1013-114 Effect of Nitric Oxide on the Pulmonary Vascular Pressure-Flow Relationship in a Canine Model of Thrombolytic Pulmonary Hypertension

Abstract

Nitric oxide (NO) has been shown to be effective in reducing pulmonary artery pressure in many forms of pulmonary hypertension. While the intracellular mechanism of action is known, the pulmonary hemodynamic effects are not fully elucidated. This study examined the effects of inhaled NO on the pulmonary vascular pressure-flow (P-Q) relationship in a canine model of pulmonary embolism. According to P-O theory, the slope of the P-Q plot defines the incremental vascular resistance (unit pressure change per unit change in flow) and the extrapolated pressure intercept defines the effective vascular outflow pressure. Six dogs were embolized with autologous blood clot to create pulmonary hypertension complicated by a low cardiac output state. To define the P-Q plot, multiple mean pulmonary artery pressure (PAP) vs cardiac output (CO) coordinates were obtained pre and post embolization, and before, during and after treatment with nitric oxide (180–200 ppm). The PAP-CO coordinates were obtained by varying flow through systemic arteriovenous fistulas. Embolization increased PAP (14.8 ± 1.2 to 34.6 ± 4.6; P < 0.001) and decreased CO (3.45 ± 0.63 to 2.25 ± 0.43; P < 0.05). All PAP-CO relationships were well described by a linear equation (mean r value 0.921 ± 0.029). Both the slope and intercept of the PAP-CO plot increased with embolization, (1.41 ± 0.09 to 3.51 ± 1.22; P < 0.05 and 9.9 ± 1.1 to 28.0 ± 6.5; p < 0.005 respectively). NO significantly improved pulmonary hemodynamics. The intercept of the PAP-CO plot decreased from the initial control of 28.0 mmHg to 22.5 mmHg (p < 0.05), and following discontinuation of the NO, increased to 26.2 mmHg (p < 0.05). The slope was not affected. Furthermore, NO did not affect systemic hemodynamics. In this model of pulmonary embolism, the increase in PAP is predominantly explained by an increase in the extrapolated pressure intercept (P I ) and NO selectively improved pulmonary hemodynamics by decreasing P I . Based on previous work, it is most likely that the decrease in P I represents a localized decrease in pulmonary vascular tone upstream from the capillary bed.