u-62840 and Acute-Disease

Significant advances have been achieved over the past few decades regarding comprehension of the pathogenesis of pulmonary arterial hypertension (PAH). The development of new agents and use of existing drug therapies have targeted the underlying abnormalities and pathways leading to progression of PAH. Milrinone, a phosphodiesterase inhibitor, remains a therapeutic option. Unfortunately, intravenous administration of the drug in patients with PAH may be limited by systemic hypotension, especially in those already receiving prostanoid treatment. We describe a 42-year-old woman with acute decompensated idiopathic PAH who was given nebulized milrinone as a novel adjunctive therapy. She was acutely treated with intravenous treprostinil 2 ng/kg/minute and inhaled nitric oxide 20 ppm. However, increasing the treprostinil infusion rate or adding other therapies such as intravenous milrinone for acute symptomatic relief was limited by her hemodynamic instability, which required treatment with dobutamine, vasopressin, and epinephrine. Nebulized milrinone was added as salvage therapy for her acute PAH crisis. After 8 days of therapy, the patient's PAH symptoms improved without compromising her mean arterial pressure and heart rate. Nebulized milrinone in addition to inhaled nitric oxide and low-dose intravenous treprostinil may have played a major role in the acute management of her PAH crisis. Further studies are needed to assess the role of nebulized milrinone in patients with PAH.

Topics: Acute Disease; Administration, Inhalation; Adult; Antihypertensive Agents; Blood Pressure; Bronchodilator Agents; Drug Therapy, Combination; Epoprostenol; Female; Heart Rate; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Milrinone; Nebulizers and Vaporizers; Nitric Oxide; Phosphodiesterase Inhibitors; Salvage Therapy

Inhaled vasodilator therapy for pulmonary hypertension may decrease the systemic side effects commonly observed with systemic administration. Inhaled medications only reach ventilated areas of the lung, so local vasodilation may improve ventilation-perfusion matching and oxygenation. We compared the effects of intravenous vs. aerosolized treprostinil on pulmonary and systemic hemodynamics in an unanesthetized sheep model of sustained acute pulmonary hypertension. Acute, stable pulmonary hypertension was induced in instrumented unanesthetized sheep by infusing a PGH(2) analog, U-44069. The sheep were then administered identical doses of treprostinil either intravenously or by aerosol. Systemic and pulmonary hemodynamics were recorded during each administration. Both intravenous and aerosol delivery of treprostinil reduced pulmonary vascular resistance and pulmonary arterial pressure, but the effect was significantly greater with aerosol delivery (P < 0.05). Aerosol delivery of treprostinil had minimal effects on systemic hemodynamics, whereas intravenous delivery increased heart rate and cardiac output and decreased left atrial pressure and systemic blood pressure. Aerosol delivery of the prostacyclin analog treprostinil has a greater vasodilatory effect in the lung with minimal alterations in systemic hemodynamics compared with intravenous delivery of the drug. We speculate that this may result from treprostinil stimulated production of vasodilatory mediators from pulmonary epithelium.

Topics: Acute Disease; Administration, Inhalation; Aerosols; Animals; Antihypertensive Agents; Blood Pressure; Disease Models, Animal; Epoprostenol; Female; Hypertension, Pulmonary; Injections, Intravenous; Male; Pulmonary Circulation; Recovery of Function; Sheep; Treatment Outcome; Vasodilation