Posthypoxic Period Research Articles

Erythropoietin production in exhypoxic polycythemic mice.

Our present study was undertaken to determine the serum erythropoietin concentration (radioimmunoassay), hematocrit, red cell mass, and body weight of mice exposed to hypoxia in a hypobaric chamber (0.42 atm, 22 h/day) for 14 days and during the 10 posthypoxic days at ambient pressure to clarify the correlation of the red cell mass and erythropoietin production during hypoxia. The mean serum erythropoietin titer was 326.23 +/- 77.04 mU/ml after 2 days, reached the highest level after 3 days (452.2 +/- 114.5 mU/ml), then gradually declined to a level of 36.5 +/- 11.4 mU/ml after 14 days of hypoxia, and was undetectable during the 10-day posthypoxic period. The hematocrit values were significantly increased from 41.09 +/- 0.50% at day 0 to 51.65 +/- 1.08% after 3 days and to 72.20 +/- 1.53% after 14 days of hypoxia. The red cell mass (calculated from initial body weight) increased from 3.24 +/- 0.1 ml/100 g at day 0 to 7.32 +/- 0.46 ml/100 g after 14 days of hypoxia and declined to 6.66 +/- 0.53 ml/100 g at the end of the 10-day posthypoxic period. The mice lost weight while they were in the hypobaric chamber and showed a significant increase in body weight during the 10-day posthypoxic period. These studies support the concept that chronic intermittent hypoxia causes an early increase, followed by a rapid decline, in erythropoietin production, which is correlated with the gradual increase in red cell mass.

The hypoxic brain: histological and ultrastructural aspects.

A brief review of structural damage to cerebral cells resulting from experimentally induced hypoxia or ischemia is presented. The histological aspect of the brain is compared in different animal models with respect to the onset and progression of damage. Cell changes detected in the early post-hypoxic period consist of microvacuolation and seem to be fully reversible. Coagulative cell change and edematous cell change which may be considered as the morphologic equivalent of irreversible cell death, develop in a later phase, often as a result of secondary events such as microcirculatory impairment or tissue lactic acidosis. A striking difference in vulnerability exists between cerebral cell types or anatomic brain regions. Possible determinant factors for this phenomenon are discussed. Finally, the special contribution of calcium in cell destructive processes is demonstrated with the aid of ultrastructural calcium distribution studies.

Role of oxygen radicals in cardiac injury due to reoxygenation

The ability of oxygen derived free radicals to induce irreversible cellular injuries during reoxygenation was studied on isolated potassium-arrested heart preparation. Enzymatic scavengers of hydrogen peroxide (H2O2) and superoxide anion (O-2), catalase and superoxide dismutase, were not effective in reversing the cardiac alterations induced by hypoxia. Cellular injuries induced by reoxygenation, 'Oxygen paradox', were partially prevented by scavengers of H2O2 (glutathione reduced form, catalase) and O-2 (superoxide dismutase). The 'oxygen paradox' was associated with a release of malonaldehyde. The inhibition of lipid peroxidation by alpha-tocopherol prevented the toxic effect of molecular oxygen on hypoxic hearts. The specific quenchers of singlet oxygen (histidine) and hydroxyl radical (mannitol) reduced the peroxidation of unsaturated lipids and the intensity of the 'oxygen paradox' phenomenon. The results indicate that in cardiac muscle (i) oxygen derived free radicals are important byproducts of abnormal oxidative metabolism present during the post hypoxic period; (ii) the 'oxygen paradox' phenomenon is related to the formation of lipid hydroperoxides leading to the cellular membrane disruption and to the irreversible alteration of cardiac integrity.

Cerebral glucose metabolism during 30 minutes of moderate hypoxia and reoxygenation.

In 50 separate experiments, isolated canine brain preparations were subjected to 15 or 30 min of either PaO2 30 mmHg or PaO2 40 mmHg perfusion followed by up to 60 min of reoxygenation at a normal PaO2. The cerebral metabolic rate for glucose (CMRGlu) increased 70-80% after 2 min of hypoxia but then returned to nearly the normal rate by the end of the 30-min period of hypoxia. Glycolytic flux appeared to be facilitated in both groups initially but was inhibited as the hypoxic period continued. This slowing of glycolysis after 15 or 30 min of hypoxia appears to be modulated by the regulatory enzyme phosphofructokinase. Glucose equivalents metabolized, based on CMRGlu plus brain glucose and glycogen disappearance, far exceed the glucose equivalents that can be accounted for on the basis of oxygen utilization and brain lactate formation. Thus, during hypoxia, some of the glucose equivalents must be utilized for synthesis of other metabolites. The glycolytic intermediates returned to normal after reoxygenation in the PaO2 40 mmHg preparations, but the PaO2 30 mmHg preparations continued to show evidence of decreased glycolysis and a lingering lactacidosis. Although posthypoxic oxygen uptake was sufficient to oxidize all glucose entering the brain, there was no significant release of accumulated lactate into the blood. Thus, the decrease in brain tissue lactate must have been the result of lactate oxidation. A significant amount of the glucose entering the brain during the posthypoxic period appears to be used for metabolite synthesis rather than energy production.

Effects of hypoxic and hormonal factors on ribonucleic acid content in spinal cord cells: Comparison of the metabolic responses in neurons, perineuronal neuroglia and ependyma cells

Quantitative changes in the amount of ribonucleic acid per cell were determined in rat spinal cord cells by means of ultraviolet and visible two-wavelength cytospectrophotometry, both these methods being shown to give similar results. After 2-h hypobaric hypoxia, the ribonucleic acid content was increased in the spinal motor neurons with no changes in the perineuronal neuroglia and ependymal cells. The posthypoxic period was characterized by a number of changes in ribonucleic acid which were rather different in neurons, neuroglial or ependymal cells. Daily injections of adrenaline to rats for 2 weeks resulted in a decrease in ribonucleic acid content in the motor neurons and led to an increase in two other kinds of spinal cord cells. Four days following adrenalectomy there was a decrease in ribonucleic acid content in spinal motor neurons without any changes in perineuronal neuroglia or in ependymal cells. After cortisol injection to adrenalectomized rats, the decrease in the ribonucleic acid content was not reversed in the motor neurons and there was also a decrease in the ependymal cells. Changes in ribonucleic acid content are complex and not obviously related to single or combined actions of adrenal hormones. Similarities and differences in the metabolic responses of ribonucleic acid to stress are discussed with respect to three main types of nerve tissue cells: neurons, neuroglia and ependyma.

Plasmodium berghei: Relationship between mitosis and erythropoiesis in spleen cells of infected rats

Rats rendered polycythemic by hypoxia show a suppression of erythropoiesis and a “rebound” granulo- and lymphopoiesis in the posthypoxic period. These rats, when infected with Plasmodium berghei had a survival rate of 80%, as compared to 8% in normally infected controls. 59Fe and [ 3H]thymidine uptake of spleen cells was measured from the initiation until peak parasitemia. As the infection progressed, the ratio of 3H to 59Fe uptake declined from 37.00 to 1.40, showing a shift towards erythropoiesis. Rebound animals showed a marked decrease in Fe uptake when infected, especially during the early stages of infection. It appears that changes in the balance between the formation of erythropoiesis-oriented cells and of immune-oriented cells in the rat spleen may prove critical to the fate of the malaria-infected animal.

Mechanism of dilatation of the limb vessels in the posthypoxic period

Mechanism of dilatation of the limb vessels in the posthypoxic period

Elimination by hypoxia cerebral blood flow autoregulation and EEG relationship.

1. The relationship between cortical blood flow and the frequency content of the EEG was studied in a circumscribed area of the exposed cerebral cortex in cats under nitrous oxide-oxygen anaesthesia. Autoregulation of the cortical blood flow was also tested during step-changes of the arterial blood pressure. Observations were made before and after an episode of severe hypoxia. 2. An episode of systemic hypoxia disrupted the normal high correlation between cortical blood flow and EEG frequency content. In the post-hypoxic period cortical flows of up to about three times normal values were recorded together with brain swelling and a slow wave EEG. The hyperemia and swelling subsided during 1–2 h after the hypoxic episode, and were accompanied by partial or complete recovery of the EEG. In the post-hypoxic period a defective autoregulation of the cortical blood flow to changes in the systemic blood pressure was demonstrated. 3. The cerebral post-hypoxic state with hyperaemia, brain swelling, EEG depression, and loss of autoregulation of blood flow, is probably caused by an accumulation of anaerobic metabolites which lead to cerebral tissue acidosis.

Rhythmic bursts in the medullary reticular formation and their connection with agonal respiration during hypoxia and the post-hypoxic period

1. 1. Rhythmic bursts that appear in the medulla oblongata during the later stages of dying and during the early stages of reanimation consist of oscillations at 7–24 c/sec; they are controlled by the respiratory centre (inspiration) and determined by the rhythm of its activity. 2. 2. Bursts appear only during agonal respiration when the relationship between the activities of inspiratory and expiratory muscles is disturbed. 3. 3. Together with the isolation of the medullary respiratory centre from central influences, the appearance of bursts requires additional hypoxic suppression of the brain-stem mechanisms. 4. 4. These bursts are accompanied by clonic changes in contraction of the respiratory and auxiliary muscles, the rhythm of clonic excitation being the same in all muscles and identical to that of the bursts. 5. 5. Bursts and alteration of muscle contraction may be a result of excitation of a phylogenetically ancient mechanism of the brain-stem reticular formation coordinating generalized tremor movements. Excitation of this mechanism is determined by the impulses from the respiratory centre. 6. 6. Association of bursts with a relatively profound hypoxic alteration of the brain-stem allows use of the former to estimate the brain damage during both agony and recovery.

The effect of hypoxia and ACTH on the carbohydrate reserve in tissues of the white rat

The author studied the effect of preliminary ACTH administration of glycogen and lactic acid concentrations in liver, skeletal muscle, and myocardium of male white rats during oxygen deficiency resulting from reduced barometric pressure and in the posthypoxic period. It was shown that preliminary administration of ACTH (with a total dose of 12 units) to rats later subjected to acute oxygen deficiency markedly reduces the fall in glycogen content in liver and skeletal muscle and simultaneously inhibits the accumulation of lactic acid in these organs. It also leads to more rapid restoration of liver and skeletal muscle glycogen reserves, and more complete elimination of excess lactic acid, during the posthypoxic period. Under conditions of hypoxia and posthypoxia, preliminary administration of ACTH has no significant effect on the cardiac glycogen reserve.