Desflurane is a new, potent, inhaled anesthetic agent that has a very low solubility in blood which permits rapid anesthetic induction and awakening. Recent observations in our lab suggest that the administration of desflurane produces marked sympathetic activation resulting in substantial tachycardia and hypertension. In addition, published data from patients with coronary artery disease receiving desflurane demonstrated an unusually high incidence of tachycardia, hypertension and myocardial ischemia. These observations raise the possibility that desflurane might adversely influence the myocardial O2 supply/demand ratio. It is currently unknown if the co-administration of adjuvant drugs (e.g. opioids or nitrous oxide) during desflurane anesthesia favorably modifies the cardiovascular effects of desflurane. It also is uncertain how the neurocirculatory responses to desflurane are altered by age, yet this knowledge would seem to be essentIal prior to desflurane's widespread use. Through this series of studies a more thorough understanding of the autonomic and cardiovascular effects of desflurane will be established. I hypothesize that desflurane activates the sympathetic nervous system and alters baroreceptor reflex control of the circulation, and that these effects are modified in important and reproducible ways by co- administration of common anesthetic adjuvants and by the aging process. The proposed studies will compare and contrast equi-potent concentrations of desflurane and isoflurane. Sympathetic outflow will be directly recorded by sympathetic microneurography and parasympathetic outflow to the heart will be indirectly evaluated by spectral analysis of heart rate variability. In addition, measurements of HR, arterial, central venous and pulmonary artery pressures, norepinephrine levels, forearm arterial blood flow (FBF) and forearm venous compliance (FVC) will be employed to compare the neurocirculatory effects of these two anesthetics. Lower body negative pressure, neck suction/neck pressure and infusions of sodium nitroprusside and phenylephrine will be employed to evaluate cardiopulmonary and arterial baroreflex function while the cold pressor test will be employed to elicit nonbaroreceptor perturbations in autonomic activity. The effects of normal aging and adjuvant drugs (fentanyl, nitrous oxide and topical anesthesia with lidocaine) on the neurocirculatory responses to desflurane will be determined. Finally, the direct effects of desflurane on FBF and FVC will be determined in sympathetically-denervated limbs of spinal cord injured patients. Through these series of studies, a more thorough understanding of the neurocirculatory effects of desflurane will be established. Such knowledge may prove crucial in providing safe anesthesia with desflurane to a diverse population of surgical candidates.
