ANESTHETICS AND AUTOMATICITY IN LATENT PACEMAKER FIBERS .4. 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 atrioventric ular junctional or ventricular rhythm disturbances. These may be cause d by alteration of automaticity of primary and subsidiary pacemakers. Methods. The direct effects of isoflurane, alone or in combination wit h epinephrine (E) and norepinephrine (NE), as well as single effects o f E and NE, were examined on automaticity of primary and subsidiary at rial 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 gm in experiments with E (n = 14), and 316 +/- 10 and 610 +/- 26 mum in experiments with NE (n = 15). Epinephrine or NE perfusat e concentrations were 2 and 5 mug/l or 5 and 10 mug/l, respectively. T o 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 locat ions of SAP. Sites of earliest activation shifts from SA node to SAP w ere scored 1, 2, or 3 depending on the distance from the control pacem aker. The summed shift scores (magnitude score) were normalized by div iding by the total number of preparations for each experimental condit ion. Results: Exposure to isoflurane, NE, or E alone did not produce a significant increase in the incidence of pacemaker shifts or normaliz ed pacemaker shift scores. Only the high dose of E significantly incre ased the incidence of pacemaker shifts and normalized shift scores. Dy srhythmogenic 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 a nd normalized shift scores. Conclusions: It was concluded that isoflur ane with E or NE acts synergistically to increase dysrhythmic potentia l in the atrial tissue.