Metabolic Alterations in Myocardial Metabolism during Ex Situ Heart Perfusion

Hatami, Sanaz; White, Christopher W.; Xiao, Qi; Buchko, Max; Himmat, Sayed; Aboelnazar, N.; Nagendran, Jeevan; Freed, Darren H.

doi:10.1016/j.healun.2019.01.584

Cited by 2 publications

(2 citation statements)

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“…Adding to the above, to the best of the authors' knowledge this is the first study on evaluation of altered global cardiac metabolome during ESHP. Previous studies were focused on a narrow scope of changes, namely on alterations in energy substrate utilization, accelerated inflammatory response and oxidative stress or ultimately the loss of coronary artery regulation which might be directly associated with endothelial dysfunction; nonetheless, they present a valuable insight in the context of metabolic alterations discussed in the current study (35,(53)(54)(55). Precisely, Hatami S. et al have proven that functional decline during ESHP has a metabolic basis and therefore might be reversible (53).…”

Section: Discussionmentioning

confidence: 84%

“…Previous studies were focused on a narrow scope of changes, namely on alterations in energy substrate utilization, accelerated inflammatory response and oxidative stress or ultimately the loss of coronary artery regulation which might be directly associated with endothelial dysfunction; nonetheless, they present a valuable insight in the context of metabolic alterations discussed in the current study (35,(53)(54)(55). Precisely, Hatami S. et al have proven that functional decline during ESHP has a metabolic basis and therefore might be reversible (53). During extended 12 hours porcine hearts perfusion they observed decoupling of glycolysis and the TCA cycle at the level of pyruvate kinase and revealed that strategy with simultaneous infusion of insulin and glucose appeared insufficient for maintenance of metabolic integrity during ESHP.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamic Metabolic Changes During Prolonged Ex Situ Heart Perfusion Are Associated With Myocardial Functional Decline

Olkowicz

Ribeiro

et al. 2022

Front. Immunol.

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Ex situ heart perfusion (ESHP) was developed to preserve and evaluate donated hearts in a perfused beating state. However, myocardial function declines during ESHP, which limits the duration of perfusion and the potential to expand the donor pool. In this research, we combine a novel, minimally-invasive sampling approach with comparative global metabolite profiling to evaluate changes in the metabolomic patterns associated with declines in myocardial function during ESHP. Biocompatible solid-phase microextraction (SPME) microprobes serving as chemical biopsy were used to sample heart tissue and perfusate in a translational porcine ESHP model and a small cohort of clinical cases. In addition, six core-needle biopsies of the left ventricular wall were collected to compare the performance of our SPME sampling method against that of traditional tissue-collection. Our state-of-the-art metabolomics platform allowed us to identify a large number of significantly altered metabolites and lipid species that presented comparable profile of alterations to conventional biopsies. However, significant discrepancies in the pool of identified analytes using two sampling methods (SPME vs. biopsy) were also identified concerning mainly compounds susceptible to dynamic biotransformation and most likely being a result of low-invasive nature of SPME. Overall, our results revealed striking metabolic alterations during prolonged 8h-ESHP associated with uncontrolled inflammation not counterbalanced by resolution, endothelial injury, accelerated mitochondrial oxidative stress, the disruption of mitochondrial bioenergetics, and the accumulation of harmful lipid species. In conclusion, the combination of perfusion parameters and metabolomics can uncover various mechanisms of organ injury and recovery, which can help differentiate between donor hearts that are transplantable from those that should be discarded.

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