Abstract | INTRODUCTION: 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 < 0.01) and decreased by 8 mm Hg after therapy (34 +/- 3 mm Hg, P = 0.04 vs. untreated). No effects of treatment on right ventricular hypertrophy could be demonstrated. Quantitative morphometry of pre- and intra-acinar pulmonary arteries revealed no effects of treatment on vessel histopathology. CONCLUSIONS:
Treprostinil treatment improved clinical course and ameliorated symptoms of heart failure in a model of advanced PAH. However, beneficial effects were not associated with reversed structural remodelling of the pulmonary vasculature.
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Authors | Mirjam E van Albada, Richard van Veghel, Adri H Cromme-Dijkhuis, Regien G Schoemaker, Rolf M F Berger |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 48
Issue 5
Pg. 249-54
(Nov 2006)
ISSN: 0160-2446 [Print] United States |
PMID | 17110807
(Publication Type: Journal Article)
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Chemical References |
- Epoprostenol
- treprostinil
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Topics |
- Animals
- Blood Pressure
(physiology)
- Disease Models, Animal
- Epoprostenol
(administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
- Hypertension, Pulmonary
(drug therapy, physiopathology)
- Pulmonary Circulation
(physiology)
- Rats
- Rats, Wistar
- Treatment Outcome
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