title: Preclinical pulmonary capillary endothelial dysfunction is present in brain dead subjects.
abstract: Pulmonary endothelium is a major metabolic organ affecting pulmonary and systemic vascular homeostasis. Brain death (BD)-induced physiologic and metabolic derangements in donors' lungs, in the absence of overt lung pathology, may cause pulmonary dysfunction and compromise post-transplant graft function. To explore the impact of BD on pulmonary endothelium, we estimated pulmonary capillary endothelium-bound (PCEB)-angiotensin converting enzyme (ACE) activity, a direct and quantifiable index of pulmonary endothelial function, in eight brain-dead patients and ten brain-injured mechanically ventilated controls. No subject suffered from acute lung injury or any other overt lung pathology. Applying indicator-dilution type techniques, we measured single-pass transpulmonary percent metabolism (%M) and hydrolysis (v) of the synthetic, biologically inactive, and highly specific for ACE substrate (3)H-benzoyl-Phe-Ala-Pro, under first order reaction conditions, and calculated lung functional capillary surface area (FCSA). Substrate %M (35 ± 6.8%) and v (0.49 ± 0.13) in BD patients were decreased as compared to controls (55.9 ± 4.9, P = 0.033 and 0.9 ± 0.15, P = 0.033, respectively), denoting decreased pulmonary endothelial enzyme activity at the capillary level; FCSA, a reflection of endothelial enzyme activity per vascular bed, was also decreased (BD patients: 1,563 ± 562 mL/min vs 4,235 ± 559 in controls; P = 0.003). We conclude that BD is associated with subtle pulmonary endothelial injury, expressed by decreased PCEB-ACE activity. The applied indicator-dilution type technique provides direct and quantifiable indices of pulmonary endothelial function at the bedside that may reveal the existence of preclinical lung pathology in potential lung donors.
authors.affiliation: First Department of Critical Care and Pulmonary Services, Evangelismos Hospital, University of Athens Medical School, Athens, Greece ; G. P. Livanos and M. Simou Laboratories, Evangelismos Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Glynos
authors.forename: Chariclea
authors.initials: C
authors.lastname: Athanasiou
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Korovesi
authors.forename: Katerina
authors.initials: K
authors.lastname: Kaziani
authors.forename: Olga
authors.initials: O
authors.lastname: Livaditi
authors.forename: Ioanna
authors.initials: I
authors.lastname: Dimopoulou
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Maniatis
authors.forename: Iraklis
authors.initials: I
authors.lastname: Tsangaris
authors.forename: Charis
authors.initials: C
authors.lastname: Roussos
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Orfanos
keywords: angiotensin converting enzyme; brain death; pulmonary endothelium