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Genetics and genomics of exposure to high altitude
Published in Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson, Ward, Milledge and West's High Altitude Medicine and Physiology, 2021
Andrew M. Luks, Philip N. Ainslie, Justin S. Lawley, Robert C. Roach, Tatum S. Simonson
The roles of HIF-1 and HIF-2 are key to regulating various physiological adaptations to chronic hypoxia yet, in cases of intermittent hypoxia, such as experienced during sleep disordered breathing, an imbalance causes oxidative stress and negative cardiorespiratory effects (Prabhakar and Semenza 2012). As already discussed, HIF-1α is expressed at low levels under normoxic conditions, and it is also induced by chronic intermittent hypoxia. However, it is remarkable that the results of intermittent hypoxia on HIF-1α and HIF-2α are diametrically opposed. Experiments conducted on rats showed that intermittent hypoxia upregulated HIF-1α but downregulated HIF-2α both in tissue from rats exposed to intermittent hypoxia and in cells in culture (Nanduri et al. 2009). The results are all the more surprising because continuous hypoxia upregulates both HIF-1α and HIF-2α in the cell cultures. Thus, intermittent hypoxia has a differential effect upon these two structurally related HIF transcriptional activators. These studies also showed that the downregulation of HIF-2α in rats exposed to intermittent hypoxia could be inhibited by calpain proteases (calpain is a protein belonging to a family of calcium-dependent proteases). This may have implications for the prevention of the pathology caused by intermittent hypoxia (Nanduri et al. 2009). Recent work suggests epigenetic modifications, such as changes in DNA methylation that influence gene expression, underlie respiratory and cardiovascular pathologies due to chronic intermittent hypoxia via the HIF pathway (Nanduri et al. 2017).
The cognitive and neurobiological effects of obstructive sleep apnea
Published in Philip N. Murphy, The Routledge International Handbook of Psychobiology, 2018
Melinda L. Jackson, Rachel Schembri
Obstructive sleep apnea (OSA) is characterised by obstruction of the upper airway and the presence of continued respiratory effort with normal central nervous system drive for respiration during sleep (Patil, Schneider et al. 2007). There are two primary nocturnal physiological abnormalities that occur in patients with OSA, which may be the underlying cause of cognitive and other daytime impairments: intermittent hypoxemia (decreased hemoglobin oxygen and reperfusion) and sleep fragmentation (disruption to the continuity and depth of sleep, via cortical arousal). Repetitive brief upper airway obstruction occurs during sleep, resulting in apneas (complete cessation of breathing) or hypopneas (a reduction in breathing). The major diagnostic criterion for OSA is frequent periods of respiratory arrest of ten seconds or more during sleep. The apnea/hypopnea index (AHI; number of events per hour of sleep) must be at least five to make a diagnosis of OSA (Flemons, Buysse et al. 1999). Patients with severe OSA may experience apneas hundreds of times per night. Apneas and hypopneas often terminate with arousal from sleep, resulting in fragmentation of sleep and reduction in total sleep time. Additionally, intermittent hypoxia causes a disruption in the biochemical and hemodynamic state of the central nervous system (Patil et al. 2007). Patients diagnosed with severe OSA may record arterial hemoglobin oxygen saturation (SaO2) reductions to below 50% of preapneic levels.
RETRACTED ARTICLE: Evaluation of macular thickness and visual pathways using optic coherence tomography and pattern visual evoked potential in different clinical stages of obstructive sleep apnea syndrome
Published in International Journal of Neuroscience, 2021
Ayşın Kısabay AK, Melike Batum, Tuğba Göktalay, Hüseyin Mayali, Emin Kurt, Deniz Selçuki, Hikmet Yilmaz
PVEP investigation was also performed in the present study in order to evaluate the optic nerve pathways. Intermittent hypoxia simulates the hypoxia/reoxygenation events and exerts metabolic, neurobiological, inflammatory and ischemic effects. It also affects the optic nerve by altering the neuronal myelin and axon components due to intermittent micro-ischemic damage [26, 31,32]. In these studies, prolonged peak latency and low amplitude were shown similar to those in our study. By PVEP; prolonged peak latency of P100 shows myelin damage and low N75-P100 amplitude shows axonal damage of optic nerve in these studies [17, 21]. The neurological consequences of OSAS appear to be associated with both demyelination and axonal damage of the optic nerve [33]. These findings suggest that intermittent hypoxia affecting PVEP amplitudes also has an effect such as an inflammation leading to damage of optic nerve myelination by way of prolonged latency [28, 34–36].
Daily rhythms of swimming activity, synchronization to different feeding times and effects on anesthesia practice in an Amazon fish species (Colossoma macropomum)
Published in Chronobiology International, 2018
Rodrigo Fortes-Silva, Silvan Vianna Do Valle, Jose Fernando Lopéz-Olmeda
This difference in daily susceptibility between species could be due to several factors, such as absorption, distribution, excretion and metabolism (Hooven et al. 2009). Tambaqui showed nocturnal swimming activity and, therefore, anesthetic absorption through gills or cell permeability could also be greater at night period, and lead to late recovery in the groups induced at night. On the other hand, fish under MD condition and exposed to anesthetic at night could recover fastest their activity due to elimination of the anesthetic by high nocturnal activity. Strong activity can increase gill perfusion in fish in the elevated metabolic rate period (McDonald and Milligan 1997). Also, this behavior in the recovery phase can be related with complex energy reward mechanisms when fish are exposed to lack of oxygen (Lefrançois et al., 2005). The optimal strategies used to cope with intermittent hypoxia may be distinct from those for coping with constant hypoxia (Borowiec et al. 2015). The metabolic rate was positively correlated with food availability (Killen et al. 2011) or swimming activity under hypoxia in sea bass (Dicentrarchus labrax) (Killen et al. 2012). On the other hand, when activity decreased, metabolism also tended to diminish, even if striking differences were exhibited in individuals’ physiological and behavioral flexibility (Auer et al. 2016). In general, the effect of the anesthetic procedure on tambaqui is strongly related to the swimming behavior and its daily rhythms of activity.
Quercetin: a savior of alveolar barrier integrity under hypoxic microenvironment
Published in Tissue Barriers, 2021
Ankit Tripathi, Puja P. Hazari, Anil K. Mishra, Bhuvnesh Kumar, Sarada S.K. Sagi
Interestingly, the rats exposed to acute hypoxia demonstrated an elevated level of HCT which might be considered as a major manifestation of either high altitude-induced dehydration or the reduced intake of water by the animals due to hypoxic stress, resulting in the reduction in total plasma volume. On contrary, the consistently higher levels of Hb in both hypoxia and hypoxia+quercetin group exhibited normal physiology to maintain cellular homeostasis. This is in corroboration with the study conducted by Leo-Velarde et.al., (2000), reporting elevated levels of HCT and Hb during chronic intermittent hypoxia.42 Another interesting finding by Patricia et.al. (2018)43 has also unraveled a persistently increased level of RBCs and WBCs in the HAPE patients, which was in relation with our study wherein, the blood profile of the animals under both hypoxia and hypoxia+quercetin group demonstrated an increased level of RBCs and WBCs. We have also assessed the blood gas composition of the animals under all the selected groups. Wherein, we observed an elevated PaO2, PaCO2, and SaO2 in the animals fed with quercetin under hypoxia, which is in support with the recent studies by Chawla et.al. (2014) and Powell et.al (1998) suggesting the occurrence of hyper-ventilation as a major manifestation of hypoxia in order to perpetuate an optimal alveolar pO2, which further causes a dramatic decline in pCO2 to below the threshold level resulting in the development of hypercapnia.44,45 However, quercetin supplementation has resulted in the amelioration and stabilization of blood gas and hematological profiles of the animals under hypoxia, which is a clear indication of elevated TJs protein expression integrity leading to improved acclimatization and enhanced fluid clearing capacity of lungs.