Anesthesia for electroconvulsive therapy (ECT) requires proper medications and airway management. Besides an induction agent such as methohexital, a neuromuscular blocker such as succinylcholine (SCh) is often given for muscle relaxation. To maintain the patient\'s oxygen saturation, mask ventilation is required due to this transient chemical paralysis even in the presence of adequate preoxygenation. A morbidly obese, middle-aged female experienced multiple life-threatening hypoxic episodes due to \"bronchospasms\" during prior ECT treatments. A drastic reduction in the SCh dose to about half of the original dose led to much smoother anesthesia courses with no more hypoxic episodes during subsequent ECT treatments. We believe that the lower dosing of SCh avoided a long period of chemical paralysis, which led to a quick return of spontaneous respiration, shortened the need for airway support, and therefore avoided hypoxic episodes in subsequent ECT treatments.

Hypoxia stabilizes hypoxia-inducible factors (HIFs), facilitating adaptation to hypoxic conditions. Appropriate hypoxia is pivotal for neurovascular regeneration and immune cell mobilization. However, in central nervous system (CNS) injury, prolonged and severe hypoxia harms the brain by triggering neurovascular inflammation, oxidative stress, glial activation, vascular damage, mitochondrial dysfunction, and cell death. Diminished hypoxia in the brain improves cognitive function in individuals with CNS injuries. This review discusses the current evidence regarding the contribution of severe hypoxia to CNS injuries, with an emphasis on HIF-1α-mediated pathways. During severe hypoxia in the CNS, HIF-1α facilitates inflammasome formation, mitochondrial dysfunction, and cell death. This review presents the molecular mechanisms by which HIF-1α is involved in the pathogenesis of CNS injuries, such as stroke, traumatic brain injury, and Alzheimer\'s disease. Deciphering the molecular mechanisms of HIF-1α will contribute to the development of therapeutic strategies for severe hypoxic brain diseases.

Coronavirus disease 2019 (COVID-19) may result in rapid onset of hypoxemic respiratory failure. This study aimed to characterize the factors and outcomes associated with prolonged hypoxia in patients with COVID-19. Prolonged severe hypoxia (PSH) was defined as hypoxia requiring ≥6 L/min of oxygen by nasal cannula or equivalent for more than 10 days.
This study was designed as a single-center retrospective analysis. Multivariable logistic regression was utilized to assess factors associated with PSH.
The sample included 554 patients with 117 (21%) having PSH. Median length of stay of patients with PSH was significantly longer (median IQR: 18 days vs 6 days, p < 0.0001). Patients with PSH had significantly higher rates of venous thromboembolism (p < 0.0001) and major bleeding (p < 0.004). The presence of cirrhosis (OR 3.32, 95% CI [1.02 to 10.83]) and hypertension (OR 1.99, 95% CI [1.12 to 3.53]) were independently associated with PSH, while outpatient use of anti-platelet agents had an inverse association (OR 0.57, 95% CI [0.36 to 0.91]).
PSH is associated with increased length of stay, morbidity, and mortality. Hypertension and liver cirrhosis were significantly associated with higher odds of PSH, while use of anti-platelet therapy had a protective effect.

UNASSIGNED: Severe hypoxia induces a series of stress responses in mammals; however, subterranean rodents have evolved several adaptation mechanisms of energy metabolisms and O2 utilization for hypoxia. Mammalian brains show extreme aerobic metabolism. Following hypoxia exposure, mammals usually experience irreversible brain damage and can even develop serious diseases, such as hypoxic ischemic encephalopathy and brain edema. To investigate mechanisms underlying the responses of subterranean rodents to severe hypoxia, we performed a cross-species brain transcriptomic analysis using RNA sequencing and identified differentially expressed genes (DEGs) between the subterranean rodent Lasiopodomys mandarinus and its closely related aboveground species L. brandtii under severe hypoxia (5.0% O2, 6 h) and normoxia (20.9% O2, 6 h).
UNASSIGNED: We obtained 361 million clean reads, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. We identified 359 and 515 DEGs by comparing the hypoxic and normoxia groups of L. mandarinus and L. brandtii, respectively. Gene Ontology (GO) analysis showed that upregulated DEGs in both species displayed similar terms in response to severe hypoxia; the main difference is that GO terms of L. brandtii were enriched in the immune system. However, in the downregulated DEGs, GO terms of L. mandarinus were enriched in cell proliferation and protein transport and those of L. brandtii were enriched in nuclease and hydrolase activities, particularly in terms of developmental functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that upregulated DEGs in L. mandarinus were associated with DNA repair and damage prevention as well as angiogenesis and metastasis inhibition, whereas downregulated DEGs were associated with neuronal synaptic transmission and tumor-associated metabolic pathways. In L. brandtii, upregulated KEGG pathways were enriched in the immune, endocrine, and cardiovascular systems and particularly in cancer-related pathways, whereas downregulated DEGs were associated with environmental information processing and misregulation in cancers.
UNASSIGNED: L. mandarinus has evolved hypoxia adaptation by enhancing DNA repair, damage prevention, and augmenting sensing, whereas L. brandtii showed a higher risk of tumorigenesis and promoted innate immunity toward severe hypoxia. These results reveal the hypoxic mechanisms of L. mandarinus to severe hypoxia, which may provide research clues for hypoxic diseases.

The pentose phosphate pathway (PPP) of glucose metabolism in the brain serves as a primary source of NADPH which in turn plays a crucial role in multiple cellular processes, including maintenance of redox homeostasis and antioxidant defense. In our model of protective mild hypobaric hypoxia in rats (3MHH), an inverse correlation between hypoxia-inducible factor-1 (HIF1) activity and mRNA levels of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP, was observed. In the present study, it was demonstrated that severe hypobaric hypoxia (SH) induced short-term upregulation of HIF1 alpha-subunit (HIF1α) in the hippocampal CA1 subfield and decreased the activity of G6PD. The levels of NADPH were also reduced, promoting oxidative stress, triggering apoptosis, and neuronal loss. Injection of a HIF1 inhibitor (HIF1i), topotecan hydrochloride (5 mg/kg, i.p.), before SH prevented the upregulation of HIF1α and normalized G6PD activity. In addition, HIF1i injection caused an increase in NADPH levels, normalization of total glutathione levels and of the cellular redox status as well as suppression of free-radical and apoptotic processes. These results demonstrate a new molecular mechanism of post-hypoxic cerebral pathology development which involves HIF1-dependent PPP depletion and support a recently suggested injurious role of HIF1 activation in the acute phase of cerebral hypoxia/ischemia. Application of PPP stimulators in early post-hypoxic/ischemic period might represent a promising neuroprotective strategy. Graphical abstract HIF1-dependent down-regulation of the pentose phosphate pathway contributes to the hypoxia-induced oxidative stress and neuronal apoptosis in the rat hippocampus.

Post-conditioning is exposure of an injured organism to the same harmful factors but of milder intensity which mobilizes endogenous protective mechanisms. Recently, we have developed a novel noninvasive post-conditioning (PostC) protocol involving three sequential episodes of mild hypobaric hypoxia which exerts pronounced neuroprotective action. In particular, it prevents development of pathological cascades caused by severe hypobaric hypoxia (SH) such as cellular loss, lipid peroxidation, abnormal neuroendocrine responses and behavioural deficit in experimental animals. Development of these post-hypoxic pathological effects has been associated with the delayed reduction of hypoxia-inducible factor 1 (HIF1) regulatory α-subunit levels in rat hippocampus, whereas PostC up-regulated it. The present study has been aimed at experimental examination of the hypothesis that intrinsic mechanisms underlying the neuroprotective and antioxidant effects of PostC involves HIF1-dependent stimulation of the pentose phosphate pathway (PPP). We have observed that SH leads to a decrease of glucose-6-phosphate dehydrogenase (G6PD) activity in the hippocampus and neocortex of rats as well as to a reduction in NADPH and total glutathione levels. This depletion of the antioxidant defense system together with excessive lipid peroxidation during the reoxygenation phase resulted in increased oxidative stress and massive cellular death observed after SH. In contrast, PostC led to normalization of G6PD activity, stabilization of the NADPH and total glutathione levels and thereby resulted in recovery of the cellular redox state and prevention of neuronal death. Our data suggest that stabilization of the antioxidant system via HIF1-associated PPP regulation represents an important neuroprotective mechanism enabled by PostC.

BACKGROUND: Postoperative pulmonary edema is a fatal adverse event after a cardiac surgery. We here report successful management using airway pressure release ventilation (APRV) for severe hypoxia with pulmonary edema after a cardiac surgery.
METHODS: A 58-year-old man underwent an uneventful mitral valve repair. Immediately afterwards, the patient became agitated and made vigorous inspiratory efforts. His oxygen saturation dropped to 90%. Coarse inspiratory rhonchi were heard on auscultation, and copious, pink, frothy sputum was obtained with suctioning. Initial chest radiograph showed right-sided patchy opacities and interstitial infiltrates. A transthoracic echocardiogram demonstrated normal cardiac function. With worsening respiratory failure on mechanical ventilation, APRV was attempted. His condition and blood gas was subsequently improved. Over the following 3days, the patient experienced an uneventful postoperative course and was discharged to home on postoperative day 14.
CONCLUSIONS: Extracorponeal membrane oxygenation (ECMO) is the most effective for severe hypoxia with pulmonary edema; however, ECMO is associated with hemorrhage and infectious complications. Alteratively, APRV was required for the successful management for severe hypoxia with pulmonary edema.
CONCLUSIONS: APRV could be effective for severe hypoxia with pulmonary edema after a cardiac surgery.

When Edmund Hillary and Tenzing Norgay reached the summit of Mt. Everest in 1953, it was the culmination of many attempts beginning in 1921. Alexander Kellas had actually predicted as early as 1920 that the mountain could be climbed, but the extreme altitude of 8848 m with the consequent oxygen deprivation had foiled previous attempts. One reason for the success of the 1953 expedition was the work done by the British physiologist Griffith Pugh in 1952 when he studied many of the physiological factors at high altitude including the oxygen requirements. Seven years later, Pugh and Hillary teamed up again for the Silver Hut Expedition in 1960-1961 that elucidated many of the problems of very high altitude. A group of physiologists spent several months at an altitude of 5800 m in a prefabricated hut and studied many aspects of exercise, pulmonary gas exchange, control of ventilation, and blood changes. Maximal exercise was measured as high as 7440 m and raised anew the question of whether Everest could ever be climbed without supplementary oxygen. The answer was shown to be yes in 1978 by Messner and Habeler, and 3 years later the American Medical Research Expedition to Everest clarified the physiological adaptations that allow humans to reach the highest point on earth. Five people reached the summit, the barometric pressure there was measured for the first time, and alveolar gas samples from the summit showed the critical importance of the extreme hyperventilation. However, the maximal oxygen consumption for the summit inspired PO2 of 43 mmHg was shown to be only about 1 l min(-1). In other words, the highest point on earth is very close to the limit of human tolerance to oxygen deprivation. As we celebrate the anniversary of Charles Darwin, it would be nice to have an evolutionary explanation for this, but in fact it is a cosmic coincidence.

Neonatal hypoxia is the leading cause of brain damage with birth complications. Many studies have reported proliferation-promoting effect of mild hypoxia on neural stem cells (NSCs). However, how severe hypoxia influences the behavior of NSCs has been poorly explored. In the present study, we investigated the effects of 5, 3, and 1 % oxygen exposure on NSCs in vitro. MTT, neurosphere assay, and 5-ethynyl-2\'-deoxyuridine (EdU) incorporation revealed a quick growth arrest of C17.2 cells and primary NSCs induced by 1 % oxygen exposure. Cell cycle analysis showed that this hypoxia exposure caused a significant increase of cells in G0/G1 phase and decrease of cells in S phase that is associated with decrease of Cyclin D1. Interestingly, the expression of cold inducible RNA-binding protein (CIRBP), a cold responsive gene reacting to multiple cellular stresses, was decreased in parallel with the 1 % oxygen-induced proliferation inhibition. Forced expression of CIRBP under hypoxia could restore the proliferation of NSCs, as showed by EdU incorporation and cell cycle analysis. Furthermore, the expression of Cyclin D1 under hypoxia was also restored by CIRBP overexpression. Taken together, these data suggested a growth-suppressing effect of severe hypoxia on NSCs and, for the first time, revealed a novel role of CIRBP in hypoxia-induced cell cycle arrest, suggesting that modulating CIRBP may be utilized for preventing hypoxia-induced neonatal brain injury.