Acute Systemic Hypoxia Research Articles

Skeletal muscle vasodilation during systemic hypoxia in humans.

In humans, the net effect of acute systemic hypoxia in quiescent skeletal muscle is vasodilation despite significant reflex increases in muscle sympathetic vasoconstrictor nerve activity. This vasodilation increases tissue perfusion and oxygen delivery to maintain tissue oxygen consumption. Although several mechanisms may be involved, we recently tested the roles of two endothelial-derived substances during conditions of sympathoadrenal blockade to isolate local vascular control mechanisms: nitric oxide (NO) and prostaglandins (PGs). Our findings indicate that 1) NO normally plays a role in regulating vascular tone during hypoxia independent of the PG pathway; 2) PGs do not normally contribute to vascular tone during hypoxia, however, they do affect vascular tone when NO is inhibited; 3) NO and PGs are not independently obligatory to observe hypoxic vasodilation when assessed as a response from rest to steady-state hypoxia; and 4) combined NO and PG inhibition abolishes hypoxic vasodilation in human skeletal muscle. When the stimulus is exacerbated via combined submaximal rhythmic exercise and systemic hypoxia to cause further red blood cell (RBC) deoxygenation, skeletal muscle blood flow is augmented compared with normoxic exercise via local dilator mechanisms to maintain oxygen delivery to active tissue. Data obtained in a follow-up study indicate that combined NO and PG inhibition during hypoxic exercise blunts augmented vasodilation and hyperemia compared with control (normoxic) conditions by ∼50%; however, in contrast to hypoxia alone, the response is not abolished, suggesting that other local substances are involved. Factors associated with greater RBC deoxygenation such as ATP release, or nitrite reduction to NO, or both likely play a role in regulating this response.

Modulation of Vasculogenesis under rhEPO Therapy Following Acute Cerebral Hypoxia in the Mouse

Background: Hypoxic-ischemic insults are a major cause of perinatal acquired central nervous system lesions and modulate vasculogenesis and angiogenesis of the immature brain. To assess the efficacy of neuroprotective therapies, proapoptotic effects as well as a comprehensive analysis of vessel formation and vessel development are essential. Against this background, we investigated the effect of a pharmacological stabilization of the system of hypoxia inducible factors (HIFs) by recombinant human erythropoietin (rhEPO) in a mouse model of neonatal acute systemic hypoxia.

Nail fold capillary diameter changes in acute systemic hypoxia

The present study was undertaken to determine the effect of arterial blood hypoxemia induced by acute systemic hypoxia (pO2=12%) on capillary recruitment and diameter, and red blood cell (RBC) velocity in human nail fold capillaries during rest, arterial post-occlusive reactive hyperemia (PRH), and venous occlusion (VO) using intravital video-capillaroscopy. Capillary recruitment was unchanged in acute systemic hypoxia (H) versus normoxia (N). There was no difference in RBC velocity measurements between normoxia and hypoxia (P<0.63). However, a statistically significant increase in nail fold capillary total width (N, 39.9±9.1 vs. H, 42.7±10.3μm; P<0.05), apical diameter (N, 15.5±4.3 vs. H, 16.8±4.3μm; P<0.05), arterial diameter (N, 11.9±3.5 vs. H, 13.9±4.1μm; P<0.05), and venous diameter (N, 15.5±4.3 vs. H, 17.2±4.8μm; P<0.05) was observed and continued to be significant most often during post-occlusive reactive hyperemia (PRH) and venous congestion (VO). These data suggest that acute systemic hypoxia does not increase capillary recruitment, but instead increases capillary diameter, resulting in increased capillary blood flow.

Circulating N-terminal brain natriuretic peptide and cardiac function in response to acute systemic hypoxia in healthy humans.

BackgroundAs it remains unclear whether hypoxia of cardiomyocytes could trigger the release of brain natriuretic peptide (BNP) in humans, we investigated whether breathing normobaric hypoxic gas mixture increases the circulating NT-proBNP in healthy male subjects.MethodsTen healthy young men (age 29 ± 5 yrs, BMI 24.7 ± 2.8 kg/m2) breathed normobaric hypoxic gas mixture (11% O2/89% N2) for one hour. Venous blood samples were obtained immediately before, during, and 2 and 24 hours after hypoxic exposure. Cardiac function and flow velocity profile in the middle left anterior descending coronary artery (LAD) were measured by Doppler echocardiography.ResultsArterial oxygen saturation decreased steadily from baseline value of 99 ± 1% after the initiation hypoxia challenge and reached steady-state level of 73 ± 6% within 20–30 minutes. Cardiac output increased from 6.0 ± 1.2 to 8.1 ± 1.6 L/min and ejection fraction from 67 ± 4% to 75 ± 6% (both p < 0.001). Peak diastolic flow velocity in the LAD increased from 0.16 ± 0.04 to 0.28 ± 0.07 m/s, while its diameter remained unchanged. In the whole study group, NT-proBNP was similar to baseline (60 ± 32 pmol/ml) at all time points. However, at 24 h, concentration of NT-proBNP was higher (34 ± 18%) in five subjects and lower (17 ± 17%), p = 0.002 between the groups) in five subjects than at baseline.ConclusionIn conclusion, there is no consistent increase in circulating NT-proBNP in response to breathing severely hypoxic normobaric gas mixture in healthy humans, a possible reason being that the oxygen flux to cardiac myocytes does not decrease because of increased coronary blood flow. However, the divergent individual responses as well as responses in different cardiac diseases warrant further investigations.

Acute systemic hypoxia activates hypothalamic paraventricular nucleus-projecting catecholaminergic neurons in the caudal ventrolateral medulla

Hypoxia activates catecholamine neurons in the caudal ventrolateral medulla (CVLM). The hypothalamic paraventricular nucleus (PVN) modulates arterial chemoreflex responses and receives catecholaminergic projections from the CVLM, but it is not known whether the CVLM-PVN projection is activated by chemoreflex stimulation. We hypothesized that acute hypoxia (AH) activates PVN-projecting catecholaminergic neurons in the CVLM. Fluoro-Gold (2%, 60-90 nl) was microinjected into the PVN of rats to retrogradely label CVLM neurons. After recovery, conscious rats underwent 3 h of normoxia (21% O2, n = 4) or AH (12, 10, or 8% O2; n = 5 each group). We used Fos immunoreactivity as an index of CVLM neuronal activation and tyrosine hydroxylase (TH) immunoreactivity to identify catecholaminergic neurons. Positively labeled neurons were counted in six caudal-rostral sections containing CVLM. Hypoxia progressively increased the number of Fos-immunoreactive CVLM cells (21%, 19 ± 6; 12%, 49 ± 2; 10%, 117 ± 8; 8%, 179 ± 7; P < 0.001). Catecholaminergic cells colabeled with Fos immunoreactivity in the CVLM were observed following 12% O2, and further increases in hypoxia severity caused markedly more activation. PVN-projecting CVLM cells were activated following more severe hypoxia (10% and 8% O2). A large proportion (89 ± 3%) of all activated PVN-projecting CVLM neurons were catecholaminergic, regardless of hypoxia intensity. Data suggest that catecholaminergic, PVN-projecting CVLM neurons are particularly hypoxia-sensitive, and these neurons may be important in the cardiorespiratory and/or neuroendocrine responses elicited by the chemoreflex.

Acute Kidney Injury at High Altitude

Acute ascent to high altitudes beyond 2400 m (300 feet) can cause acute mountain sickness (AMS) and may develop into life-threatening complications such as high altitude cerebral (HACE) and pulmonary edema (HAPE). We report a case of acute kidney injury (AKI) without other organ involvement in a previously healthy young man after sudden high altitude exposure of up to 5200 m. Acute systemic hypoxia as well as prolonged renal hypoperfusion may be responsible for his kidney injury.

Regenerative neuronal proliferation in hypoxic developing mouse brain is transient and modified by erythropoietin treatment

Aims: Impaired neuronal proliferation and migration are part of the destructive cascade following hypoxic injuries in neonatal brains. The present study aimed to elucidate regenerative changes in cell proliferation within regions of high vulnerability to hypoxia in developing mouse brain after acute systemic hypoxia and treatment with erythropoietin (EPO) at different maturational stages.

Effect of ghrelin on brain edema induced by acute and chronic systemic hypoxia

Hypoxia is an important pathogenic factor for the induction of vascular leakage and brain edema formation. Recent studies suggest a role for TNF-α in the induction of brain edema. Ghrelin attenuates the synthesis of TNF-α following subarachnoid hemorrhage and traumatic brain injury (TBI). Therefore, we examined the effects of ghrelin on the brain edema, serum TNF-α levels and body weight in a systemic hypoxia model. Adult male Wistar rats were divided into acute and chronic controls, acute or chronic hypoxia and ghrelin-treated (80μg/kg/ip/daily) acute or chronic hypoxia groups. Systemic hypoxia was induced in rats by a normobaric hypoxic chamber (O2 11%) for two days (acute) or ten days (chronic). Effect of ghrelin on brain edema and serum TNF-α levels was assessed by dry–wet and ELISA method, respectively. The results showed that acute (P<0.001) and chronic (P<0.05) hypoxia caused an increase of brain water content. Administration of ghrelin only in the acute hypoxia group significantly (P<0.001) reduced brain water content. Acute hypoxia caused an increase of serum TNF-α level (P<0.001) and ghrelin significantly (P<0.001) reduced it. TNF-α level in chronic hypoxia did not change significantly. Both acute and chronic hypoxia decreased body weight significantly (P<0.001) and administration of ghrelin only could prevent further weight loss in chronic hypoxia group (P<0.001). Our findings show that administration of ghrelin may be useful in reducing brain edema induced by acute systemic hypoxia and at least part of the anti-edematous effects of ghrelin is due to decrease of serum TNF-α levels.

Acute hypoxia modifies regulation of neuroglobin in the neonatal mouse brain

Among endogenous adaptive systems to hypoxia, neuroglobin, a recently discovered heme protein, was suggested as a novel oxygen-dependent neuroprotectant. We aimed to characterize i) maturational age-related regulation of neuroglobin in the developing mouse brain under normoxic and hypoxic conditions, and ii) the role of hypoxia-inducible transcription factors (HIFs) as possible mediators of O2-dependent regulation of neuroglobin in vitro and in vivo.During early stages of postnatal brain maturation (P0–P14) neuroglobin mRNA levels significantly increased in developing mouse forebrains. By immunohistochemical analysis we confirmed expression of neuroglobin protein in the cytoplasm of developing neurons but not glial cells under normoxic conditions. Exposure of the immature brains (P0, P7) to acute (8% O2, 6h) and chronic systemic hypoxia (10% O2, 7days) led to differential activation of neuroglobin varying with maturational stage (P0, P7) and severity of hypoxia. This observation may indicate that neuroglobin is involved in adaptive responses of immature neurons to acute hypoxia during an early stage of mouse brain maturation (P0). In response to activation of the HIF system by prolyl-4-hydroxylase inhibitor (FG-4497), neuroglobin mRNA expression was significantly up-regulated in primary mouse cortical neurons (DIV6) exposed to normoxia and hypoxia (1% O2) compared to non-treated controls.In conclusion, present results strongly indicate that cerebral regulation of neuroglobin is related to maturational stage and that hypoxia-induced neuroglobin up-regulation is modified by the HIF system.

Prolyl Hydroxylase Inhibition Attenuates Mast Cell Degranulation During Systemic Hypoxia Via Upregulation of Heme Oxygenase‐1

Acute systemic hypoxia (Hx) causes mast cell degranulation and increased leukocyte adherence in post‐capillary venules of rats. When animals are chronically hypoxic, microvascular inflammation resolves in part due to upregulation of heme oxygenase‐1 (HO‐1), which prevents mast cell activation. Inhibition of prolyl hydroxylase (PHD) increases hypoxia‐inducible factor‐1 (HIF‐1) levels, which promotes HO‐1 expression.ObjectiveOur goal was to evaluate whether inhibition of PHD attenuated Hx‐induced mast cell degranulation, and if upregulation of HO‐1 was involved.MethodsIntravital microscopy was used to measure mast cell degranulation and leukocyte adherence in mesenteric venules of anesthetized rats. The PHD inhibitor ethyl dihydroxybenzoate (EDHB) was injected s.c. to rats 24 hrs prior to experiments. Hx was produced in rats breathing 10% O2.ResultsHx caused mast cell degranulation and increased leukocyte adherence in the mesenteric microcirculation of vehicle‐ but not EDHB‐treated rats. Superfusion of the mesentery with the HO‐1 inhibitor zinc protoporphyrin caused a significant increase in mast cell degranulation and leukocyte adherence during Hx in EDHB‐ but not in vehicle‐treated rats.ConclusionInhibition of PHD reduces Hx‐induced mast cell degranulation and leukocyte adherence in part through HO‐1 upregulation, which is consistent with a HIF‐1‐dependent mechanism.

Effects of Low-Intensity Resistance Exercise Under Acute Systemic Hypoxia on Hormonal Responses

Previous studies have shown that low-intensity resistance exercises with vascular occlusion and slow movement effectively increase muscular size and strength. Researchers have speculated that local hypoxia by occlusion and slow movement may contribute to such adaptations via promoting anabolic hormone secretions by the local accumulation of metabolites. In this study, we determined the effects of low-intensity resistance exercise under acute systemic hypoxia on metabolic and hormonal responses. Eight male subjects participated in 2 experimental trials: (a) low-intensity resistance exercise while breathing normoxic air (normoxic resistance exercise [NR]), (b) low-intensity resistance exercise while breathing 13% oxygen (hypoxic resistance exercise [HR]). The resistance exercises (bench press and leg press) consisted of 14 repetitions for 5 sets at 50% of maximum strength with 1 minute of rest between sets. Blood lactate (LA), serum growth hormone (GH), norepinephrine (NE), testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures; 15 minutes after the exposures; and at 0, 15, and 30 minutes after the exercises. The LA levels significantly increased after exercises in both trials (p ≤ 0.05). The area under the curve for LA after exercises was significantly higher in the HR trial than in the NR trial (p ≤ 0.05). The GH significantly increased only after the HR trial (p ≤ 0.05). The NE and testosterone significantly increased after the exercises in both trials (p ≤ 0.05). Cortisol did not significantly change in both trials. These results suggest that low-intensity resistance exercise in the hypoxic condition caused greater metabolic and hormonal responses than that in the normoxic condition. Coaches may consider low-intensity resistance exercise under systemic hypoxia as a potential training method for athletes who need to maintain muscle mass and strength during the long in-season.

Fast reduction of peripheral blood endothelial progenitor cells in healthy humans exposed to acute systemic hypoxia

There are hints that hypoxia exposure may affect the number of circulating endothelial progenitor cells (EPCs) in humans. To test this hypothesis, the concentration of EPCs was determined by flow cytometry in the peripheral blood of 10 young healthy adults before (0 h), at different times (0.5 h, 1 h, 2 h and 4 h) during a 4 h normobaric hypoxic breathing simulating 4100 m altitude, and in the following recovery breathing room air. Results were interpreted mainly on the basis of the changes in surface expression of CXC chemokine receptor-4 (CXCR-4, a chemokine receptor essential for EPC migration and homing) and the percentage of apoptotic cells, the plasmatic levels of markers of oxidative stress induced by hypoxic breathing. Compared to 0 h, the concentration of EPCs, identified as either CD45(dim)/CD34(+)/KDR(+) or CD45(dim)/CD34(+)/KDR(+)/CD133(+) cells, decreased from 337 ± 83 ml(-1) (mean ± SEM) to 223 ± 52 ml(-1) (0.5 h; P < 0.005) and 100 ± 37 ml(-1) (4 h; P < 0.005), and from 216 ± 91 to 161 ± 50 ml(-1) (0.5 h; P < 0.05) and 45 ± 23 ml(-1) (4 h; P < 0.005), respectively. Upon return to normoxia, their concentration increased slowly, and after 4 h was still lower than at 0 h (P < 0.05). During hypoxia, CXCR-4 expression and plasmatic stromal derived cell factor-1 (SDF-1) increased abruptly (0.5 h: +126% and +13%, respectively; P < 0.05), suggesting cell marginalization as a possible cause of the rapid hypoxia-induced EPC reduction. Moreover, hypoxia exposure induced an increase in EPC apoptosis and markers of oxidative stress, which was significantly evident only starting from 2 h and 4 h after hypoxia offset, respectively, suggesting that EPC apoptosis may contribute to the later phase of hypoxia-induced EPC reduction. Overall, these observations may provide new insights into the understanding of the mechanisms operated by EPCs to maintain endothelial homeostasis.

Local control of skeletal muscle blood flow during exercise: influence of available oxygen

Reductions in oxygen availability (O(2)) by either reduced arterial O(2) content or reduced perfusion pressure can have profound influences on the circulation, including vasodilation in skeletal muscle vascular beds. The purpose of this review is to put into context the present evidence regarding mechanisms responsible for the local control of blood flow during acute systemic hypoxia and/or local hypoperfusion in contracting muscle. The combination of submaximal exercise and hypoxia produces a "compensatory" vasodilation and augmented blood flow in contracting muscles relative to the same level of exercise under normoxic conditions. A similar compensatory vasodilation is observed in response to local reductions in oxygen availability (i.e., hypoperfusion) during normoxic exercise. Available evidence suggests that nitric oxide (NO) contributes to the compensatory dilator response under each of these conditions, whereas adenosine appears to only play a role during hypoperfusion. During systemic hypoxia the NO-mediated component of the compensatory vasodilation is regulated through a β-adrenergic receptor mechanism at low-intensity exercise, while an additional (not yet identified) source of NO is likely to be engaged as exercise intensity increases during hypoxia. Potential candidates for stimulating and/or interacting with NO at higher exercise intensities include prostaglandins and/or ATP. Conversely, prostaglandins do not appear to play a role in the compensatory vasodilation during exercise with hypoperfusion. Taken together, the data for both hypoxia and hypoperfusion suggest NO is important in the compensatory vasodilation seen when oxygen availability is limited. This is important from a basic biological perspective and also has pathophysiological implications for diseases associated with either hypoxia or hypoperfusion.

The effect and clinical consequences of hypoxia on cytochrome P450, membrane carrier proteins activity and expression

Introduction: Chronic pulmonary disease and heart failure reduce drug clearance and consequently enhance adverse drug reactions. The mechanisms of action underlying the regulation of cytochrome P450 (CYP) isoforms and membrane carrier proteins by hypoxia, and the clinical consequences of the regulation of CYP by hypoxia, alone or combined with other conditions have been elucidated in the last decades. Overall, a reduced drug clearance appears to be associated with hypoxemia.Areas covered: In this review, the mechanisms of action underlying hypoxia-induced regulation of CYP enzymes are discussed. The authors also revise the effects of hypoxia on serum mediators, signal transduction pathways, orphan nuclear receptors, transcription factors and post-transcriptional mechanisms regulating CYP and membrane carrier proteins expression. Additionally, the paper also discusses the clinical repercussions of hypoxia-induced changes in CYP and membrane carrier proteins activity.Expert opinion: Acute systemic hypoxia down-regulates selected CYP isoforms and up-regulates CYP3A4 and P-glycoprotein, changing the metabolic clearance of drugs and endogenous compounds biotransformed by these isoforms as well as the kinetics. In patients with acute hypoxia, the dosage of drugs, biotransformed by CYP isoforms, may need to be adjusted. Tissue hypoxia enhances the expression of efflux membrane carrier proteins, increasing the probability of drug resistance.

Combined inhibition of nitric oxide and vasodilating prostaglandins abolishes forearm vasodilatation to systemic hypoxia in healthy humans

We tested the hypothesis that nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute independently to hypoxic vasodilatation, and that combined inhibition would reveal a synergistic role for these two pathways in the regulation of peripheral vascular tone. In 20 healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) responses to steady-state (SS) isocapnic hypoxia (O₂ saturation ~85%). All trials were performed during local α- and β-adrenoceptor blockade (via a brachial artery catheter) to eliminate sympathoadrenal influences on vascular tone and thus isolate local vasodilatory mechanisms. The individual and combined effects of NO synthase (NOS) and cyclooxygenase (COX) inhibition were determined by quantifying the vasodilatation from rest to SS hypoxia, as well as by quantifying how each inhibitor reduced vascular tone during hypoxia. Three hypoxia trials were performed in each subject. In group 1 (n = 10), trial 1, 5 min of SS hypoxia increased FVC from baseline (21 ± 3%; P < 0.05). Infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) for 5 min to inhibit NOS during continuous SS hypoxia reduced FVC by -33 ± 3% (P < 0.05). In Trial 2 with continuous NOS inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (20 ± 3%), and infusion of ketorolac for 5 min to inhibit COX during continuous SS hypoxia reduced FVC by -15 ± 3% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). In group 2 (n = 10), the order of NOS and COX inhibition was reversed. In trial 1, five minutes of SS hypoxia increased FVC from baseline (by 24 ± 5%; P < 0.05), and infusion of ketorolac during SS hypoxia had minimal impact on FVC (-4 ± 3%; NS). In Trial 2 with continuous COX inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (27 ± 4%), and infusion of L-NAME during continuous SS hypoxia reduced FVC by -36 ± 7% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). Our collective findings indicate that (1) neither NO nor PGs are obligatory to observe the normal local vasodilatory response from rest to SS hypoxia; (2) NO regulates vascular tone during hypoxia independent of the COX pathway, whereas PGs only regulate vascular tone during hypoxia when NOS is inhibited; and (3) combined inhibition of NO and PGs abolishes local hypoxic vasodilatation (from rest to SS hypoxia) in the forearm circulation of healthy humans during systemic hypoxia.

Effects of maternal hypoxia on muscle vasodilatation evoked by acute systemic hypoxia in adult rat offspring: changed roles of adenosine and A1receptors

Suboptimal conditions in utero can have long-lasting effects including increased risk of cardiovascular disease in adult life. Such programming effects may be induced by chronic systemic hypoxia in utero (CHU). We have investigated how CHU affects cardiovascular responses evoked by acute systemic hypoxia in adult male offspring, recognising that adenosine contributes to hypoxia-induced muscle vasodilatation and bradycardia by acting on A(1) receptors in normal (N) rats. In the present study, dams were housed in a hypoxic chamber at 12% O(2) for the second half of gestation; offspring were born and reared in air until 9-10 weeks of age. Under anaesthesia, acute systemic hypoxia (breathing 8% O(2) for 5 min) evoked similar biphasic tachycardia/bradycardia, fall in arterial pressure and increase in femoral vascular conductance (FVC) in N and CHU rats (+2.0 vs. +2.7 conductance units respectively). However, in CHU rats, neither the non-selective adenosine receptor antagonist 8-sulphophenyltheopylline (8-SPT), nor the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) affected the increase in FVC, but DPCPX attenuated the hypoxia-induced bradycardia. Further, in N and CHU rats, 5 min infusion of adenosine induced similar increases in FVC; in CHU rats, DPCPX reduced the adenosine-induced increase in FVC (by >50%) and accentuated the concomitant tachycardia. These results suggest that CHU rats have functional A(1) receptors in heart and vasculature, but the release and/or vasodilator influence of adenosine on the endothelium in acute hypoxia is attenuated and replaced by other dilator factors. Such changes from normal endothelial function may have implications for general cardiovascular regulation.

Effects of Acute Hypoxia on Metabolic and Hormonal Responses to Resistance Exercise

Several recent studies have shown that resistance exercise combined with vascular occlusion effectively causes increases in muscular size and strength. Researchers speculated that the vascular occlusion-induced local hypoxia may contribute to the adaptations via promoting anabolic hormone secretions stimulated by local accumulation of metabolic subproducts. Here, we examined whether acute systemic hypoxia affects metabolic and hormonal responses to resistance exercise. Twelve male subjects participated in two experimental trials: 1) resistance exercise while breathing normoxic air [normoxic resistance exercise (NR)] and 2) resistance exercise while breathing 13% oxygen [hypoxic resistance exercise (HR)]. The resistance exercises (bench press and leg press) consisted of 10 repetitions for five sets at 70% of maximum strength with 1-min rest between sets. Blood lactate, serum growth hormone (GH), epinephrine (E), norepinephrine (NE), insulin-like growth factor 1, testosterone, and cortisol concentrations were measured before normoxia and hypoxia exposures, 15 min after the exposures, and at 0, 15, 30, and 60 min after the exercises. Lactate significantly increased after exercises in both trials (P < 0.05). In the HR trial, GH and cortisol significantly increased after the exercise (P < 0.05) but not in the NR trial. The E, NE, insulin-like growth factor 1, and testosterone significantly increased after the exercises in both trials (P < 0.05). The mean values of lactate, GH, E, and NE after exercises were significantly higher in the HR trial than those in the NR trial (P < 0.05). These findings suggest that resistance exercise in hypoxic condition caused greater accumulation of metabolites and strong anabolic hormone response.

Hypoxia-induced vasodilation and effects of regional phentolamine in awake patients with sleep apnea

Obstructive sleep apnea (OSA) is associated with increased sympathetic nerve activity, endothelial dysfunction, and premature cardiovascular disease. To determine whether hypoxia is associated with impaired skeletal muscle vasodilation, we compared femoral artery blood flow (ultrasound) and muscle sympathetic nerve activity (peroneal microneurography) during exposure to acute systemic hypoxia (fraction of inspired oxygen 0.1) in awake patients with OSA (n=10) and controls (n=8). To assess the role of elevated sympathetic nerve activity, in a separate group of patients with OSA (n=10) and controls (n=10) we measured brachial artery blood flow during hypoxia before and after regional alpha-adrenergic block with phentolamine. Despite elevated sympathetic activity, in OSA the vascular responses to hypoxia in the leg did not differ significantly from those in controls [P=not significant (NS)]. Following regional phentolamine, in both groups the hypoxia-induced increase in brachial blood flow was markedly enhanced (OSA pre vs. post, 84+/-13 vs. 201+/-34 ml/min, P<0.002; controls pre vs. post 62+/-8 vs. 140+/-26 ml/min, P<0.01). At end hypoxia after phentolamine, the increase of brachial blood flow above baseline was similar (OSA vs. controls +61+/-16 vs. +48+/-6%; P=NS). We conclude that despite high sympathetic vasoconstrictor tone and prominent sympathetic responses to acute hypoxia, hypoxia-induced limb vasodilation is preserved in OSA.

Heme Oxygenase‐1 Upregulation Following Prolyl Hydroxylase Inhibition Attenuates Hypoxia‐Induced Microvascular Inflammation.

Acute systemic hypoxia (Hx) promotes leukocyte adherence in post‐capillary venules of rats. When animals are chronically hypoxic, the initial microvascular inflammation resolves in part due to upregulation of heme oxygenase‐1 (HO‐1). Inhibition of prolyl hydroxylase (PHD) has been shown to increase hypoxia‐inducible factor‐1 (HIF‐1) levels, which can increase HO‐1 expression. Increased tissue levels of HO‐1 have been shown to attenuate microvascular injury after hemorrhagic shock.ObjectiveThis study evaluated whether inhibition of PHD attenuated Hx‐induced microvascular inflammation, and if upregulation of HO‐1 was involved.MethodsIntravital microscopy was used to measure leukocyte adherence in mesenteric venules of anesthetized rats. The PHD inhibitor EDHB was administered in carboxymethyl cellulose (vehicle) s.c. to rats 24 hrs prior to experiments. HO protein levels in mesentery were measured by western blotting.ResultsHx caused a rapid increase in leukocyte adherence in vehicle‐ but not in EDHB‐treated rats. Superfusion of the mesentery with the HO inhibitor zinc protoporphyrin caused a significant increase in adherent leukocytes during Hx in EDHB‐ but not in vehicle‐treated rats. HO protein levels were significantly elevated in mesenteries of EDHB‐treated rats compared to vehicle‐treated animals.ConclusionThese results show that inhibition of PHD reduces Hx‐induced microvascular inflammation in part through HO upregulation, and are consistent with a HIF‐1‐dependent mechanism.

Intra-Operative Somatosensory-Evoked Potential Monitoring

To evaluate the usefulness of intra-operative somatosensory-evoked potentials (SSEPs) in monitoring spinal cord status via the posterior tibial nerve. 84 men and 28 women aged 16 to 66 years (72% were aged 20 to 40 years) with spinal trauma (63 in the lumbar and 49 in the thoracic spine) underwent posterior instrumentation and fusion using bone grafts. All 63 patients with lumbar spinal injury and 35 of the patients with thoracic spinal injury were treated with pedicular screws. The remaining 14 patients had their thoracic spinal injury fixed with sublaminar wires. Cortical scalp recordings were used. Baseline tracings were obtained prior to surgical intervention and after establishment of anaesthesia. If changes persisted for more than 15 to 20 minutes or if they did not show definite signs of resolution, event reversal was considered. Of the 112 patients, 74 (66%) had no changes in Cz-Fpz patterns and neurological status, whereas 14 (13%) showed improved patterns (2 of them had the same neurological status postoperatively) and 24 (21%) displayed deteriorated patterns prompting intervention. Of the 24 patients prompting intervention, 20 improved substantially (19 had no new neurological deficits and one had deteriorated neurological status) and 4 improved minimally (2 had no new deficit and 2 had new deficits), with 88% sensitivity and 78% specificity. 15 patients were true-positives with an identifiable cause; 21 were false-positives with no neurological deterioration or recognisable cause. Intra-operative SSEP monitoring helps identify acute neurological and systemic (hypoxia or hypotension) impairment and enables prompt correction. This makes surgery available to high-risk patients and enables surgeons to carry out more extensive procedures. It also provides valuable documentation in the event of medico-legal dispute.