Comparative Effects of Pancuronium and d -Tubocurarine on Blood Histamine and Sympathetic Activity

Abstract

Pancuronium bromide (Pavulon) is a new long-acting, nondepolarizing type muscle relaxant (1-3). Any drug chosen to clinically replace d-tubocurarine, must be devoid of its untoward effects. Hypotension is one of these. It has been demonstrated in cats that hypotension from d-tubocararine is associated with a decrease in spontaneous postganglionic sympathetic activity in low doses and with the added dimension of histamine release at higher doses (4). The present study was conducted to comparatively evaluate pancuronium and d-tubocurarine on those same functions that are responsible for the hypotensive action of the latter agent.Methods and Materials. Unpremedicated cats (2.1-3.2 kg) were lightly anesthetized with 20 mg/kg iv pentobarbital sodium (Nembutal) and maintained at this level with intermittent doses of 2.5-5 mg/kg as necessary. Mean arterial pressure (MAP) and heart rate were recorded from a catheter in the femoral artery. Drug injections and fluid replacement (Lactated Ringers solution, I0 ml/kg/hr) were made through a femoral venous catheter. Blood histamine was determined according to a modified method of Anton and Sayre (4, 5) on samples obtained from the right atrium via a jugular venous catheter. The trachea was cannulated and pulmonary ventilation was controlled by a Palmer pump with room air adequate to maintain arterial blood gases at Pao2 98 -+ 10 Tom and Paco2 36 ? 4 Tom. Rectal temperature was maintained at 37 ? 0.5" with a warming-cooling blanket.The tibialis anterior muscle tendon was divided and attached to a FT03B force displacement transducer under 20 g tension while the sciatic nerve was sectioned and the common peroneal nerve placed on a bipolar electrode.Stimulations were at supramaximal voltage, 0.1 msec duration and 0.2 Hz from a Grass S4 stimulator and recordings made with a Grass 5B polygraph.A postganglionic nerve from the celiac ganglion, exposed by a left flank retroperitoneal approach, was isolated and placed on a bipolar platinum electrode. Action potentials were displayed on a Tektronix 565 oscilloscope photographed with a Grass Kymographic camera at a film speed of 5 mm/sec. For quantitation the spontaneous postganglionic sympathetic activity (SPGSA) was simultaneously transmitted to a Grass 5P3 EMG integrator preamplifier with a 0.2 sec time constant and recorded on a Grass 5B polygraph at 5 m d s e c . The area under the integrated activity for 10 sec was measured with a planimeter. Injections of 0.75 mg/kg trimethaphan (Arfonad) at the conclusion of the experiment were used to prove the postganglionic nature of the activity.Results. The dose-response curve constructed for pancuronium bromide indicated that the minimum fully effective dose was between 0.02 and 0.04 mg/kg. Therefore, each of the seven cats used herein were given an initial dose of 0.04 mg/kg of pancuronium, which produced complete paralysis in all cats. Two and one-half times this dose (0.1 mg/kg) of pancuronium then was chosen for comparison with 1 mg/kg of d-tubocurarine chloride, determined in an identic...