Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?

Lindenmeyer, Maja T.; Spörri, Stefan; Stäubli, M; Studer, Anja S; Studer, H

doi:10.1111/j.1476-5381.1984.tb16468.x

Cited by 29 publications

(17 citation statements)

References 19 publications

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“…This effect of amio darone has been described previously by Singh and Vaughan Williams [1970] and Lindenmeyer et al [1984]. The development of sinus bradycardia is consistent with an antithyroid action of the drug [Freedberg et al, 1970;Johnson et al, 1973;Margolius and Gaffney, 1965].…”

Section: Cardiac Contractile Function In Isolated Cardiac Muscle Prepsupporting

confidence: 60%

“…Either the heart is more sensitive to the reduction in plasma T3 con centrations than other tissues or amioda rone produces additional actions upon other sites of thyroid hormone action. The latter possibility is suggested by the studies of Lindenmeyer et al [1984]. Iopanoic acid, an inhibitor of the intracellular generation of triiodothyronine (T3) from thyroxine (T4), fails to reproduce the sinus bradycar dia observed with the long-term administra tion of amiodarone.…”

Section: Role O F Thyroid Hormone In the Pharmacologic Actions O F Ammentioning

confidence: 99%

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Changes in Cardiac Muscle Function and Biochemistry Produced by Long-Term Amiodarone and Amiodarone + Triiodothyronine Administration in the Rabbit

Patterson¹,

Shlafer²,

Walden³

et al. 1987

Pharmacology

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Cardiac muscle function and biochemistry were examined after long-term amiodarone administration in the rabbit (20 mg/kg/day for 28 days). Isolated cardiac muscle preparations were obtained from control and amiodarone-treated rabbits, and were studied in vitro. Amiodarone treatment did not alter the magnitude of force development in isolated atrial and papillary muscle preparations, but depressed the rate of force development (dF/dt). The muscle preparations responded similarly to inotropic and chronotropic stimulation with isoproterenol, hislamine, and tyramine, although the intrinsic rate of right atrial preparations from the drug-treated animals was reduced. Na⁺-K⁺ ATPase activity in crude ventricular homogenates was increased in the amiodarone-treated group. Mitochondrial respiratory function in amiodarone-treated left ventricular tissue was depressed for glutamate, malate, and glutamate + malate. The reduction in respiratory function occurred without uncoupling oxidative phosphorylation or altering respiratory function for succinate. The pharmacologic effects of amiodarone observed in the present study were not observed with the simultaneous administration of triiodothyronine (5 μg/day). No difference in ATP-dependent calcium uptake or in calcium-dependent ATPase activity were observed in sarcoplasmic reticulum preparations from control, amiodarone, and amiodarone + T₃ groups. The pharmacologic effects of amiodarone in rabbit hearts resemble those previously reported with hypothyroidism and are not observed after triiodothyronine administration.

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Section: Cardiac Contractile Function In Isolated Cardiac Muscle Prepsupporting

confidence: 60%

Section: Role O F Thyroid Hormone In the Pharmacologic Actions O F Ammentioning

confidence: 99%

Changes in Cardiac Muscle Function and Biochemistry Produced by Long-Term Amiodarone and Amiodarone + Triiodothyronine Administration in the Rabbit

Patterson¹,

Shlafer²,

Walden³

et al. 1987

Pharmacology

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“…Conflicting with these data, however, are the observations that neither anti-thyroid drugs such as PTU, carbimazole or methimazole nor drugs that inhibit 5'monodeiodinase (such as the radiographic contrast medium iopanoic acid) have significant antiarrhythmic activity (Sogol et al, 1983;Lindenmeyer et al, 1984). This does not, of course, exclude the possibility that the anti-arrhythmic action of amiodarone may involve a number of effects, only some of which may be similar to hypothyroidism.…”

Section: Discussionmentioning

confidence: 42%

“…It was only at higher, prolonged dosage (200 mg kg-' daily for one year in the rat) that evidence of thyroid overactivity was described (Harris et al, 1986); this was assumed to be the result of the enormous iodine load. All subsequent studies have shown significant rises in reverse T3 (rT3) levels, consistent with the inhibition of 5'monodeiodinase, but the effects on T4 and T3 have varied both within and between laboratory animals (Sogol et al, 1983;Lindenmeyer et al, 1984;Kannan et al, 1984;Venkatesh et al, 1986). In animals studies where drug levels have been recorded (Kannan et al, 1984;Venkatesh et al, 1986) very high doses (in comparison to man) have been needed in small mammals in order to obtain 'therapeutic' serum levels.…”

Section: Discussionmentioning

confidence: 99%

Effects of amiodarone and thyroid dysfunction on myocardial calcium, serum calcium and thyroid hormones in the rat

Gammage

Franklyn

Logan³

1987

British J Pharmacology

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1 Myocardial calcium content was found to be elevated and serum calcium reduced in hypothyroid rats.2 Treatment of rats with amiodarone at either 30mg kg-' or 150mg kg-' daily did not result in any significant changes in myocardial or serum calcium. 3 The administration of amiodarone to hypothyroid rats attenuated the changes in serum but not myocardial calcium, suggesting that amiodarone may exert a thyroid hormone-like effect in the hypothyroid state. 4 The administration of amiodarone to thyroid hormone-treated rats resulted in attenuation of the effects on serum calcium and calculated intracellular calcium; this was consistent with an antagonistic interaction between amiodarone and thyroid hormones. 5 Administration of amiodarone resulted in significant changes in circulating thyroid hormone levels in the rat; triiodothyronine was reduced and basal thyrotrophin elevated compared to euthyroid controls. Serum thyroxine was not changed; this is in contrast to the effects in man. 6 Amiodarone does not exert its anti-arrhythmic action via changes in total myocardial calcium content in the euthyroid rat; nonetheless the described interactions between the drug and thyroid hormones may be involved in its mechanism of action.

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“…Serum T3 was not measured because, as shown earlier, it was consistently not detected in the serum of guinea-pigs (Lindenmeyer et al, 1984).…”

Section: Processingmentioning

confidence: 99%

The effects of amiodarone on the electrocardiogram of the guinea‐pig are not explained by interaction with thyroid hormone metabolism alone

Stäubli

Studer

1986

British J Pharmacology

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1 The iodine-containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine-containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T4) to triiodothyronine (T3). Using iopanoic acid, the question was investigated, in guinea-pigs, whether inhibition of T4-*T3 conversion is by itself associated with the same changes in the electrocardiogram, i.e. QT prolongation and bradycardia, as those observed during amiodarone treatment. 2 At a dose of 4 g kg-', iopanoic acid induced maximal inhibition of the T4+T3 conversion. Although these changes were even more pronounced than those in a control group of animals treated with 2.12 g amiodarone kg-', neither prolongation of the QT nor a slowing of the heart rate was observed. QT prolongation and bradycardia were induced only by amiodarone treatment but not by iopanoic acid.3 lopanoic acid at the high toxic dose of 12 g kg-' induced the same degree of inhibition of T4-*T3 conversion as the 4 g kg-' dose. QT prolongation and slowing of the heart rate were apparent at this dose in parallel with a loss of weight. 4 It is concluded that even a maximal inhibition ofthe T4-+ T3 conversion has no effect on the ECG of guinea-pigs. The inhibition of the T4+ T3 conversion alone does not explain the QT prolongation and bradycardia observed with amiodarone treatment. The amiodarone effects on the ECG may represent a combination of interactions with thyroid hormones and antiadrenergic activity.

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Does amiodarone affect heart rate by inhibiting the intracellular generation of triiodothyronine from thyroxine?

Cited by 29 publications

References 19 publications

Changes in Cardiac Muscle Function and Biochemistry Produced by Long-Term Amiodarone and Amiodarone + Triiodothyronine Administration in the Rabbit

Changes in Cardiac Muscle Function and Biochemistry Produced by Long-Term Amiodarone and Amiodarone + Triiodothyronine Administration in the Rabbit

Effects of amiodarone and thyroid dysfunction on myocardial calcium, serum calcium and thyroid hormones in the rat

The effects of amiodarone on the electrocardiogram of the guinea‐pig are not explained by interaction with thyroid hormone metabolism alone

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