Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in acute lung injury

Background-Pulmonary capillary endothelium-bound (PCEB) angiotensin-convert ing ectoenzyme (ACE) activity alteration is an early, sensitive, and quanti fiable lung injury index in animal models. We hypothesized that (I) PCEB-AC E alterations can be found in patients with acute lung injury (ALI) and (2) PCEB-ACE activity correlates with the severity of lung injury and may be u sed as a quantifiable marker of the underlying pulmonary capillary endothel ial dysfunction. Methods and Results-Applying indicator-dilution techniques, we measured sin gle-pass transpulmonary hydrolysis of the synthetic ACE substrate H-3-benzo yl-Phe-Ala-Pro (BPAP) in 33 mechanically ventilated, critically ill patient s with a lung injury score (LIS) ranging from 0 (no lung injury) to 3.7 (se vere lung injury) and calculated the kinetic parameter A(max)/K-m. Both par ameters decreased early during the ALI continuum and were inversely related to APACHE II score and LIS. Hydrolysis decreased with increasing cardiac o utput (CO), whereas 2 different patterns were observed between CO and A(max )/K-m. Conclusions-PCEB-ACE activity decreases early during ALI, correlates with t he clinical severity of both the lung injury and the underlying disease, an d may be used as a quantifiable marker of underlying pulmonary capillary en dothelial dysfunction.