Intermittent Hypoxic Preconditioning: A Potential New Powerful Strategy for COVID-19 Rehabilitation

Cai, Ming; Chen, Xuan; Shan, Jieling; Yang, Ruoyu; Guo, Qi; Bi, Xia; Xu, Ping; Shi, Xiangrong; Chu, Lixi; Wang, Liyan

doi:10.3389/fphar.2021.643619

Cited by 12 publications

(6 citation statements)

References 102 publications

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“…Additionally, HIF-1α and β heterodimers promote cell survival, glycolysis, and angiogenesis, and have been reported dysfunctional in people with type 2 diabetes ( 133 ) and cancer ( 134 ) making people with other comorbidities more susceptible to COVID-19 infection. In addition to the obese, and the elderly, and those with comorbidities who are more susceptible, the HIF-1α gene has been reported to be activated in patients who have survived COVID-19 infections ( 135 ). Research has shown that HIF-1α increases the glycolytic metabolic enzyme pyruvate dehydrogenase kinase 1(PDK1) which reduces nutrition in the brain in the long term, affecting neurotransmitters.…”

Section: Populations With Imbalanced Th1/th2 Are Among the Most Susceptible To Become Infected By Covid 19mentioning

confidence: 99%

“…Additionally, activated HIF-1α may activate the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1)-SIRT1/adenosine monophosphate-activated protein kinase (AMPK) pathway and inhibit the endothelin 1(ET-1) pathway. These factors can help reverse the virus induced cardiopulmonary hemodynamic disorder and endothelial dysfunction ( 135 ). A study suggests combined intermittent exercise with hypoxia enhanced glucose disposal and improved insulin resistance post-exercise was beneficial in the treatment of type 2 diabetes ( 138 ).…”

Section: Populations With Imbalanced Th1/th2 Are Among the Most Susceptible To Become Infected By Covid 19mentioning

confidence: 99%

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Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

Supriya

Baker

2021

Front. Immunol.

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The COVID-19 pandemic has led to several pioneering scientific discoveries resulting in no effective solutions with the exception of vaccination. Moderate exercise is a significant non-pharmacological strategy, to reduce the infection-related burden of COVID-19, especially in patients who are obese, elderly, and with additional comorbidities. The imbalance of T helper type 1 (Th1) or T helper type 2 (Th2) cells has been well documented among populations who have suffered as a result of the COVID-19 pandemic, and who are at maximum risk of infection and mortality. Moderate and low intensity exercise can benefit persons at risk from the disease and survivors by favorable modulation in Th1/Th2 ratios. Moreover, in COVID-19 patients, mild to moderate intensity aerobic exercise also increases immune system function but high intensity aerobic exercise may have adverse effects on immune responses. In addition, sustained hypoxia in COVID-19 patients has been reported to cause organ failure and cell death. Hypoxic conditions have also been highlighted to be triggered in COVID-19-susceptible individuals and COVID-19 survivors. This suggests that hypoxia inducible factor (HIF 1α) might be an important focus for researchers investigating effective strategies to minimize the effects of the pandemic. Intermittent hypoxic preconditioning (IHP) is a method of exposing subjects to short bouts of moderate hypoxia interspersed with brief periods of normal oxygen concentrations (recovery). This methodology inhibits the production of pro-inflammatory factors, activates HIF-1α to activate target genes, and subsequently leads to a higher production of red blood cells and hemoglobin. This increases angiogenesis and increases oxygen transport capacity. These factors can help alleviate virus induced cardiopulmonary hemodynamic disorders and endothelial dysfunction. Therefore, during the COVID-19 pandemic we propose that populations should engage in low to moderate exercise individually designed, prescribed and specific, that utilizes IHP including pranayama (yoga), swimming and high-altitude hiking exercise. This would be beneficial in affecting HIF-1α to combat the disease and its severity. Therefore, the promotion of certain exercises should be considered by all sections of the population. However, exercise recommendations and prescription for COVID-19 patients should be structured to match individual levels of capability and adaptability.

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Section: Populations With Imbalanced Th1/th2 Are Among the Most Susceptible To Become Infected By Covid 19mentioning

confidence: 99%

Section: Populations With Imbalanced Th1/th2 Are Among the Most Susceptible To Become Infected By Covid 19mentioning

confidence: 99%

Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

Supriya

Baker

2021

Front. Immunol.

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“…Mild hypoxic preconditioning has become a novel therapeutic target in the treatment of hypertension [ 108 ], myocardial infarction [ 109 ], cerebral ischemia [ 110 ], and depression [ 111 ]. It is even proposed as a potential application for patients with COVID-19 [ 112 ]. Hypoxia induces neuroprotection by reducing energy consumption [ 113 ] and prevents amyloid β accumulation in AD mice [ 114 ].…”

Section: Cellular Mechanisms To Cope With the Energy Crisismentioning

confidence: 99%

Why Is Iron Deficiency/Anemia Linked to Alzheimer’s Disease and Its Comorbidities, and How Is It Prevented?

Fehsel

2023

Biomedicines

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Impaired iron metabolism has been increasingly observed in many diseases, but a deeper, mechanistic understanding of the cellular impact of altered iron metabolism is still lacking. In addition, deficits in neuronal energy metabolism due to reduced glucose import were described for Alzheimer’s disease (AD) and its comorbidities like obesity, depression, cardiovascular disease, and type 2 diabetes mellitus. The aim of this review is to present the molecular link between both observations. Insufficient cellular glucose uptake triggers increased ferritin expression, leading to depletion of the cellular free iron pool and stabilization of the hypoxia-induced factor (HIF) 1α. This transcription factor induces the expression of the glucose transporters (Glut) 1 and 3 and shifts the cellular metabolism towards glycolysis. If this first line of defense is not adequate for sufficient glucose supply, further reduction of the intracellular iron pool affects the enzymes of the mitochondrial electron transport chain and activates the AMP-activated kinase (AMPK). This enzyme triggers the translocation of Glut4 to the plasma membrane as well as the autophagic recycling of cell components in order to mobilize energy resources. Moreover, AMPK activates the autophagic process of ferritinophagy, which provides free iron urgently needed as a cofactor for the synthesis of heme- and iron–sulfur proteins. Excessive activation of this pathway ends in ferroptosis, a special iron-dependent form of cell death, while hampered AMPK activation steadily reduces the iron pools, leading to hypoferremia with iron sequestration in the spleen and liver. Long-lasting iron depletion affects erythropoiesis and results in anemia of chronic disease, a common condition in patients with AD and its comorbidities. Instead of iron supplementation, drugs, diet, or phytochemicals that improve energy supply and cellular glucose uptake should be administered to counteract hypoferremia and anemia of chronic disease.

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“…Promising preliminary results of hypoxia exposure in animal model studies suggest that these interventions could be of great interest in treating anxiety disorders [22]. However, despite recent studies suggesting intermittent hypoxic preconditioning as a powerful strategy for COVID-19 rehabilitation [23], to our knowledge, there is no research in the scientific literature that has studied the effects of this novel therapeutic strategy on mental health parameters of adults who have recovered from COVID-19. Thus, this study aimed to investigate the effects of different protocols of moderate-intensity intermittent hypoxic training in adults who have recovered from COVID-19 on QoL and the state of their mental health.…”

Section: Introductionmentioning

confidence: 99%

Effects of Different Protocols of Moderate-Intensity Intermittent Hypoxic Training on Mental Health and Quality of Life in Brazilian Adults Recovered from COVID-19: The AEROBICOVID Double-Blind Randomized Controlled Study

Merellano-Navarro,

Camacho-Cardenosa,

Costa

et al. 2023

Healthcare

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The aim of this study was to investigate the effects of different protocols of moderate-intensity intermittent hypoxic training in patients who had recovered from COVID-19 on quality of life (QoL) and mental health. The sample of this clinical trial-controlled double-blind study consisted of 67 participants aged 30–69 years, who were organized randomly according to Normoxia, Hypoxia, Hypoxia Recovery or Control Group. Eight weeks of cycle ergometer training were performed with a frequency of three training sessions per week in normoxic or hypoxic conditions (with or without hypoxic recovery). Health-related QoL and Mental Health Status were evaluated by 12-Item Short Form Survey and Depression Anxiety and Stress Scale instruments, respectively. All training groups improved the QoL’s physical dimensions (Baseline–Post: Normoxia Group 42.1 (11.0)–48.7 (7.0), Hypoxia Group 46.9 (11.8)–53.5 (6.6) and Hypoxia Recovery Group 45.8 (9.2)–51.1 (5.3)) and mental dimensions (Baseline–Post: Normoxia Group 48.8 (7.9)–54.6 (4.6), Hypoxia Group 45.2 (7.7)–53.2 (3.8) and Hypoxia Recovery Group 46.5 (9.7)–52.0 (9.9)). Regarding mental health outcomes, all training groups decreased depressive symptoms (66.7% Normoxia, 31.2% Hypoxia Recovery and 31% Hypoxia groups), anxiety symptoms (46.5% Normoxia, 45.9% Hypoxia Recovery and 39.5% in the Hypoxia groups) and stress symptoms (40.6% Normoxia, 36.3% Hypoxia Recovery and 22.1% Hypoxia groups). Significant statistical difference was not found between groups. Normoxic and hypoxic training showed a similar effect on QoL and the mental health of Brazilian adults who had recovered from COVID-19.

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Intermittent Hypoxic Preconditioning: A Potential New Powerful Strategy for COVID-19 Rehabilitation

Cited by 12 publications

References 102 publications

Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

Why Is Iron Deficiency/Anemia Linked to Alzheimer’s Disease and Its Comorbidities, and How Is It Prevented?

Effects of Different Protocols of Moderate-Intensity Intermittent Hypoxic Training on Mental Health and Quality of Life in Brazilian Adults Recovered from COVID-19: The AEROBICOVID Double-Blind Randomized Controlled Study

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