Ischemic heart disease alterable

Smith JH, Green CR, Peters NS, Rothery S, Severs NJ Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microsopy. Am J Pathol 1991 139 801-821. 

The adverse effects of beta-blockers are usually mild, with occurrence rates of 10-20% for the most common in most studies. Most are predictable from the pharmacological and physicochemical properties of these drugs. Examples include fatigue, cold peripheries, bradycardia, heart failure, sleep disturbances, bronchospasm, and altered glucose tolerance. Gastrointestinal upsets are also relatively common. Serious adverse cardiac effects and even sudden death can follow abrupt withdrawal of therapy in patients with ischemic heart disease. Most severe adverse reactions can be avoided by careful selection of patients and consideration of individual beta-blockers. Hjrpersensitivity reactions have been relatively rare since the withdrawal of practolol. Tumor-inducing effects have not been estabhshed in man. 

There is some evidence that both vincristine and doxorubicin are more often associated with ischemic heart disease than other cancer chemotherapeutic agents. Whether drug-induced platelet activation, altered clotting, or endovascular damage are responsible for vascular toxicity is still unclear. The risk of ischemic heart disease must therefore be kept in mind when patients receive a combination of doxorubicin and vincristine, especially when potential risk factors have been identified. Whether the structural similarity between vinca alkaloids and ergot alkaloids, which are vasospastic, is relevant is highly speculative. 

Ischemic heart disease results in over 500,000 deaths in the United States each year. The overwhelming majority of deaths attributable to atherosclerotic heart disease results from electrophysiological alterations in zones of ischemic myocardium which predispose to ventricular fibrillation and tachycardia. Accordingly, a substantial amount of attention has focused on identifying the biochemical mechanisms which precipitate the lethal electrophysiological sequelae of coronary artery disease. 

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