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.

Doppler-derived Pulmonary Flow Reserve Detects Pulmonary Microvascular Obstruction in High Primates

“…Although increases in pulmonary vascular resistance underpin the haemodynamic changes in diseases of the lung microcirculation, our findings carry insufficient proof to imply the use of PFR dopp for the detection of human clinical conditions. A second limitation is that this study, although conceived by noting the low coefficient of variability in Doppler-derived measurements of pulmonary blood flow [4], does not offer insight as to the overall accuracy of PFR dopp vs. PFR thermo for the detection of microcirculatory obstruction.…”

“…These observations are suggestive that PFR dopp , like PFR thermo , may help detect pulmonary microcirculatory dysfunction, with possible implications for clinical use in the diagnosis of lung conditions characterised by pulmonary microvascular disease. PFR dopp can be reliably measured using either adenosine infusions at 200 g/kg/min or 24 mg papaverine boluses [4]. We utilised adenosine as pulmonary hyperaemic agent in the current study as the off-set of its effect was more predictable [8], making for more accurate identification of the return of baseline [4] necessary for serial PFR dopp assessments.…”

“…PFR dopp can be reliably measured using either adenosine infusions at 200 g/kg/min or 24 mg papaverine boluses [4]. We utilised adenosine as pulmonary hyperaemic agent in the current study as the off-set of its effect was more predictable [8], making for more accurate identification of the return of baseline [4] necessary for serial PFR dopp assessments. The absolute PFR dopp values observed in the current study (1.54 ± 0.26) are similar but not identical to those seen in our PFR dopp validation paper (1.35 ± 0.10 in healthy primate pulmonary circulation) and the PFR thermo studies (1.41 ± 0.06 vs. 1.01 ± 0.03 for baseline vs. 10 6 microspheres) [5].…”

“…However, there are currently few methods for assessing pulmonary Received 4 June 2010; accepted 28 June 2010 microcirculatory dysfunction in vivo. We have previously demonstrated that Doppler-derived Pulmonary Flow Reserve (PFR dopp = maximal hyperaemic pulmonary blood flow divided by basal pulmonary blood flow) can be measured in a high primate using a Doppler sensor guidewire (DSG) and adenosine to induce hyperaemia in the pulmonary microcirculation [4]. Subsequently, we demonstrated that PFR could also be assessed using thermodilution principles to derive flow (PFR thermo ) and that this latter index tracks experimentally induced pulmonary microvascular obstruction [5].…”

“…We thus aimed to study the relationship between PFR dopp and progressive obstruction of the pulmonary microcirculation, in high primates. [4]. In brief, under ketamine anaesthesia, a 7F multipurpose (MP) guiding catheter was placed in a segmental left lower pulmonary artery (PA) and a 5F-MP guide positioned just proximal to it.…”