Oxidative stress and cardiac disease

doi:10.1016/S0002-9343(00)00467-8

The American Journal of Medicine

Volume 109, Issue 4, September 2000, Pages 315-323

https://doi.org/10.1016/S0002-9343(00)00467-8 Get rights and content

Abstract

Reactive oxygen species (ROS) are formed at an accelerated rate in postischemic myocardium. Cardiac myocytes, endothelial cells, and infiltrating neutrophils contribute to this ROS production. Exposure of these cellular components of the myocardium to exogenous ROS can lead to cellular dysfunction and necrosis. While it remains uncertain whether ROS contribute to the pathogenesis of myocardial infarction, there is strong support for ROS as mediators of the reversible ventricular dysfunction (stunning) that often accompanies reperfusion of the ischemic myocardium. The therapeutic potential of free radical-directed drugs in cardiac disease has not been fully realized.

Section snippets

Detection of ROS in reperfused myocardium

There are three major lines of evidence that implicate ROS in the pathogenesis of myocardial reperfusion injury: 1) ROS can be detected in postischemic myocardium, 2) exposure of myocardium to exogenous ROS results in myocyte and myocardial tissue dysfunction that is comparable to that elicited by I/R, and 3) pretreatment of animals with anti-oxidant enzymes (eg, superoxide dismutase) or genetic overexpression of these enzymes in experimental animals affords protection against reperfusion

Direct effects of ROS on cardiac function

ROS have been shown to exert a direct inhibitory effect on myocardial function in vivo and in vitro. Indeed, exposure of the normal myocardium to ROS-generating systems or hydrogen peroxide alters myocardial function in a fashion that mimics reperfusion injury, including persistent cellular loss of K⁺, depletion of high-energy phosphates, elevated intracellular calcium concentration, loss of systolic force development, a progressive increase in diastolic tension, depressed metabolic function,

Myocardial infarction (irreversible injury) in animal models

The bulk of the evidence implicating ROS in the pathogenesis of myocardial I/R injury is based on experiments that examine the ability of free radical scavengers to alter the injury response. The results of a number of studies investigating antioxidant therapies in myocardial reperfusion injury are summarized in Table 1. Superoxide dismutase and catalase have received the most attention in this regard. The first assessment of antioxidant enzyme therapy in myocardial reperfusion injury was

Enzymatic and cellular sources of ROS in myocardial I/R

Although it is now generally accepted that postischemic tissues, such as heart, skeletal muscle, liver, and intestine, are exposed to a significant oxidant stress upon reperfusion, the major source(s) of the ROS remain unknown. Nonetheless, several enzymatic sources of ROS have been proposed to explain I/R-induced production, including xanthine oxidase, prostaglandin biosynthetic enzymes, mitochondrial electron transport enzymes, and neutrophilic NADPH oxidase 15, 16. Potential sources fo

Conclusions

Reactive oxygen species are generated at an accelerated level in the postischemic myocardium. Multiple cell types and different enzymes contribute to the enhanced ROS production and oxidant stress associated with ischemia and reperfusion. Although exogenously generated ROS are clearly able to damage the contractile machinery of cardiac myocytes and can produce necrosis, it remains unclear whether the ROS generated at the time of reperfusion directly mediate the myocardial necrosis that

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Physiology in medicineOxidative stress and cardiac disease

Abstract

Section snippets

Detection of ROS in reperfused myocardium

Direct effects of ROS on cardiac function

Myocardial infarction (irreversible injury) in animal models

Enzymatic and cellular sources of ROS in myocardial I/R

Conclusions

Free Rad Biol Med

Free Rad Biol Med

J Biol Chem

J Mol Cell Cardiol

J Am Coll Cardiol

J Mol Cell Cardiol

J Biol Chem

J Biol Chem

J Mol Cell Cardiol

J Mol Cell Cardiol

Ann Thorac Surg

Am J Cardiol

Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study

Ann Intern Med

Coronary heart disease in seven countries

Circulation

Prevention of myocardial damage in acute myocardial ischemia by early treatment with intravenous streptokinase

N Engl J Med

Myocardial reperfusiona double-edged sword?

J Clin Invest

Free radicals and myocardial ischemia and reperfusion injury

J Lab Clin Med

Role of neutrophils in myocardial ischemia and reperfusion

Circulation

Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat

Circulation

Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium

Circ Res

Modulation of leukocyte-mediated myocardial reperfusion injury

Annu Rev Physiol

Coronary vascular reactivity after acute myocardial ischemia

Science

Reperfusion after acute coronary occlusion in dogs impairs endothelium-dependent relaxation to acetylcholine and augments contractile reactivity in vitro

J Clin Invest

Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs

Am J Physiol

Myocardial ischemia and reperfusionthe role of oxygen radicals in tissue injury

Card Drugs Therap

Direct measurement of free radical generation following reperfusion of ischemic myocardium

Proc Natl Acad Sci USA

Direct detection of free radicals in reperfused heart using electron spin resonance spectroscopy

Circ Res

Measurement of endothelial cell free radical generationevidence for a central mechanism of free radical injury in postischemic tissue

Proc Natl Acad Sci USA

Mechanisms of myocardial stunning

Circulation

Free radicals and myocardial reperfusion injury

Br Med Bull

Oxygen free radicals in the pathophysiology of myocardial ischemia/reperfusion

Canine myocardial reperfusion injuryits reduction by the combined administration of superoxide dismutase and catalase

Circ Res

Reduction in experimental infarct size by recombinant human superoxide dismutaseinsights into the pathophysiology of reperfusion injury

Circulation

Sustained limitation by superoxide dismutase of canine myocardial injury due to regional ischemia followed by reperfusion

J Cardiovasc Pharmacol

The independent effects of oxygen radical scavengers on canine infarct size

Circ Res

Protection by superoxide dismutase from myocardial dysfunction and attenuation of vasodilator reserve after coronary occlusion and reperfusion in dog

Circ Res

Physiology in medicine
Oxidative stress and cardiac disease