Effects of Isoflurane on Cardiovascular System and Sympathovagal Balance in New Zealand White Rabbits

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Abstract
Summary We investigated the effects of isoflurane on the rabbit cardiovascular system at several end-tidal concentrations. Furthermore, because isoflurane has been reported to produce tachycardia while reducing sympathetic nervous activity and baroreflex function, we evaluated whether the chronotropic effects of isoflurane could be due to a vagal withdrawal. ECG, mean arterial pressure (MAP), and heart rate (HR) were obtained in rabbits the conscious, unsedated state and during isoflurane anesthesia by telemetric device. Measurements of pH, oxygen, carbon dioxide, plasma catecholamines, baroreflex sensitivity, and spectral analysis of HR variability were made in nonanesthetized and anesthetized animals. Isoflurane caused an increase in HR at 0.5, 1, and 1.5 minimum alveolar concentration (MAC) and a decrease in systolic and diastolic blood pressure (SBP, DBP) and MAP at 1 and 1.5 MAC. Biochemical analysis showed that isoflurane-mediated cardiovascular effects were not accompanied by any significant changes in plasma norepinephrine (NE) and epinephrine (Epi) levels. Neither were any significant differences in plasma catecholamine levels noted between anesthetized and awake animals. The analysis of spectral components of HR variability and baroreflex function indicated that isoflurane induced a marked reduction in the low- and high-frequency spectral power of HR variability and in baroreflex sensitivity. Tachycardia under isoflurane was suppressed dose dependently by the administration of clonidine or atenolol and was not influenced by bilateral vagotomy. Collectively, our results indicate that cardiovascular effects induced by isoflurane in smaller animals such as rabbits are similar to those observed in humans and other animal species. We showed that isoflurane-induced tachycardia is mainly the result of a vagal withdrawal rather than a baroreflex response, even though a marginal role of baroreflex in heart response to higher concentrations of isoflurane cannot be excluded.