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Emboli after tourniquet release (TR) during total knee arthroplasty (TKA) occur in all patients. This may lead to fat embolism syndrome with lung injury. Angiotensin-converting enzyme (ACE) lines the pulmonary endothelium, and a decrease in ACE metabolism or hydrolysis of (3)HBPAP ((3)H-benzoyl-Phe-Ala-Pro; a substrate specific for ACE) has been associated with lung injury. We evaluated the association of this assay with pulmonary changes during TKA. Eleven consecutive patients undergoing bilateral TKA had the ACE assay performed perioperatively. We determined substrate hydrolysis and pulmonary capillary surface area (capillary perfusion index; CPI) and correlated it with pulmonary vascular resistance (PVR) and clinical outcome. Ten of the 11 patients demonstrated an increase in substrate hydrolysis and CPI along with a decrease in PVR after first or second TR when compared with baseline values (P < 0.05). In the other patient, PVR continued to increase even after TR, whereas CPI and substrate hydrolysis decreased after surgery. Whereas all others did well clinically, this patient developed confusion and hypoxemia. In previous studies, a decrease in PVR with an increase in CPI, as exhibited by the 10 patients, has been associated with pulmonary capillary recruitment. We believe this to be an important mechanism by which the lungs are able to accommodate the burden of emboli at the time of TR.