Preclinical pulmonary capillary endothelial dysfunction is present in brain dead subjects

Area of Science:

• Cardiovascular Sciences
• Pulmonary Medicine
• Transplantation Immunology

Background:

• The pulmonary endothelium is a critical metabolic organ influencing vascular homeostasis.
• Brain death (BD) can induce physiological changes that impair lung function and post-transplant outcomes, even without overt lung pathology.
• Pulmonary endothelial dysfunction may contribute to graft failure in lung transplantation.

Purpose of the Study:

• To investigate the impact of brain death (BD) on pulmonary endothelial function.
• To quantify pulmonary capillary endothelium-bound (PCEB)-angiotensin converting enzyme (ACE) activity as an index of endothelial function in BD.
• To assess the utility of indicator-dilution techniques in detecting preclinical lung pathology in potential donors.

Main Methods:

• Indicator-dilution techniques were employed to measure transpulmonary substrate metabolism and hydrolysis by ACE.
• Pulmonary capillary endothelium-bound (PCEB)-angiotensin converting enzyme (ACE) activity was assessed in brain-dead (BD) patients and brain-injured controls.
• Lung functional capillary surface area (FCSA) was calculated as a measure of endothelial surface available for enzyme activity.

Main Results:

• BD patients exhibited significantly decreased PCEB-ACE activity (%M and v) compared to controls (P=0.033).
• Lung functional capillary surface area (FCSA) was significantly reduced in BD patients (P=0.003).
• These findings indicate subtle pulmonary endothelial injury in the absence of overt lung pathology.

Conclusions:

• Brain death (BD) is associated with a significant decrease in pulmonary endothelial ACE activity.
• The indicator-dilution technique offers a quantifiable method to assess bedside pulmonary endothelial function.
• This technique may identify early-stage lung injury in potential organ donors, improving transplant outcomes.