Addition of Nitric Oxide to Oxygen Improves Cardiopulmonary Function in Patients With Severe COPD
Persistent or episodic hypoxemia in patients with COPD leads to the development of pulmonary hypertension, which is exacerbated by exercise and episodes of acute inflammation. Pulmonary hypertension in COPD patients is associated with a worsened survival rate. When pulmonary hypertension is observed in COPD patients, mean pulmonary arterial pressure (MPAP) generally increases into the range of 20 to 35 mm Hg. The initiating factor is not known with certainty; it could be induced hypertrophy of the intima or pulmonary vasoconstriction leading to hypertrophy of the muscular media, which exaggerates preexisting ventilation/perfusion ratio (V/Q) mismatch. Persistent elevation of the MPAP causes remodeling of the vascular bed by secondary intimal and medial hyperplasia and hypertrophy, which decreases vascular caliber and further increases pulmonary arterial pressure.2 Left unabated, this process culminates in right ventricular dysfunction and cor pulmonale. canadian neighbor pharmacy
Many attempts have been made to use vasodilator agents to reverse pulmonary hypertension in COPD patients, including calcium-channel blockers, prazosin, nitrates, and hydralazine. All have in common the provision of only short-term benefits and a nonselective action on the pulmonary and systemic circulation, resulting in systemic hypotension. Results with nocturnal or long-term oxygen therapy (LTOT) have been considerably more encouraging. Nearly 20 years ago, both the Nocturnal Oxygen Therapy Trial and the British Medical Research Council demonstrated that LTOT improved survival in patients with COPD, almost certainly through the increase in arterial oxygen tension. However, it is not yet known specifically whether LTOT can reverse hypoxia-induced structural changes in the pulmonary vasculature and modify the development of pulmonary hypertension and right ventricular failure.
Nitric oxide (NO), a molecule produced by a variety of cells including the vascular endothelium, acts as a natural modulator of vascular tone. It stimulates the enzyme guanylate cyclase to produce the second messenger, cyclic guanosine monophosphate, which induces vascular smooth muscle relaxation. NO has a high affinity to hemoglobin and is rapidly inactivated by binding with it, so that pulmonary hypertension can be treated without systemic hypotension. Its vasodilator effects are therefore confined to the pulmonary circulation. Inhaled NO is distributed to lung zones with the greatest ventilation and improves their perfusion, thus decreasing V/Q mismatch and improving gas exchange. This accounts for its successful use in the treatment of ARDS.