INFLUENCE OF CHOLINERGIC BLOCKADE ON THE DEVELOPMENT OF EPINEPHRINE-INDUCED VENTRICULAR ARRHYTHMIAS IN HALOTHANE-ANESTHETIZED AND ISOFLURANE-ANESTHETIZED DOGS

The arrhythmogenic effects of anesthetic drugs are assessed using the arrhythmogenic dose of epinephrine (ADE) model. The purpose of this st udy was to determine the influence of cholinergic blockade (CB) produc ed by glycopyrrolate (G) on ADE in 1.5 minimum alveolar concentration (MAC) halothane (H)- and isoflurane (I)-anesthetized dogs. Eight dogs (weighing between 12.5 and 21.5 kg) were randomly assigned to four tre atment groups (H, HC, I, and IG) and each treatment was replicated thr ee times. Anesthesia was induced and maintained with H (1.31%, end-tid al [ET]) or I(1.95%, ET) in oxygen. Ventilation was controlled (carbon dioxide [PCO2] 35 to 40 mmHg, ET). G was administered 10 minutes befo re ADE determination at a dose of 22 mu g/kg(11 mu g/kg, intravenous [ IV] and 11 mu g/kg, intramuscular [IM]). The ADE was determined by IV infusion of epinephrine at sequentially increasing rates of 1.0, 2.5, and 5.0 mu g/kg/min; and defined as the total dose of epinephrine prod ucing at least four ectopic ventricular contractions (EVCs) within 15 seconds during a 3-minute infusion and up to 1 minute after the end of the infusion. Total dose was calculated as the product of infusion ra te and time to arrhythmia. Data were analyzed using a randomized compl ete block analysis of variance. When significant (P <.05) F values wer e found a least significant difference test was used to compare group means. Values are reported as means +/- standard error. The ADE (mu g/ kg) for H, HG, I, and IG were 1.53 +/- 0.08, 3.37 +/- 0.46, 1.61 +/- 0 .21, and > 15.00, respectively. Heart rates (HRs) (beats/min) and syst olic pressures (mmHg) at the time of arrhythmia formation for H, HG, I , and IG were (60.3 +/- 4.0 and 142.0 +/- 7.6), (213.0 +/- 13.1 and 23 9.2 +/- 7.1), (62.9 +/- 4.5 and 151.9 +/- 6.3), and (226.3 +/- 6.1 and 323.5 +/- 3.4), respectively. The H and I ADE were not different. The HG ADE was significantly less than the IG ADE. The H and I ADE were s ignificantly less than the HG and IG ADE. We conclude the following fr om the results of this study of epinephrine infusion in halothane- and isoflurane-anesthetized dogs: (I) two distinct mechanisms are respons ible for the development of arrhythmias, (2) CB produced by G signific antly increases ADE but is associated with higher rate pressure produc ts (RPP) and myocardial work, and (3) ADE methodology could be improve d by determining ADE with and without CB. (C) Copyright 1994 by The Am erican College of Veterinary Surgeons