Circulatory Responses to Cardioaccelerator Nerve Stimulation after Induction of Tyramine Tachyphylaxis

Abstract

It is now clear that norepinephrine (NE) can be released from sympathetic nerve endings not only by nerve stimulation, but also by a number of aromatic amines, including tyramine(1). It has recently been shown that after a prolonged infusion of tyramine, the physiologic response to subsequent injection of this amine is virtually abolished, in spite of the finding that substantial quantities of NE remain in the tissues(2). If the physiologic response to neural stimulation could be shown to remain unimpaired despite loss of responsiveness to tyramine, this would suggest that the NE released by these two stimuli is not derived from a homogeneous pool.

Methods. The chronotropic and inotropic responses to stimulation of the cardioaccelerator nerve were compared before and after an infusion of tyramine. Six dogs weighing 10.2 to 12.8 kg were lightly anesthetized with a chloralose-urethane mixture given intravenously and, following a right thoracotomy, right ventricular contractile force was determined with a Walton-Brodie strain gauge arch. Supramaximal stimulation of the right cardioaccelerator nerve at a frequency 10/second was carried out with a Grass stimulator. Tyramine was injected intravenously at a dose of 60 μg/kg before and 1000 μg/kg after a one-hour infusion of 200 μg/kg/min of this substance.

Results. Prior to the tyramine infusion cardioaccelerator nerve stimulation produced an average increase in heart rate of 75 ± 11 beats/min and of right ventricular contractile force of 58% ± 25%. Administration of 60 μg/kg tyramine at this time resulted in an average increase in heart rate of 61 ± 8 beats/min and of contractile force of 108% ± 19%. Immediately following the one-hour infusion of tyramine, the response to stimulation of the cardioaccelerator nerve was essentially unchanged, with an average increase in heart rate of 67 ± 10 beats/min and in contractile force of 54% ± 26%. At this time, 1000 μg/kg of tyramine produced an average increase in heart rate of only 13 ± 4 beats/min and in contractile force of 13% ± 9% (Fig. 1).