Differential effects of ischemia/reperfusion on endothelial function and contractility in donation after circulatory death
Section snippets
Ethics
All experiments were carried out according to the European Convention for Animal Care and were approved by the Swiss animal welfare authorities and state veterinary office (Ethics Committee for Animal Experimentation [ECAE], Bern, Switzerland).
Isolated heart preparation
Adult male Wistar rats (384 ± 35 g; Janvier Labs, Le Genest-Saint-Isle, France), housed under standard conditions with unlimited access to food and water, were anesthetized intraperitoneally with 100 mg/kg ketamine (Narketan; Vetoquinol AG, Bern,
Baseline characteristics
Sample size and baseline characteristics for all heart perfusions are shown in Tables S1 and S2 (refer to Supplementary Material online). No difference among experimental groups was observed.
Post-ischemic functional recovery
Absolute values and percentage recovery of cardiac parameters are presented in Figure 2. Left ventricular work (LV work) was significantly lower for both absolute values (at 20, 40, and 60 minutes) and percentage recovery in hearts subjected to 27, 30, and 33 minutes of ischemia vs non-ischemic hearts (p
Discussion
In this study, we have demonstrated that endothelial dysfunction is more susceptible to warm global ischemia and reperfusion than cardiac dysfunction in an isolated rat heart model of DCD. The first signs of endothelial dysfunction were already present after 24 minutes of ischemia and reperfusion, whereas cardiac and smooth muscle cell (SMC) dysfunction appeared only after ischemic periods of 27 minutes. Endothelial dysfunction occurred in parallel with increases in NOS-dependent O2‒ and ONOO‒
Disclosure statement
The authors have no conflicts of interest to disclose. We thank Dr Daniel Rodriguez Gutierrez for the conceptual diagram illustration. This article/publication is based on work from COST Action EU-CARDIOPROTECTION CA16225, supported by the European Cooperation in Science and Technology. This study was supported by a project grant from the Swiss National Science Foundation (310030_149730/1).
References (68)
- et al.
The potential of transplanting hearts from donation after circulatory determined death (DCD) donors within the United Kingdom
J Heart Lung Transplant
(2015) - et al.
Potential suitability for transplantation of hearts from human non-heart-beating donors: data review from the Gift of Life Donor Program
J Heart Lung Transplant
(2005) - et al.
Human heart transplantation from donation after circulatory-determined death donors using normothermic regional perfusion and cold storage
J Heart Lung Transplant
(2018) - et al.
Outcome after heart transplantation from donation after circulatory-determined death donors
J Heart Lung Transplant
(2017) - et al.
The Registry of the International Society for Heart and Lung Transplantation: Thirty-second official adult heart transplantation report—2015; Focus theme: Early graft failure
J Heart Lung Transplant
(2015) - et al.
Conditioning the whole heart—not just the cardiomyocyte
J Mol Cell Cardiol
(2012) - et al.
Global ischemic duration and reperfusion function in the isolated perfused rat heart
Resuscitation
(2004) - et al.
Increasing the tolerance of DCD hearts to warm ischemia by pharmacological postconditioning: increasing the tolerance of DCD hearts to warm ischemia
Am J Transplant
(2014) - et al.
Effect of ischemia duration and nitric oxide on coronary vasoconstriction after ischemia–reperfusion
Eur J Pharmacol
(2005) - et al.
Coronary no reflow
J Mol Cell Cardiol
(2012)
Decreased nitric-oxide synthase activity causes impaired endothelium-dependent relaxation in the postischemic heart
J Biol Chem
Impact of oxidative stress on the heart and vasculature
J Am Coll Cardiol
Tetrahydrobiopterin, superoxide, and vascular dysfunction
Free Rad Biol Med
Pathophysiology underlying the bimodal edema phenomenon after myocardial ischemia/reperfusion
J Am Coll Cardiol
Effects of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultralarge von Willebrand factor multimers under flow
Blood
Interleukin-10 protects the ischemic heart from reperfusion injury via the STAT3 pathway
Surgery
Tumor necrosis factor-alpha is released from the isolated heart undergoing ischemia and reperfusion
J Am Coll Cardiol
Physiologic changes in the heart following cessation of mechanical ventilation in a porcine model of donation after circulatory death: implications for cardiac transplantation: physiologic response to donor extubation
Am J Transplant
High pre-ischemic fatty acid levels decrease cardiac recovery in an isolated rat heart model of donation after circulatory death
Metabolism
The isolated blood and perfusion fluid perfused heart
Pharmacol Res
Heart transplantation with donation after circulatory determination of death
Nat Rev Cardiol
The potential of cardiac allografts from donors after cardiac death at the University of Wisconsin Organ Procurement Organization
Eur J Cardiothorac Surg
What is the potential increase in the heart graft pool by cardiac donation after circulatory death?: potential of cardiac donation after circulatory death
Transplant Int
Transplantation of hearts donated after circulatory death
Front Cardiovasc Med
Donation after circulatory death heart transplantation
Curr Opin Organ Transplant
Coronary endothelial dysfunction and the index of microcirculatory resistance as a marker of subsequent development of cardiac allograft vasculopathy
Circulation
Prevention and treatment of coronary artery vasculopathy
Curr Opin Organ Transplant
The coronary circulation in cardioprotection: more than just one confounder
Cardiovasc Res
Role of endothelial cells in myocardial ischemia-reperfusion injury
Vasc Dis Prevent
Nitric oxide and the vascular endothelium in myocardial ischemia-reperfusion injury
Ann NY Acad Sci
Time course and mechanism of endothelial dysfunction in isolated ischemic- and hypoxic-perfused rat hearts
Am J Physiol
The role of nitric oxide in myocardial repair and remodeling
Antioxid Redox Signal
Efficacy of mechanical postconditioning following warm, global ischaemia depends on circulating fatty acid levels in an isolated, working rat heart model
Eur J Cardiothorac Surg
Controlled reperfusion strategies improve cardiac hemodynamic recovery after warm global ischemia in an isolated, working rat heart model of donation after circulatory death (DCD)
Front Physiol
Cited by (16)
Donation in controlled asystole: How to start a program
2022, Cirugia CardiovascularEffects of graft preservation conditions on coronary endothelium and cardiac functional recovery in a rat model of donation after circulatory death
2021, Journal of Heart and Lung TransplantationMitochondrial integrity during early reperfusion in an isolated rat heart model of donation after circulatory death—consequences of ischemic duration
2019, Journal of Heart and Lung TransplantationCitation Excerpt :For perfusion series 2, already at the time of tissue harvest (10 minutes reperfusion), a decrease of LV work was detectable with ≥ 27 minutes compared with no ischemia (p < 0.01 for both; Supplementary Figure S3B). Baseline characteristics for perfusion series 1 are reported elsewhere23 and for perfusion series 2 are presented in Supplementary Table 1. No differences between groups were observed.
Comparison of Different Ex-Vivo Preservation Strategies on Cardiac Metabolism in an Animal Model of Donation after Circulatory Death
2023, Journal of Clinical MedicineA tomographic microscopy-compatible Langendorff system for the dynamic structural characterization of the cardiac cycle
2022, Frontiers in Cardiovascular Medicine