To the Mechanism of Adrenaline Damage to the Heart Tissue and the Mechanism of Cardioprotection by Neonatal, Xenogenic, Cardiac Cells. Dynamics of Creatine Phosphate, Lactate and Malondialdehyde

The development of disturbances in energy processes and damaging free radical reactions in various pathological processes, including cardiovascular diseases, are interrelated and lead to a significant deterioration in the course of diseases.

Aim of the study. Research of the dynamics of malondialdehyde, creatine phosphate and lactate in the cardiac tissue of rats under experimental adrenaline stress and during its correction with neonatal, xenogenic, cardiac cells.

Methods. The experiment was carried out on outbred male rats. Adrenaline damage to the heart was simulated by a single subcutaneous injection of 0.1% adrenaline solution at a dose of 0.5 mg per 100 g of body weight. The first group (37 rats) was injected subcutaneously with adrenaline, the second group (41 rats) – adrenaline and isolated heart cells of a newborn rabbit at a dose of 500 000. The third group included 6 healthy rats.

Results. It was found that a spike in the level of malondialdehyde and, accordingly, the activation of free  radical processes in adrenaline damage to the heart, occurred during the restructuring of the energy of the  heart cell from intense glycolysis to the restoration of active mitochondrial ATP synthesis (which corresponded to the end of the depletion of lactate and creatine phosphate, and the beginning of the restoration of their content in heart cells).  The dynamics of MDA sensitively reflected both the activity and the inhibition of oxidative processes in mitochondria, which manifested itself, respectively, both in the form of peaks and in a low level of MDA and corresponded to the interpretation of the dynamics of lactate and creatine phosphate.
In the cardiac tissue of rats with transplantation of neonatal, xenogenic cardiac cells, the accumulation of lactate in the early stages of the experiment decreased, the subsequent depletion of the cellular reserves of creatine phosphate and lactate was inhibited, the period of inhibition (non-increase) in MDA was shorter, the subsequent increase in MDA was more moderate than in control animals.

Conclusion. The data obtained indicate that neonatal cardiac cells are able to limit the disturbance of aerobic and of anaerobic processes in the heart tissue and promote the restoration of mitochondrial energy processes.  Moreover, they contribute to a more efficient restoration of mitochondrial ATP synthesis, accompanied by a smaller burst of damaging free radical processes.

1. Kalinina NI, Sysoeva VYu, Rubina KA, Parfenova EV, Tkachuk VA. Mesenchymal stem cells in the processes of tissue growth and repair. Acta Naturae. 2011; (4): 32-39. (In Russ.)

2. Golpanian S, Wolf A, Hatzistergos KE, Hare JM. Rebuilding the damaged heart: Mesenchymal stem cells, cell-based therapy, and engineered heart tissue. Physiol Rev. 2016; 96(3): 1127-1168. doi: 10.1152/physrev.00019.2015

3. Ju C, Shen Y, Ma G, Liu Y, Cai J, Kim IM, et al. Transplantation of cardiac mesenchymal stem cell-derived exosomes promotes repair in ischemic myocardium. J Cardiovasc Transl Res. 2018; 11(5): 420-428. doi: 10.1007/s12265-018-9822-0

4. Tang J, Cui X, Caranasos TG, Hensley MT, Vandergriff AC, Hartanto Y, et al. Heart repair using nanogel-encapsulated human cardiac stem cells in mice and pigs with myocardial infarction. ACS Nano. 2017; 11(10): 9738-9749. doi: 10.1021/acsnano.7b01008

5. Men’shchikova EB, Lankin VZ, Zenkov NK, Bondar’ IA, Krugovykh NF, Trufakin VA. Oxidative stress. Prooxidants and antioxidants. Moscow: Slovo; 2006. (In Russ.)

6. Orlic D, Hill JM, Arai АE. Stem cells for myocardial regeneration. Circ Res. 2002; 91(12): 1092-1102.

7. Parrotta EI, Scalise S, Scaramuzzino L, Cuda G. Stem cells: the game changers of human cardiac disease modelling and regenerative medicine. Int J Mol Sci. 2019; 20(22): 5760. doi: 10.3390/ijms20225760

8. Torella D, Ellison GM, Méndez-Ferrer S, Ibanez B, NadalGinard B. Resident human cardiac stem cells: Role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med. 2006; 3(1): 8-13. doi: 10.1038/ncpcardio0409

9. Wang Z, Dong N, Niu Y, Zhang Z, Zhang C, Liu V, et al. Transplantation of human villous trophoblasts preserves cardiac function in mice with acute myocardial infarction. J Cell Mol Med. 2017; 21(10): 2432-2440. doi: 10.1111/jcmm.13165

10. Chen KH, Cheng CH, Wallace CG, Yuen CM, Kao GS, Chen YL, et al. Intravenous administration of xenogenic adiposederived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke. Oncotarget. 2016; 7(46): 74537-74556. doi: 10.18632/oncotarget.12902

11. Subramani B, Subbannagounder S, Ramanathanpullai C, Palanivel S, Ramasamy R. Impaired redox environment modulates cardiogenic and ion-channel gene expression in cardiac-resident and non-resident mesenchymal stem cells. Exp Biol Med (Maywood). 2017; 242(6): 645-656. doi: 10.1177/1535370216688568

12. Bogorodskaya SL, Klinova SN, Golubev SS, Zaritskaya LV, Batunova EV, Ezhikeeva SD, et al. ATPase activity and ion level in cardiac tissue during experimental adrenaline injury and cell transplantation. Sibirskiy meditsinskiy zhurnal (Irkutsk). 2010; 97(6): 158-160. (In Russ.)

13. Bogorodskaya SL, Klinova SN, Mikashova MB, Golubev SS, Pivovarov YuI, Kuril’skaya TE, et al. Transplantation of xenogenic cardiomyocytes in experimental adrenaline myocardial injury: Enzymatic activity and morphological parameters. Kletochnye tekhnologii v biologii i meditsine. 2008; (3): 132-135. (In Russ.)

14. Runovich AA, Baduev BK, Bogorodskaya SL, Borovskiy GB, Sergeeva AS. The influence of xenogenic neonatal cardiomyocytes on the induction of heat shock proteins in catecholamine myocardial injury in experiment. Sovremennye naukoemkie tekhnologii. 2004; (3): 150-151. (In Russ.)

15. Bogorodskaya SL, Kuril’skaya TE, Runovich AA. Dynamics of lipid metabolism indices in cardiac tissue under conditions of experimental adrenaline damage and cell therapy. Sibirskiy meditsinskiy zhurnal (Irkutsk). 2018; (3): 43-47. (In Russ.)

16. Bogorodskaya SL, Klinova SN, Gutnik IN, Pivovarov YuI, Kuril’skaya TE, Runovich AA. Evaluation of myocardial energy parameters in modeling adrenaline damage in conditions of cell transplantation. Kletochnye tekhnologii v biologii i meditsine. 2009; (3): 154-156. (In Russ.)

17. Severin SE, Solov’eva GA. Biochemistry workshop: textbook. manual. Moscow: MGU Publishing; 1989. (In Russ.)