Vascular recruitment increases evidence of lung injury

Objective: Changes in pulmonary blood flow rate can alter the site of the perfused pulmonary capillary surface area. We tested the hypothesis that full recruitment of the pulmonary vascular bed may decrease evidence of lung injury by recruiting less injured capillaries, We also tested the hypothesis that endothelial ectoenzyme activity is an earlier indicator of lung injury than are permeability measures. Design: Isolated canine lung robes were perfused with autologous blood at constant blood flows of either 2.05 +/- 0.04 L/min (SEM) thigh flow, full recruitment, n =12) or 0.600 +/- 0.004 L/min (tow flow, 33% full recruitment, n = 12) after lung injury to determine the eff ect of vascular recruitment on measures of injury. Setting: Research laboratory at a medical university. Subjects: Lung lobes were obtained from 36 mongrel dogs of either gender. Interventions: Lung injury was induced by adding phorbol myristate acetate (PMA) to the blood perfusing the isolated lung. Measurements and Main Results: Indicator dilution methods were used to measure single pass hydrolysis of (3)[H]-benzoyl-Phe-Ala-Pro, a synthetic substrate for angiotensin converting enzyme, and calculate the modified first order kinetic parameter corresponding to the ratio of a normalized maximal enzymatic conversion rate (A(max)) to the Michaelis-Menten constant (K(m)), i.e., A(max)/K(m), before and after PMA. At a given flaw rate, the decrease in A(max)/K(m) serves as an index of vascular injury. PMA decreased A(max)/K(m), percent metabolism, and fractional substrate utilization, and increased permeability, vascular resistance, and vascular pressures regardless of flow rate. The decrease in enzyme activity was detected earlier than the increase in permeability. Conclusions: The greater percentage decrease in percent metabolism and fractional substrate utilization and the earlier appearance of increased permeability during high flow indicates that increasing blood flow three-fold recruited injured vessels and/or increased vascular injury by Increasing vascular perfusion pressures.