High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after circulatory death

Abstract

RationaleDonation 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. ObjectiveWe 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 ResultsHearts 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). ConclusionsAcute, 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.