Cardiac prostacyclin kinetics during cardiopulmonary bypass

We have investigated the response of systemic and myocardial prostacyclin metabolism to cardiopulmonary bypass and 30 minutes of hypothermic (22 degrees C), hyperkalemic (25 mEq K+) surgical cardioplegia. Thirteen adult mongrel dogs of either sex (range 21 to 36 kg) underwent sterile cardiopulmonary bypass without donor blood. Prostacyclin levels were obtained after cannulation, 20 minutes after onset of partial bypass, and 5 seconds after the onset of cardioplegia 1 (CP-1) and cardioplegia 2 (CP-2, 30 minutes later). Samples were drawn from the thoracic aorta, the aortic root below cross-clamping, and the coronary sinus. The stable metabolite of prostacyclin, 6-keto-PGF1 alpha was measured by double-antibody radioimmunoassay (pg/ml; values +/- standard error of the mean). We found that the onset of partial bypass is associated with significant increase in the systemic production of 6-keto-PGF1 alpha (122 +/- 33 versus 518 +/- 187; p less than 0.05), which persists throughout the experiment. A small but significant positive cardiac gradient of 6-keto-PGF1 alpha is found after cannulation (aortic root 122 +/- 33, coronary sinus 202 +/- 57, p less than 0.05). This gradient is more pronounced during partial bypass (aortic root 518 +/- 187, coronary sinus 686 +/- 186 p less than 0.05), when significant cardiac lactate extraction (p less than 0.005) is observed. After cross-clamping, a significantly increased gradient of 6-keto-PGF1 alpha is found during CP-1 (aortic root 74 +/- 10, coronary sinus 264 +/- 46, p less than 0.05 versus cannulation) in the presence of significant cardiac lactate production (p less than 0.005). A further significant increase in 6-keto-PGF1 alpha production is noted during the CP-2 infusion (aortic root 73 +/- 10, coronary sinus 483 +/- 83; p less than 0.01 versus CP-1), which is inversely related to cardiac oxygen uptake and endocardial/epicardial flow ratio. Our data demonstrate significant production of prostacyclin in the systemic and cardiac circulations during cardiopulmonary bypass and surgical cardioplegia. They further indicate that both ischemic and nonischemic stimuli regulate prostacyclin metabolism during cardiopulmonary bypass.