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CNAA / Theses / 2007 / May /

Influence of cardiac glycosides on pro- and antioxidant systems in normal and hyperbaric oxygenation conditions in acute heart failure


Author: Angela Bucaţel
Degree:doctor of medicine
Speciality: 14.00.25 - Pharmacology, Clinical Pharmacology
Year:2007
Scientific adviser: Veaceslav Gonciar
doctor habilitat, professor, State University of Medicine and Pharmacy "Nicolae Testemitanu"
Scientific consultant: Valentin Gudumac
doctor habilitat, professor, State University of Medicine and Pharmacy "Nicolae Testemitanu"
Institution:
Scientific council:

Status

The thesis was presented on the 23 May, 2007
Approved by NCAA on the 14 June, 2007

Abstract

Adobe PDF document0.37 Mb / in romanian

Thesis

CZU 616.12-008.64-036.10+ 615.835+615.711

Adobe PDF document 2.21 Mb / in romanian
137 pages


Keywords

cardiac glycosides, hyperbaric oxygenation, acute heart failure, antioxidant enzymes, lipid peroxidation, heart, brain, lungs, liver, kidneys, strophanthin, digoxin

Summary

Present work is devoted to study interaction between cardiac glycosides (CG) and hyperbaric oxygenation (HBO) at the level of pro- and antioxidant systems in healthy organisms and in acute heart failure (AHF) and to determine possibility of their application in medical practice.

Influence of CG was evaluated in normal condition and in condition of oxygenation under pressure on quantity of lipid peroxidation products (LPP) and on activity of antioxidant system key enzymes in heart, brain, lungs, liver and kidneys in AHF. Digoxin in intact rats stimulates the processes of hydroperoxides lipids (HPL) passage and transportation of amino acids through cell membranes. Antioxidant properties of CG are maintained under HBO. Digoxin used in combination with HBO, oppresses processes of lipid peroxidation (LPO) which is confirmed by decreased quantity of malondialdehyde (MDA). Significant growth of superoxide dismutase (SOD) activity in cardiomyocytes under the influence of Strophanthin points to acceleration of free radicals neutralization, which is also confirmed by increased activity of catalase (CAT), glutathione reductase (GR) and γ-glutamyl transpeptidase (γ-GTP). HBO as well as CG contribute to the significant rise of CAT activity and respectively water and oxygen formation in myocardium.

Stimulation of hydrogen peroxide disintegration and activation of the LPO processes was marked on modeling of the AHF in the myocardium. The consequences of oxidative stress are decreased by CG and its combination with HBO that is confirmed by restoring activity of studied antioxidant enzymes (SOD, CAT, GR).

In comparative evaluation of data received in research project it was established that on administration of Digoxin with HBO in AHF the following indices return to normal: level of initial hydroperoxides lipids (HPL) in kidneys, intermediate HPL in liver, lungs and kidneys, final HPL in heart, liver and lungs; MDA in brain and lungs, SOD activity in heart, liver and kidneys, CAT activity in lungs and kidneys, GR and γ-GTP in heart, lungs, liver and kidneys.

Positive effect of association of Strophanthin and HBO in animals with AHF is showed by normalization of studied antioxidant enzymes activity and decrease of MDA concentration.

Thus, Digoxin, Strophanthin, HBO and their combination in AHF optimize the antioxidant processes in most studied tissues normalizing the activity of a number of enzymes.

It was found that CG administered independently in mono therapy and in combination with HBO contributes to installation of certain types of correlations between activity of pro- and antioxidant systems in vital organs both in normal conditions and in AHF, which is necessary to take in consideration on administration of these drugs with therapeutic goals. Indices of lipid peroxidation and activity of antioxidant enzymes - CAT, SOD, GR, GTP, can be used as significant indicators in prognosis of possibility of pharmacological regulation modifications of homeostasis in concordance with metabolic and functional condition of vital organs.

Received data can be useful for elaboration and selection of methods and possibilities of pharmacological correction of metabolic disturbances that occur in cardiovascular pathology with optimization of medical practices.