Abstract
BACKGROUND: The pulmonary microcirculation is the chief regulatory site for resistance in the pulmonary circuit. Despite pulmonary microvascular dysfunction being implicated in the pathogenesis of several pulmonary vascular conditions, there are currently no techniques for the specific assessment of pulmonary microvascular integrity in humans. Peak hyperemic flow assessment using thermodilution-derived mean transit-time (T(mn)) facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of T(mn) as a surrogate of pulmonary blood flow for the purpose of measuring the novel indices Pulmonary Flow Reserve [PFR = (maximum hyperemic)/(basal flow)] and Pulmonary Index of Microcirculatory Resistance [PIMR = (maximum hyperemic distal pulmonary artery pressure)x(maximum hyperemic T(mn))]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR. METHODS AND RESULTS: Temperature- and pressure-sensor guidewires (TPSG) were placed in segmental pulmonary arteries (SPA) of 13 baboons and intravascular temperature measured. T(mn) and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10-400 microg/kg/min) and papaverine (3-24 mg). Temperature did not vary with intra-SPA sensor position (0.010+/-0.009 v 0.010+/-0.009 degrees C; distal v proximal; p = 0.1), supporting T(mn) use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 microg/kg/min) & papaverine (to 24 mg) induced dose-dependent flow augmentations (40+/-7% & 35+/-13% T(mn) reductions v baseline, respectively; p<0.0001). PFR and PIMR were then calculated before and after progressive administration of ceramic microspheres into the SPA. Cumulative microsphere doses progressively reduced PFR (1.41+/-0.06, 1.26+/-0.19, 1.17+/-0.07 & 1.01+/-0.03; for 0, 10(4), 10(5) & 10(6) microspheres; p = 0.009) and increased PIMR (5.7+/-0.6, 6.3+/-1.0, 6.8+/-0.6 & 7.6+/-0.6 mmHg.sec; p = 0.0048). CONCLUSIONS: Thermodilution-derived mean transit time can be accurately and reproducibly measured in the pulmonary circulation using TPSG. Mean transit time-derived PFR and PIMR can be assessed using a TPSG and adenosine or papaverine as hyperemic agents. These novel indices detect progressive pulmonary microvascular obstruction and thus have with a potential role for pulmonary microcirculatory assessment in humans.