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C Fisch

Publications and source records attributed to C Fisch.

At least 55 records · Page 3Linked to original sources
PubMed1990

Dual effect of amiodarone on mitochondrial respiration. Initial protonophoric uncoupling effect followed by inhibition of the respiratory chain at the levels of complex I and complex II.

The effects of amiodarone on the respiration of isolated mouse liver mitochondria have been determined. Amiodarone (200 microM) had a biphasic effect on state 4 respiration supported by either glutamate plus malate or succinate. Initially, the respiratory rate was increased. This stimulatory effect was not prevented by oligomycin (an inhibitor of ATP synthase). It was associated with marked accumulation of amiodarone in the mitochondria, and with collapse of the mitochondrial membrane potential. This initial uncoupling effect was followed by a progressive decrease in the state 4 respiration rate, leading eventually to marked inhibition. Preincubation for 5 min with amiodarone (200 microM) also decreased markedly ADP-stimulated (state 3) respiration, ATP production and dinitrophenol-stimulated (uncoupled) respiration supported by glutamate plus malate (which donate electrons to complex I), and respiration supported by succinate (which donate electrons to complex II), but did not affect respiration supported by duroquinol (donating electrons to complex III) or by ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine (donating electrons to cytochrome c). Preincubation with amiodarone (150-200 microM) decreased markedly respiration mediated by fatty acids of various chain length and respiration mediated by citrate, a tricarboxylic acid cycle substrate. We conclude that amiodarone has a dual effect on mitochondrial respiration. The initial uncoupling effect is probably due to the entry of protonated amiodarone, releasing a proton in the matrix. Accumulation of amiodarone soon leads to inhibition of the respiratory chain at the levels of complex I and complex II and to decreased ATP formation.

Adenosine Diphosphate↗
PubMed1990

Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice.

Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from [U-14C]palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of [14C]CO2 from [U-14C]palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of [U-14C]palmitic acid. One hour after 100 mg.kg-1, the exhalation of [14C]CO2 from [1-14C]palmitic acid, [1-14C]octanoic acid or [1-14C]butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of [14C]CO2 from [1-14C]palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice.

Amiodarone↗
PubMed1987

Coronary disease, cardioneuropathy, and conduction system abnormalities in the cardiomyopathy of Friedreich's ataxia.

Abnormalities of the heart are a frequent and possibly ubiquitous problem in patients with Friedreich's ataxia, but their pathogenesis is unclear. Postmortem findings are reported from the hearts of three patients with Friedreich's ataxia who died of congestive heart failure and atrial arrhythmias. Particular attention was paid to the following: the large and small coronary arteries, the nerves and ganglia, the conduction system, and the histological and cellular features of the cardiomyopathy. There were pleomorphic nuclei and focal fibrosis and degeneration throughout each heart including the conduction system. There were distinctive abnormalities of both large and small coronary arteries, and focal degeneration of nerves and ganglia. These observations suggest a mosaic concept for the pathogenesis for the cardiomyopathy of Friedreich's ataxia that involves the interplay of molecular faults, cardiomyopathy, cardioneuropathy, and coronary disease.

Adult↗
PubMed1985

Criteria for intraventricular conduction disturbances and pre-excitation. World Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc.

In an effort to standardize terminology and criteria for clinical electrocardiography, and as a follow-up of its work on definitions of terms related to cardiac rhythm, an Ad Hoc Working Group established by the World Health Organization and the International Society and Federation of Cardiology reviewed criteria for the diagnosis of conduction disturbances and pre-excitation. Recommendations resulting from these discussions are summarized for the diagnosis of complete and incomplete right and left bundle branch block, left anterior and left posterior fascicular block, nonspecific intraventricular block, Wolff-Parkinson-White syndrome and related pre-excitation patterns. Criteria for intraatrial conduction disturbances are also briefly reviewed. The criteria are described in clinical terms. A concise description of the criteria using formal Boolean logic is given in the Appendix. For the incorporation into computer electrocardiographic analysis programs, the limits of some interval measurements may need to be adjusted.

Bundle-Branch Block↗
PubMed1985

Digitalis cardiotoxicity.

Clinical manifestations of digitalis toxicity were clearly described by Withering in 1785. One hundred years later, certain digitalis-induced arrhythmias were inscribed on the smoked drum, and shortly thereafter with the introduction of the electrocardiograph, manifestations of digitalis toxicity as recognized today were recorded in animals and human beings. With popularization of the direct-writing electrocardiograph in the late 1940s and the introduction of digitoxin in recommended doses (that in retrospect appear inappropriately high), the documented prevalence of digitalis toxicity increased rapidly. With increased understanding of the interaction of electrolytes and digitalis and perhaps, and more importantly, the widespread use of digoxin in doses derived largely from its inotropic action and, thus, inappropriately low for the management of many of the arrhythmias, the prevalence of digitalis toxicity began to decline again. In addition, the advent of serum level determinations and the widespread acceptance of the concept of "therapeutic" levels which, although frequently falling short of the desired clinical end point, served to preclude digitalis toxicity. With the decline in the incidence of digitalis toxicity consequent to these factors, some of the digitalis-related arrhythmias that were common are now rarely observed. This report focuses on arrhythmias that are highly specific for digitalis toxicity and on those that now are less commonly encountered. The discussion and classification of the arrhythmias are based on their most probable electrophysiologic mechanism.

Animals↗
PubMed1985

Role of the electrocardiogram in identifying the patient at increased risk for sudden death.

Published data dealing with the electrocardiogram as a means of identifying individuals at increased risk for sudden death are meager. The available information suggests that the sensitivity of the electrocardiogram in association with other signs of heart disease is relatively good and that this may vary with the severity of the underlying disease. In contrast, its specificity for sudden death is poor; many patients with abnormal electrocardiograms do not die suddenly or of cardiac causes. The prognosis of any electrocardiographic abnormality is that of the underlying disease.

Arteriosclerosis↗