Identification of receptor mechanism mediating epinephrine-induced arrhythmias during halothane anesthesia in the dog.
The adrenergic receptor mechanism by which halothane sensitizes the myocardium to the ventricular arrhythmogenic properties of catecholamines is unknown. The new generation of selective adrenergic receptor antagonists have been used to determine which receptor blockade causes the greater increase in the dose of epinephrine needed to achieve a threshold for ventricular arrhythmias. Dogs anesthetized with 1.2 MAC halothane had an arrhythmogenic dose of epinephrine (ADE) of 2.2 micrograms X kg X min-1 that significantly increased (P less than 0.01) to 27 micrograms X kg-1 X min-1 after alpha 1 blockade with prazosin. beta 1 blockade with metoprolol also significantly increased the ADE to 12 micrograms X kg-1 X min-1 (P less than 0.05) but was less than the effect noted after prazosin treatment (P less than 0.05). The dramatic increase in the threshold for arrhythmias noted after prazosin could not be ascribed solely to its hemodynamic properties because treatment with sodium nitroprusside did not change the ADE (2.7 micrograms X kg-1 X min-1) significantly; yet nitroprusside treatment resulted in a similar drop in mean arterial pressure (59 mmHg) to that of prazosin treatment (51 mmHg) when compared with the control group. Thus postsynaptic myocardial alpha 1 adrenergic receptors mediate most of the sensitization by halothane to the ventricular arrhythmogenic effects of catecholamines, while a lesser contribution is conferred by the beta 1 adrenoceptors. These results have implications for the treatment and identification of patients particularly at risk from halothane-epinephrine interactions.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000378:metabolism; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism; D006221:Halothane; D008790:Metoprolol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D011941:Receptors, Adrenergic; D009599:Nitroprusside; D008790:Metoprolol; D006221:Halothane; D011224:Prazosin; D004837:Epinephrine