DOI: 10.1097/CCM.0b013e31818bda8d

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PMID: 19020442

Issn Print: 0090-3493

Publication Date: 2008/12/01


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The role of reactive oxygen species in the heart after electrical stimulation*

Deborah L. Carlson

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The earliest accounts of electrical cardioversion described the initial use of a 100-J direct current shock, increasing in steps to a maximum of 400-J if the initial shocks failed (1). This tentative approach, which has become the standard (2), was based on the fear that shocks of higher energy might actually damage the myocardium or other tissues, and an assumption that the tissue damage would be proportional to the intensity of the most powerful shock delivered (3). In this issue of Critical Care Medicine, Tsai et al. (4) report that although electrical defibrillation still remains the only effective treatment for fatal ventricular arrhythmias, the defibrillation does result in myocardial injury. They propose that this damage may directly be mediated through intracellular free radicals formed in the cardiomyocytes generated by the electrical shock.
Certainly, there have been several suggestions and propositions as to the route of myocardial damage after injury, but in 1973, Hearse et al. published the revolutionary “oxygen paradox” article in which they noted that reoxygenation of isolated hearts after anoxia resulted in the abrupt death of heart cells, as noted by a massive release of cardiac enzymes (5). One probable source of injury proposed to explain the sudden cell death was the release of free radicals.
It has been shown that in the mitochondria, oxygen is capable of undergoing a four-electron reduction to water as the metabolic substrate is oxidized. The addition of these electrons to the oxygen molecules results in the formation of three intermediate molecules that are collectively referred to as the reactive oxygen species: superoxide radical, hydrogen peroxide, hydroxyl radical, and water. These radicals have been shown to contain unpaired electrons in their outermost shell, thus making them very potent oxidizing or reducing agents. They have been proposed to be very hazardous in any biological system, and a significant body of research has been devoted to the damage they do in multiple tissue organ systems (6). The reactive oxygen species have been a topic of high interest and debate in relation to the cardiac system, as a recent review from 2008 by Downey and Cohen states, “at the time of writing, a PubMed search for the terms ‘myocardial ischemia’ and ‘free radical’ produced >4300 hits” (6).
The paper presented by Tsai et al. presents a new and novel approach to looking at the generation of free radicals, the source of the postdefibrillation myocardial dysfunction, and resolution of free radicals in the myocardium during electrical shock. The observations they make may provide useful information for the clinician in both method of defibrillation as well as possible methods to prevent free radical formation.
The investigators asked the question of whether electrical shock generated intracellular free radicals in cardiomyocytes. They further evaluated whether these free radicals could be reduced by pretreatment with ascorbic acid to reduce the observed contractile dysfunction, which they attribute to alterations in intracellular calcium handling as a result of the free radicals. By using isolated cardiomyocytes from rats, they conclude that electrical shock does indeed generate free radicals inside the cardiomyocyte, as measured with the probe, 2′,7′-dichlorofluorescin, that these free radicals impair the shortening length of the cardiomyocyte, and the Ca2+ transient of the cardiomyocyte. They go on to conclude that treatment of isolated cardiomyocytes with 0.2 mM ascorbic acid eliminated the generation of free radicals because of the antioxidant properties of ascorbic acid, and that this resulted in an improvement in contractile impairment and calcium handling after electrical shock.
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