The historical development, cellular electrophysiology and pharmacology of amiodarone.
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Amiodarone↗
Biomedical subjects
R Kannan
Publications and source records attributed to R Kannan.
Hymenovin. major toxic constituent of Western bitterweed (Hymenoxys odorata DC.)
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Animals↗
Lack of effect of 3,3'5'-triiodothyronine (reverse T3) on cardiac function in the rabbit.
In a recent study, we have shown that the antiarrhythmic drug, amiodarone caused significant elevations of serum rT3 levels and inhibition of the peripheral conversion of T4 to T3 (Kannan et al. Endocrinology 115:1710-1716, 1984). In this study we have examined whether or not rT3 has a direct effect on the monodeiodinase enzyme activity and electropharmacology of the rabbit myocardium. Six male New Zealand White rabbits were administered 50 ug rT3 (a dose about 100 times the daily rT3 production rate) i.p. for 5 days, while the control group received saline. Serum T4, T3 and rT3 concentrations, and myocardial as well as liver and kidney 5'monodeiodinase enzyme activities were measured. Surface ECG and electrophysiological parameters in the atrial, ventricular and sinoatrial node in control and rT3 groups were obtained. Surface ECG did not show any difference in heart rate, RR, PQ, QRS or QT intervals in the two groups. Reverse T3 administration did not produce any significant alterations in APA, MRP, Vmax, APD90 and ERP of atrial and ventricular muscle. Despite administration of a massive dose of rT3, serum levels of T3 and T4 were unchanged as compared to control group. Reverse T3 administration did not produce any alterations in the 5'monodeiodinase activities in the myocardium, liver and kidney. The studies suggest that rT3 does not appreciably affect myocardial function and that the effects of amiodarone on the heart occur via mechanisms other than its ability to cause an increase in serum rT3 levels.
Action Potentials↗
Beneficial effects of amiodarone pretreatment on early ischemic ventricular arrhythmias relative to infarct size and regional myocardial blood flow in the conscious dog.
The effects of chronic pretreatment with amiodarone on ischemic ventricular arrhythmias were evaluated in fully conscious instrumented dogs. In control dogs (n = 14) with large myocardial infarcts, early (first 30 min) ventricular arrhythmias occurred in a bimodal distribution with peaks at 3-5 min and at 12-25 min, with only the former associated with epicardial conduction delay. Ventricular fibrillation occurred equally frequently during each peak of early ventricular arrhythmias. Amiodarone (30 mg/kg daily) for 3-4 weeks had no significant effect (n = 11) on anatomic infarct size (28 +/- 6 vs. 30 +/- 5% of left ventricular weight) nor on collateral blood flow in the center of the infarct (19 +/- 11 vs. 15 +/- 7 ml/min/100 g of tissue) or on the ratio of endocardial/epicardial perfusion (0.23 +/- 0.19 vs. 0.28 +/- 19). Despite significant lengthening of peak epicardial conduction delay (191 +/- 20 to 239 +/- 81 ms, p less than 0.05), the frequency of early ventricular arrhythmias, especially during the second peak of ectopic activity, were markedly attenuated by amiodarone pretreatment, with the extrasystole-free intervals often being as long as 6 h. The incidence of ventricular fibrillation was 9% in the treated animals compared with 29% in the controls. In the control animals, arrhythmias always supervened when epicardial fractionation was significant, and no ectopy-free interval was present in the first 6 h following coronary occlusion. The data indicate that chronic amiodarone pretreatment exerts a beneficial effect on the frequency and severity of such ventricular tachyarrhythmias, with reduction in the incidence of ventricular fibrillation and ectopic activity in the early phases following coronary occlusion.
Amiodarone↗
Digoxin-desethylamiodarone interaction in the rat: comparison with the effects of amiodarone.
We have shown that there is a pharmacokinetic interaction between amiodarone and digoxin that results in an increase in steady-state serum and tissue concentrations of digoxin in rats. There is a linear correlation between serum levels of amiodarone, as well as desethylamiodarone, and steady-state serum digoxin levels in rats treated with amiodarone. Since desethylamiodarone is formed in amounts equal to that of the parent compound during chronic amiodarone therapy, we investigated the possibility of desethylamiodarone directly interacting with digoxin in rats. Rats that received digoxin alone showed a serum level of 0.32 +/- 0.08 ng/ml, whereas those that received combination therapies showed a serum level of 3.25 +/- 1.06 ng/ml (p less than 0.001) with desethylamiodarone administration, and 3.00 +/- 0.87 ng/ml with amiodarone administration. Concomitant administration of desethylamiodarone and digoxin increased digoxin concentration in the myocardium by 110% (p less than 0.001), in the skeletal muscle by 208% (p less than 0.001) and in the brain by 110% (p less than 0.001). The corresponding figures for amiodarone-digoxin administration were 94% (p less than 0.001), 172% (p less than 0.001) and 80% (p less than 0.001). The tissue/serum ratios of digoxin concentrations in the myocardium, skeletal muscle, and brain were decreased in the rats that received combination therapies, indicating reduced tissue binding of digoxin. The data indicate that desethylamiodarone interacts with digoxin in a manner similar to that of the parent compound.
Amiodarone↗
Isolated involvement of the mandible by non-Hodgkin's lymphoma.
A case report of isolated involvement of the mandible by non-Hodgkin lymphoma is presented. The patient presented with a non-healing ulcer following a tooth extraction. Biopsy revealed an undifferentiated cancer. Investigations failed to reveal any involvement of the organs. A hemimandibulectomy was performed followed by radiotherapy on receipt of the histopathological diagnosis of non-Hodgkin lymphoma. The patient is asymptomatic two and a half years after treatment.
Biopsy, Needle↗
Laser in the management of stenosing oropharyngeal scleroma.
We present here our experience of laser for the management of stenosed oropharyngeal scleroma. The diagnosis of scleroma was made 14 years ago and the patient underwent repeated procedures like dilatation, diathermy excision of adhesions and cryosurgery during this period. He attended our out-patient department with complaints of dysphagia and difficulty in breathing, progressing to stridor. On examination, severe oropharyngeal stenosis due to cicatrization extending between the base of the tongue and the post-pharyngeal wall was seen. Using CO2 laser, cicatrix was released by making radial cuts and the oropharyngeal opening was widened. No tracheostomy was needed; no blood loss occurred and the patient was discharged on the next day.
Cicatrix↗
Tissue uptake and metabolism of amiodarone after chronic administration in rabbits.
This study was designed to determine serum and tissue concentrations of amiodarone and its metabolite desethylamiodarone after chronic amiodarone administration in rabbits. Rabbits were administered 20 mg/kg amiodarone for 6 weeks. Serum, liver, kidney, heart, lung, spleen, bile, adipose tissue, and muscle were collected upon sacrifice. Amiodarone and desethylamiodarone concentrations were determined in serum and tissues by an HPLC procedure standardized in our laboratory. Amiodarone concentrations were the highest in fat tissue followed by lung, liver, and muscle, with the lowest concentration in serum and only traces in the brain. Desethylamiodarone concentrations in liver, lung, and kidney approached those of the parent drug while the metabolite was present in negligible amounts in fat tissue and in brain. Bile from amiodarone-treated rabbits showed the presence of two more new metabolites which have not been characterized. Desethylamiodarone/amiodarone ratios in serum and tissues after chronic administration in rabbits were lower than in man. Nevertheless, differential accumulation of amiodarone and desethylamiodarone may be relevant to efficacy and toxicity studies.
Amiodarone↗
Dose-dependent tissue uptake of flecainide during chronic administration in rabbits.
This study was designed to examine the metabolism of flecainide after repeated administration to rabbits. New Zealand White rabbits were administered either 7.5 mg/kg body weight (dose I) or 20 mg/kg body weight (dose II) flecainide twice daily intraperitoneally for 12-14 days. Serum, heart, liver, lung, kidney, muscle, fat, and brain were collected upon death. Flecainide concentrations in serum and tissues were determined by a liquid chromatographic procedure standardized in our laboratory. Serum and tissue flecainide concentrations showed a significant, dose-dependent increase after chronic administration. Flecainide accumulated in lung, liver, kidney, and heart, its concentration decreasing in that order. Tissue to serum flecainide ratios also followed a similar pattern. Cornea and urine contained flecainide metabolites which were not characterized. Only traces of flecainide were detected in brain and fat tissues. Substantial tissue uptake of flecainide should be considered in long term flecainide therapy.
Animals↗
Visceral larva migrans.
We present a case of visceral larva migrans which came as a complete histologic surprise. The patient was operated as a case of chronic cholecystitis and was found at operation to have multiple hepatic nodules. A cholecystectomy with a biopsy of the liver nodule was performed. Histopathologically a diagnosis of visceral larva migrans was made. To our knowledge this is the first case report of the disorder from India. A discussion based on the review of literature is presented.
Biopsy↗