Role of Prostacyclin and Thromboxane in the Circulatory Changes of Acute BacteremicPseudomonasPneumonia in Dogs

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Abstract
We investigated the role of prostacyclin (PGI2) and thromboxane A2 (TxA2), as evidenced by changes in their stable metabolites, 6-keto-prostaglandin F1.alpha. (6-keto-PGF1.alpha.) and thromboxane B2 (TxB2), in the pathophysiology of acute bacteremic gram-negative pneumonia. Three groups of dogs were inoculated endotracheally: Group I (n=5) with sterile broth, and Groups II (n=5) and III (n=10) with Pseudomonas aeruginosa. Gas exchange, hemodynamics, and plasma prostaglandins were measured before inoculation and hourly thereafter for 5 h in Groups I and II but only once in Group III, 5 h after inoculation. All animals were then killed, and the extent of pneumonia was assessed by lung wet weight and measurement of the percentage of cardiac output (CO) perfusing pneumonic lung using radionuclide-labeled microspheres. None of these measurements changed significantly in Group I, but all dogs in Groups II and III developed severe pneumonia. In Group II, mean arterial oxygen tension fell from 575 .+-. 17 to 237 .+-. 59 mm Hg (FIO2=1.0), with an increase in pulmonary shunt from 6 .+-. 2% to 24 .+-. 6%. Although TxB2 levels did not change, plasma 6-keto-PGF1.alpha. rose progressively as pneumonia developed from baseline levels (<100 pg/ml) to a peak level of 890 .+-. 114 pg/ml 5 h after inoculation. This rise in 6-keto-PGF1.alpha. was accompanied by a fall in systemic arterial pressure (Psa), 144 .+-. 10 to 91 .+-. 5 mm Hg, and systemic vascular resistance (SVR), 3,161 .+-. 186 to 1,873 .+-. 229 dyn/s/cm5), whereas CO, pulmonary arterial pressure (Ppa), and pulmonary vascular resistance remained at preinoculation levels. A significant logarithmic relationship was found between the increase in plasma 6-keto-PGF1.alpha. and fall in Psa and SVR. Combining the results from Groups II and III at 5 h after inoculation, an inverse relationship was found between plasma prostaglandin (both 6-keto-PGF1.alpha. and TxB2) levels and pneumonia size, as evidenced by lung wet weight, pulmonary shunt, and perfusion of pneumonia lung regions. We conclude that in this model of gram-negative pneumonia, plasma levels of the vasodilator PGI2 increase and dominate the accompanying circulatory changes with a fall in Psa and SVR. Unlike most other models of endotoxic and bacteremic shock in which elevated TxA2 levels lead to increased PVR and reduced CO, TxA2 levels do not increase, and Ppa and CO are maintained in the normal range. Further, there is an inverse relationship between the extent of pneumonia and plasma levels of PGI2 and TxA2, raising the possibility that while prostaglandins may be involved in the pathogenesis of the observed circulatory changes, they may also have a protective effect in reducing the extent of disease.