Effects Of Hypobaric Hypoxia Research Articles

Effects of Hypobaric Hypoxia in Various Modes on Expression of Neurogenesis Marker NeuroD2 in the Dentate Gyrus of Rats Hippocampus.

The expression of neurogenesis marker--NeuroD2 transcription factor--in the hippocampal dentate gyrus was studied in rats exposed to severe destructive hypoxia, a single or three episodes of moderate hypobaric hypoxia, preconditioned severe hypoxia, and severe hypoxia followed by 3 sessions of postconditioning by moderate hypobaric hypoxia. All the studied hypoxic exposure modes led to an increase of NeuroD2 level. Three-fold moderate hypoxia per se and in the preconditioning mode (followed by exposure to severe hypoxia) produced most pronounced up-regulatory effect on NeuroD2 expression. The results indicated that stimulation of neurogenesis processes seemed to be one of the aspects of the neuroprotective effect of three-fold preconditioning moderate hypoxia, but not of hypoxic postconditioning.

Brain Food at High Altitude.

Scenic view at high altitude is a pleasure to the eyes, but it has some shortcoming effects as well. High altitude can be divided into different categories, i.e., high altitude (3000-5000 ft), very high altitude (5000-8000 ft), and extreme altitude (above 8000 ft). Much of the population resides at high altitude, and others go there for tourism. Military personnel are also posted there to defend boundaries. As we ascent to high altitude, partial pressure of oxygen reduces, whereas concentration remains the same; this reduces the availability of oxygen to different body parts. This pathophysiological condition is known as hypobaric hypoxia (HH) which leads to oxidative stress and further causes cognitive dysfunction in some cases. Hypoxia causes neurodegeneration in different brain regions; however, the hippocampus is found to be more prone in comparison to other brain regions. As the hippocampus is affected most, therefore, spatial memory is impaired most during such condition. This chapter will give a brief review of the damaging effect of high altitude on cognition and also throw light on possible herbal interventions at high altitude, which can improve cognitive performance as well as provide protection against the deteriorating effect of hypobaric hypoxia at high altitude.

Dihydromyricetin Improves Hypobaric Hypoxia-Induced Memory Impairment via Modulation of SIRT3 Signaling.

Inadequate oxygen availability-for instance at high altitudes-leads to hippocampal neurodegeneration and memory impairment. Although oxidative stress is one factor, the mechanism underlying the effects of hypobaric hypoxia (HH) are unclear, and effective strategies for preventing the resultant damage to the brain are limited. In the present study, we demonstrate that ingesting dihydromyricetin (DM) protects against memory impairment in adult rats subjected to HH for 7days, equivalent to an altitude of 5000m above sea level. Moreover, DM treatment stimulated mitochondrial biogenesis and improved mitochondrial morphology and function, suppressed the generation of reactive oxygen species, and reduced lipid peroxidation in the hippocampus. In HT-22 cells exposed to hypoxic conditions, the neuroprotective effects of DM were shown to be exerted via attenuation of oxidative stress through sirtuin 3-induced forkhead box O3 deacetylation.

Hypobaric Hypoxia Induces Hypercoagulability Due to an Increase in Microparticles

Studies investigating the role of hypoxia on coagulation, either by going to high altitude or after a long-haul flight, reveal contrasting results. Previous work from our group suggests that the cellular part of the blood is involved in causing a prothrombotic phenotype. Therefore this study investigated the effect of hypobaric hypoxia on blood coagulation, focusing on the role of cellular components.After approval from the local medical ethics committee, 16 healthy participants (aged 20 to 50 years old) were included in this study. Exclusion criteria were a history of cardiovascular disease or pulmonary disease, impaired mobility, and medication known to interfere with coagulation. Participants ascended by cable car to 3,883 meters above sea level, after acclimatizing to altitude for 6 days. At 50 meters and 3,883 meters above sea level, blood was drawn and vital signs (SpO2, heart rate) and the Lake Louise acute mountain sickness questionnaire (LLQ) were recorded. The following tests were performed on whole blood: hemoglobin (Hb), hematocrit (Ht), leucocyte count (L), platelet count (PC) and mean platelet volume (MPV); thrombin generation (TG) in whole blood (WB-TG) with 0.5 pM tissue factor (TF); platelet activation test (PAc-T) triggered by adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and collagen related peptide (CRP) in end concentrations of respectively 10 µM, 30 µM and 1 µg ml-1. The remainder of the blood was centrifuged to obtain platelet rich plasma (PRP) (once for 15 minutes at 230 g) and platelet poor plasma (PPP) (twice for 10 minutes at 2,821 g). PRP was used to test PRP-TG (1 pM TF) and plasma was used for PPP-TG (1 pM TF) and microparticles (MP)-TG (0 pM TF). The paired t-test with p <0.05 was used to determine statistical significance within participants.At 3,883 meters above sea level, oxygen saturation decreased and heart rate increased significantly. LLQ scores revealed mild acute mountain sickness (AMS) symptoms. One participant was withdrawn from the study at 3,030 meters due to moderate AMS. After applying TG in PPP, PRP and whole blood, we found that peak height and endogenous thrombin potential (ETP) were increased. Interestingly, we found a decrease in platelet activation and a decreased MPV. To find an explanation for the increased TG in the different media, we performed a TG assay specially designed to detect microparticles. As with the PPP-TG, PRP-TG and WB-TG, we found an increase in ETP and peak height, proving increased content of MPs.In conclusion, we found that exposure to hypobaric hypoxia increased TG in PPP, PRP and in whole blood. In contrast we found that platelet activation was decreased, indicating that platelets do not play a role in hypoxia-induced hypercoagulability. The increase in peak and ETP in the MP-sensitive TG assay indicates that MPs play a major role in hypoxia-induced hypercoagulability. DisclosuresDe Laat:Synapse bv: Employment.

Effects of hypobaric hypoxia and voluntary hypocapnic hyperventilation on metabolic response during high-intensity intermittent exercise

To improve performance of short time high-intensity exercise, it is important to enhance anaerobic energy systems. High intensity intermittent exercise training stresses the anaerobic energy systems in order for improvements to occur. In addition, it is suggested that high intensity intermittent exercise under hypobaric hypoxia (HX) as well as reductions in arterial CO2 pressure (hypocapnia: HC) induced by voluntary hyperventilation could enhance anaerobic metabolic rate more effectively [1]. However, it is unclear whether the effects on anaerobic metabolic rate differ between HX and HC. Therefore, the purpose of this study was to investigate whether HX and HC have similar effects on metabolic response during high intensity intermittent exercise.

Acute Hypobaric Hypoxia Effects on Finger Temperature During and After Local Cold Exposure.

Mountain environments have combined stressors of lower ambient temperature and hypoxia. Cold alone can reduce finger temperature, resulting in discomfort, impaired dexterity, and increased risk of cold injury. Whether hypobaric hypoxia exacerbates these effects is unclear. To examine this, finger temperature responses to two cold water immersion tests were measured at sea level (SL, 99 kPa), 3000 m (70 kPa), and 4675 m (56 kPa) at the same air temperature (22°-23°C). Nine males sat quietly for 30 min, then completed the tests in balanced order. For the cold-induced vasodilation (CIVD) test, middle finger pad temperature was measured during immersion in 4°C water for 30 min. For the Rewarming test, finger temperature was measured for 30 min following a 5 min hand immersion in 16°C water. Average oxygen saturation was 98.6% during SL, 90.7% at 3000 m, and 75.8% at 4657 m. Mean finger temperature during the CIVD test (7.1°C) was similar among trials. There was no difference in CIVD parameters of nadir, apex, or mean finger temperatures; however both onset and apex times were earlier at 3000 m, compared to SL (0.6 min and 1.6 min, respectively). These differences did not persist at 4657 m. Rewarming after hand immersion was similar among trials, reaching 22.7°C after 30 min, compared to an initial finger temperature of 29.3°C. The results of this study provide no evidence that hypobaric hypoxia increases risk of cold injury. Previous findings of blunted finger temperatures at altitude are likely due to the lower ambient temperature that typically occurs at higher elevations.

Acute Mountain Sickness, Hypoxia, Hypobaria and Exercise Duration each Affect Heart Rate.

In this study, we quantified the changes in post-exercise resting heart rate (HRrst) associated with acute mountain sickness (AMS), and compared the effects of hypobaric hypoxia (HH) and normobaric hypoxia (NH) on HRrst. We also examined the modulating roles of exercise duration and exposure time on HRrst. Each subject participated in 2 of 6 conditions: normobaric normoxia (NN), NH, or HH (4 400 m altitude equivalent) combined with either 10 or 60 min of moderate cycling at the beginning of an 8-h exposure. AMS was associated with a 2 bpm higher HRrst than when not sick, after taking into account the ambient environment, exercise duration, and SpO2. In addition, HRrst was elevated in both NH and HH compared to NN with HRrst being 50% higher in HH than in NH. Participating in long duration exercise led to elevated resting HRs (0.8-1.4 bpm higher) compared with short exercise, while short exercise caused a progressive increase in HRrst over the exposure period in both NH and HH (0.77-1.2 bpm/h of exposure). This data suggests that AMS, NH, HH, exercise duration, time of exposure, and SpO2 have independent effects on HRrst. It further suggests that hypobaria exerts its own effect on HRrst in hypoxia. Thus NH and HH may not be interchangeable environments.

Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not in males.

Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males.

The physiological effects of hypobaric hypoxia versus normobaric hypoxia: a systematic review of crossover trials.

Much hypoxia research has been carried out at high altitude in a hypobaric hypoxia (HH) environment. Many research teams seek to replicate high-altitude conditions at lower altitudes in either hypobaric hypoxic conditions or normobaric hypoxic (NH) laboratories. Implicit in this approach is the assumption that the only relevant condition that differs between these settings is the partial pressure of oxygen (PO2), which is commonly presumed to be the principal physiological stimulus to adaptation at high altitude. This systematic review is the first to present an overview of the current available literature regarding crossover studies relating to the different effects of HH and NH on human physiology. After applying our inclusion and exclusion criteria, 13 studies were deemed eligible for inclusion. Several studies reported a number of variables (e.g. minute ventilation and NO levels) that were different between the two conditions, lending support to the notion that true physiological difference is indeed present. However, the presence of confounding factors such as time spent in hypoxia, temperature, and humidity, and the limited statistical power due to small sample sizes, limit the conclusions that can be drawn from these findings. Standardisation of the study methods and reporting may aid interpretation of future studies and thereby improve the quality of data in this area. This is important to improve the quality of data that is used for improving the understanding of hypoxia tolerance, both at altitude and in the clinical setting.

Isolated Generalized Tonic-Clonic Seizure at High Altitude in a Young Male Trekker with a Positive Family History of Seizure

An 18-year-old Caucasian male was trekking to Mount Everest base-camp (EBC) in Nepal during the spring of 2011. He normally lived at sea-level in the United Kingdom and had no previous medical history. His father had experienced one generalized tonic-clonic seizure at age 32, with no subsequent epileptiform events. The subject was in the control arm of a randomized controlled research study (n = 40) following a standardized ascent profile to EBC (Levett et al., 2010). Every morning he completed a Lake Louise AMS questionnaire (Roach et al., 1993) and had resting heart rate (HR), respiratory rate (RR), and peripheral oxygen saturations (Spo2) measured. Over 6 days, the subject had flown from Kathmandu (1300 meters) to Lukla (2800 meters) and trekked from Lukla to Pheriche (4250 meters). During this time, he reported no symptoms of AMS, whilst other research participants did experience symptoms (number of trekkers with AMS symptoms ranged between 0–9 per day). Additionally, the subject expressed no signs of high altitude cerebral edema (HACE), and recorded physiological variables that were similar to other study participants. At rest, on the morning of the seizure (7 day of trek), Spo2 was 85%, RR was 9 breaths.min , and HR was 55 beats.min 1 (vs. group means of 85%, 14 breaths.min , and 81 beats.min , respectively). The tonic-clonic seizure occurred in the absence of any obvious acute precipitating event in the presence of doctors at the Pheriche Himalayan Rescue Association clinic (4250 meters). The seizure was managed immediately with supplemental oxygen and 1000 mL of Dextrose Saline (4%/ 0.9%) intravenously. The seizure lasted approximately 1 minute and was followed by a 10 minute post-ictal phase characterized by drowsiness and confusion. Following recovery and a subsequent normal physical examination, the subject stated he had no memory of the episode, did not recall an aura prior to the event, and reported feeling previously well. He was repatriated to Kathmandu where an electroencephalogram and computed tomography of his head were both reported as ‘normal’ by attending specialists. He commenced a 10-day course of Lorazepam and returned to the UK, where cranial magnetic resonance imaging was reported as normal. He remains well 17 months post the event, and has had no subsequent seizures. This report highlights a young male with a family history of seizures, who experienced an isolated tonic-clonic seizure whilst hypoxemic at 4250 m. There was no evidence of AMS or HACE, and based on comparisons with his immediate trekking companions, cardiorespiratory physiological responses were normal for the altitude. Due to the limited amount of epidemiological data available, it is currently uncertain if high altitude per se is a trigger for epileptiform seizures. A number of anecdotal reports and small studies describe the occurrence of seizures at altitude and have suggested potential risk factors including sleep disturbance (Maa, 2010), hyperventilation (Daleau et al., 2006; Maa, 2011), and the direct effects of hypobaric hypoxia (Maa, 2011). Hypoxemia may have lowered the seizure threshold in this individual, something with potential implications for any person with either a personal or family history of seizure activity that is considering travelling to altitude. It is also possible that the occurrence of this seizure at altitude was coincidental; the rate of unprovoked seizures in a population from London has been reported at 57 per 100,000 per year (MacDonald et al., 2000). Given this uncertainty, this case report highlights the need for more robust epidemiological data collection to identify and quantify risk factors for high altitude seizures. Only through such studies will it be possible to establish whether altitude exposure per se increase the frequency of seizures and thereby refine advice for travellers planning ascents to high altitude.

Hypobaric Hypoxia Postconditioning Reduces Brain Damage and Improves Antioxidative Defense in the Model of Birth Asphyxia in 7-Day-Old Rats

Perinatal brain insult mostly resulting from hypoxia-ischemia (H-I) often brings lifelong permanent disability, which has a major impact on the life of individuals and their families. The lack of progress in clinically-applicable neuroprotective strategies for birth asphyxia has led to an increasing interest in alternative methods of therapy, including induction of brain tolerance by pre- and particularly postconditioning. Hypoxic postconditioning represents a promising strategy for preventing ischemic brain damage. The aim of this study was to investigate the potential neuroprotective effect of hypobaric hypoxia (HH) postconditioning applied to 7-day old rats after H-I insult. The mild hypobaric conditions (0.47 atm) used in this study imitate an altitude of 5,000 m. We show that application of mild hypobaric hypoxia at relatively short time intervals (1-6 h) after H-I, repeated for two following days leads to significant neuroprotection, manifested by a reduction in weight loss of the ipsilateral hemisphere observed 14 days after H-I. HH postconditioning results in decrease in reactive oxygen species level observed in all experimental groups. The increase in superoxide dismutase activity observed after H-I is additionally enhanced by HH postconditioning applied 1 h after H-I. The increase observed 3 and 6 h after H-I was not statistically significant. Postconditioning with HH suppresses the glutathione concentration decrease evoked by H-I and increased glutathione peroxidase activity and this effect is not dependent on the time of postconditioning initiation. HH postconditioning had no effect on catalase activity. We show for the first time that HH postconditioning reduces brain damage resulting from H-I in immature rats and that the mechanism potentially involved in this effect is related to antioxidant defense mechanisms of immature brain.

Metabolomic Analysis of Anti-Hypoxia and Anti-anxiety Effects of Fu Fang Jin Jing Oral Liquid

BackgroundHerba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL) with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics.MethodsIn our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin) and oxygen consumption increasing (exhaustive swimming) were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified.ResultsUpon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect.ConclusionsFJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug diazepam on the hypobaric hypoxia mice. FJJOL might serve as an alternative therapy for the hypoxia and anxiety disorders.

GW24-e2120 Intermittent hypobaric hypoxia promotes atherosclerotic plaque instability in ApoE-deficient mice

ObjectivesSudden cardiac death is one of the most frequent causes of death at high altitude. It has been reported that the intermittent normobaric hypoxia experienced by patients with obstructive sleep...

Intermittent Hypobaric Hypoxia Promotes Atherosclerotic Plaque Instability in ApoE-Deficient Mice

Sudden cardiac death is one of the most frequent causes of death at high altitude. It has been reported that the intermittent normobaric hypoxia experienced by patients with obstructive sleep apnea may enhance the development of atherosclerosis. However, the effect of hypobaric hypoxia, which mimics the ambient air at high altitude, in the development of atherosclerosis has not been investigated. Twenty male ApoE-deficient mice, 8 weeks of age, were subjected to either control conditions or intermittent hypobaric hypoxia (IHH) for 8 weeks. Mice in the IHH group were exposed to a hypobaric chamber that replicated the hypobaric hypoxia conditions found at 4000 m altitude for 8 hours a day. IHH-exposed mice did not significantly differ from control mice in plasma lipid levels, including triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein. The hematoxylin and eosin-stained sections of the aortic root showed similar plaque size between the groups. However, IHH-treated mice exhibited significantly decreased plaque collagen content, a feature of atherosclerotic plaque stability. Additionally, matrix metalloproteinase (MMP)-9 protein expression was significantly increased, whereas tissue inhibitor of MMP (TIMP)-2 expression was decreased after exposure to IHH. IHH may promote atherosclerotic plaque instability in ApoE-deficient mice by changing the balance of MMPs and TIMPs.

Erdosteine protects rat testis tissue from hypoxic injury by reducing apoptotic cell death

The purpose of this study was to examine the effects of hypobaric hypoxia on testis morphology and the effects of erdosteine on testis tissue. Caspase-3 and hypoxia-inducible factor 1α expressions were detected by immunohistochemistry. Adult male Wistar rats were placed in a hypobaric hypoxic chamber. Rats in the erdosteine group were exposed to the same conditions and treated orally with erdosteine (20 mg kg(-1) daily) at the same time from the first day of hypoxic exposure for 2 weeks. The normoxia group was evaluated as the control. The hypoxia group showed decreased height of spermatogenic epithelium in some seminiferous tubules, vacuolisation in spermatogenic epithelial cells, deterioration and gaps in the basal membrane and an increase in blood vessels in the interstitial area. The erdosteine group showed amelioration of both epithelial cell vacuolisation and basal membrane deterioration. Numbers of hypoxia-inducible factor 1α-immunostained Sertoli and Leydig cells were significantly higher in the hypoxia group than in the erdosteine group. The number of seminiferous tubules with caspase-3-immunostained germ cells was highest in the hypoxia group and decreased in the erdosteine and normoxia groups respectively. Based on these observations, erdosteine protects testis tissue from hypoxic injury by reducing apoptotic cell death.

Naringenin and quercetin reverse the effect of hypobaric hypoxia and elicit neuroprotective response in the murine model

Exposure to high-altitude results in hypobaric hypoxia which is considered as an acute physiological stress. This condition often leads to high-altitude illnesses such as high-altitude cerebral edema, high altitude pulmonary edema and hypoxic muscle weakness. Hypoxic injuries can be prevented by either preconditioning with cobalt chloride or treatment with drugs. The aim of current investigation was to evaluate the effect of naringenin (NGEN) and quercetin (QUR) against behavioral impairment and neuronal damage in hypoxia induced murine model. An oral administration of NGEN or QUR (10mg/kg each) was given to the animal prior to every hypoxic treatment. Behavioral changes were evaluated along with the hypoxia exposure for all the groups. After hypoxia exposure and drug administration, the mice were euthanized; brains were harvested and stored for further analysis. Expressions of hypoxia induced proteins were ensured by Western blotting. Our results demonstrate expression of hypoxia inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF), active caspase 3 and ubiquitin levels were significantly reduced upon drug treatment. However, expressions of chaperones (Hsp70, Hsp90 and C-terminus Hsp70 interacting protein) were moderately changed. We established our findings based on behavioral test, hematoxylin and eosin as well as amino-cupric silver stainings. In addition, the protective nature of these drugs was corroborated with immunoblot and immunofluorescence results, where we confirmed the down regulation of caspase 3 and ubiquitinated proteins. To conclude, treatment with NGEN and QUR alone substantially ameliorated hypoxia induced brain dysfunction and acts like a neuroprotectant.

Portal Vein Thrombosis after Splenectomy

Backgroundand Aim of the work: Splenectomy is a common operation but it carries the danger of many postoperative complications. One of the most important complications is the portal vein thrombosis (PVT), which may be fatal due to development of bowel ischemia and severe portal hypertension. Due to the effect of hypobaric hypoxia and higher liability for thrombosis encountered in high altitude areas, PVT may represent an actual problem in Taif province. The aim of this retrospective study is to detect the incidence, pattern of presentation, laboratory, radiological and results of treatment of cases of PVT following splenectomy. Methods: In this study, we reviewed all cases of splenectomy performed in King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia from January 2007 to January 2012. Cases of PVT following splenectomy were analyzed for incidence, pattern of presentation, laboratory, radiological and results of treatment. Results: This study involved 50 patients (40 males and 10 females) admitted in the surgical department of King Abdul Aziz Specialist Hospital, Taif, Saudi Arabia from January 2007 to January 2012. Eight cases of Portal vein thrombosis (16%) out of 50 splenectomies were identified. These 8 patients included: 4/10 of the patients (40%) suffering from myeloproliferative (MP), 3 of them (75%) had spleen weight greater than 3,000 g, 3/12 (25%) of the hemolytic anemia patients, and 1/10 of the patients (10%) operated upon for Hypersplenism. All patients had splenomegaly with mean weight of 1540 Gms (range 460 to 3850 g). Presenting symptoms included; anorexia in 7/8 cases (87.5%), abdominal pain in 6 (75%), and in all cases there was elevation in D-Dimer level, leukocyte and platelet counts. All diagnoses were made by contrast-enhanced computed tomography scan, and anticoagulation was initiated immediately. One/8 patients (12.5%) died from progressive liver cell failure; the others are alive with no clinical sequalae at a mean follow up of 27 months. CONCLUSIONS: PVT is a relatively common complication of splenectomy in patients with Splenomegaly, especially in Taif and related districts in which there is already a higher incidence of thrombotic disorders. The surgeon has to be with high index of suspicion, for early diagnosis by contrast-enhanced computed tomography, and prompt anticoagulation for successful outcome.

Acute Occlusive Mesenteric Ischemia in Taif Province, Saudi Arabia

Mesenteric ischemia is relatively a rare disorder seen in the emergency department (ED). Due to the effect of hypobaric hypoxia and higher liability for thrombosis encountered in high altitude areas, acute occlusive mesenteric ischemia (AOMI) would represent an actual challenge in Taif and related districts. Another risk factor is that about twenty-five percent of Saudis are victims of diabetes due to the changes in lifestyle and diet leading to increasing levels of obesity. Vague nonspecific clinical findings and limitations of diagnostic studies in addition to cultural and social factors, may lead to late presentation making the diagnosis a significant challenge and in turn higher morbidity and mortality are expected. Objectives: In this study, we review type of AOMI, pattern of presentation, laboratory, radiological, Intraoperative findings and results of treatment in 36 patients who were admitted to King Abdul Aziz Specialist Hospital and King Faisal Hospital, Al Taif, Saudi Arabia from January 2009 to January 2012. Methods: 36 patients with final diagnosis of AOMI were included in this retrospective study by means of review of their files and medical records. Results: The disease was more common in men than women (23 male and 13 females). The mean age of patients was 54 years. The mean time of presentation was 2.4 days after occurrence of symptoms. Abdominal pain was the most common symptom of patients followed by nausea, vomiting, constipation and bloody diarrhea. On physical examination; tachycardia was prevalent, Oliguria was seen in approximately 69.4% of patients, 11.1% of patients were in shock status. All patients had abdominal tenderness and 61.1% of patients had marked peritoneal signs (rebound tenderness with guarding or/and rigidity). Twenty one/36 (58.3%) patients were diabetics, 17/36 patients (47.2%) were hypertensive and 8/36 patients (22.2%) with associated cardiac disorders. In laboratory tests, Leukocytosis was present in all patients. Secondary polycythemia was seen in 38.9% of patients. D-Dimer level was high in all patients. In 61.1% of patients, exploratory laparotomies were done based on clinical, laboratory, abdominal ultrasound and plain x-ray findings without performing CT angiography due to presentation with marked peritoneal signs. In all patients gangrenous lesions were detected during surgery and resection of these parts was done. Gangrene and in turn resection, was extensive in 14/36 patients (38.9%) and they developed short bowel syndrome. There were 22/36 patients (61.1%) with superior or/and inferior mesenteric vein thrombosis, 10/36 patients (27.8%) with superior mesenteric artery thrombosis, in one of them there is associated focal thrombosis of aorta and renal arteries and 4/36 patients (11.1%) with superior mesenteric artery embolism. All patients received postoperative anticoagulant therapy. Patients with short bowel syndrome were prepared to receive total parental nutrition (TPN) for life. Intra-operative deaths were 3/36 (8.3%).There were 5/36 deaths (13.9%) accruing within one month after surgery and all died secondary to sepsis and its sequalae with total deaths of 8/36 patients (22.2%). Conclusion: Acute occlusive mesenteric ischemia (AOMI) especially of venous type will represent a challenging problem in Taif and related districts. The surgeon must pay intensive attention to patients presented by unexplained central abdominal pain and he has to be with high index of suspicion especially if it meets with the classic teaching of "pain out of proportion to physical findings ". Early diagnosis, aggressive approach to early resuscitation of the patients, correction of metabolic and hemodynamic derangements, and performing laparotomy as soon as these derangements were corrected would decrease morbidity and mortality. In some patients it is necessary to perform second look operation for re-evaluation of the viability of the intestine.

Acute Occlusive Mesenteric Ischemia in Taif Province, Saudi Arabia

Mesenteric ischemia is relatively a rare disorder seen in the emergency department (ED). Due to the effect of hypobaric hypoxia and higher liability for thrombosis encountered in high altitude areas, acute occlusive mesenteric ischemia (AOMI) would represent an actual challenge in Taif and related districts. Another risk factor is that about twenty-five percent of Saudis are victims of diabetes due to the changes in lifestyle and diet leading to increasing levels of obesity. Vague nonspecific clinical findings and limitations of diagnostic studies in addition to cultural and social factors, may lead to late presentation making the diagnosis a significant challenge and in turn higher morbidity and mortality are expected. Objectives: In this study, we review type of AOMI, pattern of presentation, laboratory, radiological, Intraoperative findings and results of treatment in 36 patients who were admitted to King Abdul Aziz Specialist Hospital and King Faisal Hospital, Al Taif, Saudi Arabia from January 2009 to January 2012. Methods: 36 patients with final diagnosis of AOMI were included in this retrospective study by means of review of their files and medical records. Results: The disease was more common in men than women (23 male and 13 females). The mean age of patients was 54 years. The mean time of presentation was 2.4 days after occurrence of symptoms. Abdominal was the most common symptom of patients followed by nausea, vomiting, constipation and bloody diarrhea. On physical examination; tachycardia was prevalent, Oliguria was seen in approximately 69.4% of patients, 11.1% of patients were in shock status. All patients had abdominal tenderness and 61.1% of patients had marked peritoneal signs (rebound tenderness with guarding or/and rigidity). Twenty one/36 (58.3%) patients were diabetics, 17/36 patients (47.2%) were hypertensive and 8/36 patients (22.2%) with associated cardiac disorders. In laboratory tests, Leukocytosis was present in all patients. Secondary polycythemia was seen in 38.9% of patients. D-Dimer level was high in all patients. In 61.1% of patients, exploratory laparotomies were done based on clinical, laboratory, abdominal ultrasound and plain x-ray findings without performing CT angiography due to presentation with marked peritoneal signs. In all patients gangrenous lesions were detected during surgery and resection of these parts was done. Gangrene and in turn resection, was extensive in 14/36 patients (38.9%) and they developed short bowel syndrome. There were 22/36 patients (61.1%) with superior or/and inferior mesenteric vein thrombosis, 10/36 patients (27.8%) with superior mesenteric artery thrombosis, in one of them there is associated focal thrombosis of aorta and renal arteries and 4/36 patients (11.1%) with superior mesenteric artery embolism. All patients received postoperative anticoagulant therapy. Patients with short bowel syndrome were prepared to receive total parental nutrition (TPN) for life. Intra-operative deaths were 3/36 (8.3%).There were 5/36 deaths (13.9%) accruing within one month after surgery and all died secondary to sepsis and its sequalae with total deaths of 8/36 patients (22.2%). Conclusion: Acute occlusive mesenteric ischemia (AOMI) especially of venous type will represent a challenging problem in Taif and related districts. The surgeon must pay intensive attention to patients presented by unexplained central abdominal and he has to be with high index of suspicion especially if it meets with the classic teaching of pain out of proportion to physical findings . Early diagnosis, aggressive approach to early resuscitation of the patients, correction of metabolic and hemodynamic derangements, and performing laparotomy as soon as these derangements were corrected would decrease morbidity and mortality. In some patients it is necessary to perform second look operation for re-evaluation of the viability of the intestine.

Effect of hypobaric hypoxia on the P2X receptors of pyramidal cells in the immature rat hippocampus CA1 sub‐field

Primary objective: This study was designed to evaluate the effect of hypobaric hypoxia (HH) on the function and expression of P2X receptors in rat hippocampus CA1 pyramidal cells.Research design: The functional changes of P2X receptors were investigated through the cell HH model and the expressional alterations of P2X receptors were observed through the animal HH model.Methods and procedure: P2X receptors mediated currents were recorded from the freshly dissociated CA1 pyramidal cells of 7‐day‐old SD rats by whole cell patch clamp recording. The expression and distribution of P2X receptors were observed through immunohistochemistry and western blot at HH 3‐day and 7‐day.Main outcomes and results: In acute HH conditions, the amplitudes of ATP evoked peak currents were decreased compared to control. The immunohistochemistry and western blot results reflected there was no change in P2X receptors expression after 3 days HH injury, while P2X receptors expression was up‐regulated in response to 7 days HH injury.Conclusions: These findings supported the possibility that the function of P2X receptors was sensitive to HH damage and long‐term function decrease should result in the expression increase of P2X receptors.