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Increases in desflurane and isoflurane concentrations can transiently Increase arterial blood pressure or heart rate or both during induction of anesthesia. The current study tested the hypothesis that a rapid increase of desflurane concentration in humans increases sympathetic activity and hormonal variables and heart rate and arterial blood pressure more than does an equivalent Increase in isoflurane concentration.Twelve healthy male volunteers were assigned randomly to receive desflurane and on a separate occasion isoflurane. After induction of anesthesia with propofol 2 mg/kg, anesthesia was maintained at 0.55 MAC (desflurane, 4.0%; isoflurane 0.71% end-tidal) for 32 min. Mechanical ventilation maintained normocapnia throughout anesthesia. Mean arterial blood pressure and heart rate were recorded continuously, and arterial blood was sampled for plasma catecholamine and vasopressin (AVP) concentrations, and plasma renin activity. Anesthetic concentration was increased rapidly to 1.66 MAC (desflurane, 12.0%; isoflurane 2.12% end-tidal), and maintained at this concentration for 32 min, and then rapidly decreased to and maintained at 0.55 MAC for an additional 32 min.Neither anesthetic produced sympathetic or cardiovascular stimulation during their initial rapid wash-in to 0.55 MAC. The rapid increase to 1.66 MAC increased mean arterial blood pressure, heart rate, and plasma epinephrine and nor-epinephrine concentrations, and plasma renin activity with both desflurane and isoflurane, the former usually producing a response of greater magnitude than the latter. Plasma AVP concentration increased with desflurane only. Increased mean arterial blood pressure returned to control in 4 min. Heart rate decreased 50% of the difference between its peak and the value at 32 min at 1.66 MAC in 2 min with desflurane and in 4 min with isoflurane but did not return to the value at 0.55 MAC with either anesthetic. With desflurane, plasma epinephrine and AVP concentrations decreased quickly from their peak values, remaining elevated for 8 min. Decrease of concentrations of desflurane and isoflurane from 1.66 MAC to 0.55 MAC rapidly decreased heart rate and increased mean arterial blood pressure with both anesthetics. Thirty-two minutes after return to 0.55 MAC, with both anesthetics, only heart rate remained Increased relative to the values at 32 min of the Initial period of 0.55 MAC anesthesia.In healthy male volunteers, rapid increases of desflurane or isoflurane from 0.55 to 1.66 MAC increase sympathetic and renin-angiotensin system activity, and cause transient increases in arterial blood pressure and heart rate. Desflurane causes significantly greater increases than isoflurane, and also causes a transient increase in plasma AVP concentration. The temporal relationships suggest that the increased sympathetic activity increases mean arterial blood pressure and heart rate, with mean arterial blood pressure also increased by increased plasma AVP concentration, whereas the delayed, increased plasma renin activity is likely a response to the ensuing hypotension, or earlier inhibition by AVP, or both.