Treprostinil in advanced experimental pulmonary hypertension: Beneficial outcome without reversed pulmonary vascular remodeling
| Autor: | Mirjam E. van Albada, Adri H. Cromme-Dijkhuis, Regien G. Schoemaker, Ro F. M. E. Berger, Richard van Veghel |
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| Přispěvatelé: | Internal Medicine, Pediatrics, Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Schoemaker lab |
| Rok vydání: | 2006 |
| Předmět: |
Pulmonary Circulation
GROWTH-FACTOR PHARMACOKINETICS medicine.medical_specialty surgical arteriovenous shunt Hypertension Pulmonary medicine.medical_treatment Hemodynamics Blood Pressure Prostacyclin THERAPY DISEASE pulmonary vascular histopathology INTRAVENOUS EPOPROSTENOL PROSTACYCLIN Right ventricular hypertrophy Internal medicine pulmonary hypertension Animals Medicine Rats Wistar Saline Pharmacology ANALOGS prostacyclin business.industry PROLIFERATION CONTINUOUS SUBCUTANEOUS INFUSION medicine.disease Epoprostenol monocrotaline Pulmonary hypertension Rats Disease Models Animal Treatment Outcome HEMODYNAMICS Anesthesia Heart failure Cardiology ARTERIAL-HYPERTENSION Histopathology Cardiology and Cardiovascular Medicine business Treprostinil medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology, 48(5), 249-254. Lippincott Williams & Wilkins Journal of Cardiovascular Pharmacology, 48(5), 249-254 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/01.fjc.0000248229.87510.9b |
| Popis: | Introduction: Beneficial effects of treprostmil, a stable prostacyclin analogue, were demonstrated in patients with pulmonary arterial hypertension (PAH). Although regression of pulmonary vascular remodeling has been suggested as therapeutic mechanism, its mode of action remains unknown.Methods: Flow-associated PAH was created in rats by injection of monocrotaline (60 mg/kg) combined with an abdominal aortocaval shunt. Subsequently, rats were treated with subcutaneous treprostinil (50 ng/kg/min, treated; n = 8) or saline (untreated; n = 9). A control group underwent sham-surgery (n = 8). Animals were sacrificed at symptoms of cardiac failure, together with their matched controls.Results: Dyspnea and weight loss determined the moment of sacrifice in 8/9 untreated animals (89%) versus in one of eight treated animals (13%; log-rank test survival curves; P = 0.02). Mean pulmonary arterial pressure increased in the model (42 +/- 2 mm Hg in untreated vs. 18 +/- 1 in controls; P Conclusions: Treprostinil treatment improved clinical course and ameliorated symptoms of heart failure in a model of advanced PAR However, beneficial effects were not associated with reversed structural remodelling of the pulmonary vasculature. |
| Databáze: | OpenAIRE |
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