Arrhythmogenic effect

MTX caused a contraction of vascular smooth muscle and positive inotropic, positive chronotropic and arrhythmogenic effects on cardiac muscle. The effect of MTX was little affected by various receptor blockers, a Na channel blocker or a catecholamine depleting agent. Further, MTX had no effect on the enzymes which were related to Ca movements, such as Na , K -ATPase, cyclic AMP phosphodiesterase, and sarcoplasmic reticulum Ca -ATPase. These results would eliminate the possible involvement of an indirect action elicited by the release of chemical mediators and direct modifications of their receptors, Na channels, or various enzymes as a major mechanism of action of MTX. 

Recent concerns over the arrhythmogenic effects of a number of marketed compounds have resulted in the issue of the Points to Consider document, CPMP 986/96 by the EMA (European Medicines Agency) (available at http //www.eudra/org/humandocs/PDFs/SWP/098696en.pdf). 

Myoblast therapy raises the possibility of arrhythmogenic effects. Consequently, many clinical studies require the placement of cardiac defibrillators in patients receiving myoblasts. 

Halothane administration can result in a marked reduction in arterial blood pressure that is due primarily to direct myocardial depression, which reduces cardiac output. The fall in pressure is not opposed by reflex sympathetic activation, however, since halothane also blunts baroreceptor and carotid reflexes. Systemic vascular resistance is unchanged, although blood flow to various tissues is redistributed. Halothane also sensitizes the heart to the arrhythmogenic effect of catecholamines. Thus, maintenance of the patient s blood pressure with epinephrine must be done cautiously. 

Anti-yeast activity. Ethanol (100%) extract of the seed, on agar plate at a concentration of 18.7 mg/mL, was active on Candida albicans. Water extract of the seed, on agar plate was inactive on Candida albicans °b Arrhythmogenic effect. Hot water extract of the dried seed, administered orally to adults with cardiac abnormalities at a dose of 200 mg/person, produced equivocal effect . 

Arrhythmogenic effect. Water extract of the dried leaf, administered intravenously to cats at doses of 10-20 mg/kg, produced weak activity h... 

Studies of the arrhythmogenic effects and the effects on heart rate of aconitine (14), X-desacetyl-lappaconitine (7), lappaconitine (6), lycoctonal (13), lycoctonine (12), lappaconine (15), avadharidine (9), lycaconitine (10), anthranoyl-lycoctonine (8), and cashmiradelphine (septentriodine) (11) were also reported.8 The alkaloids (6), (7), and (15) were found to be arrhythmogenic... 

Cardiovascular system While the hypotensive effect of most anesthetics is sometimes desirable, ischemic injury of tissues could follow reduced perfusion pressure. Should a hypotensive episode during a surgical procedure necessitate treatment, a vasoactive substance must be selected after considering the possibility that the anesthetic present may sensitize the heart to the arrhythmogenic effects of sympathomimetic agents. 

Adamantidis MM, Lacroix DL, Caron JF, Dupuis BA (1995) Electrophysiological and arrhythmogenic effects of the histamine type 1-receptor antagonist astemizole on rabbit Purkinje fibers Clinical relevance. J Cardiovasc Pharmacol 26 319-327... 

Studies of Arrhythmogenic Effects in Isolated Heart Preparations... 

Yamazaki, K., Terada, H., Satoh, H., Naito, K., Takeshita, A., Uehara, A., Katoh, H., Ohnishi, K., Hayashi, H. (2006). Arrhythmogenic effects of arsenic trioxide in patients with acute promyelocytic leukemia and an electrophysiological study in isolated guinea pig papillary muscles. Circulation Journal 70 1407-14. 

B anner AS, Sunderraj an EV, Agarwal MK, Addington WW. Arrhythmogenic effects of orally administered bronchodilators. Arch Intern Med 1979 139(4) 434 137. 

Viswanathan PC, Rudy Y. 2000. Cellular arrhythmogenic effects of congenital and acquired long-QT syndrome in the heterogeneous myocardium. Circulation 101 1192-98... 

Krylatov AV, Ugdyzhekova DS, Bernatskaya NA, Maslov LN, Mechoulam R, Pertwee RG, Stephano GB (2001) Activation of type II cannabinoid receptors improves myocardial tolerance to arrhythmogenic effects of coronary occlusion and reperfusion. Bull Exp Biol Med 131 523-525... 

Ugdyzhekova DS, Bernatskaya NA, Stefano JB, Graier VF, Tam SW, Mekhoulam R (2001) Endogenous cannabinoid anandamide increases heart resistance to arrhythmogenic effects of epinephrine role of CB(1) and CB(2) receptors. Bull Exp Biol Med 131 251-253... 

Limited use because of pro-arrhythmogenic effects leading to T sudden death post-MI and when used prophylactically in VT. 

Figure 20). Therefore, because of its pronounced anticholinergic and potential arrhythmogenic effects, amitriptyline is contraindicated in the acute recovery phase of myocardial infarction, congestive heart failure, angina, prostatic hypertrophy, paralytic ileus, and urinary retention, and in patients undergoing surgery with general anesthetics that may cause arrhythmias (e.g., halothane) (see Table 16).

Sinus bradycardia and atrioventricular rhythms occur frequently during halothane anesthesia but usually are benign and result mainly from a direct depressive effect of halothane on sinoatrial node discharge. Halothane also can sensitize the myocardium to the arrhythmogenic effects of epinephrine. 

Arrhythmogenic Effect of Inhalation Anesthetics Biochemical Heterogeneity between Conduction and Contractile Systems and Protein Unfolding Issaku Ueda and Jan-Shing Chiou... 

Cardiovascular effects Most inhaled anesthetics decrease arterial blood pressure moderately. Enflurane and halothane are myocardial depressants that decrease cardiac output, while isoflurane causes peripheral vasodilation. Nitrous oxide is less likely to lower blood pressure than are other inhaled anesthetics. Blood flow to the liver and kidney is decreased by most inhaled agents. Halothane may sensitize the myocardium to the arrhythmogenic effects of catecholamines. 

Increased cardiac output and reduced systemic and pulmonary vascular resistance.101 Since it showed a potentially arrhythmogenic effect (prolongation of the QT interval), no further clinical development has occur red.93 Carbazeran (UK 31.557) ( 3) is a potent inotropic com-... 

A. Once absorbed, benzene causes CNS depression and may sensitize the myocardium to the arrhythmogenic effects of catecholamines. 

I. Mechanism of toxicity. Carbon tetrachloride and chloroform are CNS depressants and potent hepatic and renal toxins. They may also increase the sensitivity of the myocardium to arrhythmogenic effects of catecholamines. The mechanism of hepatic and renal toxicity is thought to be a result of a toxic free-radical intermediate of cytochrome P-450 metabolism. (Bioactivation of CCI4 has become a model for chemical toxicity induced by free radicals.) Chronic use of metabolic enzyme inducers such as phenobarbital and ethanol increases the toxicity of carbon tetrachloride. Carbon tetrachloride is a known animal and suspected human carcinogen. Chloroform is embryotoxic and an animal carcincogen. 

A. Chlorinated hydrocarbons are neurotoxins that interfere with transmission of nerve impulses, especially in the brain, resulting in behavioral changes, involuntary muscle activity, and depression of the respiratory center. They may also sensitize the myocardium to arrhythmogenic effects of catecholamines, and many can cause liver or renal injury, possibly owing to generation of toxic metabolites. In addition, some chlorinated hydrocarbons may be carcinogenic. 

A. Toluene and xylene cause generalized central nervous system depression. Like other aromatic hydrocarbons, they may sensitize the myocardium to the arrhythmogenic effects of catecholamines. They are mild mucous membrane irritants affecting the eyes and respiratory and gastrointestinal tracts. 

A. Inotropic and arrhythmogenic effects of digitalis are potentiated by calcium. 

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