Longitudinal Changes and Recovery in Heart Rate Variability of Young Healthy Subjects When Exposure to a Hypobaric Hypoxic Environment

Background: The autonomic nervous system (ANS) is crucial for acclimatization. Investigating the responses of acute exposure to a hypoxic environment may provide some knowledge of the cardiopulmonary system’s adjustment mechanism.Objective: The present study investigates the longitudinal changes and recovery in heart rate variability (HRV) in a young healthy population when exposed to a simulated plateau environment.Methods: The study followed a strict experimental paradigm in which physiological signals were collected from 33 healthy college students (26 ± 2 years, 171 cm ± 7 cm, 64 ± 11 kg) using a medical-grade wearable device. The subjects were asked to sit in normoxic (approximately 101 kPa) and hypoxic (4,000 m above sea level, about 62 kPa) environments. The whole experimental process was divided into four stable resting measurement segments in chronological order to analyze the longitudinal changes of physical stress and recovery phases. Seventy-six time-domain, frequency-domain, and non-linear indicators characterizing rhythm variability were analyzed in the four groups.Results: Compared to normobaric normoxia, participants in hypobaric hypoxia had significantly lower HRV time-domain metrics, such as RMSSD, MeanNN, and MedianNN (p < 0.01), substantially higher frequency domain metrics such as LF/HF ratio (p < 0.05), significantly lower Poincaré plot parameters such as SD1/SD2 ratio and other Poincaré plot parameters are reduced considerably (p < 0.01), and Refined Composite Multi-Scale Entropy (RCMSE) curves are reduced significantly (p < 0.01).Conclusion: The present study shows that elevated heart rates, sympathetic activation, and reduced overall complexity were observed in healthy subjects exposed to a hypobaric and hypoxic environment. Moreover, the results indicated that Multiscale Entropy (MSE) analysis of RR interval series could characterize the degree of minor physiological changes. This novel index of HRV can better explain changes in the human ANS.

The effect of oxygen supply and oxygen distribution on single-head tunnel with different altitudes under mixed ventilation

Hypoxia plays a major role in limiting the construction of the high-altitude mine. Understanding the effect and the distribution of diffused oxygen supply at different altitudes is the premise for the design of a mine with oxygen supply system and the full utilization of oxygen resources. For the optimal design of an oxygen supply mode and ventilation system, a multi-component fluid model of the diffused oxygen supply of a single-head tunnel was developed. This study reveals the variation law of the average oxygen mass fraction at different altitudes. The relationship between the distance from the heading face and the oxygen mass fraction at each altitude was fitted. The results show that the distribution of oxygen mass fraction in a single head tunnel at different altitudes presents a similar trend of increasing first and then decline. In addition, the change of the average oxygen mass fraction with the increase of altitude is not linear, and the dispersion loss is larger in high-altitude areas. The largest oxygen enrichment area is distributed at the altitudes of 4000–4500 m. This study provides theoretical support for improving the hypoxic environment of high-altitude metal mines excavation work.

In silico analyses of blood flow and oxygen transport in human micro-veins and valves

BACKGROUND: Almost 95% of the venous valves are micron scale found in veins smaller than 300μm diameter. The fluid dynamics of blood flow and transport through these micro venous valves and their contribution to thrombosis is not yet well understood or characterized due to difficulty in making direct measurements in murine models. OBJECTIVE: The unique flow patterns that may arise in physiological and pathological non-actuating micro venous valves are predicted. METHODS: Computational fluid and transport simulations are used to model blood flow and oxygen gradients in a microfluidic vein. RESULTS: The model successfully recreates the typical non-Newtonian vortical flow within the valve cusps seen in preclinical experimental models and in clinic. The analysis further reveals variation in the vortex strengths due to temporal changes in blood flow. The cusp oxygen is typically low from the main lumen, and it is regulated by systemic venous flow. CONCLUSIONS: The analysis leads to a clinically-relevant hypothesis that micro venous valves may not create a hypoxic environment needed for endothelial inflammation, which is one of the main causes of thrombosis. However, incompetent micro venous valves are still locations for complex fluid dynamics of blood leading to low shear regions that may contribute to thrombosis through other pathways.

Impact of climate induced hypoxia on calcifying biota in the Arabian Sea : An evaluation from the micropaleontological records of the Indian margin

High biological productivity combined with the poor ventilation produces severe oxygen depletion (hypoxia) in upper intermediate waters of the Arabian Sea. The naturally developed Arabian Sea oxygen minimum zone (OMZ) is one of the most pronounced low oxygen ocean environments known today. The OMZ impinges the Indian margin where oxygen concentration reaches values less than 0.05 ml/l leading denitrification. In recent studies, it has been observed that the OMZ strength has varied considerably in the past, in tune with the global climate change. But the effect of changes in natural mid-water hypoxic environment on the marine biota particularly of the eastern Arabian Sea is unknown. Here, we analyzed 30,000 yr record of temporal changes in two major groups of marine calcifying microfauna pteropods secreting aragonitic shells and foraminifera secreting calcitic shells in terms of abundance and diversity variations. This study will provide an insight into our understanding of potential impact of rising atmospheric CO2 on marine ecosystem.

LRRFIP2 modulates the response to hypoxia during embryonic cardiogenesis

Oxygen is crucial for appropriate embryonic and fetal development, including cardiogenesis. The heart is the first organ formed in the embryo and is required to provide oxygen and nutrients to all cells in the body. Embryonic cardiogenesis is a complex process finely regulated and prone to congenital malformations. It takes place in a hypoxic environment that activates the HIF-1a; signaling pathway which mediates cellular and systemic adaptations to low oxygen levels. Since inhibition or overactivation of the HIF-1a; signaling pathway in the myocardium lead to severe cardiac malformations and embryonic lethality, it is important that the cellular response to hypoxia be precisely regulated. While many gene regulatory networks involved in embryonic cardiogenesis have been characterized in detail, the modulation of the response of cardiomyocytes (CM) to hypoxia has remained less studied. We identified LRRFIP2 as a new negative cofactor of HIF-1a;. Indeed, we have shown that the absence of Lrrfip2 expression in a mouse KI model led to an enhance of many HIF-1a; target genes including Igfbp3, Bnip3 and Ndufa4l2 in embryonic CM during development. As results, the absence of Lrrfip2 led to the inhibition of the PI3K/Akt survival pathway, growth defects, mitochondrial dysfunction and to a precocious maturation of the embryonic CMs. Altogether, these defects led to the formation of a smaller heart unable to provide sufficient oxygen to the embryo and finally to a severe hypoxia and a precocious lethality.

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Pancreatic cancer is one of the most lethal malignant tumors with a low survival rate, partly because the tumor microenvironment (TME), which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), immune cells, and vascular systems, prevents effective drug delivery and chemoradiotherapy. Thus, modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach. Since nanoparticles are one of the most effective cancer treatment strategies, several nano-delivery platforms have been developed to regulate the TME and enhance treatment. Here, we summarize the latest advances in nano-delivery systems that alter the TME in pancreatic cancer by depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, or improving the hypoxic environment. We also discuss promising new targets for such systems. This review is expected to improve our understanding of how to modulate the pancreatic cancer microenvironment and guide the development of new therapies. Graphical Abstract

Impact of High-Altitude Hypoxia on Early Osseointegration With Bioactive Titanium

Nowadays, the bone osseointegration in different environments is comparable, but the mechanism is unclear. This study aimed to investigate the osseointegration of different bioactive titanium surfaces under normoxic or high-altitude hypoxic environments. Titanium implants were subjected to one of two surface treatments: (1) sanding, blasting, and acid etching to obtain a rough surface, or (2) extensive polishing to obtain a smooth surface. Changes in the morphology, proliferation, and protein expression of osteoblasts on the rough and smooth surfaces were examined, and bone formation was studied through western blotting and animal-based experiments. Our findings found that a hypoxic environment and rough titanium implant surface promoted the osteogenic differentiation of osteoblasts and activated the JAK1/STAT1/HIF-1α pathway in vitro. The animal study revealed that following implant insertion in tibia of rabbit, bone repair at high altitudes was slower than that at low altitudes (i.e., in plains) after 2weeks; however, bone formation did not differ significantly after 4weeks. The results of our study showed that: (1) The altitude hypoxia environment would affect the early osseointegration of titanium implants while titanium implants with rough surfaces can mitigate the effects of this hypoxic environment on osseointegration, (2) the mechanism may be related to the activation of JAK1/STAT1/HIF-1α pathway, and (3) our results suggest the osteogenesis of titanium implants, such as oral implants, is closely related to the oxygen environment. Clinical doctors, especially dentists, should pay attention to the influence of hypoxia on early osseointegration in patients with high altitude. For example, it is better to choose an implant system with rough implant surface in the oral cavity of patients with tooth loss at high altitude.

Polyacrylamide-Sodium Alginate Hydrogel Releasing Oxygen and Vitamin C Promotes Bone Regeneration in Rat Skull Defects

Oxygen is essential for cell survival and tissue regeneration. Scaffolds releasing oxygen have been hypothesized as an ideal strategy for bone repair. However, excessive oxygen supply will disturb the redox balance, lead to oxidative stress, and affect bone regeneration. In this study, we synthesized a hydrogel from sodium alginate and loaded it calcium peroxide nanoparticles as an oxygen generating material and vitamin C as a pH regulator and antioxidant. The composite hydrogel, with a pH value close to physiological humoral fluid, could release oxygen to alleviate hypoxia in the bone defect and reduce the side effects of excessive hydrogen peroxide. In in vitro experiments, the composite hydrogel promoted the osteogenic differentiation and ALP and mineralization ability of rat bone marrow mesenchymal stem cells in a hypoxic environment (2% O2). In animal experiments, the composite hydrogel was applied in rat skull defect models. It promoted the healing of bone defects. These results suggest that sodium alginate hydrogel releasing oxygen and vitamin C is suitable for cell survival and tissue regeneration in a hypoxic environment and has good application prospects in bone defect repair.

Abstract 1122‐000055: Parenchymal and Subarachnoid Angiogenesis in Patients with Vein of Galen Aneurysmal Malformation

Introduction : Vein of Galen Aneurysmal Malformation (VGAM) is an arteriovenous malformation that accounts for 30% of all pediatric vascular malformations. VGAMs undergo significant remodeling of hemodynamic and structural anatomy due to angiogenesis. These changes not only affect the malformation on a molecular and morphological basis, but may also lead to alterations in planned surgical procedures. It is imperative to better understand the dynamic, angiogenic environment of the cerebrovasculature in order to more effectively treat this disease. Methods : We present 36 cases of secondary angiogenesis in VGAM. We also present three case reports of angiogenesis secondary to VGAM. Results : Pre‐interventional angiogenesis was identified in 16 patients (44.4%) and post‐interventional angiogenesis in 20 patients (55.6%) following a stage of embolization therapy. The cohort of patients with pre‐interventional secondary angiogenesis was significantly older than patients with post‐interventional angiogenesis at initial angiogram (12 months ± 40.1 months vs. 4.0 months ± 5.4 months; p<0.05). Choroidal VGAMs presented with angiogenesis more frequently than Mural VGAMs (4/14 Mural vs 32/42 Choroidal; p<0.01). Angiogenesis was localized to either the left, right, or bilateral thalamus in 2 cases, to the cisternal space surrounding the VOG in 16 cases, and both in 18 cases. Conclusions : Upon identification of secondary angiogenesis, our team’s strategy is to embolize the venous component of the fistula. The ideal strategy in our practice is cannulation of the primary feeder of the malformation, as close to the fistula as possible, and injection of highly concentrated n‐BCA glue (70%‐90%) in a transarterial approach. After multiple rounds of embolization, feeders become less dilated and may be difficult to distinguish from angiogenesis. In this pattern, we use low‐concentrate nBCA (40%‐50%) from an identifiable, proximal feeder and occlude the venous component of the fistula. We identified two patterns of secondary angiogenesis: 1) pre‐interventional angiogenesis identified at the initial diagnostic angiogram, 2) de‐novo, post‐interventional angiogenesis during the staged‐embolization treatment‐course. Occasionally, we noted random bursts of angiogenesis. A combination of the hypoxic environment, inflammation, and hemodynamic alterations to the VGAM caused by liquid embolic/coiling may lead to a burst of angiogenesis that subsides after repeated treatment. We hypothesize that the immature sinuses typically associated with VGAM patients, which experience a decrease in blood flow and subsequently narrow after embolization, may contribute to turbulent blood flow. Development of parenchymal and subarachnoid angiogenesis is common during the multi‐session treatment of VGAM. It represents the response to the angiogenic stimuli released from the draining vein. This angiogenesis can be observed to regress spontaneously or mature as we continue to treat the VGAM. It is unnecessary to embolize secondary angiogenesis outright and it is our recommendation to chiefly target primary feeders of the VGAM as close to the venous component as possible.

High altitude exposure affects male reproductive parameters: Could it also affect the prostate?†

Living at high altitudes and living with prostatic illness are two different conditions closely related to a hypoxic environment. People at high altitudes exposed to acute, chronic, or intermittent hypobaric hypoxia turn on several mechanisms at the system, cellular and molecular level to cope with oxygen atmosphere scarcity maintaining the oxygen homeostasis. This exposure affects the whole organism and function of many systems, such as cardiovascular, respiratory, and reproductive. On the other hand, malignant prostate is related to the scarcity of oxygen in the tissue microenvironment due to its low availability and high consumption due to the swift cell proliferation rates. Based on the literature, this similarity in the oxygen scarcity suggests that hypobaric hypoxia, and other common factors between these two conditions, could be involved in the aggravation of the pathological prostatic status. However, there is still a lack of evidence in the association of this disease in males at high altitudes. This review aims to examine the possible mechanisms that hypobaric hypoxia might negatively add to the pathological prostate function in males who live and work at high altitudes. More profound investigations of hypobaric hypoxia’s direct action on the prostate could help understand this exposure’s effect and prevent worse prostate illness impact in males at high altitudes.