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Biomedical subjects

O D Saugstad

Publications and source records attributed to O D Saugstad.

At least 163 records · Page 9Linked to original sources
PubMed1987

Consequences of asphyxia in surfactant deficiency.

Consequences of asphyxia in babies with surfactant deficiency are discussed. Several important points concerning transition from intra- to extrauterine life are underlined. In asphyxia large amounts of hypoxanthine are formed and in the postasphyxic period when high concentrations of oxygen are given large amounts of oxygen radicals are produced. Experimentally we have shown that such radicals produce lung engorgement, hemorrhage and edema. Further they inactivate surfactant. Oxygen radicals also reduce the lung compliance dramatically in animal experiments. Saline alone given intratracheally to animals ventilated artificially will also reduce lung compliance. It is therefore not recommended to give saline intratracheally as a placebo in surfactant trials.

Adenine Nucleotides↗
PubMed1986

Correlation of plasma hypoxanthine and catecholamine levels in the umbilical vein.

Hypoxanthine and the catecholamines, dopamine, norepinephrine and epinephrine were determined in umbilical venous cord plasma in 27 term babies delivered vaginally. When correlating hypoxanthine with log epinephrine a weak positive linear correlation was found (r = 0.45, p less than 0.05). The correlation between hypoxanthine and log dopamine showed a significant negative linear correlation (r = -0.65, p less than 0.01). There was also a significant correlation between log epinephrine and pH (r = 0.72, P less than 0.01) and base deficit (r = 0.46, P less than 0.05). In four babies who suffered intrauterine hypoxia, hypoxanthine was significantly elevated compared with non hypoxic babies (21.4 +/- 5.1 versus 6.3 +/- 6.6 mumol/l, P less than 0.01). In these babies norepinephrine (3710 +/- 3888 vs 789 +/- 718 Pg/ml, P less than 0.01) and epinephrine (298 +/- 229 vs 148 +/- 116 Pg/ml, P less than 0.05) were significantly elevated as well, in contrast to dopamine levels (188 +/- 94 vs 169 +/- 134 Pg/ml N. S.). This finding seems to indicate that dopamine synthesis goes down during hypoxia probably because the rate limiting enzyme in dopamine synthesis, tyrosine, hydroxylase, is inhibited in hypoxia.

Catecholamines↗
PubMed1985

Role of myoinositol in regulation of surfactant phospholipids in the newborn.

According to animal studies myoinositol decreases surfactant phosphatidylglycerol and increases phosphatidylinositol. In the present study lung effluent phospholipids and serum myoinositol were analyzed in respiratory distress syndrome (RDS, 19 cases), in other lung disease (6 cases) and in 22 newborn with no lung disease. In addition, myoinositol was studied in amniotic fluid and in serum from umbilical vessels and from maternal vein (15 healthy newborn). There was a significant correlation between the fetal and amniotic fluid levels of myoinositol, but no detectable correlation between fetal and maternal myoinositol. Serum myoinositol was higher in preterm than in term newborns. In healthy newborns there was a negative correlation between lung effluent phosphatidylglycerol (expressed as percent of the phospholipids) and serum myoinositol (r = -0.968), and a positive linear correlation between myoinositol and lung effluent phosphatidylinositol (r = 0.849). In RDS at birth, undetectable phosphatidylglycerol corresponded with high serum myoinositol. During the first 5 neonatal days serum myoinositol either (1) decreased and phosphatidylglycerol appeared, (2) remained high and phosphatidylglycerol correspondingly low in some small preterm infants, or (3) decreased but phosphatidylglycerol did not expectedly increase and disaturated lecithin/sphingomyelin ratio remained low in other small preterm babies. We propose that a premature decrease in serum myoinositol among small preterm infants with RDS is not beneficial, since myoinositol may promote hormone-induced lung maturation and healing of lung damage.

Humans↗
PubMed1984

Pathogenetic aspects of respiratory distress syndrome in adults and newborns. Experimental and clinical data.

Activation of the kallikrein-kinin system was demonstrated in experimental lung failure in dogs and respiratory distress syndrome (RDS) in newborns. Further lung damage was found in rats after intravenous infusion of hypoxanthine during exposure to 100% oxygen for 48 h. It is discussed whether such damage was mediated through free oxygen radicals produced by the hypoxanthine-xanthine oxidase system. Newborn babies with RDS had high serum myoinositol levels and the role of myoinositol as regulator of surfactant synthesis is discussed. These three different approaches demonstrate the complexity of pathogenesis of RDS in newborn babies and adults.

Adult↗
PubMed1984

Hypoxanthine and oxygen induced lung injury: a possible basic mechanism of tissue damage?

Lung injury was induced in young rats by a continuous infusion of hypoxanthine intravenously and breathing 100% oxygen for 48 h (group 1). Control animals were rats infused glucose and breathing 100% oxygen (group 2), rats infused hypoxanthine in room air (group 3), and untreated rats (group 4). In group 1 rats interstitial and alveolar edema was found with a tendency toward marked margination of polymorphonuclear neutrophils in small vessels (P less than 0.025 compared with group 2). The main elastase inhibitor alpha 1-antitrypsin (alpha-1-PI) was significantly elevated in group 1; 2-, 3- and 5-fold, respectively, when compared with groups 2, 3, and 4. The surfactant phospholipids from alveolar lavage were normal in all groups. The protein-rich fraction of the lavage fluid from group 1 rats inactivated, however, the surface properties of lung surfactant. Minimum surface tension in group 1 rats was 14.5 dyn/cm compared with 7.0 dyn/cm in group 2, 2.9 dyn/cm in group 3 and 3.5 dyn/cm in group 4 (P less than 0.05, group 1 and 2 versus 4). We conclude that the combination of hypoxanthine and high levels of oxygen causes lung injury, possibly via free oxygen radicals. We discuss the possibility that these findings demonstrate a basic pathogenetic mechanism for the hypoxic-hyperoxic insult and can contribute to the understanding of pathogenesis of a variety of diseases both in pediatrics and adult medicine.

Animals↗
PubMed1983

Increased hypoxanthine concentrations in cerebrospinal fluid of infants with hydrocephalus.

Hypoxanthine, the end product of purine metabolism, is usually very elevated in body fluids during severe hypoxia. We measured hypoxanthine in the cerebrospinal fluid of hydrocephalic preterm infants (12 with posthemorrhagic, one with congenital hydrocephalus) to determine whether hydrocephalus is associated with anaerobic metabolism of brain tissue. Cerebrospinal fluid hypoxanthine was undetectable in normal infants. In hydrocephalic infants, the concentration of hypoxanthine ranged from 7.5 mumol/L to 28 mumol (means = 14.3 mumol/L). The hypoxanthine concentrations fell from a mean of 12.8 mumol/L to a mean of 2.0 mumol/L (P less than 0.05) with successful treatment of the ventriculomegaly by lumbar puncture or by ventriculoperitoneal shunt. Patients with acute posthemorrhagic hydrocephalus had similar concentrations of hypoxanthine (means = 14.5 mumol/L) as patients with late or with congenital hydrocephalus (means = 13.8 mumol/L), indicating that brain hypoxia is probably a consequence of the ventriculomegaly and not of the hemorrhagic insult.

Cerebral Hemorrhage↗
PubMed1982

Release of hypoxanthine and phosphate from exercising human legs with and without arterial insufficiency.

Release of hypoxanthine and phosphate from exercising legs was studied in eight subjects without known obstructive arterial disease and in 20 claudicants. Lower leg blood flow was measured with a thermodilution catheter in the popliteal/distal femoral vein. The catheter allowed blood sampling from the calf before, during and after exhaustive exercise on a bicycle ergometer at a stepwise increasing load. Resting plasma hypoxanthine levels were higher in claudicants than in normal subjects (p less than 0.05). Hypoxanthine concentrations increased 2-4-fold during exercise, amounting to values ten times higher than the resting levels 5 and 10 min post exercise, in the venous effluent of the normal legs. A similar rise was found in the claudicants despite half the exercise intensity at exhaustion. Popliteal venous concentrations of phosphate increased by approximately 25% during exercise without significant differences between the two groups. During exercise the release of hypoxanthine increased 38-fold and of phosphate 21-fold in the normal lower legs, while a ten-fold increase in both metabolites was recorded in the claudicating legs. The study demonstrated a high release of hypoxanthine and phosphate from the human lower leg during rhythmic, exhaustive exercise (with maximal vasodilation). The result is compatible with the assumption that metabolites from the catabolism of adenine nucleotides (adenosine) play a role in the autoregulation of blood flow in human skeletal muscle. Increased plasma hypoxanthine concentrations at rest may indicate peripheral arterial insufficiency.

Adult↗
PubMed1982

Activation of the kallikrein-kinin system in premature infants with respiratory distress syndrome (RDS).

Plasma prekallikrein levels, kallikrein activity and antikallikrein levels were investigated in nine premature infants with respiratory distress syndrome (RDS) and six premature infants without. Plasma prekallikrein and kallikrein were determined with a chromogenic substrate measuring amidolytic activity. Antikallikrein was measured with a functional assay. In infants with severe RDS, prekallikrein levels were significantly reduced (median 58% of initial values (p less than 0.01) about 48 hours after onset of symptoms. In infants with moderate RDS prekallikrein level was reduced less, while in babies without RDS there were no significant changes in prekallikrein levels the first 5-7 days of life. Antikallikrein levels did not change significantly in any babies. The results suggest that the kallikrein-kinin system might be involved in RDS. This could explain several features of this syndrome such as hypotension and edema. Furthermore the findings show that homeostatic functions are altered in this disease, and they suggest that other cascade systems as the coagulation, fibrinolytic and complement system may be involved as well. The findings emphasize that trauma might be a significant pathogenetical factor for development of this syndrome and indicate that RDS is not simply a biochemical disease with lack of surfactant as the only pathogenetic factor.

Blood Gas Analysis↗
PubMed1982

Experimental post-traumatic lung insufficiency in dogs: ultrastructure of lung lesions.

The ultrastructure of developing lung lesions in two groups of dogs exposed to a combination of haemorrhagic hypotension and liver trauma was studied with particular attention to changes at the alveolar level and lung micro-vessels. Lung samples were obtained every four hours and at collapse in one group and 12 hrs after initiation of the trauma in the other. An interstitial oedema was recognized in biopsies obtained 4 hrs after initiation of the trauma, and before marked lesions were observed at the ultrastructural level in endothelial cells. Endothelial damage was, however, evident in biopsies obtained at 8 hrs and at collapse. Aggregates of degranulated and degenerated leucocytes and platelets were occasionally found to obstruct respiratory capillaries together with erythrocytes, some of which seemed to be haemolysing. A considerable amount of protein-rich oedema, cellular debris and fibrinoid material was found in alveolar lumina at collapse. The present experiments indicate that increased vascular permeability in lung micro-vessels is of importance for the development of the characteristic lesions seen in shock lung. Possible pathogenetic mechanisms, initiating the lung lesions, are discussed with special emphasis on the significance of kinin activation and the presence of polymorphonuclear leucocytes and microthrombi.

Animals↗
PubMed1982

Changes of components of the plasma kallikrein-kinin system during experimental lung insufficiency in dogs.

Lung insufficiency was induced in 11 dogs by combined hemorrhagic hypotension (55 mm Hg for two hours) and clamping the portal triad (20 minutes). Four dogs were ventilated spontaneously (group 1). In seven dogs thoracotomy was done giving access to lung biopsies and central hemodynamic measurements (group 2). Five dogs were used as controls without hypotension or clamping. All the dogs in group 1 and 2 developed morphological changes in the lungs characteristic of post-traumatic lung insufficiency. A significant decrease of prekallikrein levels (42% and 34% of initial levels in the two groups, respectively) was found. A significant elevation of the kallikrein activity compared to initial values and the control group was found as well. The antikallikrein levels were reduced to 76% and 67% of initial levels in group 1 and 2, respectively. This reduction was statistically significant. A significant lowering of high molecular weight kininogen was also found, 50% and 28% of initial levels in the two groups. These results demonstrate activation of the kallikrein-kinin system in this experimental model. This can give information on the pathogenesis of post-traumatic lung insufficiency and can explain, for instance, the hypotension and oedema found in this condition. This study also demonstrates that homeostatic functions are altered, this probably being of greater interest than the specific lung alterations described by several authors. Determination of the components of the kallikrein-kinin system can be of diagnostic and prognostic value in post-traumatic lung insufficiency in clinical medicine.

Animals↗