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Biomedical subjects

I Kjellmer

Publications and source records attributed to I Kjellmer.

At least 55 records · Page 3Linked to original sources
PubMed1991

Mechanisms of perinatal brain damage.

Although the perinatal brain is more resistant towards hypoxia-ischemia than at any later stage of development, perinatal asphyxia still contributes to permanent brain damage in survivors. This short review focuses on the discussion of mechanisms of late neuronal death, i.e. cerebral damage related to lack of oxygen but caused by mechanisms during the stage of reoxygenation. Evidence is presented to indicate that the transient, dense glutamatergic innervation of basal structures of the perinatal brain may induce brain damage via overflow of excitatory amino acids during oxygen lack, causing a longstanding overstimulation of excitatory neurons. Oxygen derived free radicals may be generated during reoxygenation by several mechanisms, including the oxidation of hypoxanthine and arachidonic acid accumulated in the cerebral insterstitium during hypoxia. The increase of the intracellular concentration of free Ca-ions contributes to these events. Possible avenues for prevention of post-asphyxial brain damage include glutamate receptor antagonists, calcium antagonists, antioxidants, free radical scavengers, inhibitors of libid peroxidation and blockers of arachidonic acid metabolism.

Amino Acids↗
PubMed1991

Zinc therapy in children with cystic fibrosis.

The effect of oral zinc supplementation in patients with cystic fibrosis (CF) was investigated in a placebo-controlled, double-blind, crossover study with each treatment period covering 6 months. CF patients (n = 13, aged 2 years, 3 months to 19 years, 1 month) started with placebo and after 6 months, they received zinc therapy. Another 13 patients (aged 3 years, 5 months to 16 years, 10 months) started in the reverse order. Before zinc supplementation, all CF patients had low plasma levels of zinc which normalized during treatment. This effect was, however, transient. CF patients also had low concentrations of plasma selenium. A small decrease in the number of leukocytes was also noted during zinc therapy. In response to zinc treatment, no changes in the clinical status of the patients were observed either by the investigators or by the patients. Growth velocity was the same during the placebo and zinc treatment periods. No significant changes in lung function occurred in response to either placebo or zinc. It appears that the observed low plasma zinc concentration in CF patients was due to an impaired zinc absorption from the gut which was counteracted by an increased supply of oral zinc. No beneficial effect from zinc supplementation on clinical status, growth velocity, or lung function was found in this study.

Adolescent↗
PubMed1991

Diameters of the common carotid artery and aorta change in different directions during acute asphyxia in the fetal lamb.

The aim of this experimental ultrasound study on six fetal lambs was to evaluate how blood flow variables and vessel diameters of the descending aorta and the common carotid artery change during fetal asphyxia in the acute preparation. When acute asphyxia was induced by obstructing the maternal aortic blood flow all fetuses reacted with significant decrease in the aortic diameter and blood flow. In the common carotid artery vessel diameter and the blood flow increased significantly. The results support the theory of a brain sparing effect during fetal distress with significant changes of blood vessel diameters occurring in opposite directions in the aorta and the common carotid artery, thereby contributing to the centralisation of circulation.

Animals↗
PubMed1990

Paired analysis of thromboxane and prostacyclin metabolites in urine from healthy mothers and their children.

Eicosanoids have been implicated in the adaptation of the fetal to the neonatal circulation, but biochemical support for an activation of their synthesis in relation to birth has not been presented. We addressed this by assessing in pairs the excretion of two metabolites of thromboxane A2, 11-dehydro-TxB2 (dTx) and 2,3-dinor-TxB2 (Tx-M), and one metabolite of prostacyclin, 2,3-dinor-6-keto-PGF1 a (PGI-M), in the first voided urine from 13 healthy term neonates and in the immediate pre-delivery urine from their respective mothers. The excretion of dTx was higher (p less than 0.01) in the neonates than in their mothers (7430 and 1330 pg/mg creatinine, respectively), and so was the excretion of Tx-M (3730 and 900 pg/mg creatinine, respectively, p less than 0.001). Also the excretion of PGI-M was higher (p less than 0.05) in the neonates than in their mothers (2550 vs. 1510 pg/mg creatinine). Amniotic fluid contained detectable levels of both Tx-M and PGI-M. These data indicate that activation of platelets takes place in the neonate after separation of the fetal and maternal vascular circuits. The possible physiological implication of such activation requires further studies.

Epoprostenol↗
PubMed1990

Evaluation of brain damage in a rat model of neonatal hypoxic-ischemia.

In spite of improvements in obstetric and neonatal care, hypoxic-ischemic brain damage with severe neurologic disability is still a clinical reality. A model in 7-day-old rats has been introduced to study the pathophysiology of perinatal hypoxic-ischemic brain damage. Unilateral brain damage is produced in the cerebral cortex, striatum and hippocampus, i.e. a similar distribution as is often seen in human asphyxiated neonates. In the present investigation the model was evaluated further by comparing three different methods to assess the brain damage: weighing the hemispheres, morphometry and somatosensory evoked potentials. Seven-day-old rats were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (7.7% O2 at 36 degrees C). After 2 h of hypoxic-ischemia pCO2 and pO2 decreased in mixed arterial/venous blood. The evaluation of the damage 2 weeks after the insult, demonstrated close correlation between morphometry and weighing (r = 0.836, P less than 0.01). The amplitude of evoked potentials correlated to the other parameters (r = 0.814, P less than 0.01 and r = 0.824, P less than 0.01 respectively) and displayed a greater relative attenuation than the other methods but with a more pronounced variability. These results indicate that the degree of brain damage can be assessed by weighing for screening purposes.

Aging↗
PubMed1990

Comparison of Ringer's acetate with 3% dextran 70 for volume loading before extradural caesarean section.

We have studied haemodilution and cardiovascular responses to i.v. hydration with either 3% dextran 70 (Dx70) or Ringer's acetate using a non-invasive cardiac output monitor (BoMed NCCOM3-R7) in 40 healthy parturients undergoing Caesarean section under extradural anaesthesia. Haemodilution was more pronounced, and central venous pressure, mean arterial pressure and cardiac index maintained at greater values, after treatment with Dx70. Colloid osmotic pressures (COP) decreased by 1.7 mm Hg after loading with 3% Dx70, and by 5.6 mm Hg in mothers treated with Ringer's acetate (P less than 0.001). The transthoracic fluid index decreased more after hydration with Ringer's acetate (P less than 0.001), indicating an increase in lung water. In spite of these maternal changes, there were no differences in neonatal bioimpedance or values of haemoglobin, PCV, albumin and COP in umbilical cord blood, and only one case of respiratory distress. We conclude that colloids may be preferable to crystalloids for circulatory preload for extradural Caesarean section, as greater haemodynamic stability was maintained and increases in lung water avoided.

Adult↗
PubMed1989

Extracellular increase of hypoxanthine and xanthine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia.

A microdialysis procedure was used to sample purine catabolites from the extracellular compartment of two areas of the fetal brain, the cerebral cortex and the striatum region. Seven exteriorized, anesthetized fetal sheep were studied during conditions of normal oxygenation and during asphyxia induced by stepwise lowering of maternal placental perfusion pressure. Fetal cerebral blood flow (CBF) was measured with the 133Xe washout method. Somatosensory evoked potentials were recorded during tactile stimulation of the fetal snout. The purine catabolites hypoxanthine (HX), xanthine (Xan), guanosine (Gua), inosine (Ino) and adenosine (Ade) were measured in arterial and venous plasma and in the dialysate by a HPLC method. During gradually increasing asphyxia HX increased 4-6-fold both in cerebral tissue and in arterial plasma, while Xan rose 1.5-3 times in cerebral tissue and arterial plasma. Gua did not change in either tissue or blood and Ino did not rise until at the most extreme degree of asphyxia it rose 2-4-fold. Ade concentrations remained unaltered during moderate asphyxia (when CBF rose 3-fold), but demonstrated a significant (2-3-fold) augmentation at the most extreme degrees of asphyxia. The results thus suggests a significant accumulation of oxypurines, especially HX, in the interstitium of the fetal brain during asphyxia. The rise in xanthine concentration demonstrates the presence of an activity of xanthine oxidase in brain tissue. A discrepancy between the elevation of CBF and of the tissue concentration of Ade does not support a direct role of Ade in the asphyctic cerebral vasodilation in the fetus.

Animals↗
PubMed1988

The excitatory amino acid antagonist kynurenic acid administered after hypoxic-ischemia in neonatal rats offers neuroprotection.

The neuroprotective effect of kynurenic acid, an unspecific antagonist of excitatory amino acid receptors, was evaluated in a model of hypoxic-ischemia in neonatal rats. One-week-old rats were subjected to ligation of the left carotid artery and exposure to 7.7% O2/92.3% N2 for 2 h. Kynurenic acid (300 mg/kg) was administered i.p. immediately after the period of hypoxic-ischemia in one group (n = 32) and compared with saline-treated (n = 27). After 2 weeks the rats were sacrificed and the brain damage evaluated by comparing the weight of the lesioned and unlesioned hemispheres. In rats receiving kynurenic acid the reduction in weight of the lesioned hemisphere was 25.4 +/- 3.3% as compared to 37.8 +/- 3.6% in saline-treated controls (P less than 0.001). The results suggest that excitatory amino acids are involved in the development of postischemic damage in the immature brain.

Animals↗
PubMed1988

Cerebral tolerance of hypoxia in growth-retarded and appropriately grown newborn guinea pigs.

To elucidate if there is a reduced perinatal tolerance of hypoxia in growth retardation and approach its pathophysiologic background, newborn guinea pigs of different weights were subjected to standardized hypoxia. Intrauterine growth retardation was induced through uterine artery ligation. After spontaneous delivery experiments were performed within 2 days. After stabilization, hypoxia of stepwise increased severity was instituted. Blood gases, metabolic, cardiovascular, and neurophysiologic [somatosensory-evoked potentials (SEP)] parameters were monitored. A control series in which equally large blood samples were taken at the same intervals was performed. The animals were grouped according to birth weight: greater than or equal to 101 g (n = 10, 12), 71-100 g (n = 11, 10), and less than or equal to 70 g (n = 8, 3) (hypoxic and control series, respectively). Basal SEP latencies did not differ between the groups. Under hypoxia, both the amplitude of the SEP and the time to complete loss of the SEP was reduced in proportion to the degree of growth retardation. The differences between all groups were significant. The animals in the control series did not change their SEP performance significantly. Slight differences in metabolic and cardiovascular parameters between the groups were found not likely to explain the differences in SEP performance. Therefore, it is concluded that a reduced cerebral tolerance of hypoxia prevails in growth-retarded newborn guinea pigs and that this is related to changes in the brain itself. It is also concluded that a relationship exists between the degree of growth retardation and that of reduced cerebral hypoxia tolerance.

Animals↗
PubMed1987

Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia.

Extracellular levels of excitatory and inhibitory amino acids were measured in the cortex and striatum of asphyxiated fetal lambs. The fetus was exteriorized from the anesthetized ewe and dialysis probes were placed in the parietal cortex and caudate nucleus. Cerebral blood flow was measured with Xe-clearance. Cortical somatosensory-evoked potentials and electroencephalogram (EEG) were continuously recorded. Asphyxia was induced by clamping the umbilical cord or by graded compression of the maternal aorta. Asphyxia accompanied by elevated cerebral blood flow resulted in a moderate rise in extracellular amino acid levels. During extreme asphyxia, i.e. abolished evoked potentials and reduced cerebral blood flow, marked extracellular elevations of glutamate (3- to 11-fold), aspartate (3- to 7-fold), gamma-aminobutyric acid (GABA) (3- to 5-fold) and taurine (3- to 18-fold) occurred, the higher values representing striatum. Excessive levels of excitatory amino acids may exert injurious effects on immature neurons during such hypoxic-ischemic states.

Amino Acids↗
PubMed1987

Acute blockade of beta 1-receptors in the asphyxiated sheep fetus.

The effects of acute beta 1-blockade on fetal cardiovascular reactions during asphyxia were evaluated in 11 exteriorized sheep fetuses. Gestational age was 110-142 days. Asphyxia was induced either by ventilating the mother with low oxygen gas mixture or by mechanical reduction of placental blood flow. During asphyxia all fetuses reacted to metoprolol injection with a decrease in heart rate, myocardial contractility, cardiac output and arterial blood pressure. Five experiments resulted in irreversible fetal cardiovascular collapse. Isoprenaline was given to the fetuses during hypoxia to test the ability to further increase heart rate and activate myocardial beta-adrenoceptors. In those experiments with fetal cardiovascular demise after metoprolol, the isoprenaline injection did not result in a significant tachycardia. The surviving fetuses could increase their heart rate as a sign of a capacity to further increase the sympatho-adrenergic drive.

Animals↗
PubMed1987

Postasphyxial cerebral survival in newborn sheep after treatment with oxygen free radical scavengers and a calcium antagonist.

Acute, severe intrapartum asphyxia was mimicked by tying the umbilical cord in the exteriorized fetal sheep. After a standard time period cardiopulmonary resuscitation was instituted. In the treatment group (n = 14) the lambs were given a composition of scavengers of oxygen-derived free radicals and a calcium channel blocker. The control group of lambs (n = 12) was given placebo. The trial was blind and randomized. Hemodynamic and neurophysiological variables were measured from 30 min before asphyxia to 2 h postresuscitation. Mean arterial blood pressure, sagittal sinus venous pressure, heart rate, and cardiac output did not differ between the two groups although dramatic changes took place during asphyxia and resuscitation. Cerebral blood flow measured by 133-Xe washout method increased in both groups immediately after resuscitation. The treated animals retained an augmented cerebral blood flow during the 2 h postresuscitation while the control animals lost the increase of cerebral blood flow. The treated lambs recovered their somatosensory evoked potentials partially or completely in eight of 14 cases while the same figures for the control lambs were one of 12 cases. Immediately after resuscitation the cerebral reactions recovered to some extent in both groups but during the following 2 h the cerebral cortical function deteriorated in the control group but improved in the treated lambs. It is concluded that part of the brain damage in connection with acute, severe asphyxia may be inflicted by oxygen-derived free radicals released during the reoxygenation phase after resuscitation and that oxygen-derived free radical scavengers and calcium channel blockers may find a place in cardiopulmonary resuscitation.

Animals↗
PubMed1986

Fetal cerebral, cardiovascular and metabolic reactions to intermittent occlusion of ovine maternal placental blood flow.

In 10 mature, acutely exteriorized fetal sheep cardiovascular, cerebral and metabolic reactions were followed during intermittent occlusions of maternal placenta blood flow. The response was analysed from blood pressure, heart rate, myocardial contractility, combined cardiac output, ST waveform analysis of the fetal ECG, and from the evoked EEG response. The metabolic response was judged from blood gases, pH, lactate and circulating catecholamines. Basal values were within the range seen in the 'chronic' fetal lamb preparation. During moderate asphyxia, achieved by 10 1 min occlusions separated by 2 min periods of free maternal aorta blood flow, cardiovascular performance was increased with a substantial catecholamine surge but minor effects on cerebral and metabolic functions. During the marked asphyxia, achieved by five 2 min occlusions, marked metabolic changes occurred together with abolition of cerebral function. Forty-five minutes after asphyxia, 9/10 of the fetuses had regained cerebral, metabolic and cardiovascular functions.

Animals↗