The effect of pancuronium on myocardial contraction and catecholamine metabolism

Abstract

The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min-1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml-1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to "rebound" above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate "rebound."