Rationale: Donation after circulatory death (DCD) could improve cardiac graft availability. However, strategies to optimize cardiac graft recovery remain to be established in DCD; these hearts would be expected to be exposed to high levels of circulatory fat immediately prior to the inevitable period of ischemia prior to procurement.
Objective: We investigated whether acute exposure to high fat prior to warm, global ischemia affects subsequent hemodynamic and metabolic recovery in an isolated rat heart model of DCD.
Methods and results: Hearts of male Wistar rats underwent 20min baseline perfusion with glucose (11mM) and either high fat (1.2mM palmitate; HF) or no fat (NF), 27min global ischemia (37°C), and 60min reperfusion with glucose only (n=7-8 per group). Hemodynamic recovery was 50% lower in HF vs. NF hearts (34±30% vs. 78±8% (60min reperfusion value of peak systolic pressure*heart rate as percentage of mean baseline); p<0.01). During early reperfusion, glycolysis (0.3±0.3 vs. 0.7±0.3μmol*min-1*g dry-1, p<0.05), glucose oxidation (0.1±0.03 vs. 0.4±0.2μmol*min-1*g dry-1, p<0.01) and pyruvate dehydrogenase activity (1.8±0.6 vs. 3.6±0.5U*g protein-1, p<0.01) were significantly reduced in HF vs. NF groups, respectively, while lactate release was significantly greater (1.8±0.9 vs. 0.6±0.2μmol*g wet-1*min-1; p<0.05).
Conclusions: Acute, pre-ischemic exposure to high fat significantly lowers post-ischemic cardiac recovery vs. no fat despite identical reperfusion conditions. These findings support the concept that oxidation of residual fatty acids is rapidly restored upon reperfusion and exacerbates ischemia-reperfusion (IR) injury. Strategies to optimize post-ischemic cardiac recovery should take pre-ischemic fat levels into consideration.
Keywords: Circulating fatty acids; Donation after circulatory death; Glucose metabolism; Heart transplantation; Ischemia–Reperfusion injury.
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