Myocardial depression by isoflurane is dependent on the underlying beta-adrenergic tone

Depression of myocardial contractility by muscarinic agonists is dependent on underlying beta-adrenergic tone. The negative inotropic effect of muscarinic agonists is enhanced by previous beta-adrenergic stimulation, an action that has been termed accentuated antagonism. We wished to determine whether accentuated antagonism occurs with isoflurane-induced myocardial depression. We used an isolated, electrically stimulated 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 compared with atria treated with propranolol. The decrease in contractility induced by isoflurane was attenuated in isoproterenol-stimulated preparations as compared with beta-blocked atria. The increased sensitivity to isoflurane observed in propranolol-treated muscles was reversed by 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. Isoproterenol most likely attenuates isoflurane's negative inotropic action by increasing the availability of external calcium. The results of this study demonstrate that the underlying beta-adrenergic tone greatly influences the negative inotropic response of cardiac tissue of isoflurane.