title: Systemic and pulmonary hypertension after abrupt cessation of prostacyclin: role of thromboxane A2.
abstract: 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 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 mean systemic arterial pressure (MAP) and systemic (SVR) and pulmonary vascular resistances (PVR), a rise in cardiac output (CO), and no change in pulmonary arterial or pulmonary capillary wedge pressure (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 min, and PCWP nearly doubled after stoppage of the drug. Concurrent treatment with a cyclooxygenase inhibitor did not attenuate these responses. 11-Dehydro-thromboxane B2 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.
authors.affiliation: Center for Lung Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Cuiper
authors.forename: P V
authors.initials: PV
authors.lastname: Price
authors.forename: B W
authors.initials: BW
authors.lastname: Christman
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology; D007262:Infusions, Intravenous; D015539:Platelet Activation / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology
chemical_list: D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C049235:11-dehydro-thromboxane B2; D011464:Epoprostenol