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RESEARCH PRODUCT

The effects of the tricyclic antidepressants desipramine, doxepin and iprindole on the isolated perfused rabbit heart.

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description

1. The right sympathetic nerves of isolated perfused rabbit hearts were stimulated electrically (1 msec, supramaximal strength, 15 sec) with increasing frequencies (0.25–20 Hz) at 3 min intervals before and 20 min after starting perfusion with desipramine, doxepin or iprindole. Ventricular rate, right atrial and right ventricular tensions were recorded using the transverse method. 2. Sympathic nerve stimulation caused ventricular arrhythmias in the presence of desipramine (3.3 and 5.0 · 10−6 M) and doxepin (1.6−4.7×10−6 M) but failed to produce arrhythmias in hearts not exposed to drugs, or after iprindole, cocaine and atropine. 3. When desipramine or doxepin was added to Tyrode solution containing propranolol 1.7×10−7 M, sympathetic nerve stimulation no longer elicited arrhythmias. However, quinidine 1.3×10−6 M was unable to prevent arrhythmias. 4. The incidence and duration of arrhythmias provoked by sympathetic nerve stimulation increased with time of perfusion of desipramine and doxepin. In the majority of hearts nerve stimulation ceased to elicit arrhythmias 9 min after removal of the drugs from the perfusion fluid. 5. It is concluded that the combination of noradrenaline release by nerve stimulation and atrioventricular blockade by tricyclic antidepressants is responsible for the arrhythmia-producing effect observed in the present study. The isolated rabbit heart stimulated via its sympathetic nerves appears to be suitable for testing the arrhythmogenic actions of tricyclic antidepressants.