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Reduction of Reperfusion Cardiac Injury in Donation After Circulatory Death Hearts Through Modulation of Electron Transport
Author(s) -
Chen Qun,
Toldo Stefano,
Lesnefsky Edward,
Quader Mohammed
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.580.4
Subject(s) - mitochondrial permeability transition pore , ventricle , medicine , perfusion , cardiology , heart transplantation , heart failure , mptp , myocardial infarction , ischemia , reperfusion injury , anesthesia , chemistry , parkinson's disease , programmed cell death , disease , apoptosis , biochemistry
INTODUCTION Heart transplantation (HT) is a valuable option to prolong life in an end stage heart failure (HF) patient, but this option is limited due to the availability of donor hearts, which currently come from brain death donors only. Expansion of the heart donor pool is urgently needed. One potential source of donor hearts is donation after circulatory death (DCD) donors. Since the DCD process involves substantial ischemia (ISC) and reperfusion (REP) injury to heart, strategies are needed to reduce cardiac injury in DCD hearts for HT. HYPOTHESIS Amobarbital (AMO) give during REP decreases cardiac injury. Based on the current human DCD protocol, the duration of ISC prior to heart procurement varies from 25 to 40 min. Thus, we examined if AMO given at the onset of REP can decrease cardiac injury in DCD heart following 45 min of global ISC. METHODS After 45 min of ISC, DCD hearts received AMO (2 mM) at the onset of REP for 5 min followed by buffer perfusion for 55 min; or buffer perfusion only for 60 min. Cardiac injury was measured by the left ventricle (LV) infarct size. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria(IFM) were isolated at 10 min of REP to measure calcium retention capacity (CRC, nmol calcium/mg protein) to assess mitochondrial permeability transition pore (MPTP) opening and rate of oxidative phosphorylation (nAO/min/mg). RESULTS AMO given during REP decreased the infarct size by 35% compared to untreated hearts. AMO improved the CRC in both SSM and IFM (Table), indicating a decreased susceptibility to MPTP opening during early REP. AMO did not influence oxidative phosphorylation with either complex I (glutamate) or complex II substrates (succinate+rotenone), suggesting that the protection of AMO is not due to improved oxidative phosphorylation. CONCLUSION Modulation of mitochondrial respiration at REP is a potential strategy to decrease cardiac injury in DCD hearts through inhibition of MPTP opening. Support or Funding Information Scientist development grant (MQ) from American Heart Association, Merit Review Award ( 2IO1BX001355‐01 EJ), R21AG054975‐01 (QC) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .