Selective pulmonary vasodilation with inhaled aerosolized milrinone in heart transplant candidates.

PURPOSE: Selective pulmonary vasodilation is an advantageous method for testing the responsiveness of the pulmonary vasculature of heart transplant candidates. A pilot study was under-taken to test the hypothesis that inhaled aerosolized milrinone may cause selective pulmonary vasodilation. METHODS: 18 consecutive male heart transplant candidates with either dilated or ischemic cardiomyopathy were included in this open clinical study. Nine of the patients had significant pulmonary hypertension with a mean pulmonary arterial pressure > 30 mmHg. After baseline measurements, 2 mg of milrinone was administered by ultrasonic nebulization. Pulmonary and systemic hemodynamics were measured ten, 30, and 60 min after inhalation. RESULTS: After inhalation for ten minutes, milrinone induced a significant reduction of mean pulmonary arterial pressure (32.7 +/- 9.1 vs 37.7 +/- 7.5 mmHg, P = 0.01), pulmonary vascular resistance index (296 +/- 150 vs 396 +/- 151 dyn.sec(-1).cm(-5).m(2), P = 0.02) and transpulmonary gradient (10.6 +/- 5.5 vs 15 +/- 4.9, P = 0.01) only in patients with significant pulmonary hypertension. There was no significant effect on mean arterial pressure or systemic vascular resistance at any time after inhalation in either group. Furthermore, there was no influence on extravascular lung water or intrathoracic blood volume. CONCLUSIONS: We conclude that inhaled aerosolized milrinone for a short period selectively dilates the pulmonary vasculature in heart transplant candidates with elevated pulmonary arterial pressure, without producing systemic side effects. Further comparative studies are necessary to evaluate possible advantages of milrinone compared to other inhaled vasodilators.

Drotrecogin alfa (activated) does not affect intracellular production of interleukin-6 and tumor necrosis factor-alpha in endotoxin-stimulated human monocytes.

In this ex vivo laboratory study, we investigated the effects of drotrecogin alfa (activated) (DA(a)), a recombinant form of human activated protein C, on the intracellular expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha on lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system. Whole blood samples from 10 healthy volunteers were stimulated with LPS (0.2 ng/mL) and incubated with 0.01, 0.1, 1, 10, and 100 nM of (final concentration) DA(a) for 3 h at 37 degrees C and 5% CO2. Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry. Our investigation showed that DA(a), at any of the concentrations tested, did not affect intracellular IL-6 and TNF-alpha production in LPS-stimulated human monocytes after 3 h of incubation. The results of this investigation led us to conclude that any antiinflammatory activity of DA(a), if present, does not occur via detectible decreases in the production of proinflammatory cytokines IL-6 and TNF-alpha in human monocytes.