Pulmonary injury and prostaglandin production during endotoxemia in conscious sheep

Abstract

Prostaglandins F2 alpha, E2, and I2 (as 6-keto-PGF1 alpha) and TxA2 (as TxB2) were measured by radioimmunoassay in plasma and lymph from 12 conscious sheep with chronic lung lymph fistulas given Escherichia coli endotoxin (2-10 micrograms/kg) and followed for 24 h. Endotoxin produced a two-phase pulmonary injury. Phase 1 was characterized by transient severe pulmonary hypertension and increased lymph flow rate (QL). Plasma and lymph PGF2 alpha concentrations increased from base-line values of 0.13 +/- 0.08 and 0.30 +/- 0.10 ng/ml to 0.96 +/- 0.37 and 2.8 +/- 0.80 ng/ml, respectively. Values for TxB2 increased from 0.7 +/- 0.1 to 5.5 +/- 1.1 ng/ml in lymph and to 3.2 +/- 0.6 in plasma. Plasma PGI2 increased from 0.48 +/- 0.29 to 4.97 +/- 1.21 ng/ml and lymph PGI2 from 1.80 +/- 0.73 to 14.19 +/- 2.79 ng/ml. Phase 2 was characterized by moderately elevated pulmonary vascular pressures and a maintained high flow rate of protein-rich lymph. Lung lymph and plasma PGF2 alpha concentrations returned to base line. Lymph PGI2 decreased significantly to 5.23 +/- 2.47 ng/ml, whereas plasma PGI2 decreased to 2.70 +/- 1.07 ng/ml. We conclude that prostaglandins, particularly PGF2 alpha and prostacyclin, are released from the lung after endotoxemia and appear in lung lymph as sensitive indicators of pulmonary microvascular injury. Prostanoid production appears to temporally correspond with changes in the pulmonary microcirculation.