[Inhalative strategies for improvement of pulmonary hemodynamics and gas exchange in sepsis and severe pulmonary hypertension].

Chronic pulmonary hypertension and septic lung failure display different clinical features resulting in severe disturbances in the pulmonary circulation. In these diseases, the pulmonary bloodflow is impaired by a pathologic constriction of blood vessels that may lead to right ventricular overloading as well as serious worsening of gas exchange mainly caused by ventilation/perfusion mismatch. Various mechanisms deteriorating the vascular function may induce both an irreversible and a reversible contraction of pulmonary vessels, respectively. Two pharmacological approaches exist to reduce the vascular resistance: Reduction of the increased vascular tone by relaxation of vascular smooth muscle cells (effect of vasodilators). Inhibition of thrombus-mediated obliteration of the lung perfusion by use of anticoagulant and fibrinolytic drugs. Prevention of the structural reorganization of pulmonary vessels (vascular remodeling) by use of vasodilators with anti-inflammatory and anti-proliferative potency such as prostanoids. The systemic (intravenous or oral) application of vasodilative agents in sepsis and chronic pulmonary hypertension has, however, important side effects: Antagonism of the hypoxic pulmonary vasoconstriction aggravates the ventilation/perfusion mismatch (decrease in arterial oxygenation). Side effects of these vasodilators (systemic hypotension). The inhalative route of application is superior because of the pulmonary enrichment of the applied agent (pulmonary selectivity). Furthermore, a preferential deposition in the well-ventilated areas of the lung is achieved (intrapulmonary selectivity). Thus, the decrease in pulmonary-vascular resistance is paralleled by both optimized ventilation-perfusion matching and subsequently improved gas exchange. First clinical studies with inhaled nitric oxide and aerosolized prostacyclin have been performed in intubated and mechanically ventilated patients with septic lung failure. At present, the use of the long-acting prostacyclin analogue ilomedin for ambulant treatment of patients with chronic pulmonary hypertension is under investigation.