Myocardial extraction of bupivacaine in anaesthetized sheep and by hearts of sheep and rats in vitro

Abstract

We observed the in vivo kinetics of bupivacaine in the cardiopulmonary system, particularly in the pulmonary artery, the upper part of the descending aorta and the coronary sinus of anaesthetized sheep, each of which received a high dose infusion into the central vein. In some experiments dilution curves were monitored for the non-extracted dye, indocyanine green. Concentrations of bupivacaine were approximately 20% lower in the aorta than in the pulmonary artery. This gradient of bupivacaine was present across the lung for 5-10 min. Concentrations of bupivacaine in the coronary venous plasma were also markedly lower than at the arterial site. Initially more than 50% of the amount of bupivacaine at the arterial site was removed by the heart. Later, the myocardial extraction ratio decreased and plateaued at a value of 0.30-0.40. At this time, concentrations of bupivacaine in the pulmonary artery were approximately 12 micrograms ml-1. Therefore, approximately 0.3-0.6 mg of bupivacaine were extracted per minute by the sheep heart in vivo. On the other hand, isolated perfused rat hearts did not substantially remove bupivacaine (2 micrograms ml-1) from the medium. Approximately one-third of 14C-bupivacaine was retained in slices of rat and sheep myocardial tissue. However, there was no evidence that metabolism played a substantial role in the cardiac kinetics of bupivacaine.