Addition Of Hypoxia Research Articles

Substance consumption and intoxication patterns in a medically supervised overdose prevention program for people experiencing homelessness

Background: Opioid overdose is a leading cause of death among homeless individuals. Combining psychoactive substances with opioids increases overdose risk. This study aimed to describe intoxication patterns at a drop-in space offering medical monitoring and harm reduction services to individuals who arrive intoxicated and at risk of overdose. Methods: We examined data from visits to the Supportive Place for Observation and Treatment at Boston Health Care for the Homeless Program between January 1, 2017 and December 31, 2017. We used k-means cluster analysis to characterize intoxication patterns based on clinically assessed sedation levels and vital sign parameters. Multinomial logistic regression analysis assessed demographic and substance consumption predictors of cluster membership. Linear and logistic regression models examined associations between cluster membership and care outcomes. Results: Across 305 care episodes involving 156 unique patients, cluster analysis revealed 3 distinct intoxication patterns. Cluster A (26.6%) had mild sedation and normal vital signs. Cluster B (44.5%) featured greater sedation with bradycardia and/or hypotension. Cluster C (28.9%) was comparable to cluster B but with the addition of hypoxia. Self-reported consumption of non-opioid sedatives prior to arrival was common (63.3% of episodes) and predicted membership in cluster B (aOR 2.75, 95% CI 1.40, 5.40) and cluster C (aOR 3.38, 95% CI 1.48, 7.70). In comparison to cluster A episodes, cluster C episodes were longer (mean 4.8 vs. 2.3 hours, p < 0.001) and more likely to require supplemental oxygen (27.3% vs. 2.5%, p < 0.001). Few episodes required hospital transfer (4.7%) or naloxone (1.0%). No deaths occurred. Conclusions: In a medically supervised overdose monitoring program, reported use of non-opioid sedatives strongly predicted more complex clinical courses and should be factored into overdose prevention efforts. Low-threshold medical monitoring in an ambulatory setting was sufficient for most episodes, suggesting a role for such programs in reducing harm and averting costly emergency services.

High-intensity exercise in hypoxia improves endothelial function via increased nitric oxide bioavailability in C57BL/6 mice.

AimThe optimal exercise intensity to improve endothelial function remains unclear, as well as whether the addition of hypoxia could potentiate this function. Therefore, the aim of this study was to compare the effects of different exercise intensities in normoxia and hypoxia on vascular reactivity and nitric oxide (NO) bioavailability in mice.MethodsC57BL/6 mice underwent treadmill running three times per week, for 4 weeks at either low, maximal or supramaximal intensity in normoxia or hypoxia (inspire oxygen fraction = 0.13). Vascular reactivity and expression of genes and proteins involved in NO production/bioavailability were assessed in aorta using isolated vessel tension experiments, RT‐qPCR and western blot, respectively. Circulating NO metabolites and pro‐/antioxidant markers were measured.ResultsHypoxic exercise improved both acetylcholine‐induced vasorelaxation and phenylephrine‐induced vasoconstriction compared to normoxic exercise, independently of intensity. In hypoxia, a higher acetylcholine‐induced vasorelaxation was observed with high intensities (supramaximal and maximal) compared to low intensity. Exercise protocols modulated endothelial nitric oxide synthase (eNOS) and α1‐adrenergic receptor (α1‐AR) mRNA level, but not superoxide dismutase 3 (SOD3) and p47phox. No significant differences were observed for protein expression of α1‐AR, total eNOS, phosphorylated eNOS, SOD isoforms and p47phox. However, plasma SOD and catalase activities were significantly increased in hypoxic supramaximal compared to hypoxic low intensity, while concentration of nitrotyrosine significantly decreased. The latter was also observed in hypoxic maximal and supramaximal compared to the same intensities in normoxia.ConclusionHypoxic high‐intensity exercise increases NO bioavailability and improves vascular function, opening promising clinical perspectives for cardiovascular disease prevention.

No Influence of Acute Moderate Normobaric Hypoxia on Performance and Blood Lactate Concentration Responses to Repeated Wingates.

Training in hypoxia versus normoxia often induces larger physiological adaptations, while this does not always translate into additional performance benefits. A possible explanation is a reduced oxygen flux, negatively affecting training intensity and/or volume (decreasing training stimulus). Repeated Wingates (RW) in normoxia is an efficient training strategy for improving both physiological parameters and exercise capacity. However, it remains unclear whether the addition of hypoxia has a detrimental effect on RW performance. To test the hypothesis that acute moderate hypoxia exposure has no detrimental effect on RW, while both metabolic and perceptual responses would be slightly higher. On separate days, 7 male university sprinters performed 3 × 30-s Wingate efforts with 4.5-min passive recovery in either hypoxia (FiO2: 0.145) or normoxia (FiO2: 0.209). Arterial oxygen saturation was assessed before the first Wingate effort, while blood lactate concentration and ratings of perceived exertion were measured after each bout. Mean (P = .92) and peak (P = .63) power outputs, total work (P = .98), and the percentage decrement score (P = .25) were similar between conditions. Arterial oxygen saturation was significantly lower in hypoxia versus normoxia (92.0%[2.8%] vs 98.1% [0.4%], P < .01), whereas blood lactate concentration (P = .78) and ratings of perceived exertion (P = .51) did not differ between conditions. In sprinters, acute exposure to moderate hypoxia had no detrimental effect on RW performance and associated metabolic and perceptual responses.

Programming of the Adult HPA Axis After Neonatal Separation and Environmental Stress in Male and Female Rats.

Maternal separation, hypoxia, and hypothermia are common stressors in the premature neonate. Using our rat model of human prematurity, we evaluated sexual dimorphisms in the long-term effects of these neonatal stressors on behavior of the hypothalamic-pituitary-adrenal (HPA) axis in adult rats. Neonatal rats were exposed daily on postnatal days 2 to 6 to maternal separation with normoxia, with hypoxia allowing spontaneous hypothermia, with hypothermia per se, and with hypoxia while maintaining isothermia with external heat. The major findings were that (a) prior maternal-neonatal separation during the first week of postnatal life attenuated the plasma ACTH and corticosterone response to restraint stress in adult male but not female rats, (b) prior neonatal hypothermia augmented the plasma ACTH and corticosterone response to restraint stress in adult male rats, but not female rats, and (c) changes in hypothalamic, pituitary, and adrenal mRNA expression did not account for most of these HPA axis effects. Most of the programming effects on adult HPA axis was attributed to prior maternal-neonatal separation alone (with normoxia) because the addition of hypoxia with spontaneous hypothermia, hypothermia per se, and hypoxia while preventing hypothermia during maternal-neonatal separation had minimal effects on the HPA axis. These results may inform strategies to prevent sexually dimorphic sequelae of neonatal stress including those due to medical interventions.

Glutamate infusion coupled with hypoxia has a neuroprotective effect in the rat

Traumatic brain injury leads to a rise in glutamate, interference with oxygen supply and secondary neuronal death in the region surrounding the primary lesion. In the present experiments we have examined the effect of combining glutamate infusion with hypoxia on both brain metabolism and neuronal death. We have used microdialysis in unanaesthetised rats with a novel dual assay for glucose and lactate to monitor the temporal relation of changes in these metabolites resulting from infusion of 100 mM glutamate alone or combined with a reduction of inspired oxygen to 8%. In a parallel series of experiments we have compared the size of neuronal lesions under the same experimental conditions. We have used MAP2 antibody staining to measure the size of the neuronal lesion. Our results demonstrate that a 30 min glutamate infusion causes an immediate increase in neuronal glucose utilisation and a rise in lactate production. When hypoxia is added during the last 15 min of glutamate infusion there is a small rise in glucose and a large additional increase in lactate. The size of the neuronal lesions produced by infusion of 100 mM glutamate is reduced by the addition of hypoxia.

The impact-acceleration model of head injury: Injury severity predicts motor and cognitive performance after trauma

This study examines neuropsychological dysfunction after varying severities of the Impact Acceleration Model of diffuse traumatic brain injury. Adult rats (340 g-400 g) were divided into five groups, and exposed to varying degrees of Impact Acceleration Injury (1 m, 2 m, 2.1 m/500 g and second insult). After injury, animals were allowed to recover; acute neurological reflexes, beam walk score, beam balance score, inclined plane score, and Morris Water Maze score were then assessed at multiple time points. Injury of all severities caused significant motor and cognitive deficits. With milder injuries these effects were transient; however, with more severe injuries no recovery in function was seen. The addition of hypoxia and hypotension made a moderate injury worse than a severe injury. The acute neurological reflexes, the beam balance test and the inclined plane test distinguished between the more severely injured groups, but were affected less by mild injury. The beam walk test was sensitive to mild injury, but appeared unable to distinguish between the severe groups. The Morris Water Maze was sensitive for all injury groups, but appeared to adopt a different response profile with secondary insult. This study has for the first time characterized the degree of motor and cognitive deficits in rodents exposed to differing severities of Impact Acceleration Injury. These data confirm that the tests considered, and the Injury Model used, provide a useful system for the consideration of potential therapies which might ameliorate neuropsychological deficits in diffuse brain injury. [Neurol Res 1999; 21: 742-754]

Acute blood-brain barrier changes in experimental closed head injury as measured by MRI and Gd-DTPA.

The objective of this study was to determine the early time course of blood-brain barrier (BBB) changes in diffuse closed head injury (CHI) and to what extent BBB is affected by secondary insult. The BBB disruption was quantified using T1-weighted MRI following administration of Gd-DTPA. The maximal signal intensity (SI) enhancement was used to calculate BBB disruption. A new CHI model was used to induce injury. Adult SD rats were separated into four groups: Group I: Sham (n = 4), II: Hypoxia and Hypotension (HH, n = 4), III: Trauma alone (n = 23), and IV: Trauma coupled with HH (THH, n = 14). Following trauma, a 30 minute insult of hypoxia (PaO2 = 40 mmHg) and hypotension (MABP = 30 mmHg) were imposed. In trauma animals, SI increased dramatically immediately following impact. By 15 minutes, permeability decreased exponentially and by 30 minutes was equal to that of control. In THH animals, SI enhancement was lower after the trauma, consistent with reduced blood pressure and blood flow. However, the SI increased dramatically upon reperfusion and was equal to that of control after 60 minutes. In conclusion we may consider, that CHI is associated with a rapid and transient BBB opening which begins at the time of the trauma and lasts not more than 30 minutes. It has been also shown that addition of hypoxia and hypotension prolongs the time of BBB breakdown.

Effect of hypoxia on lung lymph flow in newborn lambs with left atrial hypertension.

To determine the effect of left atrial hypertension on the vascular response to hypoxia in the newborn lung, we measured pulmonary artery and left atrial pressures, lung blood flow and lymph flow, and concentrations of protein in lymph and plasma of 13 lambs that spontaneously breathed air for 2-6 h (control period), followed by 8-11% O2 mixed with 3-5% CO2 and N2 for 2-4 h (experimental period). In eight studies, the lambs were made hypoxic first, after which we elevated their left atrial pressure by 10-12 Torr for 2-3 h. In 10 additional studies, we reversed the sequence by raising left atrial pressure first followed by addition of hypoxia. In lambs with normal left atrial pressure, alveolar hypoxia increased both pulmonary blood flow and lymph flow, with an associated reduction in lymph-to-plasma protein ratio (L/P). When left atrial pressure was increased in the presence of hypoxia, lymph flow increased by a small amount and L/P decreased further. In lambs with preexisting left atrial pressure elevation, addition of alveolar hypoxia increased both blood flow and lymph flow with no significant change in L/P. These results suggest that in newborn lambs with normal left atrial pressure, alveolar hypoxia increases lung lymph flow mainly by increasing microvascular filtration pressure, whereas in lambs with elevated left atrial pressure, hypoxia increases lymph flow by another mechanism, perhaps by increasing the perfused surface area for fluid filtration.