Modulation of cardiovascular function and platelet survival by endogenous prostacyclin released during surgery

Surgery has been reported to stimulate production of the potent vasodilating and antiaggregating agent prostacyclin (PGI₂). The consequences of this metabolic event were studied in 21 patients, with and without aspirin pretreatment, who underwent abdominal aortic aneurysmectomy. In eight patients who received a placebo, plasma concentration of 6-keto-PGF_1α, the PGI₂ degradation product rose from 35 to 950 pg/ml (P < 0.01) 30 minutes after the start of surgery. This was related to a decrease in mean arterial pressure (MAP), which averaged 12 torr (r = 0.73, P < 0.01), and an increase in cardiac index (CI), which averaged 0.5 l/min · m² (r = 0.69, P < 0.01). Ex vivo adenosine diphosphate-induced platelet aggregation decreased 28% (P < 0.001). After aortic clamping, the stable degradation product of thromboxane (Tx) A₂, TxB₂, increased from 68 to 111 pg/ml (P < 0.025), and the platelet count decreased from 190,000 to 147,000/mm³ (P < 0.025). In contrast, the concentrations of 6-keto-PGF_1α and TxB₂ were unchanged during surgery in 13 patients who received 650 mg aspirin 12 hours before operation. After the incision, the MAP increased 25 torr (P < 0.05); the CI and platelet aggregation were unchanged. The preoperative platelet counts were 211,000/mm³ in controls and 190,000/mm³ in aspirin-treated patients, whereas after 24 hours platelet counts averaged 156,000 and 105,000/mm³, respectively (P < 0.01). In vitro incubation of sections from the aneurysm wall in Ringer's solution led to a 60-fold greater production of 6-keto-PGF_1α in controls as compared to aspirin-treated patients. In a parallel experiment with ten dogs, barbiturate anesthesia and mechanical ventilation led to a small increase in 6-keto-PFG_1α from 23 to 56 pg/ml, whereas 10 minutes after the start of surgery, the levels increased to 257 pg/ml (P < 0.005) without a change in TxB₂. Arterial concentrations of 6-keto-PFG_1α were higher in every animal (P < 0.05), suggesting that the lungs were at least partially responsible for the increased prostaglandin synthesis. A decrease in ex vivo platelet aggregation and MAP and a rise in cardiac output were noted, events prevented in five dogs pretreated with indomethacin (5 mg/kg). These data indicate that surgery stimulates production of PGI₂, a metabolic event associated with systemic hemodynamic and antiaggregatory consequences.