Effects of almitrine on the ventilatory control, breathing pattern and maximal exercise tolerance in hypoxemic patients with chronic obstructive pulmonary disease

Almitrine bismesylate improves arterial blood gases in patients with chronic obstructive pulmonary disease (COPD), but side effects such as increase of ventilatory drive and dyspnea have been reported in some studies. We studied 18 COPD patients (mean age=59.1 years; mean FEV1=0.921; mean PaO2=58.6mmHg) in a double-blind randomized study using placebo or almitrine 50 mh twice a day by mouth, for 60 days. In contrast to the placebo group, 40 per cent of the patients in the almitrine group presented a significant increase in PaO2 and a decrease in P(A-a))2>=5mmHg during submaximal exercise after 60 days of treatment. Ventilatory drive and the breathing pattern were measured at rest and during submaximal exercise. Both goups showed high levels of ventilatory drive and atachypneic breathing pattern before drug tratment and no modification was found 30 and 60 days after treatment. Metabolis, cardiovascular and ventilatory variables were studied during an incremental to maximum exercise symptom-limited test (cycloergometry). Maximal VO2 ranged from 46 to 52 per cent and heart rate from 76 to 78 per cent in relation to the predicted values. The percent ratio of ventilation at maximal exercise to maximal voluntary ventilation at rest ranged from 86 to 94 per cent. These results show that the reduction of ventilatory capacity was the main factor decreasing the aerobic performance of our COPD patients. Maximal exercise tolerance (VO2 max) did not change after almitrine treatment. Negative factors like an increase in neuromuscular drive did not occur, and positive factors like an increase in PaO2 and oxygen transport had no critical influence on exercise performance in our ventilatory-limited COPD patients.

O bismesilato de almitrina melhora as trocas gasosas em cäes normais hipoventilados sob ventilaçäo controlada / Almitrine bismesylate improves gas exchange in hypoventilated normal dogs under controlled ventilation

Este estudo teve como principal objetivo testar a açäo de pequenas doses de bismesilato de almitrina (0,004 mg/kg peso corpóreo/min) sobre os gases arteriais e sobre as circulaçöes pulmonar e sistêmica sob ventilaçäo mecânica controlada. Cinco grupos de sete cäes cada um foram estudados curarizdos sob ventilaçäo mecânica controlada de maneira dupla cega: normoventilaçäo + placebo (NP); hipoventilaçäo + placebo (HP); normoventilaçäo + almitrina (NA); hipoventilaçäo + almitrina (HA); e hipoventilaçäo + hipoxemia + almitrina (HHA). Os resultados näo mostraram variaçöes significantes das trocas gasosas e variáveis hemodinâmicas em todos os grupos, exceto no HHA. Nesse grupo, durante infusäo de bismesilato de almitrina, apesar de näo haver variaçäo na ventilaçäo pulmonar, a PaO2 aumentou de 38,1 mmHg para 50,2 mmHg, a PaCO23 decresceu de 65,6 mmHg para 57,8 mmHg e com variaçäo significante da razäo PaO2/PAO2 de 0,60 para 0,69. Dessa maneira, concluímos que a droga melhorou a gasometria arterial, sem qualquer variaçäo pulmonar, em condiçöes de hipoxemia e hipercapnia acentuada