MYOCARDIAL DEPRESSION BY ISOFLURANE IS DEPENDENT ON THE UNDERLYING BETA-ADRENERGIC TONE

Depression of myocardial contractility by muscarinic agonists is depen dent on underlying beta-adrenergic tone, The negative inotropic effect of muscarinic agonists is enhanced by previous beta-adrenergic stimul ation, an action that has been termed accentuated antagonism, We wishe d to determine whether accentuated antagonism occurs with isoflurane-i nduced myocardial depression, We used an isolated, electrically stimul ated rat left atrium model to compare the dose-response curves to the muscarinic agonist carbachol and isoflurane under conditions of high ( 10(-6)M isoproterenol added to the bath) or low (10(-6)M propranolol) beta-adrenergic tone. As expected, myocardial depression by carbachol was accentuated in preparations stimulated with isoproterenol as compa red with atria treated with propranolol. The decrease in contractility induced by isoflurane was attenuated in isoproterenol-stimulated prep arations as compared with beta-blocked atria. The increased sensitivit y to isoflurane observed in propranolol-treated muscles was reversed b y increasing the concentration of calcium in the bath from 2.5 to 5.0 mM. In contrast to muscarinic agonists, isoflurane-induced myocardial depression is attenuated by previous beta-adrenergic stimulation. Isop roterenol most likely attenuates isoflurane's negative inotropic actio n by increasing the availability of external calcium. The results of t his study demonstrate that the underlying beta-adrenergic tone greatly influences the negative inotropic response of cardiac tissue to isofl urane.