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Therapeutic potential of vitamin E against myocardial ischemic-reperfusion injury
1Research Department, CIBA-GEIGY Corporation, Summit, NJ 07901.
Insights
Vitamin E, an antioxidant, may protect the heart from damage during reperfusion after ischemia. However, clinical evidence for its therapeutic benefit in ischemic heart disease patients is currently inconclusive.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Myocardial ischemia reduces blood flow to the heart muscle, impairing aerobic metabolism.
- Reperfusion, while necessary, can cause injury due to oxidative stress and lipid peroxidation.
- Vitamin E, a key antioxidant in heart muscle membranes, is investigated for its protective role.
Purpose of the Study:
- To review the evidence for vitamin E's protective and therapeutic potential against myocardial ischemic-reperfusion injury.
- To assess the existing laboratory and clinical data on vitamin E's cardioprotective effects.
- To identify the need for further clinical trials to establish vitamin E's efficacy.
Main Methods:
- Review of laboratory investigations on vitamin E's effects on isolated hearts and animal models.
- Analysis of epidemiological correlations between plasma vitamin E levels and ischemic heart disease outcomes.
- Evaluation of clinical studies assessing vitamin E's therapeutic benefit in patients with ischemic heart disease.
Main Results:
- Laboratory studies show vitamin E protects isolated hearts and some animal models from ischemic-reperfusion injury.
- Epidemiological data suggest an inverse correlation between vitamin E levels and anginal pain or mortality.
- Clinical trials remain inconclusive due to varied protocols and subjective endpoints.
Conclusions:
- Laboratory data support vitamin E's potential as a cardioprotectant against ischemia-reperfusion injury.
- Compelling clinical evidence for vitamin E's therapeutic efficacy in ischemic heart disease patients is currently lacking.
- Elective coronary revascularization presents a suitable setting for future clinical trials to evaluate vitamin E's efficacy.
Abstract:
Myocardial ischemia is a disease process characterized by reduced coronary flow such that the supply of nutritive blood to heart muscle (myocardium) is insufficient for normal myocardial aerobic metabolism. Prompt reestablishment of coronary flow by invasive and noninvasive clinical procedures is the most direct and effective means of limiting myocardial damage in ischemic heart disease patients, although reperfusion carries with it an injury component which may reflect, at least to some degree, the toxic effects of partially reduced oxygen species and their participation in degenerative cellular processes such as membrane lipid peroxidation. Vitamin E, a lipophilic, chain-breaking antioxidant, is a prominent membrane constituent in heart muscle, where it modulates/regulates various aspects of heart muscle-cell metabolism and function. Vitamin E's beneficial effects against experimentally induced oxidative damage to the heart, along with inverse epidemiological correlations between plasma vitamin E level and either anginal pain or mortality due to ischemic heart disease, suggest that vitamin E might have protective and therapeutic roles against myocardial ischemic-reperfusion injury. Laboratory investigations aimed at addressing this possibility have demonstrated that vitamin E supplementation protects isolated hearts against ischemic-reperfusion injury, and relatively more inconsistent and limited data document cardioprotective effects of vitamin E in some animal models of myocardial ischemia-reperfusion, especially when administered prior to the ischemic period. Clinical attempts to establish whether vitamin E has therapeutic benefit in ischemic heart disease patients remain inconclusive, having relied upon a variety of nonuniformly controlled protocols and a single, rather subjective endpoint (anginal pain). Consequently, although laboratory data constitute a conceptual context for and indirect support of the idea that vitamin E could be a cardioprotectant against ischemic-reperfusion injury, compelling clinical evidence regarding vitamin E's therapeutic potential in the ischemic heart-disease patient is lacking. Elective coronary revascularization would appear to provide an attractive clinical setting for evaluating the therapeutic efficacy of vitamin E in the context of cardiac ischemia-reperfusion. Further biochemical work would still be required to define how vitamin E exerts any cardioprotective effect observed in these patients.