TY - JOUR
T1 - Endothelial ectoenzyme assays estimate perfused capillary surface area in the dog lung
AU - Orfanos, S. E.
AU - Ehrhart, I. C.
AU - Barman, S.
AU - Hofman, W. F.
AU - Catravas, J. D.
N1 - Funding Information:
We thank Jim Parkerson and Hiram Ocasio for their technical assistance. This study was supported in part by HL 31422, the American Lung Association, Georgia Af®liate, HL47926, and a grant from the Medical College of Georgia Research Institute.
PY - 1997/9
Y1 - 1997/9
N2 - Whether the pulmonary vascular bed accommodates flow-induced increases in blood volume mainly through recruitment of previously unperfused capillaries or distension of already perfused vessels remains controversial. The modified first order reaction parameter of an enzyme and substrate, A(max)/K(m), is, under nontoxic conditions, proportional to enzyme mass. Thus for ACE, an endothelium-bound ectoenzyme uniformly distributed along the luminal surface of the pulmonary capillary bed, A(max)/K(m) is proportional to the dynamically perfused capillary surface area (PCSA). We estimated single-pass translobar hydrolysis and calculated the corresponding A(max)/K(m) values of the synthetic ACE substrate 3H-benzoyl-Phe-Ala-Pro (BPAP), under first-order reaction conditions, in isolated blood-perfused dog lung lobes. We additionally studied blood flow distribution using radioactive microsphere techniques. Experiments were performed under zone III conditions over a wide range of lobar blood flow rates (Q̇(b)). As Q̇(b) was increased, A(max)/K(m) rose linearly, while lobar vascular resistance (LVR) decreased, suggesting capillary recruitment rather than distension. Single pass BPAP hydrolysis (v ~ 2.9 at resting Q̇(b)) was not altered over a wide range of Q̇(b), indicative of unchanging Capillary transit times. When full capillary recruitment was achieved (at Q̇(b) > 70 ml/min/g lung wet weight), further Q̇(b) elevations failed to increase A(max)/K(m), but decreased BPAP hydrolysis, denoting shorter transit times through the fully recruited capillary bed. Our data indicate that, as previously shown for rabbit lung, in this canine model, increases in pulmonary blood volume are mainly accommodated through recruitment of previously unperfused capillaries throughout the entire lung.
AB - Whether the pulmonary vascular bed accommodates flow-induced increases in blood volume mainly through recruitment of previously unperfused capillaries or distension of already perfused vessels remains controversial. The modified first order reaction parameter of an enzyme and substrate, A(max)/K(m), is, under nontoxic conditions, proportional to enzyme mass. Thus for ACE, an endothelium-bound ectoenzyme uniformly distributed along the luminal surface of the pulmonary capillary bed, A(max)/K(m) is proportional to the dynamically perfused capillary surface area (PCSA). We estimated single-pass translobar hydrolysis and calculated the corresponding A(max)/K(m) values of the synthetic ACE substrate 3H-benzoyl-Phe-Ala-Pro (BPAP), under first-order reaction conditions, in isolated blood-perfused dog lung lobes. We additionally studied blood flow distribution using radioactive microsphere techniques. Experiments were performed under zone III conditions over a wide range of lobar blood flow rates (Q̇(b)). As Q̇(b) was increased, A(max)/K(m) rose linearly, while lobar vascular resistance (LVR) decreased, suggesting capillary recruitment rather than distension. Single pass BPAP hydrolysis (v ~ 2.9 at resting Q̇(b)) was not altered over a wide range of Q̇(b), indicative of unchanging Capillary transit times. When full capillary recruitment was achieved (at Q̇(b) > 70 ml/min/g lung wet weight), further Q̇(b) elevations failed to increase A(max)/K(m), but decreased BPAP hydrolysis, denoting shorter transit times through the fully recruited capillary bed. Our data indicate that, as previously shown for rabbit lung, in this canine model, increases in pulmonary blood volume are mainly accommodated through recruitment of previously unperfused capillaries throughout the entire lung.
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U2 - 10.1006/mvre.1997.2031
DO - 10.1006/mvre.1997.2031
M3 - Article
C2 - 9327385
AN - SCOPUS:0031239093
SN - 0026-2862
VL - 54
SP - 145
EP - 155
JO - Microvascular Research
JF - Microvascular Research
IS - 2
ER -