Differential effects of perinatal hypoxia and anoxia on long term seizure susceptibility in the rat.

We have previously demonstrated that hypoxia is acutely epileptogenic in the immature rat but not in the adult. The window during which hypoxia induces seizures in the rat ranges from postnatal day (P) 5-17, with the most severe seizures occurring at P10-12. Perinatal hypoxia resulted in significantly more acute seizure activity than perinatal anoxia. The present study evaluates the long term effects of perinatal hypoxia versus anoxia. Animals were exposed to hypoxia (3%O2) or anoxia (0%O2) at P10 and challenged later in adulthood (P55-60) with administration of pentylenetetrazol (PTZ) (45 mg/kg subcutaneously). Compared to normal littermate controls, the animals which had been exposed to perinatal hypoxia had a significantly higher frequency of generalized convulsions (GC) and a significantly shorter latency to the first myoclonic jerk (MJ) after PTZ. In contrast, perinatal anoxia did not alter long term seizure susceptibility. These results are discussed in context of previous studies which have shown variable long term effects using different models of perinatal hypoxia and/or ischemia.     

Antiepileptic effects of nifedipine]

In experiments on freely moving male Wistar rats it was shown that nifedipine in a dose 10 mg/kg (i.p.) suppressed the penicillin-induced focal epileptic activity in cerebral cortex. A similar suppressing effect of nifedipine was shown on acute generalized tonic-clonic pentylenetetrazol (PTZ) seizures (75 mg/kg, i.p.). Nifedipine in the same dose was not effective on chronic PTZ administration (PTZ-kindling, 30 mg/kg i.p. during 28 days): when injected 30 min before each PTZ administration it didn't delay the development of kindling induced seizure susceptibility and had no effect on the severity of seizures. The administration of nifedipine in a dose of 10 or 30 mg/kg to control kindled animals which had not been treated with nifedipine had no influence on the severity of seizures provoked by a testing dose of PTZ (30 mg/kg i.p.): its intensity was similar to that of caused by PTZ injection along.     

Long-term effect of postnatal hypoxia on the seizure susceptibility in rats

The effects of postnatal hypoxia at ten days of age on the pentylenetetrazol (PTZ)-induced seizure and amygdaloid kindling were investigated in male adult rats. The rats with postnatal hypoxia were significantly more susceptible to PTZ and had a significantly more easily induced amygdaloid kindling with a rapid propagation of afterdischarges to the contralateral amygdala than the control group. Light microscopic examination in one adult rat brain with postnatal hypoxia revealed no abnormal histopathological changes. The present study suggests that the consequences of postnatal hypoxia in rats remain for a long time as enhancement in seizure susceptibility.     

Brief perinatal hypoxia increases severity of pulmonary hypertension after reexposure to hypoxia in infant rats

We hypothesized that disrupted alveolarization and lung vascular growth caused by brief perinatal hypoxia would predispose infant rats to higher risk for developing pulmonary hypertension when reexposed to hypoxia. Pregnant rats were exposed to 11% inspired oxygen fraction (barometric pressure, 410 mmHg; inspired oxygen pressure, 76 mmHg) for 3 days before birth and were maintained in hypoxia for 3 days after birth. Control rats were born and raised in room air. At 2 wk of age, rats from both groups were exposed to hypoxia for 1 wk or kept in room air. We found that brief perinatal hypoxia resulted in a greater increase in right ventricular systolic pressure and higher ratio of right ventricle to left ventricle plus septum weights after reexposure to hypoxia after 2 wk of age. Moreover, perinatal hypoxic rats had decreased radial alveolar counts and reduced pulmonary artery density. We conclude that brief perinatal hypoxia increases the severity of pulmonary hypertension when rats are reexposed to hypoxia. We speculate that disrupted alveolarization and lung vascular growth following brief perinatal hypoxia may increase the risk for severe pulmonary hypertension with exposure to adverse stimuli later in life.     

Perinatal hypoxia induces a long-lasting increase in unstimulated gaba release in rat brain cortex and hippocampus. The protective effect of pyruvate

Hypoxia and seizures early in life can cause multiple neurological deficits and even chronic epilepsy. Here, we report the data obtained in rats exposed to hypoxia and seizures at age 10-12 postnatal days and taken in experiments 8-9 weeks after hypoxia treatment. A level of the extracellular GABA and the initial velocity of GABA uptake were measured in the brain cortex, hippocampus and thalamus using isolated nerve terminals (synaptosomes). It has been revealed that the extracellular [(3)H]GABA level maintained by cortical and hippocampal synaptosomes in standard conditions (with glucose as an energy substrate) was significantly higher in adult rats exposed to hypoxia/seizures at P10-12 than in the control ones, and, moreover, became unstable with tendency to increase. Pyruvate as a single energy substrate was shown to be a highly effective for lowering and stabilizing the extracellular [(3)H]GABA level. This effect of pyruvate was tightly correlated with increase in GABA uptake and GATs affinity to GABA. Thalamus was insensible to the action of perinatal hypoxia/seizures, and thalamic GATs, in contrast to cortical and hippocampal ones, had a lower affinity to GABA (the apparent Km is 39.2±3.1 μM GABA vs 8.9±1.8 μM GABA in the hippocampus). A selective vulnerability of brain regions to hypoxia is suggested to be attributed to distinct terms of their maturation at the postnatal period. Thus, perinatal hypoxia/seizures evoke a long-lasting increase in the extracellular GABA level that could be attenuated by pyruvate treatment. This effect of pyruvate is likely due to a significant increase in GATs-mediated GABA uptake and modulation of GATs kinetic properties.     

Anti-epileptic effect of the new calcium channel blocker IOS-1.1212]

In experiments on freely moving male Wistar rats it was shown that IOS-1.1212 (1,4-dihydropyridine) in a dose 2 and 10 mg/kg (i. p.) suppressed the penicillin-induced focal epileptic activity in cerebral cortex. Similar suppressing effect of IOS-1.1212 was shown on acute generalized tonic-clonic pentylenetetrazol (PTZ) seizures (75 mg/kg i. p.) and on chronic PTZ administration (PTZ-kindling, 30 mg/kg i. p. during 30 days): when injected 30 min before each PTZ administration it delayed the development of kindling-induced seizures susceptibility in randomized animals (series 1) and attenuated the severity of seizures in PTZ-sensitive animals (series 2). However, IOS-1.1212 had no effect on the strychnine-induced focal epileptic activity. In male Icr:Icl mice IOS-1.1212 in a dose 1.5 and 5 mg/kg also influenced the PTZ convulsions (i. v. titration of 1% solution at a rate of 0.01 ml/s) and had no effect on the strychnine convulsions (i. v. titration of 0.01% solution at a rate of 0.01 ml/s) and on maximal electroshock. In addition, IOS-1.1212 significantly increased antiepileptic effect of phenobarbital on maximal electroshock.     

Influence of magnesium sulphate on evoked activity of rat brain after exposure to short-term hypoxia

Young Wistar rats (aged 12, 25 and 35 days) were exposed to short-term (60 min) hypobaric hypoxia of 41 kPa. Cortical afterdischarges (ADs) were evoked by repeated direct stimulation of the sensorimotor cortex and the duration of ADs was monitored to examine the influence of magnesium sulphate injection (0.3 g/kg b.w.). In 12-day-old hypoxia-exposed rats, an increase of the mean duration of ADs after the repeated stimulation appeared. This effect was prevented by magnesium administration. In 25- and 35-day-old rats exposed to hypoxia a shortening of ADs was registered but no specific effect of magnesium sulphate pretreatment was observed. The brain susceptibility and ability to terminate evoked seizures is discussed.     

Pentylenetetrazol (PTZ)-kindling development in intact and subcortical structure lesioned rats

Kindling was induced in male wistar rats (280-320 g) by daily ip injections of PTZ in subthreshold doses (30 mg/kg). Repeated administration of PTZ to animals resulted in developing of enhanced seizures and also enhanced seizure susceptibility which could be sustained for a long time (6 months) after last seizure paroxysm. The lesioned hippocampus retarded the manifestation of PTZ kindling, where as lesioned caudate nuclei increased the seizure kindling development. Results also revealed hippocampus as a determinant structure in PTZ kindling formation, which stabilize the epileptic manifestations and make them chronic, at the same time caudate nuclei retarded the epileptic seizures stabilization. This role may be only antiepileptic, and not anti-kindling as is known for caudate nuclei.     

Korazol-induced kindling in animals with different sensitivities to the epileptogen]

To select homogeneous groups of sensitive and low-sensitive animals (male Wistar rats) for subsequent kindling experiments the animals's reaction to the threshold dose of pentylenetetrazole (PTZ) (40 mg/kg, i.p.) was defined. Rats showing convulsive response of 1 to 3 scores (seizures were estimated according to a 6-score scale) were assumed to be sensitive animals. Rats when injected with this dose showing no seizures were defined as low-sensitive animals. One week after the test kindling was started by daily administration of a subconvulsive dose of PTZ (30 mg/kg, i.p.). Low-sensitive animals displayed a 3 day delay in the development of kindling seizures and a decrease in the severity of seizures as well as an extended latency period before the first manifestations of seizures after each injection of PTZ. Thus testing by means of the threshold dose of PTZ is a comparatively simple method of preliminary estimation of the animals's sensitivity to this convulsant in order to select groups of relatively sensitive and low-sensitive animals in PTZ kindling experiments. For a more precise selection of animals it is suggested to be useful to repeat the initial test after an interval of 5-7 days. The proposed method seems to be applied in principle to other convulsants as well.     

Effects of organic calcium antagonists and magnesium on the development of corazol kindling

In experiments on rats it was shown that i.p. administration of finoptin (verapamil), magnesium sulfate or ryodipine (an 1,4-dihydropyridine) 15 min before each daily injection of pentylenetetrazole (PTZ) in a subconvulsive dose (30 mg/kg i.p.) significantly (for 10-12 days delayed the development of pentylenetetrazole-induced kindling and attenuated kindled seizure reaction as compared with the controls. In animals sensitive to PTZ which were selected on the test of their reaction to previous single PTZ injection in a dose of 40 mg/kg finoptin, magnesium or finoptin + magnesium resulted in suppression of kindling development at late stages (after 2-week administration of drugs together with PTZ). After the withdrawal of the drugs there was a tendency to an increase of seizure reaction to the testing PTZ dose (30 mg/kg). The enhanced seizure susceptibility to test PTZ dose has being persisted during all observation period (8 months). Finoptin administered 15 min prior to PTZ had no effect on the severity of seizure reaction of fully kindled animals which had not received the drugs. The results obtained show that organic Ca-antagonists and magnesium delay the development of kindling induced seizure susceptibility, but cannot completely prevent it. The results also suggest that mechanisms of the chronic epileptogenesis (development of kindling induced seizure susceptibility) and those of the acute convulsive reaction to the epileptogen are not similar.     

Hypoxic Preconditioning and Hypoxic-Ischemic Brain Damage in the Immature Rat: Pathologic and Metabolic Correlates

Abstract: It has been reported that immature rats subjected to cerebral hypoxia-ischemia sustain less brain damage if they are previously exposed to systemic hypoxia compared with animals not exposed to prior hypoxia. Accordingly, neuropathologic and metabolic experiments were conducted to confirm and extend the observation that hypoxic preconditioning protects the perinatal brain from subsequent hypoxic-ischemic brain damage. Six-day postnatal rats were subjected to systemic hypoxia with 8% oxygen at 37°C for 2.5 h. Twenty-four hours later, they were exposed to unilateral cerebral hypoxia-ischemia for 2.5 h, produced by unilateral common carotid artery ligation and systemic hypoxia with 8% oxygen. Neuropathologic analysis, conducted at 30 days of postnatal age, indicated a substantial reduction in the severity of brain damage in the preconditioned rats, such that only 6 of 14 such animals exhibited cystic infarction, but all 13 animals without prior preconditioning exhibited infarction ( p < 0.001). Measurement of cerebral glycolytic and tricarboxylic acid intermediates and high-energy phosphate reserves at the terminus of and at 4 and 24 h following hypoxia-ischemia showed no differences in the extent of alterations in the preconditioned and nonpreconditioned immature rats. A difference was seen in the restitution of high-energy stores during the first 24 h of recovery from hypoxia-ischemia, with a more optimal preservation of these metabolites in the preconditioned animals, reflecting the less severe ultimate brain damage. Accordingly, the neuroprotection afforded to the preconditioned animals was not the result of any differences in the extent of anaerobic glycolysis, tissue acidosis, or depletion in high-energy reserves during hypoxia-ischemia but rather the result of other mechanisms that improved the metabolic status of the immature brain during the early hours of reperfusion following hypoxia-ischemia.     

Influence of ethosuximide and dipropylacetate on metrazol-induced electrocorticographic changes during ontogenesis in rats

Influence of ethosuximide (ESI, 125 mg/kg i.p.) and dipropylacetate (DPA, 300 mg/kg i.p.) pretreatment on electrocorticographic changes induced by pentamethylenetetrazole (PTZ, 20 mg/kg dose every 5 min) was studied in rats aged 7, 12, 18 and 90 days. PTZ alone induced isolated spikes and/or sharp waves as the first sign of its action in all age groups except in adult animals where rhythmic theta activity was elicited. The antiepileptic effect of DPA was observed in 12- and 18-day-old rats, ESI specifically inhibited rhythmic activity in adult rats. ECoG seizures induced by high doses of PTZ were inhibited by DPA in all age groups, ESI tended to be effective in adult rats only. DPA did not change the pattern of ECoG seizures, whereas ESI led to replacement of the spike-and-wave rhythm by serrated waves in adult animals. The low ability of immature brain to generalize ictal activity was further diminished by ESI.     

Influence of pre- and postnatal exposure of rats to 2.45-GHz microwave radiation on neurobehavioral function

Rats exposed to microwaves prenatally (2,450 MHz, 10 mW/cm2, 3 h/day, days 5-20 of gestation) or perinatally (same as above plus days 2-20 postnatally) were examined by a neurobehavioral test battery on postnatal days 30 and 100. Body mass, locomotor activity, startle to acoustic and air-puff stimuli, fore- and hindlimb grip strength, negative geotaxis, reaction to thermal stimulation, and swimming endurance were assessed. The prenatally and the perinatally exposed rats (male and female) weighted more than sham-exposed rats at 30, but not at 100, days of age. In addition, the perinatally exposed animals had less swimming endurance at 30, but not at 100, days of age relative to sham-exposed rats. For the other measures, only the air-puff startle response was altered and was limited to the prenatally exposed female pups; ie, at postnatal day 30, the startle response was increased in magnitude, and at postnatal day 100, the response was decreased. No other reliable effects were observed. In a second experiment, rats treated as described above were examined for alterations in body mass, locomotor activity, reaction to air-puff stimuli, reaction to thermal stimulation, and swimming endurance at postnatal days 30-36. Again, perinatally exposed rats were larger in body mass and had less swimming endurance compared with sham-exposed rats. The latency to the air-puff startle response was longer in female pups exposed prenatally. These data indicate that altered endurance and gross motor activity result from perinatal exposure to microwave irradiation.     

Hyperthermic seizures enhance responsiveness to pentylenetetrazole and induce cognitive dysfunction: protective effect of 3-alkynyl selenophene

AimsIn this study we investigated the effect of pre-treatment with 3-alkynyl selenophene (3-ASP) against the increase in responsiveness to pentylenetetrazole [PTZ seizure threshold] and cognitive dysfunction induced by experimental febrile seizures (FS). The effects of 3-ASP were compared to those of diazepam (DZP).Main methodsYoung rats, at postnatal day 21, developed seizures after exposure to a stream of heated air to approximately 41 °C. A non-spatial long-term memory and PTZ seizure threshold were determined 30 days after FS. The behavioural seizures were stereotyped followed by facial automatisms, often followed by body flexion. Young rats were pre-treated with 3-ASP (50 and 100 mg/kg; per oral route), DZP (1 and 5 mg/kg; intraperitoneally) or vehicle.Key findings3-ASP and DZP pre-treatments were not effective in protecting against seizures induced by FS. 3-ASP pre-treatment protected against the increase in responsiveness to PTZ and cognitive dysfunction induced by FS. DZP pre-treatment was effective in protecting against the increase in responsiveness to PTZ, but not, against the impaired memory induced by FS.Significance3-ASP pre-treatment protected against impairment of memory performance in the step-down passive avoidance task and the increase in the susceptibility to seizures caused by FS early in life of rats.     

Critical developmental period for hyperoxia-induced blunting of hypoxic phrenic responses in rats.

Hypoxic ventilatory and phrenic responses are reduced in adult rats reared in hyperoxia (60% O(2)) for the first month of life but not after hyperoxia as adults. In this study, we identified the developmental window for susceptibility to hyperoxia. Phrenic nerve responses to hypoxia were recorded in anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats (aged 3-4 mo) exposed to 60% O(2) for the first, second, third, or fourth postnatal week. Responses were compared with control rats and with rats exposed to 60% O(2) for the first month of life. Phrenic minute activity (burst amplitude x frequency) increased less during isocapnic hypoxia (arterial PO(2) = 60, 50, and 40 Torr) in rats exposed to hyperoxia for the first or second week, or the first month, of life (P < 0.01 vs. control). Functional impairment caused by 1 wk of hyperoxia diminished with increasing age of exposure (P = 0.005). Adult hypoxic phrenic responses are impaired by 1 wk of hyperoxia during the first and second postnatal weeks in rats, indicating a developmental window coincident with carotid chemoreceptor maturation.     

Ontogeny of susceptibility to the convulsant, Ro 5-4864, and its relationship to audiogenic seizure susceptibility in inbred mice

The postnatal development of susceptibility to the convulsant effects of Ro5-4864 (4'-chlorodiazepam) was characterized in two inbred mouse strains (DBA/2J and BALB/c ByJ) which as adults differ markedly in their response to this convulsant. Onset of susceptibility to a dose of Ro5-4864 which caused a high frequency of clonic seizures in adults was observed at 10 days of age in DBA/2 mice, but not until 35 days in BALB/c By mice. At 14 days of age an abrupt increase in susceptibility to Ro5-4864-induced tonic seizures was found in DBA/2 but not BALB/c By mice. Both the peak of tonic seizure susceptibility (21 days) and the time course of its subsequent age-dependent decline closely paralleled the change in audiogenic seizure susceptibility in the DBA/2 strain. PK11195 (40 mg/kg) blocked Ro5-4864 (25 mg/kg)-induced, age-dependent tonic seizures but had no effect on clonic seizure induction in the same mice. These observations establish that both the susceptibility to Ro5-4864 in adult mice and the postnatal time course for development of susceptibility to this convulsant are inherently different in these two strains of mice. The lack of coincidence between the developmental onset of susceptibility to Ro5-4864-induced seizures and the onset of supersensitivity to Ro5-4864-induced tonic seizures during the period of peak audiogenic seizure susceptibility in DBA/2 mice implies that more than one neurochemical mechanism is involved in the ability of Ro5-4864 to induce seizures in this strain. However, the blockade of Ro5-4864-induced tonic seizures by PK11195 suggests that peripheral type benzodiazepine receptors may mediate this effect.     

Seizures Induced by Pentylenetetrazole in the Adult Zebrafish: A Detailed Behavioral Characterization

Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZ-induced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research.     

Role of Glutamate and GABA Transporters in Development of Pentylenetetrazol-Kindling

Kindling is a form of epileptogenesis that can be induced with pentylenetetrazol (PTZ). We undertook this study to evaluate the contribution of glutamate and GABA transporters to the process of PTZ kindling. Rats were injected i.p. three times per week with PTZ (40 mg/kg) until they were fully kindled. In rats who achieved full kindling, measurement of hippocampal glutamate and GABA transporters within 24 h by western blot showed that GLAST, GLT-1, and EAAC1 were elevated significantly. However, fully kindled rats at 30 days after their last seizure had no change in either glutamate or GABA transporters proteins. These sequential observations suggest that glutamate transporters may contribute to the occurrence of seizures, but were not associated with maintenance of epileptogenesis. During this experiment, we collected data from animals that had kindled easily and animals who were resistant to kindling. Easily-kindled rats reached full kindling with less than five injections of PTZ. Kindling resistant animals failed to achieve full kindling even after administration of 12 consecutive injections of PTZ. Levels of EAAC1 and GAT-1 in easily-kindled rats were decreased by 30% when compared to kindling resistant animals at 30 days after the last PTZ injection. Since decreased EAAC1 and GAT-1 would diminish GABA function, less quantity of these proteins would appear to be associated with the convulsive threshold at the beginning of kindling development. We wonder if glutamate and GABA transporters might be operant in a convulsion threshold set factor or as a pace factor for kindling.     

Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea.

We have described a rat model that responds to repetitive episodic hypoxia (12-s infusions of nitrogen into daytime sleeping chambers every 30 s, 7 h/day for 35 days) with an increase in diurnal systemic blood pressure. We hypothesized that afferent information from the peripheral chemoreceptors may be necessary to produce diurnal blood pressure elevation in this hypoxia model. Carotid body denervation (CBD) was accomplished by severing both carotid sinus nerves in two groups of male Wistar rats (250-375 g). Group 4 CBD rats were subjected to intermittent hypoxia for 35 days (3-5% nadir ambient O2) as described above, whereas group 5 CBD rats remained unhandled in their usual cages. Additional sham-operated controls included group 2 sham-"hypoxia" rats, which were housed in chambers identical to the hypoxia rats but supplied with compressed air instead of nitrogen, group 1 (not denervated) rats, which remained unhandled in their usual cages, and group 3 sham-operated rats, which were subjected to 35 days of intermittent hypoxia identical to group 4 CBD rats. Femoral arterial baseline and end-of-study blood pressures were measured in conscious rats. The group 3 rats exposed to episodic hypoxia displayed a 13-mmHg increase in mean blood pressure, whereas the other groups showed no significant change from baseline. Left ventricular hypertrophy was evident in all rats exposed to episodic hypoxia, but right ventricular hypertrophy was evident only in the group 4 rats. All CBD rats developed increased hematocrit and hemoglobin, while the group 3 rats (non-CBD, episodic hypoxia) did not. The baroreceptor reflex at baseline was not depressed in the CBD rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental cardiac necrosis in hypobaric and anemic hypoxia.

Resistance to isoproterenol-induced cardiac necrosis (IPRO) was compared in rats exposed to two types of hypoxia (i.e., hypobaric and anemic). IPRO was induced by two consecutive, subcutaneous injections of isoproterenol (80 mg/kg) at 24-h intervals. The animals were killed on the third day and the severity of the lesion was evaluated on a 0 (no damage) to 4 (severely damaged) scale. White male rats (HA) were exposed in a barometric chamber to a simulated altitude of 7,000 m (307 mmHg) for 4 h/day for 24 days. Two groups of control rats were kept at sea level; one group (SLA) was the same age and one group (SLW) was the same weight as the altitude-exposed rats. The HA rats were significantly more resistant to IPRO with a mean necrogenic rating of 1.8 compared to 3.3 for the SLA and SLW rats. Infant rats (AA) were made anemic by feeding full-cream milk and glucose for 100 days after weaning. Two groups of control animals were fed a standard laboratory diet; one group (AC) was the same age and one group (AW) was the same weight as the AA rats. There was no significant difference in the necrogenic ratings of the AA (3.3), AC (3.5), or WC (3.7) hearts. Thus, hypobaric hypoxia affords some protection against IPRO which is not afforded by anemic hypoxia. Similarities and differences in the two hypoxias are discussed.