title: Measurement of pulmonary flow reserve in higher primates.
abstract: 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 microg/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 microg/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 microg/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.
authors.affiliation: Cardiology Department, Royal Prince Alfred Hospital, Camperdown, Australia.
authors.forename: Rahn
authors.initials: R
authors.lastname: Ilsar
authors.forename: Chirapan
authors.initials: C
authors.lastname: Chawantanpipat
authors.forename: Kim H
authors.initials: KH
authors.lastname: Chan
authors.forename: Richard
authors.initials: R
authors.lastname: Waugh
authors.forename: Annemarie
authors.initials: A
authors.lastname: Hennessy
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
authors.forename: Martin K C
authors.initials: MK
authors.lastname: Ng
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D055806:Microvessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D010208:Papaverine / Q000494:pharmacology; D010215:Papio; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology*; D018608:Ultrasonography, Doppler; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D010208:Papaverine; D000241:Adenosine