Akihiro Ohsumi1, Katherine Marseu2, Peter Slinger2, Karen McRae2, Hyunhee Kim1, Zehong Guan1, David M Hwang1, Mingyao Liu1, Shaf Keshavjee1, Marcelo Cypel3. 1. Latner Thoracic Surgery Research Laboratories, University Health Network, University of Toronto, Toronto, Ontario, Canada. 2. Department of Anesthesiology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. 3. Latner Thoracic Surgery Research Laboratories, University Health Network, University of Toronto, Toronto, Ontario, Canada. Electronic address: marcelo.cypel@uhn.ca.
Abstract
BACKGROUND: Sevoflurane is one of the most commonly used volatile anesthetic agents with the fastest onset and offset, replacing isoflurane in modern anesthesiology. Preconditioning and postconditioning using volatile anesthetics can attenuate ischemia-reperfusion injury (IRI). However, no previous studies have evaluated the effect of sevoflurane in lung transplantation after cold ischemic injury. We aimed to study the effects of donor and recipient treatment with sevoflurane in a rat lung transplantation model. METHODS: Lewis rats were allocated to four groups: control, PreC (preconditioning), PostC (postconditioning), and PreC + PostC. Donor rats in the PreC and PreC + PostC groups were exposed to 1.5% sevoflurane for 30 minutes before donor operation. Donor lungs were flushed with Perfadex and stored for 12 hours at 4°C before transplantation. Recipients received orthotopic left lung transplantation. In the PostC and PreC + PostC groups, sevoflurane was initiated 2 minutes before reperfusion and maintained for 30 minutes. Two hours after reperfusion, lung function was evaluated, and samples were collected for histologic, inflammatory, and cell death assessment. RESULTS: Preconditioning and postconditioning using sevoflurane significantly improved the oxygenation of lung grafts (partial arterial gas pressure of oxygen: 198 mm Hg in control, 406.5 mm Hg in PreC, 472.4 mm Hg in PostC, and 409.7 mm Hg in PreC + PostC, p < 0.0001) and reduced pulmonary edema. Sevoflurane treatment reduced levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Moreover, sevoflurane significantly inhibited apoptotic cells by a decrease in cytochrome c release into cytosol and caspase-3 cleavage. CONCLUSIONS: Preconditioning or postconditioning of lungs using sevoflurane exhibits a significant protective effect against early phase of ischemia-reperfusion injury in a rat lung transplantation model.
BACKGROUND:Sevoflurane is one of the most commonly used volatile anesthetic agents with the fastest onset and offset, replacing isoflurane in modern anesthesiology. Preconditioning and postconditioning using volatile anesthetics can attenuate ischemia-reperfusion injury (IRI). However, no previous studies have evaluated the effect of sevoflurane in lung transplantation after cold ischemic injury. We aimed to study the effects of donor and recipient treatment with sevoflurane in a rat lung transplantation model. METHODS: Lewis rats were allocated to four groups: control, PreC (preconditioning), PostC (postconditioning), and PreC + PostC. Donorrats in the PreC and PreC + PostC groups were exposed to 1.5% sevoflurane for 30 minutes before donor operation. Donor lungs were flushed with Perfadex and stored for 12 hours at 4°C before transplantation. Recipients received orthotopic left lung transplantation. In the PostC and PreC + PostC groups, sevoflurane was initiated 2 minutes before reperfusion and maintained for 30 minutes. Two hours after reperfusion, lung function was evaluated, and samples were collected for histologic, inflammatory, and cell death assessment. RESULTS: Preconditioning and postconditioning using sevoflurane significantly improved the oxygenation of lung grafts (partial arterial gas pressure of oxygen: 198 mm Hg in control, 406.5 mm Hg in PreC, 472.4 mm Hg in PostC, and 409.7 mm Hg in PreC + PostC, p < 0.0001) and reduced pulmonary edema. Sevoflurane treatment reduced levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Moreover, sevoflurane significantly inhibited apoptotic cells by a decrease in cytochrome c release into cytosol and caspase-3 cleavage. CONCLUSIONS: Preconditioning or postconditioning of lungs using sevoflurane exhibits a significant protective effect against early phase of ischemia-reperfusion injury in a rat lung transplantation model.