Single Versus Double-Lung Injection of ³H-BPAP in Humans

Abstract

The pulmonary vascular endothelium participates in various important physiologic and pharmacokinetic processes, such as synthesis and degradation of vasoactive peptides. Enzymes that catalyze many of these reactions are located on the luminal surface of the capillaries and their activities may be measured in vivo by means of indicator-dilution techniques. Among these enzymes, angiotensin-converting enzyme (ACE) has been extensively studied in animals: monitoring ACE activity under toxic conditions provides an early index of lung injury, whereas under normal conditions allows estimations of the dynamically perfused capillary surface area (PCS A), (Orfanos et al., 1994). The purpose of this study was: i) to validate the use of the aforementioned techniques as a tool of pulmonary endothelial function assessment in humans, and ii) to investigate if the assays of pulmonary endothelial ACE, under normal conditions provide estimations of PCSA in the human lung.

Six human volunteers (five males and one female), 34 to 71 years old, undergoing cardiac catheterization for coronary artery disease assessment, participated in our study. Participants did not have a medical history of pulmonary disease, they were not receiving ACE-inhibitor treatment, and exhibited normal pulmonary blood pressures. Single-pass transpulmonary hydrolysis of the specific ACE substrate ³H-benzoyl-Phe-Ala-Pro (BPAP; 30μCi, 22.2 Ci/mmol) was measured by means of indicator-dilution techniques, and expressed as %metabolism (%M) and v= ln(l−M). BPAP was injected as a bolus i) into a main pulmonary artery, and ii) inside the right atrium, to assess ACE activity in one and both lungs respectively. We also calculated A_max/K_m, an index of PCSA. Pulmonary plasma flow (F_p) was determined immediately prior to each injection by thermodilution. Fp in one lung was estimated as 50% of total F_p (Lipscomb and Pride, 1977; Wernly et al, 1980). Similar values of %M (67±2.9 and 65±2.5), and v (1.13±0.09 and 1.07±0.07) were observed in both and one lung respectively, denoting homogeneous pulmonary capillary ACE concentrations and capillary transit times in both human lungs. A_max/K_m decreased from 3804±375 ml/min (both lungs) to 1899±189 (one lung), denoting a 50% reduction in PCSA, as expected. We conclude that i) pulmonary endothial ectoenzyme activity and thus pulmonary endothelial function may be assessed in humans by means of indicator-dilution techniques and ii) this procedure can be used to quatifiy PCSA in the human lung. (Supported by folds de la Recherche en Sante du Quebec, and the National Health System of Greece).