Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

Abstract

An increased sensitivity of the heart to catecholamines or cardiac sensitization is a recognized risk during acute human exposure to halogenated hydrocarbons used as solvents, foam-blowing or fire-extinguishing agents, refrigerants, and aerosol propellants. Although cardiac sensitization to such "industrial" halocarbons can result in serious arrhythmia and death, research into its mechanistic basis has been limited, whereas the literature on volatile anesthetics (e.g., halothane, chloroform) is comparably extensive. A review of the literature on halocarbons and related volatile anesthetics was conducted. The available experimental evidence suggests that volatile anesthetics at physiologically relevant concentrations interact predominantly with the main repolarizing cardiac potassium channels hERG and I Ks , as well as with calcium and sodium channels at slightly higher concentrations. On the level of the heart, inhibition of these ion channels is prone to alter both action potential shape (triangulation) and electrical impulse conduction, which may facilitate arrhythmogenesis by volatile anesthetics per se and is potentiated by catecholamines. Action potential triangulation by regionally heterogeneous inhibition of calcium and potassium channels will facilitate catecholamine-induced afterdepolarizations, triggered activity, and enhanced automaticity. Inhibition of cardiac sodium channels will reduce conduction velocity and alter refractory period; this is potentiated by catecholamines and promotes reentry arrhythmias. Other cardiac and/or neuronal mechanisms might also contribute to arrhythmogenesis. The few scattered in vitro data available for halocarbons (e.g., FC-12, halon 1301, trichloroethylene) suggest inhibition of cardiac sodium (conduction), calcium and potassium channels (triangulation), extraneuronal catecholamine reuptake, and various neuronal ion channels. Therefore, it is hypothesized that halocarbons promote cardiac sensitization by similar mechanisms as volatile anesthetics. Experimental approaches for further investigation of these sensitization mechanisms by selected halocarbons are suggested.

Electrocardiographic changes and exposure to solvents

“…In this study, workers exposed to organic and halogenated solvents too. Another study showed the mechanisms involved in cardiac sensitization by halogenated hydrocarbons . Researchers demonstrated the fatal cardiac arrhythmia after repeated exposure to halogenated hydrocarbons …”

“…Researchers studied on the cardiac toxicity of the organochloride solvent trichloromethane . Other study showed the mechanisms of cardiac sensitization caused by volatile anesthetics …”

Cocaine and the Club Drugs

“…22 All inhaled agents sensitize the myocardium to catecholamines, which could potentiate the dysrhythmogenic effects of cocaine. Inhaled agents also have bronchodilating properties, which can be beneficial as cocaine use can lead to bronchospasm, especially in patients with asthma.…”

Drug Abuse-Induced Cardiac Arrhythmias: Mechanisms and Management

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