Controlled Reperfusion Strategies Improve Cardiac Hemodynamic Recovery after Warm Global Ischemia in an Isolated, Working Rat Heart Model of Donation after Circulatory Death (DCD).
- Farine E Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- Niederberger P Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- Wyss RK Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- Méndez-Carmona N Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- Gahl B Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- Fiedler GM Center of Laboratory Medicine, University Institute of Clinical Chemistry, University Hospital Inselspital, Bern, Switzerland.
- Carrel TP Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- Tevaearai Stahel HT Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- Longnus SL Clinic for Cardiovascular Surgery, Inselspital, Bern University HospitalBern, Switzerland; Department of Clinical Research, University of BernBern, Switzerland.
- 2016-12-07
Published in:
- Frontiers in physiology. - 2016
acidic reperfusion
cardioprotection
donation after circulatory death
heart transplantation
hypoxia
ischemia reperfusion injury
mechanical postconditioning
mild hypothermia
English
Aims: Donation after circulatory death (DCD) could improve cardiac graft availability, which is currently insufficient to meet transplant demand. However, DCD organs undergo an inevitable period of warm ischemia and most cardioprotective approaches can only be applied at reperfusion (procurement) for ethical reasons. We investigated whether modifying physical conditions at reperfusion, using four different strategies, effectively improves hemodynamic recovery after warm ischemia. Methods and Results: Isolated hearts of male Wistar rats were perfused in working-mode for 20 min, subjected to 27 min global ischemia (37°C), and 60 min reperfusion (n = 43). Mild hypothermia (30°C, 10 min), mechanical postconditioning (MPC; 2x 30 s reperfusion/30 s ischemia), hypoxia (no O2, 2 min), or low pH (pH 6.8-7.4, 3 min) was applied at reperfusion and compared with controls (i.e., no strategy). After 60 min reperfusion, recovery of left ventricular work (developed pressure*heart rate; expressed as percent of pre-ischemic value) was significantly greater for mild hypothermia (62 ± 7%), MPC (65 ± 8%) and hypoxia (61 ± 11%; p < 0.05 for all), but not for low pH (45 ± 13%), vs. controls (44 ± 7%). Increased hemodynamic recovery was associated with greater oxygen consumption (mild hypothermia, MPC) and coronary perfusion (mild hypothermia, MPC, hypoxia), and with reduced markers of necrosis (mild hypothermia, MPC, hypoxia) and mitochondrial damage (mild hypothermia, hypoxia). Conclusions: Brief modifications in physical conditions at reperfusion, such as hypothermia, mechanical postconditioning, and hypoxia, improve post-ischemic hemodynamic function in our model of DCD. Cardioprotective reperfusion strategies applied at graft procurement could improve DCD graft recovery and limit further injury; however, optimal clinical approaches remain to be characterized.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.3389/fphys.2016.00543
- PMID 27920725
- Persistent URL
- https://sonar.ch/global/documents/48602
Statistics
Document views: 22
File downloads:
- Full-text: 0