Histological and ultrastructural analysis of biopsy specimens of donor heart under conditions of extended period of pharmaco-cold ischaemia

Nadeev AP, Kliver VE, Volkov AM, et al. . Histological and ultrastructural analysis of biopsy specimens of donor heart under conditions of extended period of pharmaco-cold ischaemia. Russian Journal of Archive of Pathology. 2024;86(5):33‑41. (In Russ.)
https://doi.org/10.17116/patol20248605133

Подписка 2026 Архив патологии (Russian Journal of Archive of Pathology)

Использование инфографики авторами научных работ

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OBJECTIVE

At the histological and ultramicroscopic level, compare biopsy specimens of donor heart under standard (up to 240 min) and extended (more than 240 min) periods of pharmaco-cold preservation.

MATERIAL AND METHODS

Biopsy specimens of the left atrium of donor hearts: group 1 — 8 samples after transportation with pharmaco-cold preservation of the graft in Bretschneider solution (Dr. Franz Köhler Chemie GmbH, Germany) up to 240 min, (Me 140), and group 2 — 5 samples after an extended pharmaco-cold period (more than 240 min; Me 375) were examined using light microscopy of semi-thin sections and transmission electron microscopy, followed by stereological and statistical analysis.

RESULTS

A comparative study of the myocardium of donor hearts revealed stereotypical dystrophic changes in cardiomyocytes. Semi-thin sections demonstrated a mosaic pattern of myocardial parenchyma in both groups, caused by contracture and less pronounced lytic changes in myocytes, which were accompanied by stromal edema without statistically significant differences according to stereological studies. Ultrathin sections of the perinuclear zones of cardiomyocytes visualized reduction and focal damage to myofibrils and mitochondria in combination with pronounced autophagy; at the same time, with a shorter duration of the pharmaco-cold period, the stereological indicators of cardiomyocyte organelles indicated a relatively better supply of myofibrils with mitochondria.

CONCLUSION

The results obtained suggest a sufficiently high degree of preservation of the tissue and ultrastructural organization of donor hearts with prolonged (more than 240 min) pharmaco-cold ischemia to restore adequate cardiac activity after heart transplantation.

Keywords:

donor heart

atrial biopsy

pharmaco-cold preservation

cardiomyocytes

transmission electron microscopy

stereology

Authors:

Nadeev A.P.

Novosibirsk State Medical University

ORCID: 0000-0003-0400-1011

Kliver V.E.

Novosibirsk State Medical University;
National Medical Research Center named after Academician E. N. Meshalkin

ORCID: 0000-0003-2245-1251

Volkov A.M.

National Medical Research Center named after Academician E. N. Meshalkin

ORCID: 0000-0001-9697-7091

Fomichev A.V.

National Medical Research Center named after Academician E. N. Meshalkin

ORCID: 0000-0001-9113-4204

Sirota D.A.

Novosibirsk State Medical University;
National Medical Research Center named after Academician E. N. Meshalkin

ORCID: 0000-0002-9940-3541

Zhulkov M.O.

Meshalkin National Medical Research Center

ORCID: 0000-0001-7976-596X

Kliver E.E.

Novosibirsk State Medical University;
National Medical Research Center named after Academician E. N. Meshalkin

ORCID: 0000-0002-3915-3616

Volchek A.V.

Novosibirsk State Medical University

Kazanskaya G.M.

Federal Research Center for Fundamental and Translational Medicine

ORCID: 0000-0003-2598-1805

Aidagulova S.V.

Novosibirsk State Medical University;
Federal Research Center for Fundamental and Translational Medicine

ORCID: 0000-0001-7124-1969

Received:

23.04.2024

Accepted:

26.06.2024

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References:

Fomichev AV, Khvan DS, Agaeva KhA, Zhul’kov MO, Doronin DV, Chernyavskii AM. Experience of heart transplantation with an extended cold ischemic time of donor heart. Russian Cardiological Journal. 2020;25(8):24-29. (In Russ.). https://doi.org/10.15829/1560-4071-2020-4011
Colvin M, Smith JM, Ahn Y, Skeans MA, Messick E, Bradbrook K, Gauntt K, Israni AK, Snyder JJ, Kasiske BL. OPTN/SRTR 2020 annual data report: heart. Am J Transplant. 2022;22(Suppl. 2):350-437. https://doi.org/10.1111/ajt.16977
Subramaniam K. Early graft failure after heart transplantation: prevention and treatment. Int Anesthesiol Clin. 2012;50(3):202-227. https://doi.org/10.1097/AIA.0b013e3182603ead
DiChiacchio L, Goodwin ML, Kagawa H, Griffiths E, Nickel IC, Stehlik J, Selzman CH. Heart transplant and donors after circulatory death: a clinical-preclinical systematic review. J Surg Res. 2023;292:222-233. https://doi.org/10.1016/j.jss.2023.07.050
Yuan S, Che Y, Wang Z, Xing K, Xie X, Chen Y. Mitochondrion-targeted carboxymethyl chitosan hybrid nanoparticles loaded with Coenzyme Q10 protect cardiac grafts against cold ischaemia-reperfusion injury in heart transplantation. J Transl Med. 2023;21(1):925. https://doi.org/10.1186/s12967-023-04763-7
Moskowitzova K, Shin B, Liu K, Ramirez-Barbieri G, Guariento A, Blitzer D, Thedsanamoorthy JK, Yao R, Snay ER, Inkster JAH, et al. Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation. J Heart Lung Transplant. 2019;38(1):92-99. https://doi.org/10.1016/j.healun.2018.09.025
Cowan DB, Yao R, Thedsanamoorthy JK, Zurakowski D, Del Nido PJ, McCully JD. Transit and integration of extracellular mitochondria in human heart cells. Sci Rep. 2017;7(1):17450. https://doi.org/10.1038/s41598-017-17813-0
Kazanskaya GM, Volkov AM, Tsvetovskaya GA, Knyaz’kova LG, Chasovskikh GG, D’yakonitsa TM, Zhdanov GP, Lomivorotov VN. Changes in myocardial metabolism and ultrastructure of myocardial microvessels during pharmacological and cold cardioplegia under hypothermic conditions without perfusion. Bulletin of Experimental Biology and Medicine. 2002;(11):580-584. (In Rus.).
Dare AJ, Logan A, Prime TA, Rogatti S, Goddard M, Bolton EM, Bradley JA, Pettigrew GJ, Murphy MP, Saeb-Parsy K. The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model. J Heart Lung Transplant. 2015;34(11):1471-1480. https://doi.org/10.1016/j.healun.2015.05.007
Agbor-Enoh S, Shah P, Tunc I, Hsu S, Russell S, Feller E, Shah K, Rodrigo ME, Najjar SS, Kong H, et al.; GRAfT Investigators. Cell-free DNA to detect heart allograft acute rejection. Circulation. 2021;143(12):1184-1197. https://doi.org/10.1161/CIRCULATIONAHA.120.049098
Tarazon E, Rosello-Lleti E, Ortega A, Gil-Cayuela C, Gonzalez-Juanatey JR, Lago F, Martinez-Dolz L, Portoles M, Rivera M. Changes in human Golgi apparatus reflect new left ventricular dimensions and function in dilated cardiomyopathy patients. Eur J Heart Fail. 2017;19(2):280-282. https://doi.org/10.1002/ejhf.671
Nepomnyashchikh LM, Zimmermann VG. Prenecrotic contracture damage in cardiomyocytes: photochemical fluorochrome staining and fluorescent microscopy of the myocardium. Bulletin of Experimental Biology and Medicine. 2001;132(9):343-349. (In Russ.).
Takemura G, Kanamori H, Okada H, Tsujimoto A, Miyazaki N, Takada C, Hotta Y, Takatsu Y, Fujiwara T, Fujiwara H. Ultrastructural aspects of vacuolar degeneration of cardiomyocytes in human endomyocardial biopsies. Cardiovasc Pathol. 2017;30:64-71. https://doi.org/10.1016/j.carpath.2017.06.012
Savchenko SV, Novoselov VP, Morozova AS, Skrebov RV, Grizinger VA, Ageeva TA, Aidagulova SV, Ershov KI, Voronina EI. Assessment of the severity of connexin 43 expression in the myocardium in acute ischemia in experiment. Circulation Pathology and Cardiac Surgery. 2017;21(1):81-90. (In Russ.). https://doi.org/10.21688/1681-3472-2017-1-81-90
Kliver VE, Nadeev AP, Fomichev AV, Volkov AM, Sirota DA, Kliver EE, Zhul’kov MO. Impact of the graft cold ischemia time on severity of cellular rejection and the outcome of heart transplantation. Far Eastern Medical Journal. 2023;(1):31-37. (In Russ.). https://doi.org/10.35177/1994-5191-2023-1-5
Kliver VE, Volkov AM, Nadeev AP, Fomichev AV, Sirota DA, Kliver EE, Zhul’kov MO, Pozdnyakova SV. Morphological assessment of actin and desmin expression at different cold myocardial ischemia times: observational study. Kuban Scientific Medical Bulletin. 2024;31(1):15-26. (In Russ.). https://doi.org/10.25207/1608-6228-2024-31-1-15-26
Kakturskii LV, Mikhaleva LM, Mishnev OD, Zairat’yants OV, Kurilina EV, Komlev AE. Takotsubo syndrome (stress-induced cardiomyopathy). Archive of Pathology. 2021;83(1):5-11. (In Russ.). https://doi.org/10.17116/patol2021830115
Lushnikova EL, Klinnikova MG, Molodykh OP, Nepomnyashchikh LM. Ultrastructural criteria of cardiomyocyteregeneratory and plastic insufficiency in anthracycline cardiomyopathy. Bulletin of Experimental Biology and Medicine. 2005;139(4):470-475. (In Russ.).
Avagimyan A, Kaktursky L. Cardiotoxicity of cyclophosphamide: current state of the problem. Exp Clin Med Georgia. 2022;3:1-5. https://doi.org/10.52340/jecm.2022.03.14
Tarazón E, Pérez-Carrillo L, Portolés M, Roselló-Lletí E. Electron microscopy reveals evidence of perinuclear clustering of mitochondria in cardiac biopsy-proven allograft rejection. J Pers Med. 2022;12(2):296. https://doi.org/10.3390/jpm12020296