Reactive Oxygen Species as Mediators of Cardiac Injury and Protection: The Relevance to Anesthesia Practice

Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin, United States
Anesthesia & Analgesia (Impact Factor: 3.47). 12/2005; 101(5):1275-87. DOI: 10.1213/01.ANE.0000180999.81013.D0
Source: PubMed


Reactive oxygen species (ROS) are central to cardiac ischemic and reperfusion injury. They contribute to myocardial stunning, infarction and apoptosis, and possibly to the genesis of arrhythmias. Multiple laboratory studies and clinical trials have evaluated the use of scavengers of ROS to protect the heart from the effects of ischemia and reperfusion. Generally, studies in animal models have shown such effects. Clinical trials have also shown protective effects of scavengers, but whether this protection confers meaningful clinical benefits is uncertain. Several IV anesthetic drugs act as ROS scavengers. In contrast, volatile anesthetics have recently been demonstrated to generate ROS in the heart, most likely because of inhibitory effects on cardiac mitochondria. ROS are involved in the signaling cascade for cardioprotection induced by brief exposure to a volatile anesthetic (termed "anesthetic preconditioning"). ROS, therefore, although injurious in large quantities, can have a paradoxical protective effect within the heart. In this review we provide background information on ROS formation and elimination relevant to anesthetic and adjuvant drugs with particular reference to the heart. The sources of ROS, the means by which they induce cardiac injury or activate protective signaling pathways, the results of clinical studies evaluating ROS scavengers, and the effects of anesthetic drugs on ROS are each discussed.

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Available from: David Stowe, May 18, 2015
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    • "Putative mK ATP channel openers led to mild swelling and uncoupling of mitochondria (mild loss of m ), and a " small " transient rise in ROS emission (signaling ROS) associated with a decrease in mitochondrial Ca 2+ load (Wang et al., 2001; Facundo et al., 2006a,b). VA exert cardioprotective effects that most certainly involve mitochondrial bioenergetics (discussed later), and also mK ATP channel (or other K + channels) opening, as reviewed by our group previously (Riess et al., 2004b; Stowe and Kevin, 2004; De Hert et al., 2005; Kevin et al., 2005). "
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    ABSTRACT: Mitochondria are critical modulators of cell function and are increasingly recognized as proximal sensors and effectors that ultimately determine the balance between cell survival and cell death. Volatile anesthetics (VA) are long known for their cardioprotective effects, as demonstrated by improved mitochondrial and cellular functions, and by reduced necrotic and apoptotic cell death during cardiac ischemia and reperfusion (IR) injury. The molecular mechanisms by which VA impart cardioprotection are still poorly understood. Because of the emerging role of mitochondria as therapeutic targets in diseases, including ischemic heart disease, it is important to know if VA-induced cytoprotective mechanisms are mediated at the mitochondrial level. In recent years, considerable evidence points to direct effects of VA on mitochondrial channel/transporter protein functions and electron transport chain (ETC) complexes as potential targets in mediating cardioprotection. This review furnishes an integrated overview of targets that VA impart on mitochondrial channels/transporters and ETC proteins that could provide a basis for cation regulation and homeostasis, mitochondrial bioenergetics, and reactive oxygen species (ROS) emission in redox signaling for cardiac cell protection during IR injury.
    Frontiers in Physiology 09/2014; 5:341. DOI:10.3389/fphys.2014.00341 · 3.53 Impact Factor
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    • "It is now recognized that the constitutive generation of moderate amounts of ROS is important for normal physiological processes (Owusu-Ansah and Banerjee, 2009). In the heart, moderate and controlled levels of ROS could promote myocyte growth (Sugden and Clerk, 2006), regulate vascular smooth muscle tone (Suvorava and Kojda, 2009), and act as protective signaling elements during the preischemic phase (Kevin et al., 2005). However, the precise mechanisms by which ROS maintain cardiac homeostasis have yet to be established, particularly the ROS-mediated paracrine signaling mechanisms that are crucial for proper heart function. "
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    ABSTRACT: Reactive oxygen species (ROS) can act cell autonomously and in a paracrine manner by diffusing into nearby cells. Here, we reveal a ROS-mediated paracrine signaling mechanism that does not require entry of ROS into target cells. We found that under physiological conditions, nonmyocytic pericardial cells (PCs) of the Drosophila heart contain elevated levels of ROS compared to the neighboring cardiomyocytes (CMs). We show that ROS in PCs act in a paracrine manner to regulate normal cardiac function, not by diffusing into the CMs to exert their function, but by eliciting a downstream D-MKK3-D-p38 MAPK signaling cascade in PCs that acts on the CMs to regulate their function. We find that ROS-D-p38 signaling in PCs during development is also important for establishing normal adult cardiac function. Our results provide evidence for a previously unrecognized role of ROS in mediating PC/CM interactions that significantly modulates heart function.
    Cell Reports 03/2014; 7(1). DOI:10.1016/j.celrep.2014.02.029 · 8.36 Impact Factor
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    • "In contrast, inducible NOS (iNOS) showed dramatic de novo formation 1 week after infarction, predominantly in the infarcted area and cardiomyocytes [5-7]. Moreover, a gradually increased myocardial production of superoxide (O2-) has been detected during remodeling in the peri-infarcted and remote myocardium [5,8,9]. The reaction of superoxide with NO reduces the bioavailability of NO as a vasodilator by generating peroxynitrite (a product of NO + O2-), which itself may contribute adversely to vascular function and the compensatory effects of NO and thereby influence post-infarction remodeling [8,9]. "
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    ABSTRACT: Phenylephrine (PE) produces tonic contraction through involvement of various calcium channels such as store-operated calcium channels (SOCCs) and voltage-operated calcium channels (VOCCs). However, the relative contribution of each calcium channel to PE-induced contraction has not been investigated in isolated rat aorta of early acute myocardial infarction (AMI). Endothelium-denuded rat aortic rings from rats 3 days after AMI or sham-operated (SHAM) rats were prepared in an organ chamber with Krebs-Ringer bicarbonate solution for isometric tension recording. We assessed the PE dose-response relationships in 2.5 mM calcium medium for both groups. The same procedure was repeated using rings pretreated with the SOCC inhibitor 2-aminoethoxydiphenyl borate, sarco/endoplasmic-reticulum calcium ATPase inhibitor thapsigargin (TG), diacyl glycerol lipase inhibitor RHC80267, and sodium-calcium exchanger inhibitor 3,4-dichlorobenzamil hydrochloride for 30 minutes before addition of calcium. When ongoing tonic contraction was sustained, dose-response curves to the VOCC inhibitor nifedipine were obtained to assess the relative contribution of each calcium channel under various conditions. The effect of SOCC induction with TG pretreatment on PE-induced contraction was significantly lower in the AMI group compared to the SHAM group. In addition, there were significant decreases in the sensitivity and efficacy of the VOCC inhibitor nifedipine on PE-induced contraction in the AMI group. Results suggest that the change of vascular reactivity of PE in rat aorta 3 days after AMI is characterized by a decreased contribution of L-type VOCCs. The enhanced VOCC-independent calcium entry mechanisms after AMI can be mediated by enhanced capacitative calcium entry through the activation of SOCCs.
    Korean journal of anesthesiology 02/2014; 66(2):143-52. DOI:10.4097/kjae.2014.66.2.143
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