[The reduction of beta-adrenoceptor density and the suppression of ectopic ventricular activity with low doses of amiodarone].
In 5 patients with frequent premature ventricular ectopic beats, refractory to other antiarrhythmic treatments, amiodarone, given orally at the dose of 200 mg once a day for 4 weeks, reduced beta-adrenoceptor density from 202.9 +/- 62 to 101.1 +/- 33 fmol/mg protein (p < 0.01). Similarly, kd decreased from 21.0 +/- 6 to 3.9 +/- 1 (p < 0.05). Changes in beta-adrenoceptor population were accompanied by a marked reduction in mean premature ventricular complexes (PVC) frequency from the control value of 428.9 +/- 150.3 to 13.4 +/- 10.7 PVC/h (p < 0.05) and by a decrease in heart rate, from 83.8 +/- 4 to 73.9 +/- 4 b/min (p < 0.01). On the contrary, mean arterial pressure remained unchanged. Patients did not show side effects during treatment. Therefore, low dose oral amiodarone has important pharmacologic and therapeutic effects. It significantly reduces lymphocyte beta-adrenoceptor density and is effective in treatment of ventricular arrhythmias. Additional studies were performed in vitro exposing lymphocytes to increasing concentrations of amiodarone. The analysis of variance for repeated measures showed that amiodarone-induced reduction in lymphocyte beta-adrenoceptor density is a dose-depending phenomenon. Accordingly, treatment with doses of amiodarone higher than that used in the present study may induce a major reduction in lymphocyte beta-receptor density and exert a depressant cardiac effect.
Istituto di Medicina Interna, Cardiologia e Cardiochirurgia, II Facoltà di Medicina e Chirurgia, Università degli Studi Federico II, Napoli.
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Perna
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Leone
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Farace
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Cutillo
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D'Ascia
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Picardi
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Brevetti
D000328:Adult; D000638:Amiodarone / Q000008:administration & dosage*; D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011869:Radioligand Assay / Q000706:statistics & numerical data; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D018879:Ventricular Premature Complexes / Q000097:blood / Q000188:drug therapy*
D011943:Receptors, Adrenergic, beta; D000638:Amiodarone
Riduzione della densità beta-adrenocettoriale e soppressione dell'attività ectopica ventricolare con basse dosi di amiodarone.