Anesthetic preconditioning: triggering role of reactive oxygen and nitrogen species in isolated hearts

Abstract

We postulated that anesthetic preconditioning (APC) is triggered by reactive oxygen/ nitrogen species (ROS/RNS). We used the isolated guinea pig heart perfused with L-tyrosine, which reacts with ROS and RNS to form strong oxidants, principally peroxynitrite (ONOO Ϫ ), and then forms fluorescent dityrosine. ROS scavengers superoxide dismutase, catalase, and glutathione (SCG) and NO⅐ synthesis inhibitor N G -nitro-L-arginine methyl ester (L-NAME) were given 5 min before and after sevoflurane preconditioning stimuli. Drugs were washed out before 30 min of ischemia and 120 min of reperfusion. Groups were control (nontreated ischemia control), APC (two, 2-min periods of perfusion with 0.32 Ϯ 0.02 mM of sevoflurane; separated by a 6-min period of perfusion without sevoflurane), SCG, APC ϩ SCG, L-NAME, and APC ϩ L-NAME. Effluent dityrosine at 1 min reperfusion was 56 Ϯ 6 (SE) ‡, 15 Ϯ 5, 40 Ϯ 5 ‡, 39 Ϯ 4 ‡, 35 Ϯ 4 ‡, and 33 Ϯ 5 ‡ units ( ‡P Ͻ 0.05 vs. APC), respectively; left ventricular pressure (%baseline) at 60 min of reperfusion was 30 Ϯ 5 ‡, 60 Ϯ 4, 35 Ϯ 5 ‡, 37 Ϯ 5 ‡, 44 Ϯ 4, and 47 Ϯ 4; and infarct size (%total heart weight) was 50 Ϯ 5 ‡, 19 Ϯ 2, 48 Ϯ 3 ‡, 46 Ϯ 4 ‡, 42 Ϯ 4 ‡, and 45 Ϯ 2 ‡. Thus APC is initiated by ROS as shown by improved function, reduced infarct size, and reduced dityrosine on reperfusion; protective and ROS/RNS-reducing effect of APC were attenuated when bracketed by ROS scavengers or NO⅐ inhibition. guinea pig; experimental; pathophysiology; contractile function; infarct size CARDIAC ISCHEMIC PRECONDITIONING (IPC), first described in 1986 (21), is most often assessed by observations of reduced infarct size, attenuated mechanical dysfunction, or limited ultrastructural abnormality on reperfusion after prolonged ischemia (3,5,16,25,27,28,43). Anesthetics can also precondition hearts against ischemic-reperfusion (IR) injury (3,7,14,25,28). For example, Novalija and Stowe (28) reported that anesthetic preconditioning (APC) with sevoflurane mimics IPC by improving vascular, mechanical, and metabolic function in isolated hearts.The role of reactive oxygen species (ROS) in effecting cardiac injury on aerobic reperfusion after ischemia is now well known (11, 32). The seemingly paradoxical role of ROS and reactive nitrogen species (RNS) in triggering or mediating IPC has gained increasing importance (23,33,37). Studies using inhibitors of nitric oxide (NO⅐) synthase during IR injury suggest the specific role of NO⅐ in cardioprotection is unclear (12,16,22,23,33,(42)(43)(44). However, because NO⅐ is a free radical produced constitutively and because superoxide (O 2 Ϫ ⅐) reacts faster with NO⅐ than it does with superoxide dismutase (SOD), NO⅐ is a factor that must be considered in IR injury. We showed that NO⅐ release is improved along with vascular and mechanical function after IPC and APC with sevoflurane and that these effects are blocked by ATP-sensitive K (K ATP ) channel inhibition (25,28). Peroxynitrite (ONOO Ϫ ), the product of NO⅐ and O 2 Ϫ ⅐, is released on reperfusion after ischemia (45) and ...

Avaliação de parâmetros antioxidantes em ratos tratados com sevoflurano

“…Our results also favor the importance of fasting in the modulation the enzymatic activity of the mitochondria and endoplasmic reticulum on drug metabolism because rats (high metabolic rate) did not ingest anything for more than one hour during the five days in which sevoflurane was administered (groups G2 and G4), which also favors induction of CYP2E1. Most studies have indicated a possible antioxidant effect of sevoflurane 15,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]35 ; however, depending on the tissue, this could be beneficial or harmful. For example, the cardiac protection induced by myocardial ischemic preconditioning is a benefic effect of ROS produced by sevoflurane 16 .…”

“…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 . On the other hand, recent publications have discussed the phenomenon of anesthetic preconditioning, in which short exposure to sevoflurane is capable of protecting the myocardium and other organs against the deleterious tissue effects promoted by the process of ischemia/reperfusion 15,16 . Considering the extremely reduced number of studies on the antioxidant defense mechanism after multiple exposures to sevoflurane, the objective of the present study was to evaluate the activity of antioxidant enzymes of erythrocytes in Wistar rats treated with sevoflurane, with or without enzymatic induction of CYP2E1 with isoniazid.…”

Anesthetic-induced myocardial protection in cardiac surgery: relevant mechanisms and clinical translation

“…Regarding the use of propofol-based TIVA, it is important to note that its oxygen free radical scavenging property may actually prevent other pre-conditioning effects [16,24]. Indeed, one of the triggers of anesthetic pre-conditioning is the formation of ROS species that can be inhibited by propofol.…”

“…The generation of a small amount of ROS is essential in triggering myocardial protection induced by volatile anesthetics, while excessive oxidative stress and the production of large amounts of ROS are harmful [16]. Volatile anesthetics cause a small degree of subclinical harm (e.g., ROS generation) to trigger protective signaling against persistent and clinically harmful I-R injury, which can be viewed as pre-conditioning.…”

Sevoflurane induces cardioprotection through reactive oxygen species-mediated upregulation of autophagy in isolated guinea pig hearts

“…Many potential mechanisms for this cardioprotection known as anesthetic preconditioning (APC) have been proposed [8]. Novalija et al demonstrated that APC by sevoflurane is initiated by reactive oxygen species (ROS) produced during sevoflurane exposure and reduces the burst formation of ROS after ischemia-reperfusion in isolated guinea pig hearts [9]. Recently, cardioprotection by sevoflurane has been shown to be mediated by ROS-induced 5' AMP-activated protein kinase (AMPK) activation which is a well known regulator of cellular energy status [10].…”