Arrhythmias epinephrine-induced

Animal studies indicate that trichloroethylene can sensitize the heart to epinephrine-induced arrhythmias. Other chemicals can affect these epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene. Phenobarbital treatment, which increases the metabolism of trichloroethylene, has been shown to reduce the trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1979), whereas high concentrations of ethanol, which inhibits trichloroethylene metabolism, have been found to potentiate trichloroethylene-epinephrine-induced arrhythmias in rabbits (White and Carlson 1981). These results indicate that trichloroethylene itself and not a metabolite is responsible for the epinephrine-induced arrhythmias. In addition, caffeine has also been found to increase the incidence of epinephrine-induced arrhythmias in rabbits exposed to trichloroethylene (White and Carlson 1982). 

Sarin exhibits OP-delayed cardiotoxicity. Allon et al (2005) suggest epinephrine-induced arrhythmias as a possible cause in cases of sarin intoxication. The hypothesis is supported by Khositseth et al (2005) who showed that epinephrine changes T-waves in the ECG where AT prolongation already exists. 

Lampe GH, Donegan JH, Rupp SM, Wauk LZ, Whitendale P, Fouts KE, Rose BM, Litt LL, Rampil IJ, Wilson CB, et al. Nitrous oxide and epinephrine-induced arrhythmias. Anesth Analg 1990 71(6) 602-5. 

The effects of berbamine of the isolated and perfused working heart of the guinea pig was studied. The alkaloid was observed to depress the function of the isolated working heart in a dose-dependent manner. The alkaloid (3 mol/l) decreased the left ventricular pressure, aortic pressure -dP/dtmax, aortic blood flow and coronary blood flow, and increased left ventricular end-diastolic pressure. At a concentration of 100 mol/l, ventricular asystole was produced, but there was no influence on atrial contraction. Berbamine was also observed to antagonize epinephrine-induced arrhythmias [202]. 

The acute cardiotoxic effects of 1,1,1-trichloroethane (reduced blood pressure and increased sensitization to epinephrine-induced arrhythmias) appear to be mediated by the compound and not its metabolites (Carlson 1973 Toraason et al. 1990, 1992) and have been associated with the ability of 1,1,1-trichloroethane to interfere with membrane-mediated processes including calcium mobilization during myocardial contraction (Herd et al. 1974 Hoffman et al. 1992 Toraason et al. 

CRD-401, the benzothiazepine derivative 9, reversed epinephrine-induced arrhythmias in guinea pigs, but failed to reverse arrhythmias due to two-stage coronary ligation.55 ll-1530 (10), whose structure is reminiscent of... 

Reinhardt CF, Mullen LS, Maxfield ME. 1973. Epinephrine-induced cardiac arrhythmia potential of some common industrial solvents. J Occup Med 15 953-955. 

White JF, Carlson GP. 1979. Influence of alterations in drug metabolism on spontaneous and epinephrine-induced cardiac arrhythmias in animals exposed to trichloroethylene. Toxicol Appl Pharmacol 47 515-527. 

White JF, Carlson GP. 1981. Epinephrine-induced cardiac arrhythmias in rabbits exposed to trichloroethylene Potentiation by ethanol. Toxicol Appl Pharmacol 60 466-471. 

HFC-134a is a weak cardiac sensitizer in the epinephrine challenge test in dogs. Epinephrine-induced cardiac arrhythmias were observed at a concentration of 75,000 ppm when doses of epinephrine were not individualized (Mullin and Hartgrove 1979) and at a concentration of 80,000 ppm when doses of epinephrine were individualized (Hardy et al. 1991). No evidence for cardiotoxicity was observed at <50,000 ppm. 

Cardiac arrhythmias were induced in rats injected with exogenous epinephrine and exposed to HCFC-141 b at 5,000 ppm. However, the intravenous dose of epinephrine required was 3-fold that which induced arrhythmias in the same rats administered halothane, a common clinical anesthetic. Furthermore, the arrhythmias were characterized as mild. The threshold for cardiac sensitization for dogs was approximately 5,200 ppm. Deaths occurred in one study at 10,000 ppm and in another study at 20,000 ppm (with no deaths between concentrations of 9,000 and 19,000 ppm). 

Several studies have indicated that n-butane sensitizes the myocardium to epinephrine-induced cardiac arrhythmias. In anesthetized dogs, 5000 ppm caused hemodynamic changes such as decreases in cardiac output, left ventricular pressure, and stroke volume, myocardial contractility, and aortic pressure. Exposure of dogs to 1-20% butane for periods of 2 minutes to 2 hours hypersen-... 

In rats, 90 day exposures to 1000 and 5000 ppm caused bilateral hair loss, extensive liver damage, and excessive mortality. The chronic toxicity of dichlorofluoromethane appears to be quite different from difluorinated methanes and more similar to the hepatotoxin chloroform. In mice 100,000 ppm induced arrhythmias and sensitized the heart to epinephrine. 

Carlson, GP. (1981) Effect of alterations in drug metabolism on epinephrine-induced cardiac arrhythmias in rabbits exposed to methylchloroform. Toxicol. Lett., 9, 307-313... 

Epinephrine-induced cardiac arrhythmia was not induced in beagle dogs exposed by face mask to 5,000 or 10,000 ppm tetrachloroethylene (Reinhardt et al. 1973). This study was complicated by the dogs struggling, which could represent irritant effects of these high tetrachloroethylene concentrations on the upper respiratory tract. 

Although it is an optimized model, the end point of cardiac sensitization is relevant as humans exposed at high concentrations of some halocarbons may develop cardiac arrhythmias. The concentration of 80,000 ppm along with intravenous epinephrine, which induced a marked cardiac response in the dog, was used as the basis for the AEGL-3 values. Because the dog heart is considered an appropriate model for the human heart, an interspecies UF of 1 was applied. Because the cardiac sensitization test is a conservative test, the 80,000 ppm concentration was adjusted by an intraspecies UF of 3 to protect potentially susceptible individuals. Blood concentrations were close to equi... 

Testing for cardiac sensitization consists of establishing a background (control) response to an injection of epinephrine followed by a second injection during exposure to the chemical of concern (Reinhardt et al. 1971). The dose of epinephrine chosen is the maximum dose that does not cause a serious arrhythmia (NRC 1996). Because a second injection of epinephrine during air exposure often induces a mild cardiac response, Reinhardt et al. (1971) con... 

Isobutane has been found to sensitize the myocardium to epinephrine in various animal studies. Concentrations of 50,000 ppm predisposed the dog heart to cardiac arrythmias induced by catecholamines. Monkeys administered 50,000-100,000 ppm for 5 minutes via tracheal cannulation had tachycardia, arrhythmias, and myocardial depression. Cases of sudden death due to fatal cardiac arrhythmias have been reported in humans intentionally inhaling isobutane. ... 

Cardiovascular Effects. Most studies of humans exposed to carbon tetrachloride by inhalation have not detected significant evidence of cardiovascular injury, even at exposure levels sufficient to markedly injure the liver and/or kidney. Changes in blood pressure, heart rate, or right- sided cardiac dilation have sometimes, but not always, been observed (Ashe and Sailer 1942 Guild et al. 1958 Kittleson and Borden 1956 Stewart et al. 1961 Umiker and Pearce 1953), and are probably secondary either to fluid and electrolyte retention resulting from renal toxicity, or to central nervous system effects on the heart or blood vessels. Carbon tetrachloride also may have the potential to induce cardiac arrhythmias by sensitizing the heart to epinephrine, as has been reported for various chlorinated hydrocarbon propellants (Reinhardt et al. 1971). 

Unlabeled Uses Treatment of pralidoxime-induced hypertension, arrhythmias, asthma, bladder instability, cardiac diseases, diabetes mellitus, erectile dysfunction, extravasation (dopamine and epinephrine), hyperhidrosis, myocardial infarction, Raynaud s phenomenon, surgery, sympathetic pain... 

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