Journal of Applied Physiology, Vol 60, Issue 2 546-553, Copyright © 1986 by American Physiological Society
Effect of prostacyclin on pulmonary vascular response to thrombin in awake sheep
M. B. Perlman, S. K. Lo and A. B. Malik
We determined the effects of infusion of prostacyclin (PGI2) and
6-alpha-carba-PGI2 (6-cPGI2), a stable PGI2 analogue, on pulmonary
transvascular fluid and protein fluxes after intravascular coagulation
induced by thrombin. Studies were made in control awake sheep prepared with
lung lymph fistulas (n = 6) and in similarly prepared awake sheep
pretreated with either 6-cPGI2 (n = 5) or PGI2 (n = 5). Both prostacyclin
compounds (500 ng X kg-1 X min-1) were infused intravenously. All groups
were challenged with 80 U/kg thrombin. Pulmonary arterial pressure (Ppa),
pulmonary vascular resistance (PVR), pulmonary lymph flow (Qlym), lymph
protein clearance (Qlym X lymph/plasma protein concentration ratio), and
neutrophil and platelet counts were determined. In vitro tests assessed
sheep neutrophil chemotaxis and chemiluminescence and platelet aggregation.
In both 6-cPGI2 and PGI2 groups, the increases in Qlym after thrombin were
less than those in the control group. The increase in lymph protein
clearance in the 6-cPGI2 group was the same as that in control, whereas the
increase in clearance in the PGI2 group was reduced. PVR and Ppa increased
to a greater extent in the 6-cPGI2 group than in the control group, whereas
the increases in PVR and Ppa were inhibited in the PGI2 group. Neutrophil
and platelet counts decreased after thrombin in PGI2 and 6-cPGI2 groups, as
they did in the control group. Neither 6-cPGI2 altered neutrophil
chemotaxis induced by thrombin and chemiluminescence induced by opsonized
zymosan. Both prostacyclin compounds inhibited platelet aggregation induced
by ADP or thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)
