Pulmonary vascular and hemodynamic effects of prostaglandin E1 in unanesthetized sheep.
We prepared fully instrumented sheep with chronic lung lymph fistulas and measured lung lymph and hemodynamic responses to intravenous infusions of prostaglandin (PG) E1. PGE1 decreased lung lymph flow from 8.0 +/- 0.8 S.E.M. ml/h during baseline to 6.5 +/- 0.7 ml/h (p less than 0.05) and 5.4 +/- 0.8 ml/h (p less than 0.05) at 50 and 250 micrograms/min, respectively. Lymph to plasma protein concentration ratio (L/P) did not change during PGE1 infusion and increased after PGE1 was stopped. Systemic and pulmonary vascular pressures decreased without producing reflex tachycardia. PGE1 consistently caused hypoxemia and hemoconcentration. Multiple indicator dilution studies showed consistent decreases in the 14C-urea permeability surface area product (PS urea) during PGE1 infusion. To distinguish effects of PGE1 on perfused lung vascular surface area from effects on vascular permeability, we mechanically increased lung vascular pressures, achieved a steady state lung lymph response, and infused PGE1 (50 micrograms/min) while maintaining constant left atrial pressure. PGE1 decreased lung lymph flow from 14.1 +/- 2.0 ml/h to 10.0 +/- 1.8 ml/h (p less than 0.05). Systemic and pulmonary arterial pressures fell. Cardiac output did not change and heart rate decreased. L/P increased significantly, indicating that the decrease in lymph flow could be attributed to decreased lung microvascular pressure without obligate change in microvascular permeability. During increased lung vascular permeability caused by E. coli endotoxin, PGE1 (250 micrograms/min) decreased lung lymph flow, and systemic and pulmonary vascular pressures fell. Although PGE1 decreased lymph protein clearance, L/P did not change. Decreased lymph flow with PGE1 could be attributed to decreased lung vascular pressure, decreased exchanging vessel surface area, or both.
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D004731:Endotoxins / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D008196:Lymph / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D001798:Blood Proteins; D004731:Endotoxins; D000527:Alprostadil