Expanding the horizon: using fatty acids and mannitol as alternative fuels and oncotic agents for normothermic ex vivo heart perfusions in adult rats

Normothermic machine perfusion (NMP) is an advanced technique for ex vivo organ perfusion using a nutrient- and oxygen-rich perfusate at 37°C. The main objectives are to reduce injury, increase preservation duration, assess graft viability, and facilitate transplantation. The perfusate, enriched with glucose as a vital energy source, is crucial in meeting the metabolic demands of specialized organs like the heart in rodent models. Additionally, oncotic agents like bovine serum albumin (BSA) help maintain osmotic pressure and reduces fluid build-up (edema). While glucose and BSA are commonly used in rodent heart perfusions, there is growing interest in exploring alternative fuel options such as fatty acids, which are natural fuels for the heart, and alternate oncotic agents like Mannitol which recently have shown to have some cardioprotective properties. This preliminary study used a fatty acid (Oleic acid)/Mannitol perfusate and compared it with Glucose/BSA (control group) in adult rats (n=3) to assess the cardiac physiology using Langendorff perfusion. Major markers for heart injury (Troponin), heart parameters (vascular resistance, edema, oxygen uptake rate (OUR) and heart rate) during perfusion were analysed for each group. Interestingly, in Oleic acid-Mannitol group, OUR rate was lower during 4 hr perfusion compared with control group, which was expected as fatty acids are more energy dense fuel compared to glucose and yield more energy using lower oxygen consumption. Additionally, the addition of Mannitol, which is less viscous compared to BSA, significantly reduced vascular resistance. Moreover, troponin levels were lower in Oleic acid-Mannitol group (although not significantly different), while edema levels were comparable between both groups. These findings suggest the potential for improving traditional cocktails in rodent heart perfusions to enhance preservation and transplantation outcomes in clinical settings. Further research is needed to comprehend the full benefits and implications of these alternative fuel options and oncotic agents.