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 afrium model, the dose-response curves 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 muM thiopental, > 200 muM ketamine) of thiopental or ketamine was attenuated in isoproterenol-stimulated tissue when compared with beta-adrenergic blocked muscle. Low concentrations (200 muM thiopental, 100 muM ketamine) of anesthetic caused either no change in contractility (thiopental) or small positive inotropic responses (ketamine) in pro-pranolol-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.
Thurston
T A
TA
Department of Anesthesiology, University of Texas Medical Branch at Galveston, USA.
Mathew
B P
BP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D013874:Thiopental / Q000008:administration & dosage / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D018721:Muscarinic Agonists; D011943:Receptors, Adrenergic, beta; D007649:Ketamine; D002217:Carbachol; D011433:Propranolol; D013874:Thiopental; D007545:Isoproterenol