Pulmonary vascular disease (PVD) is an insidious, fatal disorder, characterized by progressive microvascular obstruction. Current pulmonary artery pressure (PAP) based diagnosis of PVD is inadequate, as PAP only rises once >50% of the microvasculature is destroyed. We propose a novel index of pulmonary flow reserve
(PFR = maximal hyperemic divided by basal pulmonary blood flow)
that may detect microvascular disease
prior
to rises in PAP. We aimed to validate Doppler flow velocity (v
d
) use for PFR assessments, define the optimal maximal hyperemic stimulus for PFR assessments and compare PFR & PAP during progressive microcirculatory obliteration, in a primate model. Doppler sensor guidewires (DSG) were placed in segmental pulmonary arteries (SPA) of 11 ketamine-anaesthetized baboons. Vessel diameter (
D
), v
d
& hemodynamics were recorded at baseline & after intra-SPA administration of saline, adenosine (50–500μg/kg/min), acetylcholine (ACh, 10
−8
–10
−6
M) and papaverine (3– 60mg). Increasing amounts of intra-SPA microspheres (diameter 40–120μm) progressively obliterated the microvasculature. Intra-SPA saline did not alter
D
or v
d
(p>0.1) validating the use of local drug delivery. Adenosine induced dose-dependent increases in v
d
(22.5±2.3
v
32.7±4.8cm/s, baseline
v
400–500μg/kg/min, p<0.0001, plateau at 200μg/kg/min) and heart rate (HR, 92±4
v
100±4bpm, p<0.04) while causing systemic hypotension (106±6
v
77±3mmHg, p<0.0001). Papaverine induced increases in v
d
(23.9±1.1
v
34.6±4.0cm/s, baseline
v
24mg, p<0.0001) and HR (92±7
v
104±4bpm, p>0.6). Neither agent affected mean PAP or
D
(p>0.3). ACh induced small reductions in v
d
(p<0.0001) possibly due to ketamine-interaction. Normal PFR values were 1.35±0.1 & 1.39±0.1 using adenosine & papaverine, respectively. Microsphere delivery significantly reduced PFR (1.54±0.26
v
1.18±0.09, baseline
v
10
6
microspheres, p<0.02) without affecting resting mean PAP (21±6
v
22±3mmHg, p>0.7). Doppler based PFR assessments are feasible using adenosine or papaverine. PFR is capable of detecting microvascular obliteration of magnitude insufficient to raise PAP making it potentially valuable for diagnosis of early PVD.
The effect of distal pulmonary obstruction or elevated atrial pressures on pulmonary flow and pulmonary vascular disease: a mathematical flow circuit analogy model-based analysis
