Systemic and pulmonary hypertension following abrupt cessation of
prostacyclin: role thromboxane a .
Cuiper, Leslie L., Patricia V. Price, Brian W. Christman.
Center for Lung Research, Division of Pulmonary and Critical Care
Medicine, Vanderbilt University School of Medicine, Nashville,
Tennessee 37232-2650
APStracts 2:0398A, 1995.
Chronic administration of prostacyclin (PGI2) improves hemodynamics in
patients with primary pulmonary hypertension, but abrupt cessation of
infusion can cause severe dyspnea of unknown etiology. We
hypothesized that the discontinuation of PGI2 results in platelet
activation, thromboxane A2 (TxA2) production and increased pulmonary
vascular tone. To test this, six sheep with indwelling catheters were
monitored during infusion of PGI2 and after its cessation. Infusion
of PGI2 caused a reduction in MAP, SVR and PVR, a rise in CO and no
change in PAP or PCWP. After discontinuation of PGI2, MAP and SVR
rebounded to 30% and 67% above baseline, respectively, and PVR rose
26%. CO was depressed 23% within 10 minutes and PCWP nearly doubled
after stopping the drug. Concurrent treatment with a cyclooxygenase
inhibitor did not attenuate these responses. 11-dehydro-TxB2 levels
were not elevated during infusion or after cessation of PGI2 . We
conclude that the abrupt cessation of PGI2 infusion leads to systemic
and pulmonary hypertension and transient cardiac dysfunction not
mediated by cyclooxygenase metabolites of arachidonic acid.
Received 22 May 1995; accepted in final form 1 September 1995.
APS Manuscript Number A538-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.