Pyruvate-modified perfadex improves lung function after long-term hypothermic storage.
BACKGROUND
Lungs harvested for transplantation are stored while inflated with oxygen, which can serve to support oxidative metabolism. However, strategies aimed at increasing graft metabolism during storage have received little attention. In this study, we added pyruvate to the preservation solution Perfadex and measured the effects on oxidative metabolism and reperfusion lung function.


METHODS
Rat lungs were stored for 6 and 24 hours in low-potassium dextran solution at 10 degrees C containing either 5 mmol/liter uniformly carbon-13 (U-(13)C) labeled glucose (Perfadex), 32 mmol/liter 3-(13)C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of (13)C into tricarboxylic acid cycle intermediates by magnetic resonance spectroscopy. Additional groups of lungs with each substrate modification were preserved for 6 or 24 hours and then reperfused.


RESULTS
Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast, enrichment was significantly increased in both the pyruvate group (50% and 59%, respectively) and combined group (39% and 54%, respectively) compared with the Perfadex group (p<0.01). Graft function was excellent after 6-hour storage in all groups. All lungs stored for 24 hours exhibited inferior lung function, but oxygenation, pulmonary artery pressures, and airway pressures in the combined group were significantly improved compared with the Perfadex group (p<0.05).


CONCLUSIONS
Preservation solution substrate composition influences graft metabolism during storage. The addition of pyruvate to Perfadex increases metabolism during storage and improves reperfusion lung function.
Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-8879, USA.
Matthias
M
Peltz
Tian-Teng
TT
He
Glenn A
GA
Adams
Robert Y
RY
Chao
Michael E
ME
Jessen
Dan M
DM
Meyer
D000818:Animals; D002951:Citrates / Q000737:chemistry*; D015925:Cryopreservation; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D008168:Lung; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011773:Pyruvates / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002951:Citrates; D019188:Organ Preservation Solutions; C070005:Perfadex; D011773:Pyruvates; D005947:Glucose