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1. There are currently limited diagnostic methods for assessing the integrity of the pulmonary microvasculature. We hypothesized that a novel, invasively determined physiological index of ‘pulmonary flow reserve’ (PFR = maximal hyperaemic pulmonary blood flow divided by basal pulmonary flow) may facilitate microvascular assessment in the lung. Therefore, we developed a baboon model in which to: (i) validate the use of Doppler flow velocity for PFR assessment; (ii) define the optimal drug and dose regimen for attainment of maximal pulmonary hyperaemia; and (iii) demonstrate the feasibility of measuring PFR in healthy higher primates. 2. Doppler sensor guidewires were placed in segmental pulmonary arteries of 11 ketamine-anaesthetized baboons. Vessel diameter, flow velocity and haemodynamics were recorded before and after direct intrapulmonary artery administration of saline, adenosine (50–500 µg/kg per min) and papaverine (3–60 mg), enabling calculation of PFR. 3. Saline (either bolus injection or infusion) did not alter vessel diameter or flow velocity ( P > 0.1), validating local drug administration. Both adenosine and papaverine induced dose-dependent increases in flow velocity from baseline (from 22.5 ± 2.3 to 32.7 ± 4.8 cm/s for 400–500 µg/kg per min adenosine; and from 23.9 ± 1.1 to 34.6 ± 4.0 cm/s for 24 mg papaverine; both P < 0.0001), without affecting pulmonary artery pressure or vessel diameter ( P > 0.3). Healthy primate PFR values were 1.35 ± 0.10 and 1.39 ± 0.10 using 200 µg/kg per min adenosine and 24 mg papaverine, respectively ( P > 0.8). 4. In conclusion, pulmonary flow reserve in higher primates can be assessed using Doppler sensor guidewire and either adenosine or papaverine as microvascular hyperaemic agents. Measurements of PFR may facilitate pulmonary microvascular assessments. [ABSTRACT FROM AUTHOR]