Pathogenic Factors for Cardiotoxicity of Isoniazid when Used Long
DOI: 10.22138/2500-0918-2018-15-1-60-70
N.S. Gritsenko, V.T. Dolgikh, O.V. Korpacheva, A.N. Zolotov, S.V. Pal'yanov
Omsk State Medical University, Omsk, Russian Federation
Abstract. Objective. To identify the leading pathogenic factors for heart failure with long-term administration of isoniazid. Materials and methods. Experiments were conducted on 140 white outbred male rats weighing 249±10,0 g. Animals were divided into four groups: I group — control animals, which were not injected with isoniazid; II group — animals with enteral isoniazid administration at a dose of 15 mg/kg body weight daily for two months; III group — animals, which were given isoniazid at a dose of 30mg/kg and IV group — animals, which were given isoniazid at a dose of 75 mg/kg for two months as well. The V group included the animals; whos isolated hearts were perfused with Krebs-Henseleit solution containing isoniazid at a dose of 1.65 g/l. At the first stage, the following parameters, such as ECG, rheographic systemic hemodynamic values and endogenous toxemia were registered in a whole body. At the second stage, simulating the isolated isovolumically contracted heart the pathogens, causing deficiencies in contractility and lusitropy of the left ventricle myocardium, efficiency of ionic pumps of the sarcolemma and sarcoplasmic reticulum using the loading with rhythm of high frequency contractions, adrenaline and hypoxia were examined. At the same time, the efficacy of glucose consuming by the isolated hearts and the release of pyruvate and enzymes into the coronary duct were investigated. Results. During the study it has been determined that the long-term daily enteral administration of isoniazid to white outbred male rats leads to the development of circulatory insufficiency, which is most pronounced in animals receiving an injection at a dose of 75 mg/kg, which is manifested by the low cardiac output syndrome associated with an increase in peripheral vascular resistance, and also induces a decrease in the voltage of the R wave and a change in the terminal part of the ECG ventricular complex, specific for myocardial hypoxia. It has been detected that the suppression of power and speed parameters of myocardial contractility, a decrease in its functional reserves, which is due to coronary spasm, bio-energetics disorder, inhibition of Са2+-pump of the sarcoplasmic reticulum, destruction of cardiomyocyte membranes, increased myocardial sensitivity to exogenous catecholamines all stand at the basis of low cardiac output with continuous intrajejunal administration of isoniazid. Isoniazid induces a dose-dependent intensification of free-radical oxidation processes associated with a change in the ratio of pro- and antioxidant activity and the development of endotoxemia as a pathogenetic factor in cardiodepression. Conclusion. Mechanisms of cardiodepression and hemodynamic disorders of systemic isoniazid hemodynamics have been revealed, and it has been noted that Isoniazid’s metabolites and other metabolic products have a maximal cardiotoxic effect than isoniazid itself.
Keywords: isoniazid, circulatory insufficiency, functional and metabolic disorders of the heart
Received 22.01.2018
For citation:
N.S. Gritsenko, V.T. Dolgikh, O.V. Korpacheva, A.N. Zolotov, S.V. Pal,yanov. Pathogenic Factors for Cardiotoxicity of Isoniazid when Used Long. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2018, Vol. 15, no. 1, pp. 60–70. DOI: 10.22138/2500-0918-2018-15-1-60-70 (In Russ)
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Authors
Nikolay S. Gritsenko
M.D., Cand. Sci. (Med.), Assistant of the Pathophysiology, Clinical Pathophysiology Department
greets@mail.ru
Vladimir T. Dolgikh
M.D., Dr. Sci. (Med.), Professor, the Honoured Scientist of the Russian Federation, the Head of Pathophysiology, Clinical Pathophysiology Department
prof_dolgih@mail.ru
Olga V. Korpacheva
M.D., Dr. Sci. (Med.), Professor of the Pathophysiology, Clinical Pathophysiology Department
olgkor@mail.ru
Aleksandr N. Zolotov
M. D., Cand. Sci. (Med.), Senior Lecturer of the Pathophysiology, Clinical Pathophysiology Department
azolotov@mail.ru
Sergey V. Pal,yanov
M. D., Cand. Sci. (Med.), Associate Professor of the Pathophysiology, Clinical Pathophysiology Department
vetadent@bk.ru
Omsk State Medical University
12, ul. Lenina, Omsk, 644099, Russian Federation