Hydrogen peroxide mediates reperfusion injury in the isolated rat heart

Abstract

In an isolated, normothermic rat heart model (Langendorff, 37 degrees C), dimethylthiourea (DMTU) infusion only during reperfusion reduced both injury and measurable hydrogen peroxide (H2O2) concentrations after global ischemia. Cardiac function was assessed by measurement of ventricular developed pressure (DP). H2O2 was assessed using H2O2 dependent aminotriazole inactivation of myocardial catalase. Depletion of xanthine oxidase by two methods (tungsten or allopurinol inhibition) also improved recovery of function and H2O2 production. The results indicate that XO derived H2O2 contributes to myocardial reperfusion injury.

Glucocorticoids Activate Cardiac Mineralocorticoid Receptors During Experimental Myocardial Infarction

“…Although thrombolytic therapy and percutaneous coronary interventions reduce mortality from acute myocardial infarction, additional therapeutic strategies are needed, given that reperfusion of the ischemic myocardium generates oxygen free radicals 1,2 and that impaired myocardial antioxidant defense capacity leads to tissue injury. 3 Several clinical trials, the Randomized Aldactone Evaluation Study 4 and the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study, 5 showed decreased mortality with the use of mineralocorticoid receptor antagonists in addition to standard therapy, evidence for a role of mineralocorticoid receptor (MR) activation in myocardial infarction and heart failure.…”

Attenuation of Myocardial Ischemia-Reperfusion Injury by Trimetazidine Derivatives Functionalized with Antioxidant Properties

“…ROS play an important role in the etiology of myocardial ischemia reperfusion (I/R) injury (Brown et al, 1988;Ambrosio et al, 1993). During ischemia, the coronary blood supply to the heart is reduced or stopped preventing oxygen, glucose, and fatty acids from reaching the target tissue (Weiss et al, 2003).…”

“…Ischemia inactivates oxidative phosphorylation, leading to a loss of adenine nucleotides and cytochrome c, accumulation of free phosphate, fatty acids, and lactic acid, increased cellular calcium, and a decrease in cellular pH (Dennis et al, 1991). Upon reperfusion, oxygen interacts with the damaged mitochondrial respiratory chain to produce a burst of ROS leading to I/R injury (Brown et al, 1988;Ambrosio et al, 1993). Apart from the mitochondrial respiratory chain, the activations of xanthine oxidase, arachidonic pathway, and NADPH oxidase have also been reported to contribute to the generation of ROS during I/R (Kloner et al, 1989;Kukreja and Hess, 1992;Griendling et al, 1997).…”

Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.

“…Hydrogen peroxide generated by xanthine oxidase appears to contribute to reperfusion injury of isolated ischemic rat hearts (1)(2)(3)(4). This impression is based on observations that inhibition of xanthine oxidase or scavenging of H202 by addition of exogenous 02-metabolite scavengers decreases reperfusion injury of isolated ischemic hearts (1)(2)(3)(4).…”

“…This impression is based on observations that inhibition of xanthine oxidase or scavenging of H202 by addition of exogenous 02-metabolite scavengers decreases reperfusion injury of isolated ischemic hearts (1)(2)(3)(4). Because endotoxin pretreatment increases endogenous lung antioxidant activities and decreases lung injury from hyperoxia (5), we hypothesized that endotoxin pretreatment would also increase endogenous myocardial antioxidant activities and, as a result, decrease myocardial susceptibility to ischemiareperfusion injury.…”