Sevoflurane Exposure Generates Superoxide but Leads to Decreased Superoxide During Ischemia and Reperfusion in Isolated Hearts

Abstract

Reactive oxygen species (ROS) are implicated in triggering anesthetic preconditioning (APC). The ROS superoxide (O(2)(.-)) was measured continuously in guinea pig isolated hearts. Sevoflurane directly increased O(2)(.-) but led to attenuated O(2)(.-) formation during ischemia. This demonstrates triggering of APC by ROS and clarifies the mechanism of cardioprotection during ischemia.

Proteção miocárdica pelo pré- e pós-condicionamento anestésico

“…Varredores de radicais livres administrados durante o tratamento prévio com isoflurano aboliram os efeitos protetores contra a lesão de I/R 71,72 . Um estudo realizado em corações isolados de cobaias utilizou o diidroetídio para observar a geração de ROS por meio de um espectrofotômetro, em que uma sonda de fibra óptica foi colocada contra a parede do ventrículo esquerdo 73 . A administração de sevoflurano provocou aumento imediato e reversível na fluorescência do etídio, consistente com a produção de pequenas quantidades de ROS sinalizadores.…”

“…Os anestésicos voláteis também protegem o miocárdio pela atenuação das conseqüências da explosão de ROS durante a reperfusão. Um exemplo seria o efeito protetor do PCA associado a marcante redução na formação de ROS durante a I/R 73 . A produção aumentada de ROS durante a reperfusão eleva o influxo de Ca ++ para a mitocôndria, cujo efeito é a abertura dos poros de PTM que resultará na morte celular pela via da apoptose.…”

“…Free radicals scavengers administered during treatment with isoflurane abolished the protective effects against the I/R damage 71,72 . A study of isoflurane in isolated guinea pigs hearts used dihydroethidium to observe the generation of ROS through a spectrophotometer, in which a fiberoptic probe was placed against the wall of the left ventricle 73 . The administration of isoflurane caused an immediate and reversible increase in ethidium bromide fluorescence, which is consistent with the production of small amounts of signaling ROS.…”

“…Volatile anesthetics also protect the myocardium by attenuating the consequences of ROS burst during reperfusion. The protective effect of APC associated with a markedly reduction in the formation of ROS during I/R is an example 73 . The increased production of ROS during reperfusion increases the influx of Ca ++ into the mitochondria, opening TMP pores, resulting in cell death by apoptosis.…”

Avaliação de parâmetros antioxidantes em ratos tratados com sevoflurano

“…The enzyme CYP2E1, responsible for the hepatic biotransformation of sevoflurane, is capable of producing ROS like superoxide anion (O 2 -) and hydrogen peroxide (H 2 O 2 ) during the catalytic cycle 8 . The presence of iron ions during this production of O 2 is capable of generating the highly reactive ROS hydroxyl radical (OH -) 9 Regarding the antioxidant effects of sevoflurane, some authors have suggested that this drug is capable of producing ROS, such as the hydroxyl radical (OH), anion peroxide (O 2 -) 10 , and hydrogen peroxide (H 2 O 2 ) 11 , besides promoting lipoperoxidation 12 , therefore weakening the antioxidant enzyme 13 system in several tissues. It has been speculated that sevoflurane is capable of changing the flow of electrons along the respiratory chain, at the mitochondrial level, promoting the formation of ROS 14 .…”