A one year double blind follow-up of blood gas tensions and haemodynamics in almitrine bismesylate therapy.

Almitrine bismesylate, a chemoreceptor agonist, improves blood gases in chronic obstructive lung disease (COLD). Some authors have observed an increase in pulmonary artery pressure (Ppa) after single doses of almitrine bismesylate (A). This led to the present one year double blind placebo (P) controlled study to assess haemodynamic effects of long-term oral treatment in COLD (1.5 mg/kg/day for one year), together with clinical benefit and blood gas improvement. Twenty moderately severe patients entered the study, fifteen of whom completed it (eight in group (A), seven in group (P]. Blood gas values, minute ventilation (VE), mean pulmonary artery pressure (Ppa) and cardiac output (Qc) were periodically measured. Ppa and Qc remained unchanged in both groups throughout the study. We observed relevant clinical improvement without side effects and no significant increase in VE in group (A). Arterial oxygen tension (PaO2) showed a 1.2 kPa (9 mmHg) mean increase in group (A) and remained unchanged in group (P). These data and those from the literature seem to indicate that almitrine induces a vascular effect, especially after a single dose. However, as long as PaO2 improves simultaneously no long-term haemodynamic consequence is apparent. The discrepancy between immediate and long-term vascular effects of almitrine might be explained by the improvement in gas exchange which could reduce and/or counter-balance the vasoactive response. In conclusion, after one year of therapy almitrine bismesylate results in considerable clinical and blood gas improvements without significant haemodynamic change.

Effects of adenosine triphosphate on pulmonary circulation in chronic obstructive pulmonary disease. ATP: a pulmonary vasoregulator?

Extracellular adenosine triphosphate (ATP) has potent systemic vasodilator and endothelial-dependent relaxant effects on precontracted vessels. Pulmonary uptake and metabolism of ATP have been described, but experimental effects on pulmonary vessels remain controversial in animals. The effects of an intravenously administered infusion of ATP on pulmonary hemodynamic and gasometric data were assessed in 18 patients with stable chronic obstructive pulmonary disease (COPD). Low doses of ATP (successive rates, 1 and 2 mumol/kg body weight, each for 20 min) were infused in pulmonary hypertensive (H; n = 6) and nonhypertensive (N; n = 6) patients. They were compared with a control group (C; n = 6) that received only solvent, using ANOVA. During ATP infusion, a significant pulmonary vasodilation was demonstrated as simultaneous decreases reached, respectively, -14.2% (Group H; p less than 0.005) and -13.8% (Group N; p less than 0.001) for mean pulmonary artery pressure (Ppa), and -31.7% (H; p less than 0.05) and -20.7% (N; p less than 0.01) for pulmonary vascular resistances (PVR), associated with some worsening of hypoxemia: -6.9% (H; p less than 0.01) and -11.8% (n; p less than 0.005). After ATP withdrawal, significant rebound of these data (above baseline values) reached +10.9% (H; p less than 0.05) and +4.4% (N; p less than 0.05) for Ppa and +24.9% (H; p less than 0.05) and +10.2% (N; p = NS) for PVR. At the low infusion rate used, ATP appeared to be a well-tolerated, short-acting, selective pulmonary vasolidating compound in patients with COPD, but therapeutic use remains premature.

Long term studies on almitrine bismesylate in COPD patients.

Almitrine bismesylate is a chemoreceptor agonist which has been shown to improve arterial blood gas values in chronic obstructive pulmonary disease (COPD) patients, possibly through better ventilation/perfusion matching. On these basis, long term studies were undertaken to evaluate the therapeutic activity of almitrine bismesylate in COPD. We report here the overall results of 4 studies: a 6 months double blind placebo controlled study on clinical and biochemical data in 200 patients. a 12 months double blind placebo controlled study on clinical and hemodynamic data in 15 patients. a 12 months open study on clinical and biochemical data in 108 patients. a 52 months follow-up including therapeutic gap in 8 patients. Almitrine bismesylate group showed significant improvement of PaO2 and PaCO2 levels as compared with placebo group; this was found after 6 months of treatment and persisted after 12 months of treatment. 75% of almitrine treated patients were considered as responders, i.e. improved PaO2 and PaCO2 levels by at least 5 mmHg (0.665 KPa). Almitrine bismesylate groups showed significantly decreased dyspnea scores, received significantly less hospital care for acute decompensation or pulmonary infection and showed no significant change in hemodynamic parameters. After 20 months treatment interruption, patients showed progressively impairmed blood gas levels. Almitrine bismesylate ws well tolerated; nausea was occasionally observed and usually disappeared. Paresthesia was observed in some patients with identified predisposition. Altogether, these studies showed long term efficacy and acceptability of almitrine bismesylate in COPD patients with chronic respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pulmonary hemodynamic monitoring in chronic respiratory insufficiency treated with almitrine bismesilate for 4 months in a double-blind study]. / Surveillance hémodynamique pulmonaire d'insuffisants respiratoires chroniques traités à double insu pendant 4 mois par le bismesilate d'almitrine.

Six subjects suffering from chronic airflow obstruction and respiratory failure were treated with oral almitrine bismesylate (3 mg/kg/day). Studies were made before and after 2 and 4 months treatment on: total ventilation, arterial blood gases, pulmonary artery pressure by a micro-catheter and cardiac out-put by rebreathing CO2. The results were compared with those of a placebo group of 3 subjects. While in the almitrine group a significant improvement in blood gases was observed, no change was seen in the two populations in either the haemodynamic or ventilatory variables. The medium term haemodynamic stability observed is contrasting with single dose effects of almitrine. This discrepancy could be due, at least in part, to a balance between the possible vasoconstrictor effect of almitrine bismesylate and vasodilator consequences of blood gases improvement.