Abstract 501: The Measurement of Pulmonary Flow Reserve for Early Detection of Pulmonary Vascular Disease

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.

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A Novel Index of Pulmonary Flow Reserve Detects Pulmonary Microvascular Destruction Prior to the Development of Pulmonary Hypertension—Implications for Diagnosis of Early Pulmonary Vascular Disease

Heart Lung and Circulation ◽

10.1016/j.hlc.2008.05.007 ◽

2008 ◽

Vol 17 ◽

pp. S4-S5

Author(s):

Rahn Ilsar ◽

Chirapan Chawantanpipat ◽

Kim Hoe Chan ◽

Richard Waugh ◽

Annemarie Hennessy ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Vascular Disease ◽

Pulmonary Vascular Disease ◽

Pulmonary Flow ◽

Flow Reserve ◽

Pulmonary Flow Reserve

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Abstract 2106: Quantification of Doppler Flow Velocity-Derived Pulmonary Flow Reserve in Healthy Primates

Circulation ◽

10.1161/circ.116.suppl_16.ii_456-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Rahn Ilsar ◽

Chirapan Chawantanpipat ◽

Annemarie Hennessy ◽

Richard Waugh ◽

David S Celermajer ◽

...

Keyword(s):

Blood Flow ◽

Pulmonary Artery ◽

Flow Velocity ◽

Pulmonary Blood Flow ◽

Pulmonary Vascular Disease ◽

List Type ◽

Doppler Flow ◽

Pulmonary Flow ◽

Flow Reserve ◽

Pulmonary Flow Reserve

Background: Pulmonary vascular disease (PVD), characterized by progressive pulmonary microvascular destruction, is only clinically evident late in its course when pulmonary artery pressure (PAP) rises. We hypothesized that changes in pulmonary flow reserve (PFR, maximal hyperemic vs. basal flow) may precede the PAP rise and thus aimed to: validate invasively-measured Doppler flow-velocity (v dopp ) as a marker of pulmonary blood flow and define the optimal hyperemic agent and dose for v dopp -derived PFR (PFR dopp ) assessment, in healthy baboons. Methods: Eight baboons were anaesthetized and a Doppler-sensing guidewire (DSG) placed in a segmental pulmonary artery. Angiographically-determined vessel diameter ( D ) and DSG-measured v dopp were obtained at baseline and at increasing intrapulmonary normal saline (NS) infusion rates and boluses. Escalating local doses of adenosine, acetylcholine & papaverine were administered, v dopp obtained and PFR dopp calculated. Results: NS administration did not change D or v dopp (panels A & B, p≥0.4). Adenosine produced a dose-dependent increase in v dopp maximal at 200μg/kg/min (p<0.0001, panel C), papaverine to 24mg significantly increased v dopp (p<0.0001, panel D) but acetylcholine to 10 − l concentration reduced v dopp (p=0.0008). Adenosine and papaverine-derived PFR dopp values were 1.5–2.0. Conclusions: As D does not vary with NS or hyperemic agent administration, v dopp is a valid marker of pulmonary blood flow. Adenosine and papaverine can be used with a Doppler-flow wire to derive PFR, with normal baboon PFR dopp being 1.5 – 2.0. Thus PFR dopp may be a potential novel marker for investigating early PVD.

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Morphology of the elastic pulmonary arteries in pulmonary hypertension: a quantitative study

Cardiology in the Young ◽

10.1017/s1047951100005151 ◽

1999 ◽

Vol 9 (4) ◽

pp. 364-370 ◽

Cited By ~ 6

Author(s):

Karen A. McLeod ◽

Leon M. Gerlis ◽

Gordon J. Williams

Keyword(s):

Pulmonary Hypertension ◽

Vascular Disease ◽

Intravascular Ultrasound ◽

Morphological Changes ◽

Pulmonary Arteries ◽

Sudden Infant Death ◽

Pulmonary Vascular Disease ◽

Sudden Infant ◽

Major Drawback ◽

Medial Thickening

AbstractRecent studies of intravascular ultrasound of the pulmonary arteries suggest that the technique can detect intimal and medial thickening in patients with pulmonary hypertension, potentially providing a method of assessing severity of pulmonary vascular disease in life. A major drawback of the technique is that only the elastic pulmonary arteries are accessible to current ultrasound catheters. The aim of this study was to determine whether morphological changes in vessels accessible to intravascular imaging reflect severity of pulmonary vascular disease and are of a sufficient degree to be detectable by current ultrasound catheters. Morphometric studies of the elastic pulmonary arteries were performed in specimens of lungs from 24 patients who had died with pulmonary hypertension (aged 3 weeks–9 years) and compared with measurements from infants who had died from sudden infant death syndrome. Morphological changes evident in the elastic pulmonary arteries in pulmonary hypertension included luminal dilation and medial thickening but these changes were too variable to be predictive of the severity of peripheral pulmonary vascular disease. Intimal thickening and atherosclerosis were present only in those with advanced pulmonary hypertensive disease. The changes of medial thickening and luminal dilation, nonetheless, are too variable to be predictive of the severity of peripheral pulmonary vascular disease. Thus, imaging by intravascular ultrasound may help confirm advanced pulmonary vascular disease, but is unlikely to differentiate less severe pulmonary vascular disease when the patient may still potentially be operable.

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Measurements of Mouse Pulmonary Artery Biomechanics

Journal of Biomechanical Engineering ◽

10.1115/1.1695578 ◽

2004 ◽

Vol 126 (2) ◽

pp. 309-313 ◽

Cited By ~ 25

Author(s):

Naomi C. Chesler ◽

John Thompson-Figueroa and ◽

Ken Millburne

Keyword(s):

High Pressure ◽

Pulmonary Artery ◽

Vascular Disease ◽

Measurement Techniques ◽

Circumferential Stress ◽

Pulmonary Arteries ◽

Biomechanical Properties ◽

Pulmonary Vascular Disease ◽

Internal Diameter ◽

Stress Strain

Background: Robust techniques for characterizing the biomechanical properties of mouse pulmonary arteries will permit exciting gene-level hypotheses regarding pulmonary vascular disease to be tested in genetically engineered animals. In this paper, we present the first measurements of the biomechanical properties of mouse pulmonary arteries. Method of Approach: In an isolated vessel perfusion system, transmural pressure, internal diameter and wall thickness were measured during inflation and deflation of mouse pulmonary arteries over low (5–40 mmHg) and high (10–120 mmHg) pressure ranges representing physiological pressures in the pulmonary and systemic circulations, respectively. Results: During inflation, circumferential stress versus strain showed the nonlinear “J”-shape typical of arteries. Hudetz’s incremental elastic modulus ranged from 27±13kPan=7 during low-pressure inflation to 2,700±1,700kPan=9 during high-pressure inflation. The low and high-pressure testing protocols yielded quantitatively indistinguishable stress-strain and modulus-strain results. Histology performed to assess the state of the tissue after mechanical testing showed intact medial and adventitial architecture with some loss of endothelium, suggesting that smooth muscle cell contractile strength could also be measured with these techniques. Conclusions: The measurement techniques described demonstrate the feasibility of quantifying mouse pulmonary artery biomechanical properties. Stress-strain behavior and incremental modulus values are presented for normal, healthy arteries over a wide pressure range. These techniques will be useful for investigations into biomechanical abnormalities in pulmonary vascular disease.

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Pulmonary vascular remodeling in rats with unilaterally banded lobar pulmonary veins

Cardiology in the Young ◽

10.1017/s1047951100000731 ◽

1992 ◽

Vol 2 (2) ◽

pp. 121-128 ◽

Cited By ~ 1

Author(s):

Carol M. Cottrill ◽

William N. O'Connor ◽

Robert Fitz ◽

Mark N. Gillespie

Keyword(s):

Vascular Disease ◽

Pulmonary Veins ◽

Pulmonary Arteries ◽

Group Versus ◽

Laboratory Animals ◽

Pulmonary Venous Obstruction ◽

Pulmonary Vascular Disease ◽

External Diameter ◽

Pulmonary Arterial ◽

Medial Area

AbstractAlthough pulmonary vascular disease occurs in association with pulmonary venous obstruction, a model of pulmonary vascular lesions in this setting in small laboratory animals has yet to be described. The objective of this study was to determine if unilateral banding of pulmonary veins in the rat would produce pulmonary vascular disease that mimicked key aspects of the human disorder. Rats were anesthetized and, after mechanical ventilation and thoracotomy, one of the four pulmonary veins was banded to reduce its external diameter by approximately 65–75% to 0.8 mm. Additional animals, sham-operated controls, were treated identically except for venous banding. Mortality did not differ between groups and was less than 20%. Eight weeks after surgical preparation, moderate pulmonary hypertension was demonstrated with a mean pressure in the pulmonary artery of 24.9 mm Hg (range 19.25 – 30.0) in the banded group versus 18.7 mm Hg (range 16.6 – 19.3) for sham-operated animals. Pulmonary cineangiography in rats with banded pulmonary veins demonstrated marked pulmonary congestion and a prolonged residence time of contrast medium in the capillary circulation of the lung region subjected to banding. Angiographically, non-banded lungs were similar to shams. Histopathology of the vein-banded region revealed venous congestion, arterialization of veins, perivenular edema, and sparse to moderate inflammation. Prominent bronchial vessels, pulmonary arterial medial and occasional intimal thickening, and periarterial inflammation were also observed in banded regions. Similar inflammation around pulmonary arterial and pulmonary venous vessels was noted in contralateral lung lobes but not in sham-operated control rats. Morphometric evaluation of all muscular pulmonary arteries from 50–200μ external diameter accompanying airways to the level of terminal and respiratory bronchioles indicated that the medial area in lung regions subjected to venous banding was over three times greater than in shams. Pulmonary arteries from the contralateral, unbanded lungs of treated animals also exhibited a two-fold increase in medial area. These findings indicate that a modest degree of pulmonary venous banding in rats produces congestion and causes alterations in lung vessels which are reminiscent of those observed in humans with pulmonary venous outflow obstruction. Such a model in a cost-effective laboratory animal should be useful for delineating the specific mechanisms underlying these alterations.

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MEASUREMENT OF PULMONARY FLOW RESERVE IN HIGHER PRIMATES

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/j.1440-1681.2009.05160.x ◽

2009 ◽

Vol 36 (8) ◽

pp. 797-802 ◽

Cited By ~ 4

Author(s):

Rahn Ilsar ◽

Chirapan Chawantanpipat ◽

Kim H Chan ◽

Richard Waugh ◽

Annemarie Hennessy ◽

...

Keyword(s):

Pulmonary Flow ◽

Flow Reserve ◽

Pulmonary Flow Reserve

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

Heart Lung and Circulation ◽

10.1016/j.hlc.2010.06.1057 ◽

2010 ◽

Vol 19 (10) ◽

pp. 592-594

Author(s):

Rahn Ilsar ◽

Chirapan Chawantanpipat ◽

Kim H. Chan ◽

Timothy A. Dobbins ◽

Richard Waugh ◽

...

Keyword(s):

Microvascular Obstruction ◽

Pulmonary Flow ◽

Flow Reserve ◽

Pulmonary Flow Reserve

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Digital Subtraction Pulmonary Angiography in Children with Pulmonary Hypertension due to Bronchopulmonary Dysplasia

Medical Sciences ◽

10.3390/medsci7020026 ◽

2019 ◽

Vol 7 (2) ◽

pp. 26 ◽

Cited By ~ 3

Author(s):

Bibhuti Das ◽

Michelle-Marie Jadotte ◽

Jaime Mills ◽

Kak-Chen Chan

Keyword(s):

Pulmonary Hypertension ◽

Vascular Disease ◽

Bronchopulmonary Dysplasia ◽

Preliminary Data ◽

Pulmonary Arteries ◽

Pulmonary Angiography ◽

Pulmonary Vascular Disease ◽

Digital Subtraction ◽

Extreme Prematurity

Bronchopulmonary dysplasia (BPD) is the most common respiratory sequelae of prematurity and histopathologically features fewer, dysmorphic, pulmonary arteries. We present our experience with the digital subtraction pulmonary angiography (DSPA) findings of a segmental vascular filling abnormality in three children who were born at extreme prematurity and have pulmonary hypertension due to severe BPD. Our preliminary data suggest that DSPA may be useful in evaluating the severity of pulmonary vascular disease in children with BPD.

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