ABSTRACT
An intriguing feature of the acute respiratory distress syndrome (ARDS) is marked maldistribution of pulmonary perfusion in favor of nonventilated, atelectatic, and edematous areas of the lungs, the cause of pulmonary right-to-left shunting and arterial hypoxemia. This indicates that the physiological response to hypoxia, hypoxic pulmonary vasoconstriction (HPV), an important regulatory mechanism to balance pulmonary perfusion between well-and poorly ventilated areas, is severely impaired. In contrast, vasoconstriction occurs in other, relatively normal parts of the lungs, possibly contributing to an increased shunt perfusion as well as an elevated dead space fraction. In fact, pulmonary vascular resistance (PVR) is usually increased, especially in more progressed phases of ARDS when vascular obliteration takes place, leading to pulmonary arterial hypertension as a predominant feature. Since an increase in pulmonary artery pressure can be a driving force for the development of pulmonary edema and impairs loading conditions of the right ventricle, an important goal in the therapy of ARDS has been to lower pulmonary artery pressure (PAP) and PVR. In contrast to the
pulmonary and systemic effects of intravenously administered vasodilators, inhalation of the endogenous vasodilator nitric oxide (NO) selectively dilates the pulmonary vasculature (1, 2). When inhaled NO was used in ARDS, it appeared that PAP and PVR could be lowered and arterial oxygenation could be improved, indicating that the maldistribution of pulmonary perfusion was reduced (3, 4). This redistribution of pulmonary blood flow by selectively acting inhaled vasodilators such as NO and prostacyclin (5, 6) represented a new approach to reduce pulmonary right-to-left shunting, an alternative to ventilatory strategies such as positive end-expiratory pressure (PEEP), that are designed to recruit closed alveolar spaces (7). In fact, the effects of PEEP and inhaled NO on are surprisingly similar, but the mechanisms of actions are completely different (Fig. 1).
