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Biomedical subjects

I Kjellmer

Publications and source records attributed to I Kjellmer.

At least 73 records · Page 4Linked to original sources

Placental blood flow and fetal weight following uterine artery ligation. Temporal aspects of intrauterine growth retardation in the guinea pig.

Placental blood flow (microsphere distribution), placental weight and fetal weight were examined at three stages of gestation following unilateral uterine artery ligation at days 30-32 in 23 guinea pigs. Placental blood flow and placental weight were reduced in the ligated horn at days 45, 55, and 65. The fetal weight was decreased at days 55 and 65. We suggest that ligation of the uterine artery reduces placental blood flow which, in turn, restricts placental growth without any significant effect on fetal weight before day 45. At this stage of gestation no correlation was found between fetal weight and placental blood flow. Later in gestation, however, fetal growth becomes limited by placental blood flow, and between days 45 and 55 ligation impedes the increase in blood flow, and consequently the fetal growth rate declines.

Animals↗

Maternal treatment with a cardioselective beta-blocking agent--consequences for the ovine fetus during intermittent asphyxia.

To evaluate the effect of chronic beta 1-adrenoceptor blockade on physiological adaptation to asphyxia a study was done on exteriorized sheep fetuses of 127-142 days gestational age. Eleven pregnant ewes were infused with metoprolol for 5 days prior to experiment. Another 10 ewes were infused with saline and served as controls. Asphyxia was induced by intermittent complete obstruction of maternal placental blood flow. Fetal electro-cardiogram, heart rate, cardiac output, myocardial contractility and cerebral blood flow were measured together with blood pH, lactate and hypoxanthine. Neurophysiological responses were evaluated by changes in somatosensory evoked electroencephalogram. The beta 1-blocked fetuses showed less responsiveness in myocardial contractility and heart rate during reoxygenation. This curtailed reaction resulted in accelerated lactic acidosis, increased break-down of intracellular energy rich substances and impaired cerebral function. Nine of the ten controls survived the experiment and 8 of them regained their somatosensory evoked EEG potentials, whereas 7 of the 11 beta-blocked fetuses survived and only 3 regained original somatosensory evoked EEG potentials. It is concluded that beta 1-adrenoceptor blockade impairs the adaptive responses to asphyxia in the ovine fetus and decreases its ability to survive severe asphyxia.

Animals↗

The relationship between circulating catecholamines and ST waveform in the fetal lamb electrocardiogram during hypoxia.

Previous studies from this laboratory have shown that changes in the ST waveform in the fetal electrocardiogram are a sign of fetal asphyxia. In the present study, seven chronically instrumented fetal lambs between 117 and 143 days' gestation were studied during 16 one-hour periods of maternally induced hypoxia. The aim was to test the hypothesis of a relationship between the concentration of circulating catecholamines and T-wave amplitude. The response to hypoxia was aged-dependent. Fetuses below 126 days of gestation did not react with electrocardiographic changes and output of epinephrine unless acidosis occurred. In more mature fetuses, hypoxia per se would induce a surge of epinephrine and changes in the ST waveform. Overall there was a strong correlation between the T/QRS ratio and the level of circulating epinephrine. During normoxia, epinephrine was undetectable (less than 0.1 nmol/L) in most fetuses; norepinephrine showed an increase at term. The analysis showed one fetus with chronic changes in the ST waveform (T/QRS ratio greater than 0.30) related to a marked increase in the plasma level of epinephrine in spite of normal blood gas values. These findings complement previous results in the acute and chronically instrumented fetal lamb and suggest that changes in the ST waveform expressed as T/QRS ratio identify a change to anaerobic myocardial metabolism mediated by beta-adrenergic stimulation.

Acidosis↗

Prevention and control of neonatal pyoderma with chlorhexidine.

The extent of staphylococcal colonisation and neonatal pyoderma was studied in 5 220 infants in two large Swedish hospitals in 1979-1982. A method for routine cord care with 4% chlorhexidine detergent solution was evaluated in one hospital. Nursery colonisation with Staph. aureus and streptococci decreased significantly. The method proved to be clinically efficient for prevention of pyoderma in the nursery as well as for controlling staphylococcal infection after discharge from hospital. The combined use of a quantitative sampling method and phage-typing showed that most post-discharge lesions were nursery-derived. In one of the hospitals, daily cord care with 70% ethanol failed to prevent streptococcal and staphylococcal omphalitis in the nursery whereas daily cord care with chlorhexidine reduced the incidence of omphalitis from 21 to 1%.

Chlorhexidine↗

Contribution of heart muscle, liver, skeletal muscle and placenta to the asphyxial hypoxanthine elevation in the acutely exteriorised fetal lamb.

The metabolic response to different degrees of hypoxia was studied in 14 lamb fetuses. We have previously found a substantial rise in the fetal arterial plasma hypoxanthine (HX) level, in parallel with alterations of other hypoxia indices during induced asphyxia. Measurements of the arterio-venous (A-V) difference in the HX level across the CNS demonstrated a late efflux of this substance from the fetal brain, with a high resistance to asphyxia. In this study, the effluxes of HX, lactate, and in some cases glucose, from the myocardium, liver, hindleg (skeletal muscle) and placenta were investigated in acutely exteriorised sheep fetuses with graded asphyxia. The main findings were as follows: (a) myocardium: a release of HX early during asphyxia, the magnitude of which paralelled the amount of mechanical work performed by the heart; a significant lactate influx into the heart during normoxia and recovery period; (b) liver: hepatic HX release even during normoxia, increasing to substantial amounts in connection with increasing asphyxia; (c) hindleg: release of HX only during the recovery period; lactate efflux during all periods apart from severe asphyxia, when an influx was seen for both substances; (d) placenta: production of lactate during normoxia, and an efficient clearance of both lactate and HX from the fetal plasma in combination with their concentration increasing during asphyxia. It is concluded that the myocardium and liver are the main contributors to the elevated HX level during fetal asphyxia among the fetal organs investigated, while skeletal muscle releases HX mostly during the period of reoxygenation.

Animals↗

Heart rate variability and electrocardiogram changes in the fetal lamb during hypoxia and beta-adrenoceptor stimulation.

Hypoxic changes in the ST waveform of the fetal electrocardiogram (FECG), with elevated T waves as the main response, have earlier been described in the fetal lamb as mediated via the beta-adrenoceptor cells, initiated by catecholamine release. A similar background to the increase in fetal heart rate variability (FHRV) during hypoxemia has been suggested. The aim of the present study was to elucidate this question and also to compare FHRV and changes in the ST waveform of the FECG as indicators of fetal distress. Twenty-six acutely exteriorized mature lamb fetuses were submitted to periods of graded hypoxemia. Fetal blood gases were measured and oxygen content was calculated. The FHRV was analyzed by a computer program and calculated as the differential index (DI) and the interval index (II). Eighty seconds of the recorded ECG coinciding in time with each fetal blood sample were analyzed using a PDP 11/40 minicomputer. The ECG signal was sampled at a rate of 1250 samples per second giving a resolution in time of 0.8 msec. Each QRS complex was detected with a semi-automatic program using a cross-correlation algorithm. QRS complexes that by the program were signalled to be doubtful were visually examined and either rejected or approved. Hence, the resulting list of R-R intervals was practically free from artefacts. From this list of R-R intervals the DI and II were computed according to YEH et al. [30]. Hypoxemia resulted in initially strongly increased DI from 3.1 +/- 2.5 to 17.7 +/- 13.8 (p less than 0.001) and in II from 1.88 +/- 0.65 to 3.77 +/- 2.06 (p less than 0.001) (Fig. 1). Obviously the change in oxygen content per se was strongly associated with the variability indices, as we found a strong correlation between delta oxygen content/min and delta DI/min (r = 0.81). In five fetuses the effect of prolonged hypoxemia on DI was studied (Fig. 2). After the initial rise from 1.6 +/- 1.1 to 31.2 /+- 9.0 (p less than 0.02) DI decreased to 19.4 +/- 20.7. A regression analysis showed a strong connection between DI and PaO2, (n = 93, T = - 5.34), whether there was no relation between DI and pH (T = - 1.85). There is strong evidence that hypoxemia and asphyxia induce an increase in the concentration of catecholamines in fetal blood [2, 23].(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Does glucose administration affect the cerebral response to fetal asphyxia?

This study was designed to test whether the fetal brain has an increased resistance towards asphyxia at high levels of blood-glucose, compared with low levels. 35 fetal sheep were exteriorized and investigated under general anesthesia. Cerebral blood flow (CBF) was estimated with the 133Xenon-washout method. Cerebral uptake of oxygen, glucose, and lactate was measured. Somatosensory evoked potentials (SEP) were recorded. The fetuses were subjected to controlled asphyxia by ventilating the ewes with gas mixtures low in oxygen. The blood sugar levels of the fetuses were varied over a four-fold range. During normal oxygenation of the fetus variations in the blood glucose concentration induced considerable changes in the cerebral glucose uptake, whereas CBF and oxygen uptake were unaffected. During asphyxia, hyperglycemia was associated with rapid development of acidosis and reduction in cerebral oxygen consumption together with deterioration of the neurophysiological characteristics of the brain. Far from being beneficial during asphyxia, fetal hyperglycemia appeared to reduce the tolerance of the fetal brain towards asphyxia. This report together with other evidence provides support for the view that extra glucose might be disadvantageous for the asphyxiated fetus.

Animals↗

Maternal beta-adrenoceptor blockade reduces fetal tolerance to asphyxia. A study in pregnant sheep.

Maternal and fetal beta 1-adrenoceptor blockade was induced in sheep by infusing i.v. 11 pregnant ewes with metoprolol in doses producing maternal plasma concentrations of metoprolol comparable to those obtained in clinical use. Ten other ewes and their fetuses served as controls. Under acute anaesthesia the fetus was exteriorized and subjected to two levels of controlled asphyxia by intermittent, complete obstruction of the maternal placental blood flow. Fetal haemodynamic reactions were assessed by measuring fetal heart rate, cardiac contractility, cardiac output and cerebral blood flow. The metabolic reactions were evaluated from blood gases, pH, lactate and hypoxanthine concentrations, while the electrophysiological status of the brain was evaluated from the somatosensory evoked EEG potentials (SEP). Already during the period of moderate asphyxia the beta-blocked fetuses demonstrated a blunted haemodynamic response, in comparison with the control fetuses, resulting in an accelerating lactic acidosis, signs of a breakdown of intra-cellular energy-rich phosphates and an impaired cerebral function. During the period of severe asphyxia, both groups of fetuses exhibited signs of extensive cerebral deterioration. During the ensuing recovery phase, 80% of the control fetuses regained their brain function, as assessed by SEP, whereas this was true for only 30% of the beta 1-blocked fetuses. It is concluded that the ovine fetus relies heavily on greatly increased sympatho-adrenal activity to adapt itself to asphyxia and that blockade of the fetal beta 1-adrenoreceptors by maternal medication is a hazard to the potentially asphyctic fetus.

Adrenergic beta-Antagonists↗

A case of near-miss SIDS developing an abnormal respiratory reaction to hypoxia.

A SIDS sibling is described who showed a normal respiratory regulation at 1.5 months but who was equipped with an apnea monitor at home on psychological indications. At 3 months he had a near-miss SIDS episode. He was then found to have developed a reaction to hypoxia with appearance of periodic breathing. With theophylline this response pattern was normalized but despite theophylline medication episodes of prolonged apnea occurred.

Apnea↗

Cerebral arterio-venous difference for hypoxanthine and lactate during graded asphyxia in the fetal lamb.

Hypoxanthine (HX) and lactate are degradation products from energy-rich intracellular substrates (ATP and glycogen), and their concentration will increase during anaerobic conditions, such as fetal asphyxia. In this study the accumulation of the two metabolites in blood during asphyxia was studied in 7 acutely exteriorized fetal lambs. The arterio-venous difference of HX and lactate over the brain was related to the function of the fetal brain as reflected by the somato-sensory evoked electroencephalogram potentials (SEP). Increased concentrations of HX in plasma and lactate in blood occurred simultaneously with deterioration of the SEP and the 3 variables correlate highly significantly. During normoxia, a net cerebral influx was found for HX, which in combination with severe asphyxia gradually changed to a net efflux. A linear correlation was found between the cerebral arterio-venous differences of HX and the impairment of the SEP. No such correlation existed for lactate. The results suggest, that the fetal brain has a high threshold for degrading its energy-rich intracellular purines.

Animals↗

Mineralization defects in deciduous teeth of low birthweight infants.

A group of 91 children with birthweights below 2000 g and 48 healthy full-term children, reference group, were examined for mineralization disturbances of the enamel of deciduous teeth. Perinatal data were collected retrospectively from obstetric and neonatal records. Within the low birthweight group, children with enamel hypoplasia had on the 5% level a significantly lower intake of breast milk during the first week of life than children without disturbances. The only perinatal complication associated with development of mineralization defects was IRDS. Infants with IRDS, however, had a significantly lower intake of breast milk during the first week of life than low birthweight without IRDS. A low frequency of enamel defects was found in the growth-retarded sub-group of the low birthweight infants. These infants had a significantly higher intake of breast milk during the first week compared to the AGA-group. A seasonal variation was found, with the highest prevalence of mineralization disturbances in infants born during winter months. It is concluded that the occurrence of mineralization defects of the deciduous teeth in LBW infants seems to be dependent upon the amount of breast milk given during the early neonatal period and also possibly in which season of the year they are born.

Child↗

Fetal cardiovascular reactions during labour and asphyxia modified by adrenergic receptor agonists and antagonists.

In the human fetus the adrenergic system develops morphologically at an early stage. The development of adrenergic receptors occurs to a large extent before birth. The human fetus is capable of a large production of catecholamines, particularly during the last two months of fetal life. Normal labour and delivery elicits an increased release of catecholamines, a reaction that is markedly enhanced by asphyxia. beta-Receptor stimulants not only relax the uterine smooth muscle but also tend to modify the concentration of surfactant in lung fluid. beta-Receptor blocking agents, both non-selective and cardioselective, create a problem in clinical medicine since they provide an effective means of treating hypertension in pregnancy. Theoretical implications of such treatment present a risk to the fetus. Experimental evidence from the fetal sheep preparation indicate that beta-receptor blockade carriers an immediate risk to the severely asphyxiated fetus when the blockade is induced acutely. In this situation heart muscle contractility, heart rate and cardiac output fall abruptly while the capacity for anaerobic glycolysis is greatly diminished. Even though such acute animal experiments are far removed from clinical practice the results suggest that great caution should be exercised in the use of adrenergic blocking agents in obstetric practice.

Adrenergic beta-Agonists↗

Children of female renal transplant recipients.

Results of follow-up of 5 children, aged 4.5-9 years, who were born to kidney transplanted mothers are presented. Various immunological parameters were mainly within normal limits with the possible exception of 1 child who exhibited a granulocytopenia which normalized at about 5 years of age. Three children whose mothers were carriers of HBsAg during and after pregnancy have become antigen carriers and show slightly elevated levels of liver transferases. One child has a cardiac anomaly and signs of slight neurological dysfunction. In other respects the children are well and show normal psychomotor and somatic development. The rather sparse information from the literature regarding this group of children indicates a surprisingly low frequency of severe physical complications.

Adult↗

Myocardial metabolism in relation to electrocardiographic changes and cardiac function during graded hypoxia in the fetal lamb.

Previous studies from this laboratory have demonstrated early and progressive alterations in the ST-T period of the fetal and neonatal electrocardiogram in relation to asphyxia. The aims of the present study were to investigate the metabolic background of these hypoxic ECG changes by means of serial myocardial biopsies in fetal lambs, relating these changes to the hypoxic depletion of glycogen, ATP and creatine phosphate stores in the heart and to the altered myocardial performance as measured by heart rate, mean arterial blood pressure, combined cardiac output and max. dP/dt. The experiments were performed on 21 fetal lambs, acutely exteriorized and subjected to graded hypoxia. During hypoxia there was a significant relationship between the degree of changes in the ST-T period according to a scoring system and the depletion of myocardial glycogen and ATP, a highly significant correlation between the rate of myocardial glycogenolysis and the rate of increase in T wave amplitude, and a parallelism between the amount of glycogen available and fetal cardiovascular function. The myocardium was capable of regenerating its glycogen stores under conditions of adequate oxygenation and in the absence of acidosis and hypoglycaemia.

Adenosine Triphosphate↗

Anesthesia for cesarean section--VII. Early effects on neonatal renal function of enflurane anesthesia for cesarean section.

Fourteen women undergoing elective cesarean section were anesthetized with enflurane for induction and maintenance of anesthesia. Blood enflurane and serum inorganic fluoride levels were studied in the mothers at delivery and in the neonates at delivery and in the early neonatal period. Also neonatal urinary excretion of inorganic fluoride was determined. Renal function of the neonates was tested with a sodium load at the age of 1 day. Enflurane showed the expected distribution between mothers and neonates. The enflurane level of the neonates declined rapidly after delivery. Serum inorganic fluoride level increased significantly in the mothers from start of anesthesia until delivery. The neonatal level was lower and did not reach the level of neonates in areas with a high natural fluoride content in drinking water. The level of inorganic fluoride in urine was higher than the corresponding serum level, indicating an inorganic fluoride concentrating effect of the neonatal kidney. The difference between urinary excretion and serum content of inorganic fluoride showed neonatal metabolism of enflurane. The urinary sodium excretion did not differ from that of infants delivered without halogenated inhalation agents given to the mothers.

Anesthesia, Inhalation↗

Plasma hypoxanthine in exteriorized, acutely asphyxiated fetal lambs.

Plasma hypoxanthine (HX) concentrations were measured in 16 acutely exteriorized fetal lambs during induced, graded hypoxia, and the values found were compared to established indicators of poor oxygenation in the fetus, such as oxygen saturation, blood gases, pH, base excess, and lactate. Highly significant correlations were found to all parameters of hypoxia except PaO2. When the duration of hypoxia was taken into account, the HX concentrations showed highly significant correlation to constructed variables of oxygen debt. In multiple correlation analysis, pH turned out as the strongest single variable, explaining 80% of the variance in HX concentration with the remaining parameters increasing the value to 87%. The highest concentrations of HX were obtained when hypoxemia was combined with acidemia or with a large fetomaternal PaCO2-gradient which correlated to a reduced cardiac output in the fetus. These findings appear to corroborate the conclusion that plasma HX concentration reflects tissue hypoxia in the fetal lamb.

Acute Disease↗

ECG-changes in the fetal lamb during asphyxia in relation to beta-adrenoceptor stimulation and blockade.

Progressive changes in the S-T interval of the fetal electrocardiogram (FECG) were studied in 14 lamb fetuses, acutely exteriorized and subjected to graded hypoxia. The aims of the study were to investigate whether beta-adrenoceptor stimulation and hypoxia exerted additive or potentiating effects on the FECG and several cardiovascular parameters and whether the hypoxic changes of the FECG could be blocked by beta-adrenoceptor blocking agents. The FECG changes were studied in order to correlate them with cardiovascular function, as measured by heart rate, mean arterial pressure, end diastolic pressure, maximum dP/dt and combined cardiac output, estimated by the thermodilution method, as well as with blood gases, acid base status, blood lactate and glucose. Injections of small doses (0.02 to 0.4 microg kg-1 min-1) of isoprenaline induced the same pattern of changes in the FECG as we have previously recorded during hypoxia. By increasing the isoprenaline dose an increase in the duration of the FECG changes and amplitude of the T-wave changes was obtained. Propranolol was found to completely abolish the FECG changes induced by isoprenaline, as well as by mild hypoxia. During severe hypoxia the FECG changes could not be abolished by propranolol. Our previous findings indicated that the hypoxic changes could be regarded as a sign of myocardial glycolysis. Thus, the present finding that even small doses of isoprenaline given to the fetus, initiates the same pattern of FECG changes corroborate this hypothesis.

Animals↗