| Abstract: | Patients undergoing abdominal aortic aneurysmectomy (AAA) develop depressed cardiac function during aortic clamping. The importance of volume status and thromboxane (Tx) mediated declines in cardiac contractility in determining this event was studied. In a blinded fashion, patients received the cyclo-oxygenase inhibitor ibuprofen 12 mg/kg by mouth (n = 11) or a placebo (n = 15), 1.5 hours prior to surgery. In the placebo group levels of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin (PGI2) rose from 20 +/- 10 to 1170 +/- 80 pg/ml (p less than 0.05) soon after incision. Concentrations of TxB2, the stable hydrolysis product of TxA2, were unchanged until 30 minutes after the aorta was clamped when arterial TxB2 concentrations rose from 90 +/- 20 to 230 +/- 30 pg/ml (mean +/- SEM) (p less than 0.05). A pulmonary source for PGI2 and TxA2 was indicated by the observation that arterial 6-keto-PGF1 alpha and TxB2 levels exceeded those in pulmonary arterial blood by 180 +/- 50 and 110 +/- 30 pg/ml, respectively (p less than 0.05). Levels of TxB2 in circulating platelets remained unchanged from baseline in the placebo group. During aortic clamping, cardiac index (CI) fell 0.7 +/- 0.2 1/min X m2 (p less than 0.05) in placebo treated patients, and there was a 6% decline in plasma contractility as bioassayed with a rat papillary muscle (p less than 0.05). Placebo patients entered surgery with a PAWP greater than or equal to 10 mmHg (mean 13 mm). Ibuprofen suppressed production of TxB2, such that 30 minutes after aortic clamping TxB2 was 70 +/- 30 pg/ml, a value lower than control patients (p less than 0.05). Further, plasma no longer depressed contractility of the papillary muscle. Five patients given ibuprofen had an initial pulmonary arterial wedge pressure (PAWP) of 10 mmHg or greater (mean 12 mmHg). During aortic clamping there was an insignificant decrease in CI of 0.2 +/- 0.1 1/min X m2. This was in contrast to the CI decrease in six other ibuprofen treated patients of 0.9 +/- 0.2 1/min X m2 whose PAWP at the start of surgery was less than 10 mmHg (mean 6 mmHg) (p less than 0.05), and to placebo patients whose initial PAWP was greater than or equal to 10 (p less than 0.05). Platelet counts fell from 185,000 to 121,000/mm3 in placebo patients (p less than 0.05), but did not fall when ibuprofen was given. Creatinine concentrations were unaffected by ibuprofen. Blood replacement in placebo and ibuprofen patients was similar, 1.90 +/- 0.20 and 0.65 +/- 0.15 1, respectively. Results indicate that CI will not decrease during AAA if sufficient volume is given before surgery to increase PAWP above 10 mmHg, and secondly, if TxB2 synthesis is inhibited. |
