POSITIVE EFFECT OF ENTEROSORPTION IN DOXORUBICIN-INDUCED CARDIOHEMODYNAMICS ALTERATION
Background. Anthracycline antibiotics are one of the most effective anti-cancer drugs, but their cardiotoxicity what limits its therapeutic use.
Objective. To analyze the efficiency of enterosorption in doxorubicin-induced cardiohemodynamics violation.
Methods. Subchronic doxorubicin toxicity was modeled by injecting the anthracycline antibiotic intraperitoneally at a dose of 5 mg/kg once a week for 4 weeks, in total 20 mg/kg. Male Wistar rats were randomly distributed into 3 groups: control; DOX-group and DOX + enterosorbent C2 rats (γ = 0.18 g/cm3, BET area 2162 m2/g). Cardiohemodynamics was studied by the Millar Instruments, heart morphometry – by Avtandilov’s method.
Results. Mortality rate in DOX-group was 25%. Ejection fraction and Stroke work indices were lower compared to the control group, preload adjusted maximal power decreased by 57.6%, minimum volume and end-systolic volume increased by 76,2 and 67.5% respectively. End-systolic stiffness of left ventricle (Emax) as well as arterial elastance (Ea) and end-systolic pressure had tended to decrease. Indices of left ventricle (LV) volume at systole increased: V@dPdtmax – by 73.3%, V@dPdtmin – by 81.9%. End-diastolic volume increased by 54.6%. As for the dPdtmin, and Tau constant we observed the slight tendency to its decline. Endocardial surface of LV increased by 42.7%, Planimetric Index – by 40.4% compared to the control group of rats.
In DOX+C2 group mortality rate was 18.75%. We observed the strong tendency to normalization of the main indices compared to the DOX group and shrinking of the LV. We want to underline the positive trends especially in Ejection Fraction (from 39.62±10.50% to 46.23±11.46%) and Stroke Work (from 6406.50±3345.83 to 10363.14±7329.55 mmHg×uL) as important indicators of the effectiveness of cardiac pump function.
Conclusions. Enterosorption demonstrated positive impact on the doxorubicin-induced violated cardiohemodynamics and decreased the mortality rate. It is a ground for further investigations.
Jain D, Russell RR, Schwartz RG, Panjrath GS, Aronow W. Cardiac Complications of Cancer Therapy: Pathophysiology, Identification, Prevention, Treatment, and Future Directions. Curr Cardiol Rep 2017;19:36.
Linnik O, Drevytska TI, Tarasova K, Portnichenko G, Dosenko VE, Mankovskaya IN. Doxorubicin-Induced Disturbances of Cardiomyocyte Contractile Activity. Int J Physiol Pathophysiol 2018;9:9–16.
Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology 2010;115: 155–62.
Curigliano G, Cardinale D, Dent S, Criscitiello C, Aseyev O, Lenihan D, et al. Cardiotoxicity of Anticancer Treatments : Epidemiology , Detection , and Management. CA Cancer J Clin 2016;66:309–25.
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin. Cancer 2003;97:2869–79.
Mitry MA, Edwards JG. Doxorubicin induced heart failure: Phenotype and molecular mechanisms. Int J Cardiol Hear Vasc 2016;10:17–24.
Shaul P, Frenkel M, Goldstein EB, Mittelman L, Grunwald A, Ebenstein Y, et al. The structure of anthracycline derivatives determines their subcellular localization and cytotoxic activity. ACS Med Chem Lett 2013;4:323–8.
Volkova M, Russell R, III. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev 2011;7:214–20.
Shevchuk OO, Posokhova EA, Sakhno LA, Nikolaev VG. Theoretical ground for adsorptive therapy of anthracyclines cardiotoxicity. Exp Oncol 2012;34:314–22.
Trachtenberg BH, Landy DC, Franco VI, Henkel JM, Pearson EJ, Miller TL, et al. Anthracycline-Associated Cardiotoxicity in Survivors of Childhood Cancer. Pediatr Cardiol 2011;32:342–53.
Nikolaev VG. Sorption Therapy with the Use of Activated Carbons: Effects on Regeneration of Organs and Tissues. Hemoperfusion, Plasmaperfusion Other Clin. Uses Gen. Biospecific, Immuno Leucoc. Adsorbents, 2017, p. 221–43.
Shevchuk OO, Posokhova KA, Sidorenko AS, Bardakhivska KI, Maslenny VM, Yushko LA, et al. The influence of enterosorption on some haematological and biochemical indices of the normal rats after single injection of melphalan. Exp Oncol 2014;36:94–100.
Shevchuk OO, Posokhova KA, Todor IN, Lukianova NY, Nikolaev VG, Chekhun VF. Prevention of myelosuppression by combined treatment with enterosorbent and granulocyte colony-stimulating factor. Exp Oncol 2015;37:135–8.
Sakhno LA, Yurchenko OV, Maslenniy VN, Bardakhivskaya KI, Nikolaeva VV, Ivanyuk AA, et al. Enterosorption as a method to decrease the systemic toxicity of cisplatin. Exp Oncol 2013;35:45–52.
Shevchuk OO, Bodnar YY, Bardakhivska KI, Datsko T V., Volska AS, Posokhova KA, et al. Enterosorption combined with granulocyte colony stimulating factor decreases melphalan gonadal toxicity. Exp Oncol 2016;38:172–5.
Shevchuk OO, Snezhkova EA, Bardakhivskaya KI, Nikolaev VG. Adsorptive Treatment of Acute Radiation Sickness: Past Achievements and New Prospects. Hemoperfusion, Plasmaperfusion Other Clin. Uses Gen. Biospecific, Immuno Leucoc. Adsorbents, vol. 4, 2017, p. 245–56.
Stefanov O. Preclinical studies of drugs: methodical instructions. Kyiv: Avicenna; 2001. (In Ukrainian).
Pacher P, Nagayama T, Mukhopadhyay P, Bátkai S, Kass DA. Measurement of cardiac function using pressure-volume conductance catheter technique in mice and rats. Nat Protoc 2008;3:1422–34.
Avtandilov G. Basics of quantitative pathological anatomy. 2nd ed. Moscow: Medicina; 2002. (In Russian).
Esypova IK, Aliskevych VI, Purdiaev YS. Method of urgent differential diagnosis of different types of pulmonary hypertension at section table. Sud Meditsinskaia Ekspert 2003:27–30. (In Russian).
Kostakou PM, Kouris NT, Kostopoulos VS, Damaskos DS, Olympios CD. Cardio-oncology: a new and developing sector of research and therapy in the field of cardiology. Heart Fail Rev 2018:1–10.
Ward E, Sherman RL, Henley SJ, Jemal A, Siegel DA, Feuer EJ, et al. Annual Report to the Nation on the Status of Cancer, 1999–2015, Featuring Cancer in Men and Women ages 20–49. JNCI J Natl Cancer Inst 2019.
Adão R, De Keulenaer G, Leite-Moreira A, Braś-Silva C. Cardiotoxicity associated with cancer therapy: Pathophysiology and prevention strategies. Rev Port Cardiol 2013;32:395–409.
Rodrigues PG, Miranda-Silva D, Costa SM, Barros C, Hamdani N, Moura C, et al. Early myocardial changes induced by doxorubicin in the nonfailing dilated ventricle. Am J Physiol Circ Physiol 2018;316: H459–75.
Lodi M, Priksz D, Fulop GA, Bodi B, Kocsis J, Edes I, et al. Advantages of prophylactic versus conventionally scheduled heart failure therapy in an experimental model of doxorubicin-induced cardiomyopathy. J Transl Med 2019;17:229.
Shevchuk OO, Datsko T V., Posokhova KA, Nikolaev VG. Histological findings at application of newly designed granular carbon enterosorbent under subchronic doxorubicin toxicity in rats. Pharmacol Drug Toxicol 2019;13:119–30.
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