Almitrine bismesylate treatment in patient with chronic obstructive pulmonary disease and moderate chronic respiratory failure. Open prospective multicentre trial

The efficacy and safety of almitrine bismesylate treatment was assessed in COPD patients in 6 month open prospective multicentre trial. 77 COPD patients with moderate hypoxemia were included (males / females — 57 / 20, mean age 63.2 ± 9.7 years; mean FEV1 0.95 ± 0.38 L, mean PaO2 63.3 ± 5.4 mmHg, mean PaСO2 44.1 ± 7.3 mmHg). We used an intermittent regime of almitrine administration: 1 mg / kg / day, for 3 months, then a "window" of 1 month, and again active therapy for 2 months. Almitrine therapy resulted in improvement of РаО2: rise after 1 month to 71.5 ± 10.6 mmHg, after 3 month — to 70.3 ± 8.3 mmHg, and after 6 month — to 72.5 ± 14.2 mmHg (р < 0.001). There was a significant fall in dyspnea during daily life activities (MRC score): from 3.5 ± 0.9 to 3.0 ± 0.9 (1 month), 2.8 ± 0.9 (3 month), 2.6 ± 0.7 (6 month) (р < 0.001). The distance during 6 minute walk test (6 MWT) increased from 334 ± 108 m to 371 ± 101 m (1 month), 377 ± 88 m (3 month), 398 ± 104 m (6 month) (р < 0.001). The levels of desaturation and Borg dyspnea score during 6 MWT significantly decreased (both р < 0.001). During almitrine treatment an improvement in almost all domains of SF 36 quality of life questionnaire was noted. 58 COPD patients completed the study. The most common adverse effects were parasthesia (6.4 %) and worsening of dyspnea (5 %), pulmonary artery pressure did not change during study. Conclusions: almitrine treatment in COPD patients with moderate hypoxemia resulted in improvement of arterial oxygenation, reduction of dyspnea during daily life activities and exercise, increase of physical capacity and improvement of health related quality of life.

Effect of position, nitric oxide, and almitrine on lung perfusion in a porcine model of acute lung injury

In a porcine model of oleic acid-induced lung injury, the effects of inhaled nitric oxide (iNO) and intravenous almitrine bismesylate (ivALM), which enhances the hypoxic pulmonary vasoconstriction on the distribution of regional pulmonary blood flow (PBF), were assessed. After injection of 0.12 ml/kg oleic acid, 20 anesthetized and mechanically ventilated piglets [weight of 25 ± 2.6 (SD) kg] were randomly divided into four groups: supine position, prone position, and 10 ppm iNO for 40 min followed by 4 μg · kg−1 · min−1ivALM for 40 min in supine position and in prone position. PBF was measured with positron emission tomography and H2 15O. The redistribution of PBF was studied on a pixel-by-pixel basis. Positron emission tomography scans were performed before and then 120, 160, and 200 min after injury. With prone position alone, although PBF remained prevalent in the dorsal regions it was significantly redistributed toward the ventral regions ( P < 0.001). A ventral redistribution of PBF was also obtained with iNO regardless of the position ( P = 0.043). Adjunction of ivALM had no further effect on PBF redistribution. PP and iNO have an additive effect on ventral redistribution of PBF.