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Previous studies have shown that desflurane and isoflurane produce similar hemodynamic actions. This investigation examined the cardiovascular effects of desflurane and isoflurane in the presence or absence of dexmedetomidine, a highly selective α2-adrenergic agonist that may be clinically useful as a premedicant or anesthetic adjuvant.Four groups, comprising 40 experiments, were performed using ten dogs that were chronically instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dtmax), diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experimental days, systemic and coronary hemodynamics were recorded, and plasma concentrations of catecholamines were measured with or without oral dexmedetomidine pretreatment (30 μg/kg) in the conscious state and after 15 min of equilibration at 1.0, 1.3, and 1.6 end-tidal MAC desflurane or isoflurane in a random fashion.In conscious dogs, dexmedetomidine significantly decreased heart rate, cardiac output, percent segment shortening (%SS), left ventricular dP/dtmax, myocardial oxygen consumption (as estimated by the pressure-work index), and plasma norepinephrine concentration. Concomitant increases in systemic and diastolic coronary vascular resistance were observed. Pretreatment with dexmedetomidine decreased peak increases in heart rate during desflurane and isoflurane anesthesia. Mean arterial pressure was reduced less by desflurane than by isoflurane in the absence of dexmedetomidine. This difference was abolished in dogs pretreated with dexmedetomidine. Desflurane, but not isflurane, decreased cardiac output in dexmedetomidine-pretreated dogs when compared with untreated dogs. Concomitantly, systemic vascular resistance was greater in desflurane- versus isoflurane-anesthetized dogs pretreated with dexmedetomidine. No differences in myocardial contractility, as assessed by left ventricular dP/dtmax and %SS, were observed between desflurane and isflurane groups in the absence or presence of dexmedetomidine.The results indicate that the cardiovascular actions of desflurane or isoflurane are similar in the absence or presence of dexmedetomidine; however, some differences between anesthetic groups were noted. In the presence of dexmedetomidine, systemic vascular resistance during desflurine anesthesia was higher when compared with that during isoflurane anesthesia, indicating that desflurane produces less pronouced direct effects on peripheral vascular tone. The concomitant greater reductions in cardiac output are consistent with greater impedance to left ventricular outflow in desflurane-anesthetized dogs pretreated with dexmedetomidine, because no differences in contractile function were observed between volatile anesthetics. In contrast, cardiac output during isoflurane anesthesia after pretreatment with oral dexmedetomidine is better maintained secondary to the peripheral vasodilator actions of this agent.