Prostacyclin therapy increases right ventricular capillarisation in a model for flow-associated pulmonary hypertension

Pulmonary hypertension, and consequently right ventricular failure, complicates several congenital heart defects. Although intervention in the prostacyclin-thromboxane ratio is known to improve outcome, the underlying mechanism is not clear. Therefore, effects of acetyl salicylic acid and iloprost are studied in an animal model for flow-associated pulmonary hypertension. Male Wistar rats with flow-associated pulmonary hypertension, an aortocaval shunt in addition to monocrotaline induced pulmonary hypertension, were treated with low-dose aspirin (25 mg/kg/day) or iloprost (72 μg/kg/day). Effects on pulmonary hemodynamics and pulmonary vascular remodeling as well as right ventricular hemodynamics and remodeling were evaluated. Ninety percent (n = 7 / 8) of the untreated pulmonary hypertensive rats developed dyspnea and pleural fluid, whereas this was seen in 50% (n = 4 / 8, ns) and 10% (n = 1 / 8, P < 0.05 vs. untreated animals) of the aspirin and iloprost-treated rats, respectively. This could not be attributed to changes in pulmonary artery pressure, wall-lumen ratio of the pulmonary vasculature or right ventricular hypertrophy. However, both therapies restored reduced right ventricular capillary to myocyte ratio in pulmonary hypertensive rats (0.95 ± 0.10 in untreated rats vs. 1.38 ± 0.18 in control animals; P < 0.05, and 1.32 ± 0.11 in aspirin-treated and 1.29 ± 0.9 in iloprost-treated rats; both P < 0.05 vs. non-treated animals), which was associated with improved right ventricular contractility (iloprost). Thus, interventions in the prostacyclin-thromboxane metabolism improve outcome in rats with flow-associated pulmonary hypertension. However, these effects may be attributed to effects on cardiac rather than on pulmonary vascular remodeling.

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