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)