Measurement of Pulmonary Flow Reserve and Pulmonary Index of Microcirculatory Resistance for Detection of Pulmonary Microvascular Obstruction

Abstract

BackgroundThe 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 (Tmn) facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of Tmn 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)×(maximum hyperemic Tmn)]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR.Methods and ResultsTemperature- and pressure-sensor guidewires (TPSG) were placed in segmental pulmonary arteries (SPA) of 13 baboons and intravascular temperature measured. Tmn and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10–400 µg/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°C; distal v proximal; p = 0.1), supporting Tmn use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 µg/kg/min) & papaverine (to 24 mg) induced dose-dependent flow augmentations (40±7% & 35±13% Tmn 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, 104, 105 & 106 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).ConclusionsThermodilution-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.

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

“…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]. This disparity is most likely attributable to the small number of animals in the current study.…”

“…In keeping with our work using thermodilution-based assessment of PFR [5], cumulative microsphere administration in the current study did not affect heart rate, mean systemic artery pressure or mean PAP, making it unlikely that the observed reductions in PFR dopp were due to microsphere-induced reductions in cardiac output, and suggesting that PFR dopp tracked microvascular loss. Moreover, while the first microsphere doses reduced PFR dopp without affecting baseline v dopp , the final dose did not reduce PFR further but rather decreased baseline v dopp .…”

“…By contrast, our studies of the pulmonary circulation, although not directly comparable to these coronary reports, found a low coefficient of variability for repeated Doppler measures (approximately 3.5% for triplicate values), perhaps as repeated Doppler recordings could be more accurately gated to the phase of the respiratory cycle [5]. Noting this theoretical advantage of Doppler in the pulmonary circulation, and greater physician familiarity with Doppler-derived flow compared with temperature sensing technologies, we proposed that PFR dopp , like PFR thermo , might also be able to detect changes in pulmonary microvascular integrity.…”

“…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].…”

Biomedizinische Technik heute

“…Euro Jahresumsatz) klein zu nennen [7,8,13] [27]. Angesichts der demografischen Entwicklung rücken jedoch auch andere Krankheitsbilder in den Blickpunkt der Entwickler, so zum Beispiel chronische Lungenerkrankungen [28], für die eine sogenannte "Peakflow-Messsensorik" entwickelt wird, und Diabetes, bei dem die Bestimmung der Blutzuckerkonzentration zukünftig über verschiedene extrakorporale und implantierbare Sensoren möglich werden soll [29]. Auch Implantate wie Herzschrittmacher werden zunehmend in Telemonitoringsysteme eingebunden [30].…”