Antiarrhythmic effects of disulfiram on epinephrine-induced cardiac arrhythmias in rabbits exposed to trichloroethylene

Approved drugs ezetimibe and disulfiram enhance mitochondrial Ca2+ uptake and suppress cardiac arrhythmogenesis

“…Although these results speak against the use of disulfiram as an antiarrhythmic agent in clinical use, on the other hand and consistent with our findings, previous preclinical studies already demonstrated an antiarrhythmic potential of disulfiram in different animal models (Fossa et al, 1982;Fossa & Carlson, 1983). These effects might now be explained by activation of mitochondrial-Ca 2+ uptake.…”

“…Furthermore, disulfiram was shown to influence the permeability of the inner mitochondrial membrane and to release Ca 2+ from mitochondria at higher concentrations (Chávez et al, 1989;Balakirev and Zimmer, 2001) which is in line with our results from intact cells. Although these results speak against the use of disulfiram as an anti-arrhythmic agent in clinical use, on the other hand and consistent with our findings, previous preclinical studies already demonstrated an antiarrhythmic potential of disulfiram in different animal models (Fossa et al, 1982;Fossa and Carlson, 1983). These effects might now be explained by activation of mt-Ca 2+ uptake.…”

Antiarrhythmic Effect of Disulfiram in Various Cardiotoxic Models

“…Ear lier studies showed that as the concentration of trichloroethylene increases in the blood, the heart becomes increasingly more sensi tized to epinephrine-induced arrhythmia de velopment [White and Carlson, 1979], The arrhythmias were shown to be correlated with the parent compound, trichloroethy lene, and not with its metabolites trichloroethanol and trichloroacetic acid [While and Carlson, 1981], Although disulfiram inhibits the metabolism of trichloroethylene leading to higher blood levels, it produces a paradox ical antiarrhvthmic effect on the rabbit heart [Fossa et al" 1982], Disulfiram in this study was tested in different cardiotoxic models to further examine its antiarrhvthmic in fluence.…”

“…However, disulfiram was found to cause a paradoxical decrease in the number of epi nephrine-induced arrhythmias in rabbits ex posed to trichloroethylene although, as ex pected. there was a decrease in metabolism of trichloroethylene [Fossa et al, 1982], This suggested that disulfiram might have antiarrhythmic properties of its own.…”