The rationale for considering the combined use of vasodilators and low-flow oxygen in patients with COPD and hypoxemia is based on five hypotheses. The extent to which these hypotheses are correct will likely determine the long-term usefulness of vasodilators in these patients.
1. Hypoxic pulmonary vasoconstriction and hypoxia-induced vascular smooth muscle hypertrophy play key roles in the pathogenesis of pulmonary hypertension in patients with COPD.
2. The changes caused by alveolar hypoxia—hypertrophy of vascular smooth muscle, pulmonary hypertension, and right ventricular hypertrophy—are potentially reversible.
3. Even short periods of hypoxia on a chronic basis will cause arterial smooth muscle hypertrophy, pulmonary hypertension, and right ventricular hypertrophy.
4. Low-flow oxygen therapy may not, in portions of the lung, eliminate alveolar hypoxia, especially during exercise. Consequently, low-flow oxygen may be insufficient therapy to cause regression of the hypoxia-induced pathologic changes.
5. Long-term therapy with vasodilator drugs may augment the beneficial hemodynamic effects of low-flow oxygen therapy.
Although polycythemia and destruction of the pulmonary vascular bed by emphysema may contribute to the development of pulmonary hypertension in patients with COPD, the clinical and pathologic evidence available indicates that alveolar hypoxia is probably the major mechanism. Ample evidence exists in laboratory animals that the pathologic changes caused by hypoxia will reverse. Although little clinical data exist, the study of Sime et al clearly demonstrates the potential for reversibility in man. They found that high-altitude natives with hypoxic pulmonary hypertension had remarkable regression of their pulmonary hypertension after living at sea level for two years. Intermittent exposure to hypoxia is a potent stimulus for the development of the physiologic and pathologic changes caused by hypoxia. In bet, a recent report suggests that two hours per day of hypoxia may be sufficient to produce these pathologic changes. Intermittent periods of hypoxia will also maintain the pathologic changes caused by hypoxia, whereas continuous relief of hypoxia will promote regression of these changes. Not to be involved into severe troubles concerning your health you should either undergo medical screenings or take drugs which may be ordered via Canadian Neighbor Pharmacy.
Low-flow oxygen therapy improves mortality in patients with COPD and hypoxemia. Although long-term low-flow oxygen therapy slows the rate at which pulmonary vascular resistance increases in these patients, it does not lead to a dramatic reduction in pulmonary vascular resistance. If continuous inhibition of hypoxia is required for regression of the pathologic changes, part of the lack of dramatic improvement in pulmonary vascular resistance may be the intermittent use of oxygen by patients. Most patients, because of social, psychologic, or financial reasons, refuse to use oxygen continuously. Additionally, low-flow oxygen therapy may not completely eliminate focal areas of alveolar hypoxia in these patients, especially during exercise. The further reduction in pulmonary vascular resistance produced when nifedipine is added to low-flow oxygen therapy supports the concept that focal areas of hypoxic pulmonary vasoconstriction persist despite low-flow oxygen therapy.
Calcium channel Blockers
The effects of a variety of vasodilators have been assessed in patients with COPD and hypoxemia.’ We have been most interested in the possible role of calcium channel blockers because these compounds inhibit hypoxic pulmonary vasoconstriction.’ In 1976 McMurtry et al reported that verapamil inhibited hypoxic pulmonary vasoconstriction in rats. Subsequent studies have shown that nifedipine will inhibit acute hypoxic pulmonary vasoconstriction in laboratory animals. Although few studies have compared the effectiveness of different calcium channel blockers, Young et al found that nifedipine was more effective in inhibiting the acute hypoxic pressor response in dogs than were verapamil or diltiazem.
A number of investigators have also addressed the question of whether chronic therapy with calcium channel blockers will attenuate the physiologic and pathologic changes produced in a rat model of hypoxic pulmonary hypertension. Overall, these studies demonstrate that verapamil or nifedipine therapy will attenuate the development of these pathologic changes in the rat. Stanbrook et al recently published an article comparing the acute and chronic effects of verapamil, hydralazine, and nifedipine in hypoxic rats. Although all three vasodilator drugs prevented acute hypoxic pulmonary vasoconstriction in the rat, only long-term therapy with nifedipine significandy reduced the pulmonary vascular remodeling and right ventricular hypertrophy caused by chronic hypoxia. Stanbrook et al also found that nifedipine promoted the regression of the pulmonary vascular changes in rats with hypoxic pulmonary hypertension despite their continued exposure to intermittent hypoxia. Thus, studies in laboratory animals clearly demonstrate that calcium channel blockers will inhibit hypoxic pulmonary vasoconstriction and, more importantly, attenuate the pathologic changes caused by alveolar hypoxia.
Calcium channel blockers have also been studied in patients with COPD and hypoxemia. Simonneau et al studied the acute effect of nifedipine in 13 COPD patients with acute respiratory failure. They found that nifedipine acutely inhibited hypoxic pulmonary vasoconstriction, reducing pulmonary artery pressure and pulmonary vascular resistance. All measurements were made at rest in these critically ill patients. They also found that nifedipine did not further lower pulmonary vascular resistance when combined with high-flow oxygen therapy (average PaOz, 277 mm Hg). Brown et al studied the acute effect of intravenous verapamil during rest and exercise in stable COPD patients who were not hypoxic on room air. They failed to find any significant pulmonary hemodynamic effects of verapamil in this subset of COPD patients. Our group undertook a double-blind, controlled trial in clinically stable COPD patients with cor pulmonale and hypoxemia. Our objective was to determine whether nifedipine would acutely inhibit hypoxic pulmonary vasoconstriction during rest and exercise in these patients. We also sought to quantify the acute hemodynamic effects of nifedipine and determine whether nifedipine would augment the hemodynamic effects produced by low-flow oxygen.