Disproportional and paradoxical changes in blood pressure, heart rate and baroreflex under isoflurane anesthesia

Abstract

For the biomedical researchers, the mandatory employment of anesthetics in experiments involving animals is often regarded as a major limitation because the results may be different from those obtained under a conscious state. For the anesthesiologists, whether patients may have been subjected to unnecessarily deep anesthesia that might jeopardize functions of the cardiovascular system and create inadvertent damage to the nervous system is a recurrent concern. Using isoflurane as the representative anesthetic agent, the goal of this study was to address the issue of whether general anesthetics induce their depressive actions equally on all aspects of cardiovascular functions and their regulations and whether the degree of depression is directly related to the doses. To mimic the clinical setting during surgery, changes of blood pressure (BP), heart rate (HR) and baroreflex in mice instrumented for radiotelemetry were recorded under a conscious state, to be followed by the delivery of incremental concentrations of isoflurane. We found that there was a significant but disproportional reduction in the cardiovascular parameters when C57BL/6 mice were subjected to 1.5% isoflurane anesthesia. Compared with the conscious state, the averaged reduction in BP or HR amounted to 23.5% or 20.5%. On the other hand, the experimental indices for baroreflex‐mediated sympathetic vasomotor tone or cardiac vagal baroreflex manifested a precipitous decline of 90.0% or 63.4%. On incremental concentrations of isoflurane up to a maximum of 4%, mice exhibited sustained BP and HR, alongside returning of both arms of the baroreflex towards the conscious level. We further found that bilateral adrenalectomy exerted minimal effects on the changes in BP, HR and baroreflex in mice subjected to incremental concentrations of isoflurane. It is therefore unlikely that norepinephrine and epinephrine released from the adrenal medulla may account for the disproportional and paradoxical changes in BP, HR and baroreflex under isoflurane anesthesia. These surprise observations offer at least two challenges to the general assumptions on general anesthesia. The effects of isoflurane on cardiovascular functions and their regulations are not exerted proportionally, and both baroreflex‐mediated sympathetic vasomotor tone and cardiac vagal baroreflex exhibit large functional capacity and plasticity in terms of regulating BP and HR.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.