Biomedical subjects

D Kerem

Publications and source records attributed to D Kerem.

At least 19 recordsLinked to original sources

PubMed1997

Thermal status of wet-suited divers using closed circuit O2 apparatus in sea water of 17-18.5 degrees C.

A wet suit may not provide adequate thermal protection when diving in moderately cold water (17-18 degrees C), and any resultant mild hypothermia may impair performance during prolonged diving. We studied heat exchange during a dive to a depth of 5 m in sea water (17-18.5 degrees C) in divers wearing a full wet suit and using closed-circuit oxygen breathing apparatus. Eight fin swimmers dived for 3.1 h and six underwater scooter (UWS) divers propelled themselves through the water for 3.7 h. The measurements taken throughout the dive were the oxygen pressure in the cylinder and skin and rectal temperatures (Tre). Each subject also completed a cold score questionnaire. The Tre decreased continuously in all subjects. Oxygen consumption in the fin divers (1.40 l.min-1) was higher than that of the UWS divers (1.05 l.min-1). The mean total insulation was 0.087 degree C.m2.W-1 in both groups. Mean body insulation was 37% of the total insulation (suit insulation was 63%). The reduction in Tre over the 1st hour was related to subcutaneous fat thickness. There was a correlation between cold score and Tre at the end of 1 h, but not after that. A full wet suit does not appear to provide adequate thermal protection when diving in moderately cold water.

Altitude↗

PubMed1996

Susceptibility of the injured rat brain to CNS oxygen toxicity.

The possibility of an altered susceptibility of the injured brain to central nervous system (CNS) oxygen toxicity was examined in awake rats. Moderate to severe closed head injury with diffuse axonal damage was produced in anesthetized rats by the fluid percussion method (2-2.5 atm), after which chronic EEG electrodes were implanted. Twenty-four hours later, the rats were exposed to 5 atm abs (506.5 kPa) oxygen and the time to appearance of paroxysmal EEG patterns was noted. The difference between the 19 minute median latency of this group and 16 minute of a control group which underwent a sham operation did not reach statistical significance. Some injured animals convulsed with minimal or no EEG changes. The clinical implication could be that brain injured patients are not at higher risk of CNS oxygen toxicity but the EEG alterations that could potentially be used to forecast incipient convulsions, or be the indication of actual convulsions in the intact brain of a paralyzed patient, may not always be present.

Analysis of Variance↗

PubMed1995

Effect of accumulation of CO2 on the survival of immature pigs in a confined atmosphere. A: Gas exchange.

Our purpose is to develop a survival strategy for man trapped in a confined space. We used immature pigs to assess the applicability of findings in rats for a larger mammal. The pig consumed oxygen in a sealed chamber until hypoxic collapse. We measured blood pressure, oxygen consumption, inspired O2 and CO2, minute ventilation, ECG and body temperatures, in three groups: no accumulation of CO2; CO2 level maintained at 5%, and maximal accumulation of CO2. Hypoxic oxygen consumption and ventilation were affected by the presence of CO2. Despite the pig's body mass being two orders of magnitude greater than that of the rat, its terminal PIO2 (35.9 torr) did not differ from that of the rat (35.3 torr). Accumulation of CO 2 had no significant effect on the terminal PIO2.

Animals↗

PubMed1995

Effect of accumulation of CO2 on the survival of immature pigs in a confined atmosphere. B: Blood gas exchange.

As part of a study for developing survival strategy for humans in a confined space, we used immature pigs to assess the applicability of findings in rats and to evaluate the effect of body size. The cannulated unanesthetized animal was placed in a sealed chamber and depleted the oxygen until hypoxic collapse. Three groups were: no accumulation of CO2, CO2 maintained at 5%, and maximal accumulation of CO2. In hypoxia arterial and venous oxygen tension were higher in the pigs exposed to CO2 than in the no CO2 pigs. Oxygen extraction increased and oxygen transport decreased in hypoxia in the presence of CO2. Similarity in the P50 of the oxygen dissociation curve may explain the similar terminal PIO2 in the pig and the rat. There was a positive correlation between terminal PIO2 and terminal venous pH.

Animals↗

PubMed1995

CO2 retention during hyperbaric exercise while breathing 40/60 nitrox.

We evaluated CO2 retention in 24 Navy construction divers breathing air at 1 atm abs (101.3 kPa) and 40% O2 (40/60) nitrox at 4 atm abs (Po2 of 162.1 kPa) inside a pressure chamber. The divers sat immersed to the sternal notch and exercised against pneumatically loaded pedals at a Vo2 of approximately 1.3 liter/min. The mean end-tidal CO2 tension (PET(CO2)2) at 1 atm abs (45.7 +/- 5.0 SD torr) was significantly higher than that of non-divers and diving trainees (40 +/- 5.0) but did not increase significantly at depth (47.1 +/- 6.3). The ranking of CO2 retention was not maintained at depth. Unpredictable upward and downward shifts of up to 10 torr occurred in some divers. The PET(CO2) of six of the divers at pressure was greater than 50 torr, which based on animal studies markedly increases the risk of central nervous system oxygen toxicity. We translated their values into individual depth limits with 40/60 nitrox: three with 50 < PET(CO2) < 55 torr were forbidden to dive beyond 25 m and three with values > 55 torr were restricted to 20 m. We propose that whenever possible, PET(CO2) during exercise at pressure be measured in potential nitrox users and that the above PO2 limits be enforced on moderate and extreme CO2 retainers, respectively.

Adult↗

PubMed1992

Recovery of the hypoxic ventilatory drive of rats from the toxic effect of hyperbaric oxygen.

Hyperbaric oxygen (HBO) exposure reduces the hypoxic ventilatory drive (HVD), probably by damaging the carotid bodies. The recovery of the HVD from HBO exposure was studied. The HVD was calculated from whole body plethysmographic recordings of the ventilatory response to greater than 85% and 2% O2 in N2 mixtures. Five groups of rats were exposed to HBO for 9 h at pressures of 1.9, 2.0, 2.1, 2.2, and 2.4 ATA, respectively. Each rat underwent three control measurements on different days prior to HBO exposures and then at various intervals following the exposure. Postexposure HVD was reduced to 28% of control values in the high PO2s. Ninety percent recovery of pre-exposure HVD was evident by 12-48 h although in some animals exposed to relatively low PO2s (1.9 and 2.0 ATA) HVD stabilized at a level lower than 100%. The recovery of the HVD in percent during the first 4 d following exposure can be expressed as an exponential function of the time from the termination of HBO: HVD = 28 + 72(1 - exp-0.053t) (t in hours). This information may be of importance in cases of repeated exposures to HBO where one tries to avoid cumulative damage to the carotid bodies, and in the care of the poorly oxygenated patient after HBO treatment.

Air Pressure↗

PubMed1991

The effect of carbamazepine and ethosuximide on hyperoxic seizures.

The main manifestations of CNS oxygen toxicity are generalized tonic-clonic seizures. We tested the protective effect of 2 antiepileptic drugs, carbamazepine and ethosuximide, which are commonly used for the treatment of generalized seizures, on hyperbaric oxygen-induced convulsions. Rats implanted with chronic cortical electrodes for continuous EEG monitoring were injected i.p. with either carbamazepine (5 doses in the range of 1.5-50 mg/kg), ethosuximide (400 mg/kg), or their vehicles (40% propylene glycol and saline, respectively). The rats were exposed to 5 ATA (0.5 MPa) oxygen. The duration of the latency until the appearance of electrical discharges in the EEG was used as an index of toxicity. Ethosuximide did not protect against hyperoxic seizures. In contrast, rats pretreated (30 min) with carbamazepine exhibited a dose-related protective effect against hyperoxically induced seizures. The results of our study suggest that carbamazepine should be considered for prevention of oxygen-induced seizures during hyperbaric oxygen therapy.

Animals↗

PubMed1991

Effects of dietary supplementation with vitamin E, riboflavin and selenium on central nervous system oxygen toxicity.

We attempted to modify the resistance of rats to hyperbaric oxygen (HBO)-induced central nervous system (CNS) toxicity, by increasing the tissue antioxidant potential through dietary factors. Groups of rats were fed excesses of vitamin E (VIT E) alone or in combinations with riboflavin (RIB), selenium (Se) or both, for 30 days. A control group was maintained on an unsupplemented diet. On the 23rd day animals to be exposed were implanted with chronic electrodes for electrocorticographic (ECoG) recording. Later, each group was divided into two subgroups, of which one was exposed to 4.5 atmospheres absolute (ATA) of 100% oxygen (O2) for 30 min., hereafter referred to as "exposed", noting the time of appearance of first electrical discharge (FED) in their ECoG. The remaining subgroups were left unexposed. Forty-eight hours later, all animals were sacrificed and some of their tissues were analyzed for glutathione (GSH). The GSH level in the liver, brain, lungs and blood of all experimental subgroups were significantly higher than in the control unexposed counterparts. Combinations of RIB and/or Se with VIT E failed to show a greater increase in GSH over VIT E alone. This increase was, however, not accompanied by a meaningful delay in the appearance of FED. Forty-eight hours post-exposure, the brain GSH levels of all exposed subgroups were still lower than the respective pre-exposure levels. Yet, in the treated exposed subgroups the GSH levels observed 48 hr after exposure were already higher than in the untreated unexposed controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of dietary factors on antioxidant enzymes in rats exposed to hyperbaric oxygen.

To delineate the effect of dietary supplementation with vitamin E (Vit E) alone or in combination with riboflavin (Rib) or selenium (Se) or both, on biological oxidative damage in rat brain and lungs we exposed rats to hyperbaric oxygen (HBO) and measured the activities of glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G-6-PD) prior to or 48 h after exposure. Rats fed the dietary supplements, and a control group maintained on an unsupplemented diet, for 30 d, were each divided into 2 subgroups, of which 1 was exposed to 4.5 absolute atmospheres (ATA) of 100% oxygen for 30 min, hereafter referred to as "exposed". The remaining subgroups were left unexposed. Pre-exposure GSSG-R activity in brain was elevated in all experimentally fed groups (ranging from 23 to 84%) compared with the unexposed control, whereas GSH-Px, G-6-PD and SOD activities were unchanged. The lungs showed significant increases in pre-exposure GSSG-R, ranging from 15 to 28%, and GSH-Px, ranging from 13 to 23%, activities in all the groups fed the supplemental nutrients, except those on Vit E alone. Increases in G-6-PD activity were observed only in those fed supplements of Rib. In most cases exposure to oxygen caused an increase in GSSG-R, GSH-Px and G-6-PD activities. However the increases were higher in the supplemented groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effect of N-acetyl-cysteine, D-penicillamine and buthionine sulfoximine on glutathione levels and CNS oxygen toxicity in rats.

The effect of glutathione (GSH) synthesis modulators - L-buthionine sulfoximine (BSO), N-acetyl cysteine (NAC) and D-penicillamine (DPA) - on the susceptibility of rat CNS to O2 toxicity was investigated. The animals were given 5% sucrose or 40 mM solutions of BSO, NAC or DPA in 5% sucrose as drinking water for one week and sacrificed prior to or after exposure to 4.5 ATA O2. The GSH content in brain, liver, lung and blood, and the activity of glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), glucose-6-phosphate dehydrogenase (G-6-PD) and superoxide dismutase (SOD) in brain and lungs were measured. The brain GSH content and the enzyme activities were not changed by any of the drugs. BSO decreased the GSH content in all the other tissues; NAC and DPA treatments increased the GSH content in lungs, blood and/or liver. The CNS toxicity threshold as measured by the time of appearance of first electrical discharge (FED) on ECoG recording was not changed by NAC or DPA, but BSO brought about a significant delay in FED time. It is suggested that increased extracerebral GSH levels do not protect against CNS oxygen toxicity, and that BSO provides some protection, probably via a glutathione-independent mechanism.

Acetylcysteine↗

PubMed1990

Vestibulo-ocular reflex as a parameter of seasickness susceptibility.

The vestibulo-ocular reflex (VOR) is known to be modulated in response to changing vestibular and optokinetic stimuli. The purpose of this study was to investigate possible relationships between VOR and future susceptibility and habituation to seasickness. Thirty candidates for future maritime service were exposed to a series of yaw axis smooth harmonic accelerations before and after 6 months of regular sailing, and their VOR gain and phase responses were recorded. Seasickness severity was estimated after 1 and 6 months of service by a questionnaire. We conclude that VOR gain at 0.01 Hz may serve as a physiologic correlate helping to predict seasickness susceptibility, and that the increase in phase lead at 0.02 Hz may mark the habituation process to sea conditions.

Acceleration↗

PubMed1990

Magnesium sulfate suppresses electroencephalographic manifestations of CNS oxygen toxicity.

We studied the effects of parenteral magnesium sulfate (MgSO4) administration on electroencephalographic seizures induced by hyperbaric oxygen (HBO) in awake rats. Sixteen rats chronically implanted with electrocorticographic electrodes were preinjected i.p. with either vehicle or 3 mmol/kg MgSO4 (the latter resulted in serum levels of 3.5-5.5 mmol/liter) and then exposed to 6 ATA O2 in a pressure chamber. The time to develop an electric ichtal seizure was measured and compared to that in the same animal receiving the alternate treatment 3 days later. Mean and median times after the magnesium treatment were almost double those of vehicle administration. A central anticonvulsive action of magnesium, which should be investigated over the entire HBO range, is indicated.

Animals↗

PubMed1989

Attenuation of hypoxic ventilation by hyperbaric O2: effects of pressure and exposure time.

Hyperoxia affects O2 chemoreception in the highly perfused carotid bodies and causes a reduction of the ventilatory hypoxic drive (HD) as was shown for anesthetized cats and awake rats. We looked for a quantitative description of such an effect on HD as a function of both O2 pressure and exposure duration. Ventilation of rats was measured using the barometric method before and after hyperbaric O2 (HBO) exposure, at either air, 80% O2, or 4% O2. We used three exposure durations: 180, 550 and 900 min. The O2 pressure ranged between 1.2 and 3.0 ATA. At each time duration we used four to five groups of rats at a range of O2 pressures that yielded the full scale of effect on HD but avoided obvious lasting difficulties in breathing. HBO caused a reduction of breathing frequency and elevation of tidal volume in both air and 80% O2 but almost no change in minute ventilation. Hypoxic minute ventilation (4% O2) decreased after HBO, mainly through reduced frequency. HD was described by a power function of O2 pressure for each HBO duration. HD did not decline below 20% of the full control response. Ventilatory HD diminution is pictured as a function of both O2 pressure and HBO duration. The dependency of HD on exposure time and on pressure is similar to other known toxic effects of HBO.

Animals↗

PubMed1988

The glycine-prodrug, milacemide, increases the seizure threshold due to hyperbaric oxygen; prevention by 1-deprenyl.

The novel glycine-prodrug anticonvulsant, milacemide (2-N-pentylaminoacetamide) (500 mg/kg), significantly increased (greater than 400% the seizure threshold induced by hyperbaric oxygen (4.5 atmosphere). This effect was significantly reduced by the selective inhibition of monoamine oxidase B by 1-deprenyl (2.0 mg/kg). 1-Deprenyl alone hardly affected the seizure threshold. These results suggest that, in the brain, milacemide is oxidized to glycine and that this reaction is mediated primarily by monoamine oxidase B. However, the interaction of milacemide metabolites (glycine amide, pentanoate and glycine) as antagonists of receptors of the glutamate NMDA (N-methyl-D-aspartate) subtype cannot be excluded.

Acetamides↗

PubMed1988

Hyperoxic exposure affects the ventilatory response to hypoxia in awake rats.

We tested whether hyperbaric O2 (HBO) has an adverse effect on the hypoxic ventilatory drive. Four groups of rats were exposed for 550 min to O2 at 1.67, 1.90, and 2.15 ATA and to air at 1.90 ATA, respectively. Ventilatory parameters (frequency, tidal volume, and minute ventilation) were measured using whole-body plethysmography, before the hyperbaric exposure, immediately after the exposure, and up to 20 days after the exposure. Resting ventilation was not affected after exposure at 1.90 ATA to air or at 1.67 ATA to O2. HBO at 1.90 and 2.15 ATA caused a reduction of frequency and an elevation of tidal volume at different inspired gases: air, 5% CO2 balance O2, 80% O2, and 4.5% O2. However, minute ventilation on the day after the hyperoxic exposure was not different from the control at either air, 5% CO2, or 80% O2 but was markedly attenuated on the first three breaths at 4.5% O2. The hypoxic ventilation decreased to 48 +/- 13 (SD) and 32 + 11% after 1.90 and 2.15 ATA, respectively. The ventilatory parameters recovered in the days after HBO. We conclude that HBO reversibly depresses the hypoxic ventilatory drive, most probably by a direct effect on the carotid O2 chemoreceptors.

Animals↗

PubMed1988

Central nervous system oxygen toxicity in the resting rat: postponement by intermittent oxygen exposure.

Intermittent O2 breathing is a proven means of delaying pulmonary O2 toxicity during exposure to hyperbaric oxygen. The effect of an intermittent exposure in the pressure range toxic to the CNS was studied. Conscious, unrestrained rats, implanted with cortical EEG electrodes were subjected at 5 and 6 ATA to alternating periods of 7 min O2 and 7 or 10 min of either air, normoxic nitrox, or N2O-air (the latter mixture being equinarcotic to pure O2). Altogether, nearly half of the animals survived 90 min of intermittent breathing, with no grossly abnormal EEG patterns. At that time, labored breathing (associated with mild lung pathology) supervened. In the remaining animals, seizure patterns in the EEG appeared after a mean cumulative O2 breathing time of 20 min (compared to 9 min during a continuous exposure). Forty percent were affected while breathing the alternating mixture (low-PO2 seizures), mostly soon after switching of the gas. The nature of the alternating mixture did not affect the outcome of the high-PO2 seizures nor did the length of the interim periods. Normoxic nitrox increased and N2O-air reduced the incidence of low-PO2 seizures. At 5 ATA only 10% of the animals experienced high-PO2 seizures. While swift reversibility of the toxic process is indicated, the low-PO2 seizures with as yet an undetermined mechanism pose a serious obstacle for intermittent exposures at this pressure range.

Animals↗

PubMed1988

Ventilatory response to transient hypoxia in O2 divers.

This study addresses the question of whether repeated acute exposure to hyperbaric oxygen, such as encountered in O2 diving, affects the peripheral oxygen chemosensors. Groups of nondivers, active O2 divers, and ex-O2 divers, as well as active air scuba divers, were given 1 or both of 2 tests that measure the ventilatory response to transient hypoxia. Results showed that all groups of divers have a mean response similar to or higher than that of nondivers as well as that of normal subjects, as reported in the literature. A repeat test on 10 diving candidates before and after 200 h of accrued O2 diving also did not show an impairment in the hypoxic ventilatory response. Oxygen diving within the established depth and time limits does not seem to cause cumulative damage to the peripheral O2 chemosensors.

Adult↗

PubMed1984

Independence of hypoxic death of inspiratory PCO2 in rats and fossorial mole rats.

Laboratory white rats and fossorial mole rats (Spalax ehrenbergi) were subjected to progressive hypoxia by enclosure in a thermoregulated, confined atmosphere. Variable levels of environmental CO2 were obtained by controlling the duration of CO2 absorbance. Rats had preimplanted electroencephalographic (EEG) and electrocardiographic (EKG) electrodes and a rectal temperature probe. Animals were followed until their last gasp and EEG flattening, at which time the chamber's atmosphere was analyzed. The mole rat demonstrated a significantly lower terminal PIO2 [20.9 +/- 3.5 (SD) vs. 38.0 +/- 8.4 (SD) Torr]; however, in both animals terminal PIO2 was independent of PICO2 over a range of the latter of 0-117 Torr. Rats showed a progressive decline in rectal temperature from a PIO2 of 80 Torr on, amounting finally to 2.3 degrees C. The rats' oxygen consumption was maintained down to a PIO2 of 65 Torr and declined from then on. A group of rats with maximal CO2 accumulation showed a greater decline of rectal temperature and a steeper drop of VO2 with respect to PO2 compared to a group with no CO2 buildup. The main result was unexpected, in view of the theoretical synergism of the adverse effects of hypoxia and hypercapnia, and should reorient current thinking on survival and resuscitation in confined spaces.

Animals↗