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Updated: May 8, 2026
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Warm ischemic time-dependent effects on oxidative stress, endoplasmic reticulum stress, and inflammation in cold
Shiyi Li1, Rishav Bhattacharya1, Abdussalam E Elsenousi1
1Division of Cardiothoracic Transplantation and Circulatory Support, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex.
Insights
Celsior solution (CS) effectively reduces cellular stress in donor hearts, but its anti-inflammatory benefits diminish with prolonged warm ischemia time (WIT). Tailoring preservation strategies to WIT is crucial for optimal outcomes in heart transplantation.
Area of Science:
- Cardiology
- Organ Transplantation
- Biomedical Engineering
Background:
- Standard heart preservation uses Celsior solution (CS) for donors after brain death (DBD).
- The efficacy of CS in donors after circulatory death (DCD) remains unestablished.
- Ischemic injury involves oxidative stress, endoplasmic reticulum (ER) stress, and inflammation.
Purpose of the Study:
- Compare CS with normal saline (NS) in preserving human DBD and DCD hearts.
- Investigate the impact of warm ischemic time (WIT) and cold ischemia on preservation.
- Assess effects on myocardial oxidative stress, ER stress, and inflammation pathways.
Main Methods:
- Analyzed 47 human hearts (16 DBD, 31 DCD) preserved with NS or CS.
- Hearts were grouped by donor type, preservation solution, and WIT (≤30 min or >30 min).
- Left ventricular biopsies were assessed for oxidative stress, ER stress, and inflammatory markers over 6 hours of cold storage.
Main Results:
- DCD hearts showed higher baseline stress and inflammation, particularly with WIT > 30 min.
- CS reduced oxidative and ER stress in DBD and DCD hearts (WIT ≤30 min).
- CS demonstrated anti-inflammatory effects in DBD and DCD hearts (WIT ≤30 min) but not in DCD hearts with WIT > 30 min.
Conclusions:
- Warm ischemic time (WIT) is a critical determinant of ischemic injury severity.
- CS mitigates upstream cellular stress but loses anti-inflammatory efficacy after prolonged WIT (>30 min).
- Development of WIT-stratified preservation strategies is essential for improving heart transplant outcomes.
Objective:
Direct procurement and cold preservation with Celsior solution are standard for donor hearts after brain death; however, whether Celsior solution can be used in donor after circulatory death hearts is unknown. Because myocardial oxidative stress, endoplasmic reticulum stress, and inflammation are pivotal in ischemic injury, we compared Celsior solution with normal saline with respect to these pathways in human donor after brain death and donor after circulatory death hearts, assessing the impact of warm ischemic time and cold ischemia.
Methods:
Forty-seven human donor after brain death (n = 16) and donor after circulatory death (n = 31) hearts that received Del Nido cardioplegia were procured for research and assigned to 6 groups based on donor type (donor after brain death/donor after circulatory death), preservation solution (normal saline/Celsior solution), and warm ischemic time (≤30 minutes/>30 minutes): (1) normal saline: donor after brain death (n = 10); (2) Celsior solution: donor after brain death (n = 6); (3) normal saline: donor after circulatory death 30 minutes or less (n = 6); (4) Celsior solution: donor after circulatory death 30 minutes or less (n = 7); (5) normal saline: donor after circulatory death more than 30 minutes (n = 12); and (6) Celsior solution: donor after circulatory death more than 30 minutes (n = 6) and cold stored for 6 hours. Left ventricular biopsies at 0, 2, 4, and 6 hours (T0-T6) were analyzed for oxidative stress (4-hydroxynonenal, superoxide dismutase), endoplasmic reticulum stress (activating transcription factor 6, heat shock 70 kDa protein 5), and inflammatory markers (tumor necrosis factor-α and interleukin-6).
Results:
At baseline, donor after circulatory death hearts exhibited greater cellular stress and inflammation, especially with warm ischemic time of 30 minutes or more. During cold storage, Celsior solution attenuated oxidative and endoplasmic reticulum stress in both donor after brain death hearts and donor after circulatory death hearts with warm ischemic time of 30 minutes or less. Inflammatory markers were reduced by Celsior solution only in donor after brain death hearts and donor after circulatory death hearts with warm ischemic time of 30 minutes or less. Celsior solution preservation has no anti-inflammatory effect in donor after circulatory death hearts with warm ischemic time of more than 30 minutes.
Conclusions:
Warm ischemic time determines the extent of ischemic injury. Celsior solution ameliorates upstream cellular stress, but its anti-inflammatory effect is lost after prolonged warm ischemia (>30 minutes), underscoring the need for warm ischemic time-stratified preservation strategies.
