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Anesthetics and Automaticity in Latent Pacemaker Fibers: IV. Effects of Isoflurane and Epinephrine or Norepinephrine on Automaticity of Dominant and Subsidiary Atrial Pacemakers in the Canine Heart

Background: Anesthesia and surgery may be associated with atrioventricular junctional or ventricular rhythm disturbances. These may be caused by alteration of automaticity of primary and subsidiary pacemakers. Methods: The direct effects of isoflurane, alone or in combination with epinephrine (E) and norepinephrine (NE), as well as single effects of E and NE, were examined on automaticity of primary and subsidiary atrial pacemakers (SAP) using a perfused canine right atrial preparation (n = 29). Preparations were perfused with oxygenated Krebs' ; solution at a constant perfusion pressure of 87 mmHg and a temperature of 36.5 +/- 0.5[degrees] C. Delivered concentrations of isoflurane of 1.4 and 2.8% corresponded to measured perfusate concentrations of 315 +/- 7 and 617 +/- 16 [micro]M in experiments with E (n = 14), and 316 +/- 10 and 610 +/- 26 [micro]M in experiments with NE (n = 15). Epinephrine or NE perfusate concentrations were 2 and 5 [micro]g/l or 5 and 10 [micro]g/l) respectively. To determine the site of earliest activation, extracellular recordings were made from the SA node region and distal sites (approximately 1, 2, and 3 cm) along the sulcus terminalis, the previously reported locations of SAP. Sites of earliest activation shifts from SA node to SAP were scored 1, 2, or 3 depending on the distance from the control pacemaker. The summed shift scores (magnitude score) were normalized by dividing by the total number of preparations for each experimental condition. Results: Exposure to isoflurane, NE, or E alone did not produce a significant increase in the incidence of pacemaker shifts or normalized pacemaker shift scores. Only the high dose of E significantly increased the incidence of pacemaker shifts and normalized shift scores. Dysrhythmogenic potential of E and NE tended to be greater after earlier exposure to isoflurane. Every combination of Isoflurane with E or NE produced a significant increase in the incidence of pacemaker shifts and normalized shift scores. Conclusions: It was concluded that isoflurane with E or NE acts synergistically to increase dysrhythmic potential in the atrial tissue.

isoflurane; epinephrine; norepinephrine; atrial pacemaker

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