Doppler-derived pulmonary flow reserve detects pulmonary microvascular obstruction in high primates

Background: Despite increasing evidence implicating the pulmonary microcirculation in the pathogenesis of lung conditions such as pulmonary vascular disease, there remain few methods for its evaluation in vivo. We recently demonstrated that the novel index of Doppler-derived pulmonary flow reserve (PFRdopp=maximal hyperaemic/basal pulmonary flow) could be reliably measured in high primates. Noting that the microvasculature is the chief regulator of pulmonary blood flow, we hypothesised that PFRdopp may detect microcirculatory loss. We therefore studied the relationship between PFRdopp and experimentally induced pulmonary microvascular obstruction using microspheres in higher primates. Methods: Under ketamine anaesthesia, Doppler sensor-guidewires were placed in the segmental pulmonary artery of three adult baboons. Doppler flow velocity and haemodynamics were recorded at rest and during hyperaemia [as induced by intrapulmonary artery adenosine (200μg/kg/min)]. Serial PFRdopp evaluations were made after cumulative intrapulmonary artery ceramic microspheres administration. Results: Cumulative microsphere administration progressively reduced PFRdopp (1.54±0.26, 1.48±0.20, 1.12±0.04 and 1.18±0.09; baseline, 104, 105 and 106 microspheres boluses; p<0.02) without affecting pulmonary artery pressure, systemic artery pressure or heart rate. Conclusions: Doppler-derived PFR can detect partial, progressive pulmonary microvascular obstruction in higher primates. PFRdopp may thus have a potential role in the assessment of the pulmonary microcirculation in vivo.