In vitro myocardial depression by ketamine or thiopental is dependent on the underlying beta-adrenergic tone

Background: Depression of myocardial contractility by muscarinic stimulation is dependent on the underlying beta-adrenergic tone. Prior beta-adrenergic stimulation enhances muscarinic negative inotropic responses, an effect that has been termed accentuated antagonism. The purpose of this study was to determine whether accentuated antagonism occurs with myocardial depression caused by thiopental or ketamine. Methods: Using an isolated, electrically stimulated rat left atrium model, the dose-response curies to the muscarinic agonist carbachol and the anesthetics ketamine and thiopental were compared under conditions of high (10(-6)M isoproterenol bath concentration) or low (10(-6)M propranolol) beta-adrenergic tone. Results: As expected, depression by carbachol was accentuated in preparations stimulated with isoproterenol compared with atria treated with propranolol. The decrease in tension by high doses (>400 mu M thiopental, >200 mu M ketamine) of thiopental or ketamine was attenuated in isoproterenol-stimulated tissue when compared with beta-adrenergic blocked muscle. Low concentrations (200 mu M thiopental, 100 mu M ketamine) of anesthetic caused either no change in contractility (thiopental) or small positive inotropic responses (ketamine) in propranolol-treated but not isoproterenol-stimulated tissue. Conclusions: In contrast to muscarinic agonists, myocardial depression by high concentrations of ketamine or thiopental is attenuated by prior beta-adrenergic stimulation. Positive inotropic responses may be seen with low concentrations of ketamine in muscle with low beta-adrenergic tone. The results of this study demonstrate that the underlying beta-adrenergic tone greatly influences the in vitro response of cardiac tissue to ketamine or thiopental.