Effect of intermittent normobaric hypoxia on dynamics of disease state in patients with hypertension]

Curative effect of intermittent normobaric hypoxia created when breathing in gaseous hypoxic mixture containing 10% of oxygen and 90% of nitrogen has been examined in 41 patients with hypertonic disease. Adaptation to hypoxia has been studied for its effect on the central hemodynamics psychoemotional state and kinetics of oxygen supply of the skin. The pronounced positive effect of treatment was achieved in 70.7% of patients, the arterial pressure decreasing at the expense of different mechanisms depending on the type of blood circulation. Besides, a decrease in the emotional tension of patients and normalization of oxygen consumption and transport were observed.     

Use of a One-man,Mobile Pressure Chamber in the Treatment of Carbon Monoxide Poisoning

For the past five years a mobile pressure chamber has been used to treat patients suffering from severe carbon monoxide poisoning with oxygen at 2 atmospheres pressure. Of the 25 patients treated, 20 recovered completely and only three died. This apparatus could also be used for hyperbaric oxygen therapy in other conditions for which it is indicated.     

A mathematical model for the laser treatment of heart disease

Transmyocardial laser revascularisation (TMLR) is used to treat patients with severe coronary artery disease. A laser is used to create narrow tunnels within ischemic heart muscle in an attempt to reperfuse the area with oxygenated blood directly from the left-ventricular chamber. It has been hypothesised that initially blood flow through the patent tunnels plays an important role in the efficacy of the treatment (J. Am. College Cordiol. 25(1) (1995) 258) and Waters (J. Fluid Mech. 433 (2001) 193) developed a simple mathematical model to show that this blood flow enhances the quantity of oxygenated blood drawn into the tunnel and the subsequent delivery of oxygen to the tissue.To date, however, the optimum parameter values for this clinical technique have not been determined, e.g. the radius of the laser-drilled tunnels and their relative spacing. We present a mathematical model to determine the distribution of oxygen for a wide range of the governing parameters. Our results indicate that the tunnel radius has a significant effect on the degree of tissue reperfusion and predictions for the optimum tunnel spacing are made.     

综述与专论: 高压氧疗法治疗脑缺血的相关机制

脑缺血是指大脑各部分血液供应不足导致脑组织缺血缺氧，进而导致密集缺血区脑组织出现不可逆的损伤坏死，其高致残率、高死亡率会对患者及其家庭造成严重的伤害。在脑缺血发生后，及时采取一定的治疗措施控制梗死灶的大小，并挽救半暗带中的细胞是脑缺血预后的关键。高压氧疗法是针对脑缺血的一种潜在治疗方法，在近年来得到了越来越广泛的关注和研究，本文旨在综述近年来国内外关于高压氧疗法治疗脑缺血的相关机制及研究进展，为脑缺血患者的治疗和预后提供新思路。     

On the Oxygen Affinity of Bird Blood

In oxygen affinity characteristics bird blood appears to haveseveral features that distinguish it from mammalian blood. Fordomesticated species at least the range of oxygen half saturationvalues is extremely wide. A difference in the shape of the oxygendissociation curve has been recorded by several authors withan increase in sigmoidocity with increasing oxygen saturation.There is evidence that the oxygen affinity determining organicphosphate of bird red blood cells inositol pentaphosphate (IP5)is relatively metabolically inert. This suggests that modulationof blood oxygen affinity is primarily achieved by altering theIP5 hemoglobin interaction rather than varying IP5 levels perse. In contrast to mammals carbon dioxide has no direct effecton whole blood oxygen affinity for some bird species (hen chickgoose) or it may cause the oxygen affinity to increase (pigeonflamingo). Carbon dioxide is a blood oxygen affinity modulatorof some flexibility its effect in both direction and magnitudebeing dependent on the hemoglobin type red cell pH and organicphosphate levels. The physiological significance of these distinguishingfeatures is discussed.     

Oxygen therapy at low flow causes oxidative stress in chronic obstructive pulmonary disease: Prevention by N-acetyl cysteine

Exposure to high oxygen concentration produces toxicity by free radical release. We aimed to study: whether stable chronic obstructive pulmonary disease (COPD) patients present an unbalance in the blood redox status; the effect of oxygen administration on blood redox balance; the efficacy of N-acetyl-cysteine (NAC) treatment against the oxidative stress-induced by oxygen administration and whether it is dose-related. To this, 45 stable state III COPD patients were recruited and reduced glutathione (GSH) and oxidised glutathione (GSSG) in erythrocytes and thiol proteins (P-SH) and carbonyl proteins (PC) in both erythrocytes and plasma were evaluated. All COPD patients underwent 2 l/m oxygen for 18 h and NAC at 1200 or 1800 mg/day or placebo for 48 h starting with oxygen administration. Blood samples were collected at basal conditions, after 8 and 18 h of oxygen administration and 24 h after oxygen withdrawal. Results: COPD patients present an unstable redox equilibrium mainly due to plasma sulphydryl protein depletion. Oxygen administration oxidize erythrocyte GSH, decrease P-SH and increase PC levels in both plasma and erythrocytes. NAC administration counteract the oxidative stress and at the highest dose completely prevent protein oxidation. In conclusion, stable state III COPD patients present an unstable redox balance; long term low flow oxygen administration induces systemic oxidative stress, which is prevented by NAC treatment.     

Thyroid hormone analog, diiodothyropropionic acid (DITPA), exerts beneficial effects on chamber and cellular remodeling in cardiomyopathic hamsters

Diiodothyropropionic acid (DITPA) is a thyroid hormone analog that is currently in phase II clinical trials. However, there have not been any studies to comprehensively analyze its effect on myocyte morphology. In addition, long-term studies with DITPA have not been done. This study compares the effects of DITPA with L-thyroxine (T4) on chamber remodeling, cardiac function, cellular morphology, cardiac blood flow, and protein expression. Normal and cardiomyopathic hamsters were treated with T4 or DITPA for 2 months. At the end of the treatment, echos, hemodynamics, coronary blood flow, cell morphology, and protein expression data were collected. Both T4 and DITPA treatment reduced chamber diameter during diastole, suggesting attenuated chamber dilatation in cardiomyopathic hamsters. Wall thickness also tended to increase, which was supported by cell morphology data in which DITPA significantly increased cross-sectional growth of myocytes specifically in the minor dimension, which is oriented transmurally. T4 and DITPA also increased myocardial blood flow both at baseline and after maximal dilation. This suggests there was increased angiogenesis or reduced loss of arterioles. Both T4 and DITPA had beneficial effects on chamber remodeling, which was most likely due to beneficial changes in cell shape and improved vascular supply.     

Effect of hypothermia on radiosensitization

Hypothermia reduces metabolism and oxygen utilization by tissues. If the blood supply to a solid tumour can be maintained at a sufficient level, the hypoxic fraction of tumour cells may be reduced and radiosensitivity increased. This may be achieved if hyperbaric oxygen is used in combination with the hypothermia. The blood supply and oxygen tension have been measured in C3H mouse mammary tumours under hypothermia and hyperbaric oxygen, and the enhancement of radiosensitivity by hyperbaric oxygen has been estimated in mice irradiated at different temperatures with and without anaesthesia. Measurement of xenon-133 clearance showed that the blood supply of a tumour tended to increase when anaesthetized mice became hypothermic. Oxygen cathode data showed that the oxygen tension tended to be relatively higher in tumours and lower in subcutaneous tissue when mice exposed to hyperbaric oxygen became hypothermic under anaesthesia. Hyperbaric oxygen enhanced the radiation response of the tumour in terms of an increase in regrowth delay by a factor of 1.7 when the mice had been anaesthetized, whether or not they became hypothermic. A lower factor of 1.4 was obtained without anaesthesia although induced hypothermia increased the response to a small extent. We conclude that anaesthesia and hypothermia affect oxygen metabolism in tumours by different mechanisms.     

Oxygen therapy at low flow causes oxidative stress in chronic obstructive pulmonary disease: Prevention by N-acetyl cysteine

Exposure to high oxygen concentration produces toxicity by free radical release. We aimed to study: whether stable chronic obstructive pulmonary disease (COPD) patients present an unbalance in the blood redox status; the effect of oxygen administration on blood redox balance; the efficacy of N-acetyl-cysteine (NAC) treatment against the oxidative stress-induced by oxygen administration and whether it is dose-related. To this, 45 stable state III COPD patients were recruited and reduced glutathione (GSH) and oxidised glutathione (GSSG) in erythrocytes and thiol proteins (P-SH) and carbonyl proteins (PC) in both erythrocytes and plasma were evaluated. All COPD patients underwent 2 l/m oxygen for 18 h and NAC at 1200 or 1800 mg/day or placebo for 48 h starting with oxygen administration. Blood samples were collected at basal conditions, after 8 and 18 h of oxygen administration and 24 h after oxygen withdrawal. Results: COPD patients present an unstable redox equilibrium mainly due to plasma sulphydryl protein depletion. Oxygen administration oxidize erythrocyte GSH, decrease P-SH and increase PC levels in both plasma and erythrocytes. NAC administration counteract the oxidative stress and at the highest dose completely prevent protein oxidation. In conclusion, stable state III COPD patients present an unstable redox balance; long term low flow oxygen administration induces systemic oxidative stress, which is prevented by NAC treatment.     

Effects of nasal continuous positive airway pressure and oxygen supplementation on norepinephrine kinetics and cardiovascular responses in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by noradrenergic activation. Nasal continuous positive airway pressure (CPAP) is the treatment of choice and has been shown to effectively reduce elevated norepinephrine (NE) levels. This study examined whether the reduction in NE after CPAP is due to an increase in NE clearance and/or a decrease of NE release rate. Fifty CPAP-naive OSA patients with an apnea-hypopnea index >15 were studied. NE clearance and release rates, circulating NE levels, urinary NE excretion, and blood pressure and heart rate were determined before and after 14 days of CPAP, placebo CPAP (CPAP administered at ineffective pressure), or oxygen supplementation. CPAP led to a significant increase in NE clearance (P < or = 0.01), as well as decreases in plasma NE levels (P < or = 0.018) and daytime (P < 0.001) and nighttime (P < 0.05) NE excretion. NE release rate was unchanged with treatment. Systolic (P < or = 0.013) and diastolic (P < or = 0.026) blood pressure and heart rate (P < or = 0.014) were decreased in response to CPAP but not in response to oxygen or placebo CPAP treatment. Posttreatment systolic blood pressure was best predicted by pretreatment systolic blood pressure and posttreatment NE clearance and release rate (P < 0.01). The findings indicate that one of the mechanisms through which CPAP reduces NE levels is through an increase in the clearance of NE from the circulation.     

Wet wound healing

Wound treatment in a flexible transparent chamber attached to the perimeter of the wound and containing a liquid has been extensively tested in preclinical experiments in pigs and found to offer several advantages. It protects the wound; the liquid medium or saline in the chamber provides in vivo tissue culture-like conditions; and antibiotics, analgesics, and various molecules can be delivered to the wound through the chamber. The wound chamber causes no injury to the wound itself or to the surrounding intact skin. Topical delivery of, for instance, antibiotics can provide very high concentrations at the wound site and with a favorable direction of the concentration gradient. A series of 28 wounds in 20 patients were treated with a wound chamber containing saline and antibiotics. Most patients had significant comorbidity and had not responded to conservative or surgical management with débridement and delayed primary closure or skin grafts. Six wounds had foreign bodies present; four of these were joint prostheses. Seven patients were on corticosteroids for rheumatoid arthritis, lupus, or chronic obstructive pulmonary disease, and four patients had diabetes. Most patients were treated with the wound chamber in preparation for a delayed skin graft or flap procedure, but one was treated with a wound chamber until the wound healed. Twenty-five of the wounds (89 percent) healed, and five wounds (18 percent) required additional conservative management after the initial chamber treatment and grafting procedure. Of the three wounds that did not heal, one healed after additional chamber treatment, one had a skin graft that did not take, and one required reamputation at a higher level. Antibiotic delivery was less than one intravenous dose daily, which avoided the potential for systemic absorption to toxic levels. Antibiotics such as vancomycin and gentamicin could be used in concentrations of up to 10,000 times the minimal inhibitory concentration. Forty-eight hours after application, 20 percent or more of the original antibiotic concentration was present in the wound chamber fluid. In conclusion, the wound chamber provides a safe, powerful tool in the treatment of difficult infected wounds.     

Water fleas (Daphnia magna) provide a separate ventilatory mechanism for their brood

The planktonic filter feeder Daphnia magna depends on a steady oxygen supply by convection. In the ventral carapace chamber, this convection is established by the feeding current which is generated by the movement of the thoracic limbs. The present study revealed that this movement can cause an additional flow of medium which passes through the brood chamber of the animal. To visualise this current, ink or fluorescent microspheres were released by a microcapillary near the posterior opening of the brood chamber. The tracks of these probes were monitored by video microscopy. Digital motion analysis was used for the determination of flow velocity and flow rate. Ambient medium entered the brood chamber at the abdomen of the animal and moved then to the anterior end of the brood chamber before entering the ventral carapace chamber. Two horizontal lamellae, which are attached at both sides of the trunk and project laterally to contact the carapace walls, almost completely separate the dorsal brood chamber from the ventral carapace chamber. Water can only pass these barriers through small depressions in these lamellae at the level of the 3rd and 4th appendages. Female daphnids with embryos at late developmental stages showed more rapid water currents in the brood chamber than those with younger embryos. Moreover, animals showed higher flow rates when exposed to hypoxic conditions. As the oxygen uptake rate of older embryos is approximately three times higher than that of younger embryos, the enhanced brood chamber current could improve the oxygen availability for both the mother and its brood under conditions of reduced oxygen availability.     

THE MECHANISM OF AQUEOUS HUMOR FORMATION INFERRED FROM CHEMICAL STUDIES ON BLOOD-AQUEOUS HUMOR DYNAMICS

The importance of considering the effect of a possible flow out of the anterior chamber before inferring any mechanism of aqueous humor formation from the relative concentration of a substance in the aqueous humor and plasma under equilibrium conditions has been stressed. Several processes to account for the chemical equilibria between aqueous humor and blood based on the ultrafiltration and secretion hypotheses with a possible simultaneous loss of aqueous humor by flow have been outlined. On the basis of these processes, equations were formulated which would relate the rates of transfer into and out of the anterior chamber to the ratio of concentration of a substance in the aqueous to that in the blood at various intervals after its introduction into the blood. The explanation of equilibrium ratios above and below one for aqueous constituents is made apparent from the mathematical formulations. For each substance tested a determination was made of the best fit when the concentration in the aqueous humor is plotted against time. This fit was obtained by plotting the rate of transfer in against the rate of transfer out of the anterior chamber for all of the experimentally found concentration ratios on the basis of both the ultrafiltration and secretory hypotheses. Two sets of values were obtained from these calculations, one set for each hypothesis. The substantial agreement of all the experimental data with an assumed rate of leakage out of the anterior chamber of approximately 4 c. mm. per minute was shown to be compatible only with the idea that all the monovalent electrolytes tested entered the anterior chamber as a result of secretory process. It could not be decided from these chemical studies whether the non-electrolytes and the one multivalent electrolyte tested enter the anterior chamber by ultrafiltration or secretion. Experimental findings from other sources were cited which would suggest that non-electrolytes enter the anterior chamber as a result of ultrafiltration. The implications of the mechanism outlined in the paper with respect to intraocular pressure have been discussed. Supplementary evidence from the literature has been given in support of the conclusions presented here.     

Short duration hyperbaric oxygen treatment effects blood flow in rats: pilot observations

Hyperbaric oxygen (HBO) treatment has been found to improve healing in living tissues, especially those poor in oxygen. The effects of HBO have also been tested in rat experiments. However, oxygen partial pressure in rat's arterial blood is normally about twice that in humans. Disregarding this, a human HBO protocol has been applied in previous rat experiments with HBO. Laser Doppler flowmetry (LDF) is a non-invasive means for measuring blood flow. Using LDF, we measured the blood perfusion rate in rats receiving HBO, according to a modified protocol, in a region of healing soft tissue with bone defect. The results indicate that, in rats, shorter HBO treatment with high O2 pressure can significantly improve the blood flow of healing tissues. In this study, an elevated blood perfusion rate was still evident 2 weeks after the ending of HBO therapy, which indicates improved revascularization in the wound area. A short HBO protocol would save time and effort in future HBO experiments on rats.     

Variants of the tissue-sensor array window chamber

Sensors are being developed that can be implanted in tissues for continuous monitoring of oxygen, glucose, and other metabolites. However, there have been difficulties in inferring metabolite concentrations in blood from the signals of tissue sensors due to the properties of tissues at the implant site and local physiological phenomena that can affect sensor responses. A multisensor array has been previously developed for implantation in a hamster skinfold window chamber preparation to study these effects. The preparation allows recording of concentration-dependent signals from multiple sensors while nondestructively visualizing the adjacent tissue and microvascular function. Variants of the tissue-sensor array window chamber described here have respective advantages over the original chamber design, including improved tissue visualization and reduced surgical intervention, and allow exposure of the sensor to different tissues. Results indicate that mass transfer within tissues is heterogeneous, and sensor signals are affected by variable perfusion of local microvasculature in addition to vascular metabolite concentration. These observations suggest new strategies for sensor design and operation. Window chamber variants are important tools for validation of implanted sensors.     

A procedure for anaerobic column chromatography employing an anaerobic freter-type chamber

A technique is described for the anaerobic fractionation of oxygen-sensitive material. A Freter-type chamber in which the oxygen concentration is maintained at 2 to 5 μl/liter is used in conjunction with anaerobic chromatographic columns that are exterior to the chamber. The column inlet and outlet are connected via thick-walled polyethylene tubing to access ports in the chamber wall. Anaerobic buffer inside the chamber is pumped from the chamber to equilibrate the column. The oxygen-labile sample then is pumped onto the anaerobic column followed by the elution gradient buffer. Column eluate is returned to a fraction collector inside the chamber. At no stage is the sample exposed to air. This technique has been used effectively for fractionation of highly oxygen-sensitive enzymes from methanogenic bacteria where use of other methods failed.     

Evaluation of energy metabolism and physical work capacity of divers for determining the optimal oxygen level during breathing gas mixture under pressure up to 5.1 MPa]

A complex evaluation of energy metabolism, oxygen-transport function of blood and physical work capacity of aquanauts has been performed during three imitation divings at depths of 400, 450 and 500 m in heliox as a breathing medium. These experiments have shown that optimal levels of partial oxygen pressure in artificial chamber environment are 30-33 kPa at 4.1 MPa, 32-35 kPa at 4.6 MPa and 33-34 kPa at 5.1 MPa. It is established that 24-days exposure of aquanautes to 4.6 MPa and 10-days exposure to 5.1 MPa yield no unfavourable changes of the examined organism functions. The activated lipid exchange in combination with stable carbohydrate catabolism, the elevated levels of oxygen consumption and its partial pressure in blood and transient fluctuations of erythropoiesis activity are interpreted as compensatory responses of diverse organisms under the influence of hyperbaric factors.     

Combined heat and controlled atmosphere quarantine treatments for control of western cherry fruit fly in sweet cherries

Nonchemical quarantine treatments, using a combination of short duration high temperatures under low oxygen, elevated carbon dioxide atmospheric environment were developed to control western cherry fruit fly, Rhagoletis indifferens Curran, in sweet cherries, Prunus avium (L.). The two treatments developed use a chamber temperature of 45 degrees C for 45 min and a chamber temperature of 47 degreesd C for 25 min, both under a 1% oxygen, 15% carbon dioxide, -2 degrees C dew point environment. Both these treatments have been shown to provide control of all life stages of western cherry fruit fly while preserving commodity market quality. There was no definitive egg or larval stage, which was demonstrated to be the most tolerant to either controlled atmosphere temperature treatment system treatment. Efficacy tests for both treatments resulted in 100% mortality of >5000 western cherry fruit flies in each treatment. These treatments may provide, with further study, quarantine security in exported sweet cherries where western cherry fruit fly is a quarantine concern and fumigation with methyl bromide is not desired.     

Water fleas (Daphnia magna) provide a separate ventilatory mechanism for their brood

The planktonic filter feeder Daphnia magna depends on a steady oxygen supply by convection. In the ventral carapace chamber, this convection is established by the feeding current which is generated by the movement of the thoracic limbs. The present study revealed that this movement can cause an additional flow of medium which passes through the brood chamber of the animal. To visualise this current, ink or fluorescent microspheres were released by a microcapillary near the posterior opening of the brood chamber. The tracks of these probes were monitored by video microscopy. Digital motion analysis was used for the determination of flow velocity and flow rate. Ambient medium entered the brood chamber at the abdomen of the animal and moved then to the anterior end of the brood chamber before entering the ventral carapace chamber. Two horizontal lamellae, which are attached at both sides of the trunk and project laterally to contact the carapace walls, almost completely separate the dorsal brood chamber from the ventral carapace chamber. Water can only pass these barriers through small depressions in these lamellae at the level of the 3rd and 4th appendages. Female daphnids with embryos at late developmental stages showed more rapid water currents in the brood chamber than those with younger embryos. Moreover, animals showed higher flow rates when exposed to hypoxic conditions. As the oxygen uptake rate of older embryos is approximately three times higher than that of younger embryos, the enhanced brood chamber current could improve the oxygen availability for both the mother and its brood under conditions of reduced oxygen availability.List of symbols:a specific oxygen consumption rate (nmol mm-³ h-¹), K Krogh constant for oxygen diffusion (nmol mm-¹ h-¹ kPa-¹, P_c critical oxygen partial pressure (kPa), P o₂ oxygen partial pressure (kPa), r radius (mm), s distance (mm), t time (ms)