IN-VITRO MYOCARDIAL DEPRESSION BY KETAMINE OR THIOPENTAL IS DEPENDENTON THE UNDERLYING BETA-ADRENERGIC TONE

Background: Depression of myocardial contractility by muscarinic stimu lation is dependent on the underlying beta-adrenergic tone. Prior beta -adrenergic stimulation enhances muscarinic negative inotropic respons es, 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 anest hetics 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 w as accentuated in preparations stimulated with isoproterenol compared with atria treated with propranolol. The decrease in tension by high d oses (>400 mu M thiopental, >200 mu M ketamine) of thiopental or ketam ine was attenuated in isoproterenol-stimulated tissue when compared wi th beta-adrenergic blocked muscle. Low concentrations (200 mu M thiope ntal, 100 mu M ketamine) of anesthetic caused either no change in cont ractility (thiopental) or small positive inotropic responses (ketamine ) in propranolol-treated but not isoproterenol-stimulated tissue. Conc lusions: In contrast to muscarinic agonists, myocardial depression by high concentrations of ketamine or thiopental is attenuated by prior b eta-adrenergic stimulation. Positive inotropic responses may be seen w ith low concentrations of ketamine in muscle with low beta-adrenergic tone. The results of this study demonstrate that the underlying beta-a drenergic tone greatly influences the in vitro response of cardiac tis sue to ketamine or thiopental.