Protamine-heparin-induced pulmonary hypertension in pigs: Effects of treatment with a thromboxane receptor antagonist on hemodynamics and coagulation

G. A. Nuttall, M. J. Murray, E. J.W. Bowie

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Adverse hemodynamic reactions after protamine neutralization of heparin are an infrequent but important clinical problem. Pre-treatment of swine with a thromboxane A2 receptor antagonist has been reported to prevent the pulmonary hypertensive response occasionally seen after protamine reversal of heparin anticoagulation. In the current study, a control group of pigs (n = 9) received intravenous heparin (300 IU/kg), followed after 10 min by a neutralizing dose of protamine (3 mg/kg). A treatment group of pigs (n = 11) was treated identically, except that the thromboxane A2 receptor antagonist L-670596 (2 mg/kg) was infused intravenously 2 min after the protamine infusion. Hemodynamic and coagulation profiles were monitored during these procedures. Pulmonary hypertension developed and reached a peak within 2 min of protamine administration, often at the same time that L-670596 was administered in the treatment group. There was no statistical difference between control and treatment groups' peak pulmonary arterial pressure and peak pulmonary vascular resistance. However, the interval for return of mean pulmonary artery pressure from peak to baseline values was 11.6 ± 3.1 versus 5.5 ± 1.9 min (mean ± SD) for control and treatment groups, respectively (P < 0.01). Thromboxane B2 plasma concentrations increased in both groups and were correlated with the pulmonary hypertensive response (r = 0.86, P < 0.01). Platelet aggregation to collagen was inhibited by the thromboxane A2 receptor antagonist (P < 0.05). Bleeding time was prolonged beyond normal range in 50% of L-670596-treated pigs. All other coagulation tests in both groups returned to baseline after reversal of heparin with protamine and were unaffected by L-670596. Selective TxA2 receptor antagonists may have a role in managing protamine's adverse hemodynamic disturbances.

Original languageEnglish (US)
Pages (from-to)138-145
Number of pages8
Issue number1
StatePublished - 1991


  • cardiopulmonary bypass
  • coagulation
  • eicosanoids
  • heparin
  • protamine

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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