it has been demonstrated that oxygen free radicals may be generated by autooxidation of noradrenaline. Superoxide dismutase (SOD) protects the myocardium against injury by superoxide anion radicals. We, therefore, examined whether the cardioprotective effect of superoxide dismutase still could be demonstrated after depletion of catecholamine stores by reserpine (7 mg/kg intraperitoneally 24 h premortem). We used electrically paced isolated hearts perfused according to Langendorff (Tyrode's solution, Ca2+ 1.8 mmol/L, constant perfusion pressure: 70 cm H2O, 3 Hz). Myocardial ischemia was induced by occlusion of a left coronary artery branch. Epicardial NADH-fluorescence was used for quantitation of the myocardial ischemia. SOD (48 U/mL) did not influence global coronary flow or left ventricular pressure significantly (P > 0.05). In control hearts, SOD significantly diminished both size and intensity of epicardial NADH-fluorescence after repetitive coronary ligatures (-45%) (P < 0.05). In hearts with depleted catecholamine stores, this cardioprotection by SOD was no longer observed (P > 0.05). Stimulation of noradrenaline overflow by increasing the pacing rate of control hearts from 180/min up to 300/min after coronary occlusion also significantly enlarged myocardial ischemia (P < 0.05). This pacing rate-dependent growth of myocardial ischemia could be prevented completely by either prior depletion of catecholamine stores with reserpine or SOD. Therefore, noradrenaline seems to be the most important source for the generation of oxygen free radicals during myocardial ischemia in isolated saline-perfused rabbit hearts.
authors.affiliation: Institut für Pharmakologie, Universität Köln, Germany.
authors.forename: A F
authors.initials: AF
authors.lastname: Rump
authors.forename: R
authors.initials: R
authors.lastname: Rösen
authors.forename: W
authors.initials: W
authors.lastname: Klaus
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000502:physiology*; D005609:Free Radicals / Q000009:adverse effects; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000627:therapeutic use*
chemical_list: D002395:Catecholamines; D005609:Free Radicals; D013482:Superoxide Dismutase