Mitochondrial energy metabolism in brain-dead organ donors

Abstract

Objectives: Change from aerobic to anaerobic metabolism has been described in brain-dead organ donors (BDOD) managed for organ procurement. Such modifications could lead to a depletion in intracellular adenine nucleotides and in part explain primary graft dysfunction. The purpose of this study was to investigate the mitochondrial energy metabolism in BDOD using permeabilized muscle fibers.

Methods: With institutional approval, the study was performed prospectively in 15 consecutive BDOD. In each patient, muscle biopsy and blood samples for the determination of plasma lactate and pyruvate were obtained just before organ removal. Mitochondrial respiratory parameters of skeletal muscle were determined in saponin-skinned muscle fibers. Mitochondrial oxygen consumption rates were measured polarographically using different substrates and inhibitors of the respiratory chain complexes. Results were compared to those obtained from muscle biopsies performed in 10 healthy patients during orthopedic surgery.

Results: Fifteen donors, 13 men and 2 women, aged 35 +/- 11 yrs, were studied. All patients had a high lactate-to-pyruvate ratio (10). Mitochondrial respiration rates were significantly decreased during adenosine triphosphate (ATP) synthesis.

Conclusions: Major changes in energy metabolism occurred during brain death with a decrease in ATP synthesis capacity. High-risk donors should be recognized for a better graft evaluation.