High Oxygenation During Normothermic Regional Perfusion After Circulatory Death Is Beneficial on Donor Cardiac Function in a Porcine Model

Background. Thoracoabdominal normothermic regional perfusion (NRP) is a new method for in situ reperfusion and reanimation of potential donor organs in donation after circulatory death by reperfusion of the thoracic and abdominal organs with oxygenated blood. We investigated effects of high oxygenation (HOX) versus low oxygenation (LOX) during NRP on donor heart function in a porcine model. Methods. Pigs (80 kg) underwent a 15-min anoxic cardiac arrest followed by cardiac reanimation on NRP using a heart-lung bypass machine with subsequent assessment 180 min post-NRP. The animals were randomized to HOX (FiO2 1.0) or LOX (FiO2 0.21 increased to 0.40 during NRP). Hemodynamic data were obtained by invasive blood pressure and biventricular pressure-volume measurements. Blood gases, biomarkers of inflammation, and oxidative stress were measured. Results. Eight of 9 animals in the HOX group and 7 of 10 in the LOX group were successfully weaned from NRP. Right ventricular end-systole elastance was significantly improved in the HOX group compared with the LOX group, whereas left ventricular end-systole elastance was preserved at baseline levels. Post-NRP cardiac output, mean arterial, central venous, and pulmonary capillary wedge pressure were all comparable to baseline. Creatinine kinase-MB increased more in the LOX group than the HOX group, whereas proinflammatory cytokines increased more in the HOX group than the LOX group. No difference was found in oxidative stress between groups. Conclusions. All hearts weaned from NRP showed acceptable hemodynamic function for transplantation. Hearts exposed to LOX showed more myocardial damage and showed poorer contractile performance than hearts reperfused with high oxygen.

[1]  C. Hassager,et al.  Treatment Effects of Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest (The IMICA Trial) , 2021, Circulation.

[2]  S. Cánovas,et al.  Spanish experience with heart transplants from controlled donation after the circulatory determination of death using thoraco‐abdominal normothermic regional perfusion and cold storage , 2020, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[3]  J. González-Costello,et al.  Heart Donation From Donors After Controlled Circulatory Death , 2020, Transplantation.

[4]  F. Rosenfeldt,et al.  Combined Assessment of Functional and Metabolic Performance of Human Donor Hearts: Possible Application in Donation After Circulatory Death. , 2020, Transplantation.

[5]  M. Goddard,et al.  A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors. , 2020, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[6]  Bihua Chen,et al.  Hyperoxygenation With Cardiopulmonary Resuscitation and Targeted Temperature Management Improves Post–Cardiac Arrest Outcomes in Rats , 2020, Journal of the American Heart Association.

[7]  Xiaohong Jin,et al.  The Effects of Dexmedetomidine Post-Conditioning on Cardiac and Neurological Outcomes After Cardiac Arrest and Resuscitation in Swine. , 2020, Shock.

[8]  A. Cheung,et al.  Oligonucleotide-based Preconditioning of DCD Cardiac Donors and its Impact on Cardiac Viability. , 2019, Transplantation.

[9]  D. Ledoux,et al.  Successful clinical transplantation of hearts donated after circulatory death using normothermic regional perfusion. , 2019, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[10]  V. Rao,et al.  Hearts Donated After Circulatory Death and Reconditioned Using Normothermic Regional Perfusion Can Be Successfully Transplanted Following an Extended Period of Static Storage , 2019, Circulation. Heart failure.

[11]  K. Muthiah,et al.  Outcomes of Donation After Circulatory Death Heart Transplantation in Australia. , 2019, Journal of the American College of Cardiology.

[12]  P. Macdonald,et al.  Heart Transplantation With Donation After Circulatory Death: What Have We Learned From Preclinical Studies? , 2019, Circulation. Heart failure.

[13]  V. Rao,et al.  Recipient hypertonic saline infusion prevents cardiac allograft dysfunction , 2019, The Journal of thoracic and cardiovascular surgery.

[14]  R. Axell,et al.  Human heart transplantation from donation after circulatory-determined death donors using normothermic regional perfusion and cold storage. , 2018, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[15]  M. Goddard,et al.  Outcome after heart transplantation from donation after circulatory-determined death donors. , 2017, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[16]  E. Ashley,et al.  Functional assessment and transplantation of the donor heart after circulatory death. , 2016, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[17]  P. Jansz,et al.  Pathophysiological Trends During Withdrawal of Life Support: Implications for Organ Donation After Circulatory Death , 2016, Transplantation.

[18]  J. Mira,et al.  Hyperoxia toxicity after cardiac arrest: What is the evidence? , 2016, Annals of Intensive Care.

[19]  B. Xiang,et al.  Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[20]  P. Jansz,et al.  Normothermic Ex Vivo Perfusion Provides Superior Organ Preservation and Enables Viability Assessment of Hearts From DCD Donors , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[21]  J. Vincent,et al.  How much oxygen in adult cardiac arrest? , 2014, Critical Care.

[22]  E. Ashley,et al.  Rat model of veno-arterial extracorporeal membrane oxygenation , 2014, Journal of Translational Medicine.

[23]  F. Hausler,et al.  Increasing arterial oxygen partial pressure during cardiopulmonary resuscitation is associated with improved rates of hospital admission. , 2013, Resuscitation.

[24]  R. Bellomo,et al.  The effect of hyperoxia following cardiac arrest - A systematic review and meta-analysis of animal trials. , 2012, Resuscitation.

[25]  B. Xiang,et al.  Hearts From DCD Donors Display Acceptable Biventricular Function After Heart Transplantation in Pigs , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[26]  V. Rao,et al.  Donor Pretreatment With Hypertonic Saline Attenuates Primary Allograft Dysfunction: A Pilot Study in a Porcine Model , 2009, Circulation.

[27]  M. Angelos,et al.  Oxygen requirement during cardiopulmonary resuscitation (CPR) to effect return of spontaneous circulation. , 2009, Resuscitation.

[28]  T. Wilgus,et al.  Hyperoxemic reperfusion after prolonged cardiac arrest in a rat cardiopulmonary bypass resuscitation model. , 2013, Resuscitation.

[29]  J. Parrillo,et al.  CARING FOR THE CRITICALLY ILL PATIENT Association Between Arterial Hyperoxia Following Resuscitation From Cardiac Arrest and In-Hospital Mortality , 2010 .

[30]  G. Gebhart,et al.  Special Report: The 1996 Guide for the Care and Use of Laboratory Animals. , 1997, ILAR journal.