MYOCARDIAL EXTRACTION OF BUPIVACAINE IN ANESTHETIZED SHEEP AND BY HEARTS OF SHEEP AND RATS IN-VITRO

We observed the in vivo kinetics of bupivacaine in the cardiopulmonary system, particularly in the pulmonary artery, the upper part of the d escending aorta and the coronary sinus of anaesthetized sheep, each of which received a high dose infusion into the central vein. In some ex periments dilution curves were monitored for the non-extracted dye, in docyanine green. Concentrations of bupivacaine were approximately 20% lower in the aorta than in the pulmonary artery. This gradient of bupi vacaine was present across the lung for 5-10 min. Concentrations of bu pivacaine in the coronary venous plasma were also markedly lower than at the arterial site. Initially more than 50% of the amount of bupivac aine at the arterial site was removed by the heart. Later, the myocard ial extraction ratio decreased and plateaued at a value of 0.30-0.40. At this time, concentrations of bupivacaine in the pulmonary artery we re approximately 12 mu g ml-l Therefore, approximately 0.3-0.6 mg of b upivacaine were extracted per min ute by the sheep heart in vivo. On t he other hand, isolated perfused rat hearts did not substantially remo ve bupivacaine (2 mu g ml(-1)) from the medium. Approximately one-thir d of C-14-bupivacaine was retained in slices of rat and sheep myocardi al tissue. However, there was no evidence that metabolism played a sub stantial role in the cardiac kinetics of bupivacaine.