beraprost and Pulmonary-Embolism

This study investigated whether treatment with beraprost sodium (BPS), an orally active prostacyclin analog, improves hemodynamics and survival in patients with peripheral-vessel chronic thromboembolic pulmonary hypertension (CTEPH), for which there is no surgical option.. Oral administration of BPS has been shown to improve the hemodynamics and prognosis in patients with primary pulmonary hypertension; however, whether BPS has beneficial effects in CTEPH remains unknown.. Forty-three patients with peripheral-vessel CTEPH were classified into two groups: patients treated with BPS (BPS group, n = 20) and those without BPS (conventional group, n = 23). Baseline demographic and hemodynamic data did not significantly differ between the two groups.. BPS therapy improved New York Heart Association functional class in 10 patients (50%) and significantly decreased total pulmonary resistance from 18 +/- 6 to 15 +/- 8 Wood units (p < 0.05) [mean +/- SD]. Sixteen patients died of cardiopulmonary causes in the conventional group during a mean follow-up period of 58 +/- 45 months. In contrast, only three patients died of cardiopulmonary causes in the BPS group during a mean follow-up period of 44 +/- 30 months. The absence of BPS therapy, elevated total pulmonary resistance, heart rate, and age were independently related to the mortality by Cox proportional hazard analysis. The 1-year, 3-year, and 5-year survival rates for the BPS group were 100%, 85%, and 76%, respectively, compared to 87%, 60%, and 46% in the conventional group.. This preliminary study suggests that oral administration of BPS may improve hemodynamics and survival in patients with peripheral-vessel CTEPH, for which there is no surgical option.

Topics: Administration, Oral; Chronic Disease; Epoprostenol; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Embolism; Vasodilator Agents

To investigate the effect of beraprost sodium, an orally active prostacyclin analogue, on exercise capacity and ventilatory efficiency in patients with primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension.. Symptom limited cardiopulmonary exercise testing was performed before and 3 (1) months (mean (SEM)) after beraprost treatment in 30 patients with precapillary pulmonary hypertension (14 with primary pulmonary hypertension and 16 with chronic thromboembolic pulmonary hypertension).. Long term treatment with beraprost resulted in significant increases (mean (SEM)) in peak workload (87 (4) W to 97 (5) W, p < 0.001) and peak oxygen consumption (peak VO2, 14.9 (0.7) ml/kg/min to 16.8 (0.7) ml/kg/min, p < 0.001). Beraprost decreased the ventilatory response to carbon dioxide production during exercise (VE-VCO2 slope, 42 (2) to 37 (1), p < 0.001). No significant difference in the responses of these variables to beraprost treatment was observed between patients with primary pulmonary hypertension and chronic thromboembolic pulmonary hypertension.. Oral administration of beraprost sodium may improve exercise capacity and ventilatory efficiency in patients with both primary and chronic thromboembolic pulmonary hypertension.

Topics: Administration, Oral; Adult; Epoprostenol; Exercise; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Oxygen Consumption; Platelet Aggregation Inhibitors; Pulmonary Embolism; Respiration

We examined whether beraprost sodium (beraprost), a stable analogue of PGI2, has an anti-inflammatory effect on the permeability barrier through endothelial cells in vivo. The injection of collagen (5 micrograms/head) plus epinephrine (0.6 microgram/head) showed time-dependently the increased Evans blue dye leakage of the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose-dependently (control; 11.26 +/- 1.64 micrograms/lung, beraprost 10 micrograms/kg; 7.49 +/- 1.36 micrograms/lung, 30 micrograms/kg; 5.33 +/- 0.71 micrograms/lung, 100 micrograms/kg; 5.52 +/- 0.79 micrograms/lung). Pulmonary thromboembolism-induced Evans blue dye leakage was also reduced significantly by aspirin (5 mg/kg), but PGE1 (170 micrograms/kg) showed a tendency to potentiate the edematogenic response. One week after the injection of same dosage of collagen plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to-dry weight ratio of the lung (normal; 3.84 +/- 0.01, control; 3.96 +/- 0.04) and right ventricular hypertrophy (normal; 28.2 +/- 0.9%, control; 32.3 +/- 0.9%) compared to normal mice. Beraprost significantly suppressed lung edema and hypertrophy dose-dependently, and over 30 micrograms/kg/day of beraprost, the effects were statistically significant (beraprost 30 micrograms/kg/day; 3.85 +/- 0.02 and 27.8 +/- 1.4%, 100 micrograms/kg/day; 3.85 +/- 0.02 and 27.3 +/- 1.1%). Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced rat paw edema dose-dependently (5-HT alone; 100%, beraprost 10(-13) mol/paw; 91.19 +/- 2.22%, 10(-12) mol/paw; 85.79 +/- 4.85%, 10(-11) mol/paw; 78.49 +/- 3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection of (-)-isoproterenol (10(-12) mol/paw), but PGE1 (10(-11) mol/paw) significantly potentiated the edematogenic response. From these results, we propose that the anti-inflammatory effect of beraprost may be contributed, in part, to the permeability barrier through end othelial cells in vivo.

Topics: Alprostadil; Animals; Anti-Inflammatory Agents; Aspirin; Cell Membrane Permeability; Collagen; Dose-Response Relationship, Drug; Edema; Endothelium, Vascular; Epinephrine; Epoprostenol; Lung; Male; Mice; Organ Size; Pulmonary Embolism; Rats; Rats, Wistar; Serotonin

Topics: Administration, Oral; Alprostadil; Animals; Aspirin; Bridged Bicyclo Compounds; Collagen; Diltiazem; Drug Evaluation, Preclinical; Epinephrine; Epoprostenol; Fatty Acids, Monounsaturated; Fibrinolytic Agents; Heparin; Hydralazine; Injections, Intravenous; Isosorbide Dinitrate; Male; Mice; Nifedipine; Nitroprusside; Platelet Aggregation Inhibitors; Pulmonary Embolism; Superoxide Dismutase; Vasodilator Agents