Differences in Production of Reactive Oxygen Species and Mitochondrial Uncoupling as Events in the Preconditioning Signaling Cascade Between Desflurane and Sevoflurane

Abstract

Background Signal transduction cascade of anesthetic-induced preconditioning has been extensively studied, yet many aspects of it remain unsolved. Here we investigated the roles of reactive oxygen species (ROS) and mitochondrial uncoupling in cardiomyocyte preconditioning by 2 modern volatile anesthetics: desflurane and sevoflurane. Methods Adult rat ventricular cardiomyocytes were isolated enzymatically. The preconditioning potency of desflurane and sevoflurane was assessed in cell survival experiments by evaluating myocyte protection from the oxidative stress-induced cell death. ROS production and flavoprotein fluorescence, an indicator of flavoprotein oxidation and mitochondrial uncoupling, were monitored in real-time by confocal microscopy. The functional aspect of enhanced ROS generation by the anesthetics was assessed in cell survival and confocal experiments using the ROS scavenger Trolox. Results Preconditioning of cardiomyocytes with desflurane or sevoflurane significantly decreased oxidative stress-induced cell death. That effect coincided with increased ROS production and increased flavoprotein oxidation detected during acute myocyte exposure to the anesthetics. Desflurane induced significantly greater ROS production and flavoprotein oxidation than sevoflurane. ROS scavenging with Trolox abrogated preconditioning potency of anesthetics and attenuated flavoprotein oxidation. Conclusion Preconditioning with desflurane or sevoflurane protects isolated rat cardiomyocytes from oxidative stress-induced cell death. Scavenging of ROS abolishes the preconditioning effect of both anesthetics and attenuates anesthetic-induced mitochondrial uncoupling, suggesting a crucial role for ROS in anesthetic-induced preconditioning and implying that ROS act upstream of mitochondrial uncoupling. Desflurane exhibits greater effect on stimulation of ROS production and mitochondrial uncoupling than sevoflurane.

TUNEL-positive cells in the surgical border of an amputation due to infected diabetic foot

“…The apoptosis observed in these patients may be explained in numerous ways: preexisting metabolic acidosis, the initial ischemia, an inflammatory response to the infection induced by the trauma of surgery or anesthetics, which could increase the production of reactive oxygen species in the mitochondria (45,46). In all patients in this study, apoptotic cells were identified and associated with vascular injury.…”

Choice of Anesthetic Combination Determines Ca2+Leak after Ischemia-Reperfusion Injury in the Working Rat Heart

“…This confirms previous experiments showing the essential role of ROS in sevoflurane preconditioning. 16,17 Finally, when remifentanil 3 nM was added to sevoflurane 2 vol.-%, functional recovery was similar to sevoflurane alone or to remifentanil alone. Unexpectedly, this combination markedly increased peak ischemic …”

Mitochondrial depolarization underlies delay in permeability transition by preconditioning with isoflurane: roles of ROS and Ca2+

“…Cardiomyocytes were isolated from ventricles of adult male Wistar rats (180 -250 g) using collagenase and protease for enzymatic dissociation, as previously reported (46). Rats were anesthetized with sodium thiobutabarbital (Inactin, Sigma-Aldrich, St. Louis, MO, 150 mg/kg, administered intraperitoneally).…”

“…The number of live cells was counted at the beginning and at the end of the experiment. Rod-shaped cells without membrane blebs that excluded Trypan blue were considered alive (46). Cell death was normalized to control (Ctrl), expressed as 100%.…”