scholarly journals Modulation of Perturbed Cardiac Metabolism in Rats Under High-Altitude Hypoxia by Combination Treatment With L-carnitine and Trimetazidine

2021 ◽  
Vol 12 ◽  
Author(s):  
Hebing Xie ◽  
Gang Xu ◽  
Jiye Aa ◽  
Shuhua Gu ◽  
Yuqi Gao
Keyword(s):  
Fatty Acids ◽  
High Altitude ◽  
Cardiac Tissue ◽  
Aerobic Glycolysis ◽  
Tca Cycle ◽  
Cardiac Metabolism ◽  
Altitude Hypoxia ◽  
Altitude Exposure ◽  
High Altitude Hypoxia ◽  
Branched Chain

High-altitude hypoxia has long been recognized as a vital etiology for high-altitude illnesses. High-altitude myocardial injury (HAMI) usually occurs in people who suffered from high-altitude exposure. To date, the molecular mechanism of HAMI remains elusive, which seriously hinders the prevention and treatment of HAMI. L-carnitine and trimetazidine are classic cardiovascular protective medicines. In this study, we used the metabolomic method, based on GC/MS, to explore the changes in metabolites in rats exposed to high-altitude hypoxia and then illustrate the metabolic pathways associated with the modulatory effect of L-carnitine combined with trimetazidine on rats with high-altitude exposure. The results showed that metabolites in the myocardium in rats under high-altitude hypoxia were markedly changed, such as branched-chain amino acids (BCAA, leucine, isoleucine, and valine), taurine, succinic acid, fumaric acid, lactic acid, pyruvic acid, 3-hydroxybutyrate, and docosahexaenoic acid (DHA), while L-carnitine combined with trimetazidine modulated and improved the abnormal changes in energy substances caused by high-altitude hypoxia. L-carnitine mainly promoted the metabolism of fatty acids, while trimetazidine enhanced the glycolysis process. The combined administration of the two components not only increased the metabolism of fatty acids but also promoted aerobic glycolysis. Meanwhile, it contributed to the decrease in the elevation in some of the intermediates of the tricarboxylic acid (TCA) cycle, decrease in the production of 3-hydroxybutyric acid, and relief of the abnormal energy metabolism process in organisms and the cardiac tissue. Our analysis delineates the landscape of the metabolites in the myocardial tissue of rats that were exposed to high altitude. Moreover, L-carnitine combined with trimetazidine can relieve the HAMI through modulated and improved abnormal changes in energy substances caused by high-altitude hypoxia.

Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart

2002 ◽  
Vol 282 (4) ◽  
pp. H1452-H1460 ◽  
Author(s):  
C. Chouabe ◽  
J. Amsellem ◽  
L. Espinosa ◽  
P. Ribaux ◽  
S. Blaineau ◽  
...  
Keyword(s):  
Right Ventricular ◽  
High Altitude ◽  
Current Density ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Heart Weight ◽  
Altitude Hypoxia ◽  
Altitude Exposure ◽  
High Altitude Hypoxia ◽  
The Right

Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities.

scholarly journals Integrative plasma proteomic and microRNA analysis of Jersey cattle in response to high-altitude hypoxia

2019 ◽  
Vol 102 (5) ◽  
pp. 4606-4618 ◽  
Author(s):  
Zhiwei Kong ◽  
Chuanshe Zhou ◽  
Bin Li ◽  
Jinzhen Jiao ◽  
Liang Chen ◽  
...  
Keyword(s):  
High Altitude ◽  
Altitude Hypoxia ◽  
Jersey Cattle ◽  
High Altitude Hypoxia

Seeding drug discovery: telomeric tankyrase as a pharmacological target for the pathophysiology of high-altitude hypoxia

2021 ◽  
Author(s):  
Manjula Miglani ◽  
Qadar Pasha ◽  
Archana Gupta ◽  
Anjali Priyadarshini ◽  
Ramendra Pati Pandey ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Altitude ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Pharmacological Target

Role of Rho kinases in PKG-mediated relaxation of pulmonary arteries of fetal lambs exposed to chronic high altitude hypoxia

2007 ◽  
Vol 292 (3) ◽  
pp. L678-L684 ◽  
Author(s):  
Yuansheng Gao ◽  
Ada D. Portugal ◽  
Sewite Negash ◽  
Weilin Zhou ◽  
Lawrence D. Longo ◽  
...  
Keyword(s):  
High Altitude ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Regulatory Subunit ◽  
Fourth Generation ◽  
Minor Effect ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia ◽  
Rock Activity

An increase in Rho kinase (ROCK) activity is implicated in chronic hypoxia-induced pulmonary hypertension. In the present study, we determined the role of ROCKs in cGMP-dependent protein kinase (PKG)-mediated pulmonary vasodilation of fetal lambs exposed to chronic hypoxia. Fourth generation pulmonary arteries were isolated from near-term fetuses (∼140 days of gestation) delivered from ewes exposed to chronic high altitude hypoxia for ∼110 days and from control ewes. In vessels constricted to endothelin-1, 8-bromoguanosine-cGMP (8-Br-cGMP) caused a smaller relaxation in chronically hypoxic (CH) vessels compared with controls. Rp-8-Br-PET-cGMPS, a PKG inhibitor, attenuated relaxation to 8-Br-cGMP in control vessels to a greater extent than in CH vessels. Y-27632, a ROCK inhibitor, significantly potentiated 8-Br-cGMP-induced relaxation of CH vessels and had only a minor effect in control vessels. The expression of PKG was increased but was not accompanied with an increase in the activity of the enzyme in CH vessels. The expression of type II ROCK and activity of ROCKs were increased in CH vessels. The phosphorylation of threonine (Thr)696 and Thr850 of the regulatory subunit MYPT1 of myosin light chain phosphatase was inhibited by 8-Br-cGMP to a lesser extent in CH vessels than in controls. The difference was eliminated by Y-27632. These results suggest that chronic hypoxia in utero attenuates PKG-mediated relaxation in pulmonary arteries, partly due to inhibition of PKG activity and partly due to enhanced ROCK activity. Increased ROCK activity may inhibit PKG action through increased phosphorylation of MYPT1 at Thr696 and Thr850.

scholarly journals High-altitude hypoxia and preeclampsia

10.2741/2286 ◽  
2007 ◽  
Vol 12 (8-12) ◽  
pp. 2967 ◽  
Author(s):  
Stacy Zamudio
Keyword(s):  
High Altitude ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia

scholarly journals High-altitude hypoxia and periodic breathing during sleep: gender-related differences

2013 ◽  
Vol 22 (3) ◽  
pp. 322-330 ◽  
Author(s):  
Carolina Lombardi ◽  
Paolo Meriggi ◽  
Piergiuseppe Agostoni ◽  
Andrea Faini ◽  
Grzegorz Bilo ◽  
...  
Keyword(s):  
High Altitude ◽  
Periodic Breathing ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia

Modulation of urinary peptidome in humans exposed to high altitude hypoxia

2012 ◽  
Vol 8 (4) ◽  
pp. 959-966 ◽  
Author(s):  
Veronica Mainini ◽  
Erica Gianazza ◽  
Clizia Chinello ◽  
Grzegorz Bilo ◽  
Miriam Revera ◽  
...  
Keyword(s):  
High Altitude ◽  
Altitude Hypoxia ◽  
High Altitude Hypoxia
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