Experimental Hypobaric Hypoxia Research Articles

ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕ ВЛИЯНИЯ ПОЛИФЕНОЛОВ ВИНОГРАДА НА МИОКАРД НА ФОНЕ ХОЛОДОВОЙ ГИПОБАРИИ

The aim of this research was to reveal the cardioprotective properties of food concentrate polyphenols grapes during experimental hypobaric hypoxia. The study was conducted on mature male Wistar rats (n = 25) aged 1-1.5 months divided into three experimental groups. In the I (control) group 0,9% NaCl solution was administered intragastrically to intact animals. Hypobaric cold hypoxia was modeled for rats of groups II and III once a day for 30 days. Animals III series 30 minutes before hypoxia intragastrically through a tube were injected an aqueous solution of «Fenokor» containing grape polyphenols. In rats of II group without correction there was an unreliable decrease in heart mass by 8.71%, a decrease in the diameter of cardiomyocytes by 20.3% was accompanied by a decrease in their concentration in 1 mg of myocardium. Accelerated compensatory physiological growth of cardiomyocytes in animals of group III caused a slight decrease in the diameter of a number of cardiomyocytes by 3.75% with almost no decrease in their concentration, that mostly preserved of the total number of cardiomyocytes in the heart by the end of the experiment. Hypertrophic growth of the number of cardiomyocytes is caused by the end of the experiment statistically nonsignificant compensatory increase in the mass of the heart. Thus, the main morphological signs of hypoxic myocardial damage in young rats were presented by the phenomena of mixed dystrophy, edema and destruction of contractile cardiomyocytes, lysis of myofibrils and mitochondrial cristae, contracture changes. The administration of «Fenokor» demonstarated its cytoprotective properties, contributed to the preservation of myocardial structure of rats exposed to hypobaric hypoxia.

Myocardial interstitial matrix as novel target for succinic acid treatment strategies during experimental hypobaric hypoxia

Objective — Quantitative morphological studies of myocardial cellular elements. Aim of research is to study myocardial interstitial matrix with and without succinic acid treatment in the rats exposed to intermittent hypobaric hypoxia. Material and Methods — The study was conducted on 26 adult males of Wistar rats weighing 220-310 g, divided into 3 groups. The first control group consisted of 6 intact animals. The second group included 10 rats which were exposed to hypobaric hypoxia without medication for 30 days. Third group was composed of 10 rats, which were medicated by succinic acid solution which was injected intraperitoneally once a day at the rate of 0.5 ml/100 g of animal body weight 15 minutes before hypoxic exposure for 30 days. Results — In the second group almost the entire stroma was consisting of the thickened collagen fibers and proliferating cells of the connective tissue. Their total number increased relatively to the control by 31% initiating the processes of collagenases. An increase in the number of myofibroblasts which was observed in the hypoxic rat heart in the second group followed by high MPP-9 expression. Hypoxic effects in the third group were not significantly different from control according to the observed changes in the stroma. In rats of the third group the capillary diameter exceeded the indicator of the second group, but was significantly lower than the control indicator. Accordingly, compared with the series without correction, the cross-sectional area of the capillaries was increased – 28.44±0.14 μm2 against 24.53±0.20 μm2. The total cross-sectional area of the capillaries is 0.77±0.10 x103 μm2. The relative surface area of the vascular area was lower than the control by 21.8%. Conclusion ― Fibrosis in the myocardium inevitably leads to increased myocardial stiffness, resulting in systolic and diastolic dysfunction, neurohormonal activation and, ultimately, heart failure caused by hypobaric hypoxia. Reduced oxygen delivery by microvascular damage, increased perivascular fibrosis may contribute to contractile failure. Succinic acid combined with inosine acts as a high-energy phosphate reserve, to maintain adenosine triphosphate at levels sufficient to support contractile function.

Investigation of markers for myocardial remodeling during experimental hypobaric hypoxia in the correction with cytoflavin

To reveal the peculiarities of changes in the markers of myocardial remodeling in experimental hypobaric hypoxia. The investigation was conducted on 26 mature male Wistar rats weighing 220-310 g, which were divided into 3 groups: 1) 6 intact animals; 2) 10 rats that were exposed to 30-day simulated hypobaric hypoxia without correction; 3) 10 rats that were given once-daily intraperitoneal injections of cytoflavin solution at a rate of 0.5 ml/100 g of body weight for 30 days before immersion in a hypobaric chamber. The early stages of myocardial remodeling in hypobaric hypoxia were found to be characterized by structural re-systematization of the components of the normal ventricular wall, which was manifested by cardiomyocyte hypertrophy and ischemia; circulatory disorders; fibroblast proliferation that dramatically enhances the extracellular expression of protein matrix, which can lead to the formation of fibrous tissue and irreversible myocardial dysfunction. Elevated matrix metalloproteinase levels are evidence for collagen degradation and cardiac remodeling. In the authors' opinion, the cyto- and angioprotective effects of cytoflavin in rats treated with the latter used in combination therapy are associated with the composition of the drug, the active components of which have mutually potentiating effects, are inducers of the major metabolic pathways in the cells and are also activators of key energy-generating processes. Identification of the molecular mechanisms of myocardial remodeling is of great practical importance. This enables remodeling markers to be considered as a potential therapeutic target in the treatment of hypoxia-induced myocardial injury.

Adaptogenic effects of dihydroquercetin-chitosan composition during modeling of acute hypoxia.

The course of preventive oral treatment with a dihydroquercetin-chitosan composition produced a strong antihypoxic effect under conditions of experimental hypobaric hypoxia (arbitrary altitude 12,000m). The lactate/pyruvate ratio in composition-receiving rats was much lower than in hypoxic animals (by 83%), but higher than in intact specimens (by 29%). The composition of chitosan and dihydroquercetin also possessed a strong antioxidant activity.

Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals.

1. Carnosine, anserine, and homocarnosine are endogenous dipeptides concentrated in brain and muscle whose biological functions remain in doubt. 2. We have tested the hypothesis that these compounds function as endogenous protective substances against molecular and cellular damage from free radicals, using two isolated enzyme systems and two models of ischemic brain injury. Carnosine and homocarnosine are both effective in activating brain Na, K-ATPase measured under optimal conditions and in reducing the loss of its activity caused by incubation with hydrogen peroxide. 3. In contrast, all three endogenous dipeptides cause a reduction in the activity of brain tyrosine hydroxylase, an enzyme activated by free radicals. In hippocampal brain slices subjected to ischemia, carnosine increased the time to loss of excitability. 4. In in vivo experiments on rats under experimental hypobaric hypoxia, carnosine increased the time to loss of ability to stand and breath and decreased the time to recovery. 5. These actions are explicable by effects of carnosine and related compounds which neutralize free radicals, particularly hydroxyl radicals. In all experiments the effective concentration of carnosine was comparable to or lower than those found in brain. These observations provide further support for the conclusion that protection against free radical damage is a major role of carnosine, anserine, and homocarnosine.