Evaluation of the suitability of a donor heart for transplantation after various asystole periods in experiment

The lack of donor hearts for transplantation in patients with end-stage chronic heart failure makes us look for new ways to increase the pool of donors. One of the possible ways to increase the donor base may be the use of asystolic donors, i. e. patients with in-hospital cardiac arrest or patients with cardiac arrest after brain death. The aim of the study was to examine the morphofunctional state of the heart after various periods of normothermic asystole in an experiment on rats. Materials and methods. Experiments were performed on female Wistar rats. After cervical dislocation and registration of respiratory arrest, the body temperature of the rat was maintained above at 36.5±0.5 °C for 10, 15 and 20 minutes, depending on the group. After asystole period, the heart was connected to the Langendorff apparatus to provide perfusion for 90 minutes. During perfusion of the heart, the pulse pressure inside the left ventricle (LVPP) and the volumetric flow rate of coronary perfusion (CP) were recorded every 15 minutes. After the end of the experiment, the volume of necrosis was calculated. Results. In the group with 20-minute ischemia, there was no recovery of ventricular contractions, the volume of necrosis was 34,9±11,7 %. In the group with 15-minute ischemia, the volume of necrosis was 19,5±7,6 %. In the group with 10-minute normothermic ischemia, the volume of necrosis was 13,1±5,1 %. Conclusions. 15 minutes of normothermic cardiac arrest in situ causes irreversible damage to the heart of the animal, which does not allow us to consider it as a potential donor heart. However, this volume of damage to the myocardium and microvasculature, together with the restoration of the contractile activity of the heart, makes this group the main one for the continuation of such experiments using various methods of heart reconditioning.

heart, donation, ischemia, microcirculation, reperfusion

1. Gautier SV, Khomyakov SM. Organ donation and transplantation in the Russian Federation in 2018. 11th report of the Registry of the Russian Transplant Society. Russian Journal of Transplantology and Artificial Organs. 2019;21(3):7–32. (In Russ.). Doi: 10.15825/1995-1191-2019-3-7-32.

2. Poptsov VN, Spirina EA, Koloskova NN, Masyutin SA, Ukhrenkov SG, Dogonasheva AA. Heart transplantation from older donors. Russian Journal of Transplantology and Artificial Organs. 2017;19(1):89–102. (In Russ.). Doi: 10.15825/1995-1191-2017-1-89-102.

3. Poptsov VN, Spirina EA, Koloskova NN, Masyutin SA, Ukhrenkov SG, Dogonasheva AA. Heart transplantation from older donors. Russian Journal of Transplantology and Artificial Organs. 2017;19(1):89–102. (In Russ.). Doi: 10.15825/1995-1191-2017-1-89-102.

4. Noterdaeme T, Detry O, Hans MF et al. What is the potential increase in the heart graft pool by cardiac donation after circulatory death? Transpl Int. 2013;26:61–66. Doi: 10.1111/j.1432-2277.2012.01575.x.

5. Messer S, Page A, Axell R, Berman M, Hernández-Sánchez J, Colah S, Parizkova B, Valchanov K, Dunning J, Pavlushkov E, Balasubramanian SK, Parameshwar J, Omar YA, Goddard M, Pettit S, Lewis C, Kydd A, Jenkins D, Watson CJ, Sudarshan C, Catarino P, Findlay M, Ali A, Tsui S, Large SR. Outcome following heart transplantation from donation after circulatory determined death (DCD) donors. Journal of Heart and Lung Transplantation. 2017 Dec;36(12):1311–1318. Doi: 10.1016/j.healun.2017.10.021.

6. Dhital KK, Iyer A, Connellan M, Chew HC, Gao L, Doyle A, Hicks M, Kumarasinghe G, Soto C, Dinale A, Cartwright B, Nair P, Granger E, Jansz P, Jabbour A, Kotlyar E, Keogh A, Hayward C, Graham R, Spratt P, Macdonald P. Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series. Lancet. 2015;385:2585–2591. Doi: 10.1016/S0140-6736(15)60038-1.

7. Messer S, Page A, Axell R, Berman M, Hernández-Sánchez J, Colah S, Parizkova B, Valchanov K, Dunning J, Pavlushkov E, Balasubramanian SK, Parameshwar J, Omar YA, Goddard M, Pettit S, Lewis C, Kydd A, Jenkins D, Watson CJ, Sudarshan C, Catarino P, Findlay M, Ali A, Tsui S, Large SR. Outcome after heart transplantation from donation after circulatorydetermined death donors. J Heart Lung Transplant. 2017;36:1311–1318. Doi: 10.1016/j.healun.2017.10.021.

8. Iyer A, Chew HC, Gao L, Villanueva J, Hicks M, Doyle A, Kumarasinghe G, Jabbour A, Jansz PC, Feneley MP, Harvey RP, Graham RM, Dhital KK, Macdonald PS. Pathophysiological trends during withdrawal of life support: implications for organ donation after circulatory death. Transplantation. 2016;100:2621–2629. Doi: 10.1097/TP.0000000000001396.

9. Minasian SM, Galagudza ММ, Sonin DL, Zverev DA, Korolev DV, Dmitriev YuV, Vasilieva МS, Grigorova YuN, Vlasov ТD. The technique of isolated rat heart perfusion. Reg. Circ. Microcirc. 2009;8(4):54–59. (In Russ).

10. Korolev DV, Alexandrov IV, Galagoudza MM, Syrensky AV, Sonin DL, Egorova EI. Automation of data acquisition and processing in physiological experiments. Reg. Circ. Microcirc. 2008;7(2):79–84. (In Russ).

11. Stadelmann M, Dornbierer M, Clément D, Gahl B, Dick F, Carrel TP, Tevaearai HT, Longnus S. Mild hypothermia during global cardiac ischemia opens a window of opportunity to develop heart donation after cardiac death. Transpl Int. 2013;26:339–348. Doi: 10.1111/tri.12022.

12. Kearns MJ, Miller SD, Kong HJ et al. Oligonucleotidebased Preconditioning of DCD Cardiac Donors and Its Impact on Cardiac Viability. Transplantation. 2019;103(12):24792485. Doi: 10.1097/TP.0000000000002849.

13. Lan H, Su Y, Liu Y et al. Melatonin protects circulatory death heart from ischemia/reperfusion injury via the JAK2/ STAT3 signalling pathway. Life Sci. 2019;228:35–46. Doi: 10.1016/j.lfs.2019.04.057.

14. Quader M, Akande O, Toldo S, Cholyway R, Kang L, Lesnefsky EJ, Chen Q. The Commonalities and Differences in Mitochondrial Dysfunction Between ex vivo and in vivo Myocardial Global Ischemia Rat Heart Models: Implications for Donation After Circulatory Death Research. Front. Physiol. 2020;11:681. Doi: 10.3389/fphys.2020.00681.

15. Galagudza MM. Stunned myocardium: mechanisms and clinical significance. Bulletin FSBI named after V. A. Almazov. 2011;2:5–11. (In Russ.).

16. Shlyakhto EV, Petrishchev NN, Galagudza MM, Vlasov TD, Nifontov EM. Cardioprotection: basic and clinical aspects. St. Petersburg, NP-Print Studio Ltd., 2013:399. (In Russ.).