Recovery In Room Air Research Articles

Acute severe carbon monoxide exposure in the rat: effects of hyperglycemia and hypoglycemia on mortality, recovery, and neurologic deficit

Human and animal studies suggest a poorer outcome in the presence of abnormal blood glucose concentration during cerebral hypoxia-ischemia. It is unknown whether this is also the case in acute severe carbon monoxide poisoning. Using Levine-prepared rats, three groups were established and exposed to CO to answer this question: (1) hyperglycemics resulting from the administration of a 50% glucose solution, (2) hypoglycemics resulting from the administration of normal saline, and (3) untreated controls. The rats inhaled 2400 ppm CO for 90 min in the absence of anesthesia. Blood glucose was raised to a mean value of 402 mg/dL just prior to CO exposure in group 1. This resulted in an increased mortality rate (i.e., 54%), and during 4 h of room air recovery an impaired ability to regain body temperature, an increased plasma lactate dehydrogenase activity, and an increased neurologic deficit as compared with group 3. Hypoglycemia, which developed during CO exposure in group 2 (mean minimum glucose after 90 min, 44 mg/dL), resulted in an increased mortality rate (i.e., 46%), and during 4 h of room air recovery an impaired ability to regain body temperature and an increased neurologic deficit as compared with group 3. Blood glucose concentration in the rats in groups 2 and 3 that died during or shortly after CO exposure was significantly depressed relative to the survivors of those groups. Plasma insulin activity was elevated during CO exposure in group 1 as compared with group 3, but fell during recovery; insulin remained low throughout CO exposure and recovery in group 2. The results demonstrate the deleterious effects of both a very high and a very low blood glucose concentration during acute CO exposure.

Prevention of chronic pulmonary oxygen toxicity in young rats with liposome‐encapsulated catalase administered intratracheally

The lungs and hearts of young rats exposed to 100% oxygen (O2) for 8 days (27 to 35 days of age) were studied following recovery in room air at 60 days of age using morphometric, biochemical, and physiological techniques. In an attempt to prevent chronic oxygen toxicity 153 rats had transtracheal catheters surgically implanted and were treated during the O2 exposure with daily intratracheal injections of liposome-encapsulated superoxide dismutase (SOD) and/or catalase (CAT). Oxygen exposure in this model results in chronic cardiopulmonary alterations which include pulmonary hypertension, right ventricular hypertrophy, and a decrease in number of pulmonary arterioles 25 to 50 microns in diameter with increased muscularization of their walls. The volume densities of the parenchyma, parenchymal air space, and the alveolar space are increased, while that of the combined alveolar ductal and respiratory bronchiolar space is decreased. Daily intratracheal administration of liposome-encapsulated CAT (160 U) during the O2 exposure prevented these chronic changes. Liposome-encapsulated SOD (110 U) or SOD (50 U) + CAT (70 U) did not appear to have a preventive effect. During the first 3 to 5 days following oxygen exposure the lung tissue enzymes SOD, CAT, and glutathione peroxidase markedly increased. We conclude that in the young rat animal model liposome-encapsulated CAT (160 U) given intratracheally during the period of O2 exposure is safe and will prevent the chronic vascular and parenchymal damage due to oxygen toxicity.

Elevated blood glucose is associated with poor outcome in the carbon-monoxide-poisoned rat

Levine-prepared, unanesthetized rats exposed to 2400 and 2700 ppm carbon monoxide (CO) for 90 min were used to examine the effect of acute CO poisoning on plasma glucose and insulin concentrations, and neurologic dysfunction. Body temperature and mean arterial blood pressure fell progressively during CO exposure. Glucose rose during initial CO exposure, then declined; glucose increased again after 2 h of room air recovery. Neurologic deficit, behaviorally-assessed after 4 h of recovery, was strongly correlated ( r = 0.71, P < 0.001) with glucose increase during the first 2 h of recovery. Recovery hyperglycemia was, in turn, correlated ( r = 0.69, P < 0.001) with the fall in glucose during the second half of CO exposure. Neurologic deficit was also correlated, but less strongly so, with hypoglycemia during CO exposure. Failure to rapidly regain body temperature during recovery was correlated with the post-CO rise in glucose concentration and with increased neurologic deficit. Plasma insulin activity was depressed immediately following CO exposure, and increased during recovery. CO-induced hypothermia was greater at 2700 than at 2400 ppm CO, as were post-CO recovery hyperglycemia, neurologic deficit and mortality, while body temperature recovery was less complete. The results provide evidence of an association between neurologic deficit and general morbidity following acute CO poisoning and the magnitude of post-CO hyperglycemia.

Variations in the severity of retinopathy seen in newborn rats supplemented with oxygen under different conditions of hyperbarism

The purposes of this experimental study were to evaluate the effects of oxygen supplementation delivered under hyperbaric conditions on the retinas of newborn rats and to determine the minimum and maximum levels of hyperbarism capable of protecting the retinal vessels from the toxic effects of oxygen without determining lethal effects in this experimental model. A control group of newborn rats were maintained with their mother for the first 12 days of life under room-air conditions. A second group of animals were exposed to a hyperbaric environment (+81 kPa) under normoxic conditions for the first 7 days of life and subsequently returned to normobaric conditions for the next 5 days. Examination of the retinal flat mounts from this latter group of animals revealed essentially normal vascular networks with only a modest degree of vasoconstriction. Two other litters of ratlings, with their mothers, were given supplemental oxygen at an FiO2 of 80% under a compression pressure of +101.25 kPa. In this group of animals, death of both of the mother rats from pulmonary edema occurred on the first day of treatment, and, in spite of immediate mother substitution, the newborn rats succumbed to the same complication. Five other groups, each containing two litters of newborn rats with their mothers, were exposed to FiO2s of 80% at hyperbaric levels ranging from +20.25- to +81.0 kPa for the first 7 days of life. On the eighth day, the FiO2s were reduced to 21%. After 5 days of room-air recovery, the animals were killed.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional Brain Glucose Utilization in the Conscious Rat Exposed to Prolonged Hypobaric Hypoxia

Because of the physiologic and metabolic changes that occur during acclimatization, we hypothesized that LCGU may be normal during prolonged hypoxia. We exposed five Sprague-Dawley rats to hypoxia (air at 380 mm Hg) for 2 weeks (hypoxic group) and six rats to 2 weeks of hypoxia followed by 2 weeks of recovery in room air (recovered group). Six control rats breathed room air (control group). Regional brain glucose utilization was measured in awake animals by using 2-[C]deoxyglucose autoradiography. Glucose utilization was comparable in the control and recovered groups and in most brain regions of hypoxic animals. Glucose utilization was decreased slightly in 10 of 12 gray matter regions examined and was 20 to 25% lower (p <0.05) in the olfactory and auditory cortices, the caudate nucleus, and the superior olive of the hypoxic group. White matter glucose utilization was unchanged. Hypoxic rats, compared to controls, had a lower PaO2 (53 +/- 3 vs. 76 +/- 3 mm Hg, mean SEM, respectively), a lower PaCO2 (22 +/- 1 vs. 36 +/- 2 mm Hg), and a higher mean pulmonary artery pressure (46 +/- 3 vs. 14 +/- 3 mm Hg) and hematocrit (61 +/- 2% vs. 48 +/- 1%; p <0.005 for all comparisons). Pulmonary hypertension and polycythemia persisted in recovered rats. Arterial pressure, pH, and plasma glucose were unaffected. Therefore, while acute hypoxia may increase glucose utilization in most brain structures, prolonged exposure does not.

Effects of variable oxygenation and gradual withdrawal of oxygen during the recovery phase in oxygen-induced retinopathy: kitten model.

The effects of two types of prolonged oxygen supplementation were tested in the kitten model of oxygen induced retinopathy. Thirty-one litters were placed in 80% oxygen for 65 h starting the 3rd day after birth to initiate a moderately severe retinopathy. One-half of each litter thereafter served as controls, remaining in room air during the development of the retinopathy. In the remaining half, the retinopathy was allowed to develop in either a variably hyperoxic/hypoxic environment (one-half of each of 16 litters) or in an oxygen environment that was gradually reduced to room air by 4 wk (one-half of each of 15 litters). The retinopathy scores in the controls were comparable in both studies and the same as in previous experience with this model. Kittens exposed to the variable oxygen recovery environment had significantly less severe retinopathy than their room air recovery littermates (p less than 0.05). The retinopathy scores in the group with gradually withdrawn oxygen did not differ from the littermate controls (power greater than 80%). These data support the hypothesis that conditions of oxygenation during the recovery process from an acute oxygen-induced vascular injury have a significant effect on the healing process.

VARIABLE OXYGENATION DURING RECOVERY FROM OXYGEN INDUCED RETINOPATHY IN THE KITTEN

Premature infants who experience prolonged oxygen administration and apnea/bradycardia have an increased incidence of retinopathy of prematurity. Therefore, we predicted and tested the hypothesis that alternating hypoxia and hyperoxia would adversely affect the oxygen induced retinopathy developing after hyperoxic vascular injury in the kitten. Following 65 hrs of 80% oxygen on day 3 of life, each of 15 litters (67 kittens) were randomly divided between room air recovery and recovery in an incubator where the FiO2 varied from 10% to 43% within each 18 min. period. Fifteen litters would permit us to detect a mean difference in scores of 2 points, α = 0.05, with a power of 80%. After 3 weeks in the recovery phase, the retinopathy was scored on a scale of O (normal) to 13 (worst) by two masked investigators. The mean retinopathy score from the room air recovered controls in one litter was compared to the mean score from the experimental kittens in the same litter. Unexpectedly, the scores in the experimental group were significantly better than the room air matched littermates, [d = 4.0±3.1, (SD), paired t test, p <0.001] [or Sign test, 14/15 litters were better, p <0.01]. We found that variable oxygenation resulted in a less severe retinopathy than stable oxygenation (room air = 21%) during recovery. The clinical implications of this finding are not known, except to speculate that variable oxygenation may not be a contributing factor to retinopathy of prematurity in the human.

Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery.

To study the influence of age and sex on the hemodynamic and structural response of the pulmonary vascular bed to chronic hypobaric hypoxia, "infant" Sprague-Dawley rats from 8 days old and "adult" rats from 9 wk old, each group including both sexes, were exposed to half atmospheric pressure for 1 mo and then allowed to recover in room air for up to 3 mo. During hypoxic exposure, pulmonary artery hypertension (Ppa) developed in all groups. The level of Ppa was similar in both male and female infant and in male adult rats but was significantly lower (P < 0.01) in the female adult rats. After recovery in room air, only partial regression of Ppa had occurred in all groups (P < 0.001). In male and female adult rats, recovery values were similar but infant rats had more residual Ppa than adults (P < 0.001). The structural changes that developed during hypoxia, especially the abnormal presence of muscle in small and peripheral intra-acinar arteries, were more severe in male adult rats compared with female adults (P < 0.01) and in infants of both sexes compared with male adults (P < 0.01). After recovery, residual structural changes were present in all rat groups but were most severe in the infants (P < 0.01).

Effects of nitrogen dioxide on elastin and collagen contents of lung.

Male Syrian hamsters were exposed to 30 +/- 5 ppm nitrogen dioxide for 22 hr daily for 3 wk. Nitrogen dioxide-exposed hamsters sacrificed at various times during the 3 wk exposure showed a general loss of body weight and an increased dry lung weight when compared with the controls, which were housed in a similar, but nitrogen dioxide-free environment. Analysis of total lung collagen and total lung elastin revealed a net decrease in the moieties within 4 and 10 days, respectively, following commencement of nitrogen dioxide exposure. Total lung collagen returned toward pre-exposure levels by the 14th day of nitrogen dioxide exposure. Total lung elastin did not return toward normal until termination of nitrogen dioxide exposure. Recovery in room air for 3 wk following 21 days of nitrogen dioxide exposure restored the total pulmonary collagen and elastin to valutin and collagen degradation and synthesis differ during and after nitrogen dioxide exposure. Lung collagen loss was observed earlier and was restored to normal values during the continuation of nitrogen dioxide exposure. Lung elastin loss occurred later and persisted during the entire period of exposure but returned to normal after exposure was terminated.

Blood replacement in dogs by dextran-hemoglobin.

Exchange transfusions in dogs were performed with a solution of either dextran or a covalent complex between dextran and human hemoglobin. Dogs transfused with dextran alone died when their hematocrit was lowered to 6-10%. Dogs transfused with dextran-hemoglobin complex, however, survived a reduction of their hematocrit to 2% or below. In the latter animals, the dextran-hemoglobin complex disappeared from the circulation with an average half-life of 2.4 days. Correcting for oxidation of the hemoglobin moiety to methemoglobin, the half-life of functional unoxidized dextran-hemoglobin in the circulation was 1.9 days. In compensation for the loss of dextran-hemoglobin, vigorous erythropoiesis was observed at a rate of close to 5% hematocrit per day over the first 2 days following the exchange transfusion. As a result, the total hemoglobin concentration in blood was maintained at 5-6% during this period, and the animals went on to complete recovery in room air without the need for further transfusion with dextran-hemoglobin.