Anesthetics and automaticity in latent pacemaker fibers. III. Effects of halothane and ouabain on automaticity of the SA node and subsidiary atrial pacemakers in the canine heart

Abstract

Atrial tachyarrhythmias are a common manifestation of digitalis toxicity. Such arrhythmias could be due to enhanced automaticity of subsidiary atrial pacemakers (SAP) compared to the sinoatrial (SA) node. Halothane is known to oppose digitalis-induced ventricular arrhythmias. Its effect on digitalis-caused atrial arrhythmias is unknown. Therefore, we tested two hypotheses, as follows. First, increasing ouabain concentrations would enhance automaticity of SAP compared to the SA node and that such enhanced automaticity could explain digitalis-caused atrial tachyarrhythmias. Second, halothane would oppose such enhanced automaticity of SAP, thereby opposing digitalis-caused atrial tachyarrhythmias. A canine right atrial preparation was perfused via the SA node artery with Krebs' solution (36.0 ± 0.5°C) equilibrated with 97% oxygen-3% carbon dioxide. Four bipolar extracellular electrodes recorded the site of earliest activation (SEA), which in this preparation could be the SA node or increasingly remote sites of SAP approximately 1, 2, and 3 cm distal to the SA node along the sulcus terminalis. Pacemaker shifts to SAP during exposure to drugs were scored for magnitude of shift as 1, 2, or 3 depending on which SAP site was the SEA. Magnitude scores were summed for each test condition and normalized by dividing the total number of preparations tested. Preparations (n = 48) were exposed to 1 or 2% halothane (perfusate concentrations of 0.51 ± 0.01 or 0.79 ± 0.03 mM, respectively) and/or to low- or mid-therapeutic (2.5 or 5 X 10-8 M) or borderline toxic ouabain (1 X 10-7 M). Normalized magnitude scores were not significantly different from zero (control value) with any halothane or ouabain concentration alone. The normalized magnitude score for 1% halothane with 1 X 10-7 M ouabain (0.36) was borderline significant (P = 0.055), and scores for 2% halothane with 5 X 10-8 M (0.47) or 1 X 10-7 M ouabain (1.16) were significantly different from zero (P < 0.05). Regardless of pacemaker location, spontaneous heart rate tended to be increased by ouabain and slowed by halothane alone; this tendency was most pronounced for 1 X 10-7 M ouabain or 2% halothane. In preparations with pacemaker shifts, spontaneous rate was not different from control. Finally, total atrial arrest was observed in six preparations exposed to 1 or 2% halothane with 1 X 10-7 M ouabain. It is concluded that in the perfused canine right atrial preparation, increasing ouabain does not sufficiently enhance automaticity of SAP or SA node to account for digitalis-caused atrial tachyarrhythmias. Further, borderline toxic ouabain with halothane favors pacemaker shifts from the SA node to sites of SAP and in some preparations may cause atrial electrical quiescence.