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Background: Machine perfusion preservation improves reperfusion function of many solid organs, compared with conventional storage, but has received limited clinical attention in preserving hearts for transplantation. We evaluated representative extracellular (Celsior) and intracellular (University of Wisconsion) storage solutions using static and perfusion protective strategies over a clinically relevant preservation period. Methods: Rat hearts were preserved for 200 minutes by either static storage or perfusion preservation in Celsior or University of Wisconsin solutions. Three conditions were studied: conventional static storage; static storage using either solution with 5.5 mmol/L glucose added; and perfusion preservation using either solution with 5.5 mmol/L glucose added. Glucose was provided as U-13C-labeled glucose, and glycolysis and oxidative metabolism during preservation were quantified from incorporation of 13C into glycolytic and tricarboxylic acid cycle intermediates. Adenosine triphosphate levels after preservation, and apoptosis and cardiac function after reperfusion were measured. Results: Both perfusion preservation groups had higher myocardial oxygen consumption during storage and better early graft function, compared with static preservation groups (P < .05). Adenosine triphosphate levels were higher after storage in the perfusion groups (P < .01). Apoptosis was reduced in the perfusion groups (P < .01). Comparing perfusion groups, hearts preserved with Celsior had higher myocardial oxygen consumption and glucose utilization during perfusion storage and exhibited decreased reperfusion coronary vascular resistance and myocardial water content, compared with the UW perfusion group (P < .05). Conclusions: Perfusion preservation results in greater metabolism during storage and superior cardiac function with improved myocyte survival, compared with static storage. Extracellular preservation solutions appear more effective for perfusion preservation, possibly by augmenting cellular metabolism. [Copyright &y& Elsevier]

Background. Hypothermia lowers the metabolic rate and increases ischemic tolerance but the effects of temperature on myocardial substrate selection are not well defined.Methods. Isolated rat hearts were perfused with physiologic concentrations of 13C labeled lactate, pyruvate, acetoacetate, mixed long-chain fatty acids, and glucose. Hearts were cooled over 5 to 10 minutes to one of four target temperatures (37°, 32°, 27°, or 17°C), then perfused for an additional 30 minutes, freeze-clamped, and extracted. 13C NMR spectra were obtained and substrate oxidation patterns were determined by isotopomer analysis.Results. Although hearts in all groups were supplied with identical substrates, the percentage of acetyl-CoA oxidized within the citric acid cycle that arose from fatty acids decreased significantly from 53.8% ± 0.8% in the 37°C group to 33.1% ± 3.3% in the 17°C group. Lactate or pyruvate utilization increased from 3.3% ± 0.5% to 25.7% ± 3.6%, respectively (p < 0.05 by one-way ANOVA).Conclusions. These data suggest that moderate hypothermia suppresses fatty acid oxidation and deep hypothermia significantly increases utilization of lactate and pyruvate. These effects may result from relative inhibition of catabolism of complex molecules such as fatty acids, or stimulation of pyruvate dehydrogenase. These effects on substrate metabolism may play a role in myocardial protection afforded by hypothermia. [Copyright &y& Elsevier]

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°C containing either 5 mmol/liter uniformly carbon-13 (U-13C) labeled glucose (Perfadex), 32 mmol/liter 3-13C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of 13C 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 &#60; 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 &#60; 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. [Copyright &y& Elsevier]