Indicators of Bioelectrical Activity of the Rat Heart After Prenatal Hypoxia and Pharmacological Correction




Background. Posthypoxic cardiopathy is one of the risk factors for the development of cardiovascular pathology (rhythm disturbances, vascular dystonia, etc.) in subsequent age periods and requires the development of treatment approaches.

Objective. to evaluate the cardioprotective effect of modulators of the NO system by the effect on the ECG of rats after intrauterine hypoxia.

Methods. Modeling of prenatal hypoxia (PH) by daily intraperitoneal administration of sodium nitrite solution to pregnant female white rats weighing 220–240 g, aged 4.5 months, from the 16th to the 21st day of pregnancy at a dose of 50 mg/kg. The offspring were administered daily from the 1st to the 30th day of life – tiazotic acid (morpholinium 3-methyl-1,2,4-triazolyl-5-thioacetic acid), 50 mg/kg, angiolin ([S]-2,6-diaminohexane acid 3-methyl-1,2,4-triazolyl-5-thioacecate), 50 mg/kg, L-arginine, 200 mg/kg, meldonium (2-(2-carboxyethyl)-1,1,1-trimethylhydrazinium), 100 mg/kg. Аnd then after 2 months of life, an ECG was recorded using the ECG TUNNEL system (without anesthesia).

Results. Postponed PG leads to a decrease in heart rate and significant dominance of parasympathetic innervation in regulation of electrical activity of the heart, which can be caused by sinus blockade and may be a reflection of parasympathetic regulation of the heart instead of sympathetic control of electrical activity in the norm. The effectiveness of drugs can be presented in descending order: angiolin > tiazotic acid > meldonium. Angiolin proved to be more effective than tiazotic acidin normalizing the electrical activity of the heart and restoring the neurogenic regulation of the automatism of the function of the sinus node.

Сonclusions. The prospects of further study of modulators of the NO system with different mechanisms of action as means of cardioprotection of posthypoxic disorders of the cardiovascular system in newborns are experimentally substantiated.


Giussani DA, Camm EJ, Niu Y, Richter HG, Blanco CE, Gottschalk R, et al. Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS ONE 2012;7(2):e31017. DOI: 10.1371/journal.pone.0031017

Lamberto F, Peral-Sanchez I, Muenthaisong S, Zana M, Willaime-Morawek S, Dinnyés A. Environmental alterations during embryonic development: Studying the impact of stressors on pluripotent stem cell-derived cardiomyocytes. Genes (Basel) 2021;12(10):1564. DOI: 10.3390/genes12101564

Prabhakar NR, Semenza GL. Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiol Rev. 2012 Jul;92(3):967-1003. DOI: 10.1152/physrev.00030.2011

Hutter D, Kingdom J, Jaeggi E. Causes and mechanisms of intrauterine hypoxia and its impact on the fetal cardiovascular system: a review. Int J Pediatr. 2010;2010:401323. DOI: 10.1155/2010/401323

Little PJ, Askew CD, Xu S, Kamato D. Endothelial dysfunction and cardiovascular disease: History and analysis of the clinical utility of the relationship. Biomedicines. 2021 Jun;9(6):699. DOI: 10.3390/biomedicines9060699

Belenichev IF, Abramov AV, Puzyrenko A, Bukhtiyarova NV, Gorchakova NO, Bak PG. Molecular mechanisms of myocardial damage in the hypertensive rats and hypertensive rats with metabolic disorders (diabetes mellitus, atherosclerosis). Res Results Pharmacol. 2022;8(4):25-33. DOI: 10.3897/rrpharmacology.8.78534

Belenichev I, Gorbachova S, Pavlov S, Bukhtiyarova N, Puzyrenko A, Brek O. Neurochemical status of nitric oxide in the settings of the norm, ishemic event of central nervous system, and pharmacological intervention. Georgian Med News. 2021 Jun;(315):169-76.

Palmer RM, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun;333(6174):664-6. DOI: 10.1038/333664a0

Li G, Bae S, Zhang L. Effect of prenatal hypoxia on heat stress-mediated cardioprotection in adult rat heart. Am J Physiol Heart Circ Physiol 2004;286(5):H1712-9. DOI: 10.1152/ajpheart.00898.2003

Sjakstea N, Kalvinshb I. Meldonium: An antiischemic drug with multiple indications. Pharmacologyonline. 2006;1:1-18.

Chen X, Zhang L, Wang C. Prenatal hypoxia-induced epigenomic and transcriptomic reprogramming in rat fetal and adult offspring hearts. Sci Data. 2019 Oct 29;6(1):238. DOI: 10.1038/s41597-019-0253-9

Sutovska H, Babarikova K, Zeman M, Molcan L. Prenatal hypoxia affects foetal cardiovascular regulatory mechanisms in a sex- and circadian-dependent manner: A review. Int J Mol Sci. 2022 Mar 7;23(5):2885. DOI: 10.3390/ijms23052885

Belenichev IF, Mazur IA, Abramov AV, Kucherenko LI, Bukhtiyarova NV, Egorov AA, et al. The endothelium-protective effect of 3-methyl-1,2,4-triazolyl-5-thioacetate (S)-2,6-diaminohexanic acid (lysinium): Effects on the expression of vascular endothelial growth factor (VEGF) and the characteristics of the endotheliocytes of the cerebral vessels of animals with cerebral ischemia. Neurochem J. 2013;7:296-302. DOI: 10.1134/S181971241304003X

Bednov A, Espinoza J, Betancourt A, Vedernikov Y, Belfort M, Yallampalli C. L-arginine prevents hypoxia-induced vasoconstriction in dual-perfused human placental cotyledons. Placenta. 2015;36(11):1254-9. DOI: 10.1016/j.placenta.2015.08.012

Belenichev IF, Vіzіr VA, Mamchur VYo, Kuriata OV. Place of tiariazoline in the gallery of modern metabolitotropic medicines. Zaporozhye Med J. 2019;1(112):118-28. DOI: 10.14739/2310-1210.2019.1.155856

Kumar P, Srivastava P, Gupta A, Bajpai M. Noninvasive recording of electrocardiogram in conscious rat: A new device. Indian J Pharmacol. 2017 Jan-Feb;49(1):116-8. DOI: 10.4103/0253-7613.201031

Pereira-Junior PP, Marocolo M, Rodrigues FP, Medei E, Nascimento JH. Noninvasive method for electrocardiogram recording in conscious rats: Feasibility for heart rate variability analysis. An Acad Bras Cienc. 2010;82(2):431-7. DOI: 10.1590/s0001-37652010000200019

Richardson BS, Bocking AD. Metabolic and circulatory adaptations to chronic hypoxia in the fetus. Comp Biochem Physiol A Mol Integ Physiol. 1998;119(3):717-23. DOI: 10.1016/S1095-6433(98)01010-1

Tomat AL, Juriol LV, Gobetto MN, Veiras LC, Mendes Garrido Abregú F, Zilberman J, et al. Morphological and functional effects on cardiac tissue induced by moderate zinc deficiency during prenatal and postnatal life in male and female rats. Am J Physiol Heart Circ Physiol. 2013 Dec 1;305(11):H1574-83. DOI: 10.1152/ajpheart.00578.2013

Sesti C, Simkhovich BZ, Kalvinsh I, Kloner RA. Mildronate, a novel fatty acid oxidation inhibitor and antianginal agent, reduces myocardial infarct size without affecting hemodynamics. J Cardiovasc Pharmacol. 2006 Mar;47(3):493-9. DOI: 10.1097/01.fjc.0000211732.76668.d2

Izhar U, Schwalb H, Borman JB, Merin G. Cardioprotective effect of L-arginine in myocardial ischemia and reperfusion in an isolated working rat heart model. J Cardiovasc Surg (Torino). 1998;39(3):321-9.

Dakshinamurti S, Abman SH, Cheung PY, Lakshminrusimha S, McNamara P, Milsom WK. Hypoxic respiratory failure in the newborn: From origins to clinical management. 1st ed. CRC Press; 2021. DOI: 10.1201/9780367494018

Burlaka BS, Belenichev IF, Ryzhenko OI, Ryzhenko VP, Aliyeva OG, Makyeyeva LV, et al. The effect of intranasal administration of an IL-1b antagonist (RAIL) on the state of the nitroxydergic system of the brain during modeling of acute cerebrovascular accident. Pharmacia. 2021;68(3):665-70. DOI: 10.3897/pharmacia.68.e71243




How to Cite

Popazova O, Belenichev I, Abramov A, Bukhtiyarova N, Chereshniuk I, Skoryna D. Indicators of Bioelectrical Activity of the Rat Heart After Prenatal Hypoxia and Pharmacological Correction. Innov Biosyst Bioeng [Internet]. 2023Mar.2 [cited 2023Mar.30];6(3-4):148-60. Available from: