Alterations in the arrhythmogenic dose of epinephrine after adrenergic receptor blockade with prazosin, metoprolol, or yohimbine in halothane-xylazine-anesthetized dogs.
Recent evidence has linked alpha-receptor and beta-receptor activations with ventricular arrhythmia genesis. In order to assess the relative contribution of specific adrenoceptors (alpha 1, alpha 2, beta 1) on ventricular arrhythmogenic activity during xylazine (1.1 mg X kg-1 X hr-1)-halothane (1.35%) anesthesia, the arrhythmogenic dose of epinephrine (ADE) was repeatedly determined before and after prazosin (alpha 1 antagonist; 0.1 mg X kg-1), metoprolol (beta 1 antagonist; 0.5 mg X kg-1), and yohimbine (alpha 2 antagonist; 0.125 mg X kg-1) administration in 6 dogs. The ADE was expressed as infusion rate and total dose. The ADE was defined as the dose which produced 4 or more intermittent premature ventricular contractions within 15 s during a 3-minute infusion period or within 1 minute from end of infusion. Control ADE was 2.69 +/- 0.372 (micrograms X kg-1 X min-1) and 4.17 +/- 0.544 (micrograms X kg X -1) for infusion rate and total dose, respectively. The ADE significantly increased after prazosin (P less than 0.005), metoprolol (P less than 0.005), and yohimbine (P less than 0.05) administration. The ADE values increased to 5.42 +/- 1.22 (rate) and 8.10 +/- 1.95 (dose) after alpha 2 blockade, but were significantly less than the alpha 1 and beta 1 blockade ADE values. In conclusion, although both alpha- and beta-adrenoceptor blockade depressed ventricular arrhythmia genesis in xylazine-halothane-anesthetized dogs, alpha 2 blockade, which was achieved with the recommended dose of yohimbine for reversal of anesthetic-induced CNS depression, was not as protective as alpha 1 (prazosin) or beta 1 (metoprolol) blockade.
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000633:toxicity*; D005260:Female; D006221:Halothane; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D014991:Xylazine; D015016:Yohimbine / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D014991:Xylazine; D015016:Yohimbine; D008790:Metoprolol; D006221:Halothane; D011224:Prazosin; D004837:Epinephrine