Halothane-epinephrine arrhythmias and adrenergic responsiveness after chronic imipramine administration in dogs.
The incidence of halothane-epinephrine arrhythmias increases after the short-term administration of imipramine, probably because of enhanced noradrenergic transmission. To determine whether this effect persists after long-term imipramine treatment, we have studied the arrhythmogenicity and adrenergic responsiveness in halothane anesthetized dogs after six weeks of imipramine administration, 150 mg X day-1, orally. The mean (+/- SD) arrhythmogenic dose of epinephrine (ADE) in nine dogs anesthetized with 1.2 MAC halothane was 2.57 (+/- 1.04) micrograms X kg-1 X min-1. The alpha-adrenergic responsiveness, assessed as the dose of phenylephrine that caused a 75% increase in mean arterial pressure (alpha 75), was 5.78 +/- 2.39 micrograms X kg-1 X min-1. The dose of isoproterenol that increased heart rate by 75% (beta 75) was 309 +/- 180 ng X kg-1 X min-1. After imipramine treatment, the ADE (2.63 +/- 1.26), alpha 75 (5.16 +/- 2.05), and beta 75 (386 +/- 266) were not statistically different from the pre-imipramine values (P greater than 0.05), despite a fivefold increase in circulating norepinephrine. We conclude that chronic imipramine does not alter arrhythmogenicity and adrenergic responsiveness, since compensatory mechanisms, at the sympathetic nerve terminal, may revert the initial hyper-responsiveness to normal.
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D003891:Desipramine / Q000097:blood; D004285:Dogs; D004347:Drug Interactions; D004837:Epinephrine / Q000009:adverse effects* / Q000097:blood; D005260:Female; D006221:Halothane / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D007099:Imipramine / Q000009:adverse effects* / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology
D010656:Phenylephrine; D007099:Imipramine; D003891:Desipramine; D006221:Halothane; D009638:Norepinephrine; D004837:Epinephrine