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.

Correlation between arterial oxygen and carbon dioxide levels and response to almitrine bismesylate in normal dogs

The objectives of this study were: 1) to test the action of small doses of almitrine bismesylate (0.004 mg/Kg body weight/min) on the arterial blood gases and on pulmonary and systemic circulation during hypoventilation under controlled mechanical ventilation; and 2) to investigate possible correlations between arterial blood. O2 and CO3 levels and the response to the drug. Twenty one dogs divided into two groups were studied under controlled ventilation in a double-blind fashion: hypoventilation + placebo (HP) (seven dogs); hypoventilation + almitrine (HA) (fourteen dogs). The results showed no significant variations of the gas ex-change and hemodynamic varibles in the HP group. In the HP group, during almitrine bismesylate infusion, despite the lack of variation in the pulmonary ventilation, the PaO2 increased from 46.1 torr to 51.7 torr, the PaCO2 decreased from 61.9 torr to 57.7 torr. There were no significant variations of hemodynamic variables in the HA group. Thus we conclude that the drug improved arterial blood gases (PaO2 increased) with small increase in alveolar ventilation (PaCO2 decreased) despite the lack of changes in pulmonary ventilation, and that the drug has action on the arterial PO2 potentiated by hypoxemia and hypercapnia