Biomedical subjects

K Haaland

Publications and source records attributed to K Haaland.

14 recordsLinked to original sources

PubMed1997

Lidocaine pharmacokinetics and toxicity in newborn pigs.

In newborn infants suffering from perinatal asphyxia seizures, lidocaine (LD) has proved to be an effective anticonvulsant. At high concentrations, however, LD can itself cause convulsions. The convulsive concentration of LD (LD(conv)) varies among species. The aim of this study was to describe LD pharmacokinetics and to define the LD(conv) in awake newborn pigs. Eighteen Land race newborn pigs aged 12-60 h, weight 1.0-2.5 kg, were enrolled. LD, 2 mg/kg intravenous (IV) bolus, (n = 11) was given to estimate pharmacokinetic variables. Continuous LD infusion 2 mg x kg(-1) x min(-1) IV (n = 5) and repeated bolus doses of 15 mg/kg (n = 4) were given until electroencephalogram-confirmed seizures appeared. After the bolus injection, the elimination half-life for LD was 0.87-5.44 h. Increasing plasma concentration (LD(pl)) during infusion resulted in sedation after 5-10 min and in shivering, nystagmus, neck extension, tonic-clonic seizures at LD(conv) of 40.6 +/- 12.7 mg/L (mean +/- SD). The unbound LD(pl) at seizures was 4.4 +/- 2.4 mg/L. Younger animals convulsed at higher LD(conv) (r2 = 0.85). LD pharmacokinetics in newborn pigs were found to be dose-dependent at high plasma concentrations. At lower plasma concentrations, LD pharmacokinetics appeared to be linear. The central nervous system is the primary target for the toxic effect of LD in awake newborn pigs. LD neurotoxicity is age-dependent, and younger pigs convulse at a higher LD(conv).

Age Factors↗

PubMed1997

Posthypoxic hypothermia in newborn piglets.

The purpose of this study was to determine whether mild hypothermia after a moderate hypoxic-ischemic insult reduces the extent of brain damage. Hypoxia was achieved in newborn piglets (n = 24; age, 14-72 h) by abrupt reduction of the inspired oxygen concentration (FiO2) to the maximum concentration (approximately 6%) giving low amplitude (< 7.0 microV) EEG. FiO2 was temporarily increased if heart rate, blood pressure, or end expiratory partial pressure of alveolar CO2 (PAco2) were markedly reduced. This intermittently resulted in EEG amplitude greater than 7 microV, the EEG traces were therefore later examined to determine the duration of low amplitude EEG. After 45 min of hypoxia, the animals were randomized to normothermia (39 degrees C) or hypothermia (35 degrees C) for 3 h. Hypothermia was achieved by applying packs containing ice water. Neurologic assessments and EEG recordings were performed regularly until 3 d when the brains were perfusion fixed. Histologic damage in cortex/white matter, cerebellum, hippocampus, basal ganglia, and thalamus was graded by a pathologist blind to treatment allocation. We found that the severity of brain damage (by histopathologic and neurologic evaluation) was not significantly different when the piglets were normothermic after hypoxia compared with the group made hypothermic. Increased duration of low amplitude EEG and seizure activity were associated with increased damage. When controlling for duration of hypoxia and excluding seizures, piglets undergoing hypothermia had approximately 50% less severe histopathologic damage in cortex/white matter, cerebellum, and hippocampus than those kept normothermic. Thalamus and basal ganglia had no or minor damage. It was concluded that there was no general beneficial effect of postinsult hypothermia. However, when controlling for the duration of the insult and occurrence of seizures, hypothermia reduced the severity of brain damage. This indicates a significant neuroprotective effect of 3 h of mild hypothermia on moderate, but not severe, hypoxic-ischemic insults.

Animals↗

PubMed1996

Cerebral, tympanic and colonic thermometry in the piglet.

The temperature of the brain is crucial for the outcome of hypoxic/ischaemic brain damage. In clinical medicine and in animal experiments involving survival after hypoxia/ischaemia, non-invasive measurement of cerebral temperature is needed. We have therefore compared tympanic and colonic temperature with cerebral temperature in the newborn piglet during hypothermia. Ten piglets aged 12-60 h were cooled to 35 degrees C (mild hypothermia) for 150 min and rewarmed. Thereafter, four of the piglets were again cooled to approximately 29 degrees C for less than one hour (moderate hypothermia). During stable mild hypothermia and normothermia the cerebro-tympanic temperature difference in individual piglets was less than +/- 0.4 degrees C (95% confidence intervals < or = 0.18 degrees C) and the cerebro-colonic temperature difference was -0.7 to 0.4 (95% confidence interval < or = 0.28 degrees C). The differences were larger during moderate than during mild hypothermia and largest during rapid changes in body temperature. Then the tympanic temperature correlated with the cerebral temperature significantly better than did the colonic temperature (95% confidence interval -0.3 to 0.3 versus -0.6 to 1.4 for the ten minutes with the least good correlation).

Animals↗

PubMed1996

MAC for halothane and isoflurane during normothermia and hypothermia in the newborn piglet.

BACKGROUND: Halothane and isoflurane are frequently used in studies of perinatal hypoxia and ischemia. Little information exists on the minimum alveolar concentration (MAC) necessary to prevent movement to a painful stimulus in newborn pigs and no information on the effects of hypothermia on MAC in pigs. Hypothermia is currently investigated as a posthypoxic neuroprotective intervention. METHODS: The MAC of halothane and isoflurane necessary to prevent movement when a 25 cm hemostatic clamp was applied to the tail were determined in six 20-48-hour-old piglets, and when the same stimulus was applied to the hoof. MAC for halothane was first determined at 39 degrees C, then at 35 degrees C, whereafter halothane was discontinued and MAC for isoflurane determined first at 35 degrees C and then at 39 degrees C. RESULTS: In all six piglets MAC was lower at 35 degrees C than at 39 degrees C for both anesthetics with both tail and hoof determination, lower for halothane than isoflurane for both stimuli at both temperatures, and lower for tail than hoof determination for both anesthetics at both temperatures. For halothane at 39 degrees C, mean (SD) MAC hoof was 0.82 (0.05)% vs tail 0.60 (0.12)%, and at 35 degrees C, hoof 0.65 (0.06)% vs tail 0.42 (0.10)%. For isoflurane at 39 degrees C, MAC hoof was 2.47 (0.28)% vs tail 1.83 (0.28)%, and at 35 degrees C, hoof was 1.83 (0.18)% vs tail 0.85 (0.25)%. CONCLUSION: In the newborn piglet, MAC should be determined by hoof clamp, MAC of isoflurane is approximately three times that of halothane, and both are reduced during hypothermia.

Anesthetics, Inhalation↗

PubMed1996

Haemoglobin is inversely related to plasma lactate and heart rate in the newborn piglet.

It has been hypothesized that an increased level of plasma lactate (La), the product of anaerobic glycolysis, may identify infants with anaemia and early tissue hypoxia. In the newborn piglet, a frequently used model in experimental neonatology, there is a substantial decrease in haemoglobin (Hb) during the first days of life. We have investigated whether a low level of Hb is associated with an increased level of La in the newborn piglet. Arterial blood gas, Hb, glucose, La, and continuous blood pressure and heart rate (HR) recordings were obtained from 66 newborn piglets. In 4 additional piglets recordings were obtained before isovolemic anaemia, during isovolemic anaemia, and after retransfusion of packed red cells. A low concentration of Hb in the newborn piglet correlates with an increased level of La as well as with an increased HR. A reduction of Hb causes an increase in La and in HR. We hypothesize that increased La and increased HR are caused by mild hypoxia due to normal, low Hb levels in the apparently healthy, resting newborn piglet.

Animals↗

PubMed1996

A piglet survival model of posthypoxic encephalopathy.

The aim of this study was to produce a neonatal piglet model which, avoiding vessel ligation, exposed the whole animal to hypoxia and produced dose-dependent clinical encephalopathy and neuropathologic damage similar to that seen after birth asphyxia. Twenty-three piglets were halothane-anesthetized. Hypoxia was induced in 19 piglets by reducing the fractional concentration of inspired oxygen (FiO2) to the maximum concentration at which the EEG amplitude was below 7 microV (low amplitude) for 17-55 min. There were transient increases in Fio2 to correct bradycardia and hypotension. Posthypoxia, the piglets were extubated when breathing was stable. Four were sham-treated controls. We aimed at 72-h survival; seven died prematurely due to posthypoxic complications. EEG and a videotaped itemized neurologic assessment were recorded regularly. We found that 95% of the animals showed neuropathologic damage. The duration of low amplitude EEG during the insult and the arterial pH at the end of the insult correlated with cortical/white matter damage; r = 0.75 and 0.81, respectively. Early postinsult EEG background amplitude (r = 0.86 at 3 h) and neurologic score (r = 0.79 at 8 h) correlated with neuropathology. Epileptic seizures in seven animals were always associated with severe neuropathologic damage. We conclude that EEG-controlled hypoxia and subsequent intensive care enabled the animals to survive with an encephalopathy which correlated with the cerebral hypoxic insult. The encephalopathy was clinically, electrophysiologically, and neuropathologically similar to that in the asphyxiated term infant. This model is suitable for examining mechanisms of damage and evaluation of potential protective therapies after birth asphyxia.

Animals↗

PubMed1995

Postnatal development of the cerebral blood flow velocity response to changes in CO2 and mean arterial blood pressure in the piglet.

Cerebral blood flow velocity was studied during changes (haemorrhage) in mean arterial blood pressure or P(a)CO2 in 56 (aged 0-26 days) anaesthetized and ventilated piglets. The CO2 reactivity increased with age from 6.5% kPa-1 (< 1 day) to adult levels of 25% kPa-1 for piglets over 4 days old. The mean arterial blood pressure reactivity was reduced from 1.3% mmHg-1 (< 1 day old) to 0.0%/mmHg (> 4 days old). The reactivities were similar with two different anesthetics: chloralose/urethane or pentobarbital. To validate the cerebral blood flow velocity data, both electromagnetic flow and precerebral Doppler ultrasound velocity were recorded from the same common carotid artery with extracranial branches tied off. There were no differences between the results with these two methods nor between these results and those obtained when the cerebral blood flow velocities were recorded from an intracerebral artery and the electromagnetic flowmeter recorded from the carotid artery. The vessel diameter appears stable during these interventions. In conclusion, the autoregulatory response and the reaction to P(a)CO2 appear poorly developed in the newborn piglet, but rapidly mature during the first 4 days of life.

Age Factors↗

PubMed1995

The piglet as a model for cerebral circulation: an angiographic study.

The aim of this study was to further investigate the possibilities and limitations of the newborn piglet as a model for neonatal cerebral circulation and injury. The precerebral and cerebral circulation was visualized by aortic arch contrast injection and selective injections into internal carotid and vertebral arteries. Due to the well-developed collateral circulation, it is not possible to produce severe focal cerebral ischemia in the piglet by ligation of extracranial arteries. It is possible to produce a modified common carotid artery which supplies mainly intracerebral tissues and is accessible for continuous measurements of cerebral blood flow.

Animals↗

PubMed1994

Cerebral Doppler and misrepresentation of flow changes.

To determine whether cerebral blood flow velocity (CBFV) measurements were representative of cerebral blood flow (CBF) changes in pathological flow situations five newborn piglets were investigated. They underwent measurements of CBF by electromagnetic flowmetry on a modified common carotid artery where extracerbral branches were tied off simultaneously with Doppler recording either from the same precerebral or an intracerebral artery. The two methods agreed well within moderate carbon dioxide and blood pressure changes. During severe hypotension and hypertension Doppler overestimated CBF by 25-100%. During transfusion of infected or incompatible blood the two methods differed in opposite directions with Doppler reading from 30-200% of CBF. Transfusion of chilled blood caused CBFV to overestimate 15% and heated blood caused 20% underestimation. These results could be explained by diameter changes in response to variation in myogenic tone or vasoactive substances. CBFV measurements could be seriously misleading in severe clinical derangements where neonatal brain damage might occur.

Animals↗

PubMed1994

Simultaneous measurements of cerebral circulation with electromagnetic flowmetry and Doppler ultrasound velocity in the newborn pig.

Cerebral blood flow measurement has been an important investigative tool in newborns at risk for perinatal brain damage. The validity of Doppler cerebral blood flow velocity measurements depends on a constant vessel diameter. We have validated Doppler against the electromagnetic flowmeter (EM) using a modified common carotid artery model in the 1-d-old piglet. Two sets of continuous and simultaneous recordings were performed: 1) the Doppler and EM probe on the same common carotid artery (extracerebral branches were ligated), and 2) the EM probe on the common carotid artery and the Doppler probe recording from an intracerebral artery through an artificial fontanel. Arterial partial pressure of carbon dioxide (PaCO2) was manipulated (2.8-7.4 kPa), as was arterial blood pressure (3.7-9.3 kPa). Simultaneous EM flow and estimated Doppler flow were compared. Ninety-three recordings were obtained with both transducers on the modified carotid artery, and 49 were obtained with the Doppler insonicating an intracerebral artery. A multiple regression model was used for statistical analysis. The correlation between EM and both sets of Doppler measurements for individual animals was > 0.95 and was unaffected by changes in arterial blood pressure or PaCO2. Thus, the common carotid and the intracerebral artery investigated did not change their diameter significantly in response to PaCO2 or arterial blood pressure. The relationships between EM and Doppler in the individual animal were all linear but revealed great variability in the slopes due to the unknown vessel diameter and angle of insonication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

[Crib death, sleeping position and temperature].

Sudden infant death syndrome (SIDS) is the commonest cause of death in children over one week of age. Norway has the highest incidence in Scandinavia and the figure has increased during the last 20 years. There has been much discussion as to whether sleeping in the prone position rather than in the supine or lateral position may be a predisposing factor to cot death. In all 14 studies in seven countries where the question has been investigated, there was a higher proportion of prone infants in the SIDS group than in the control group. Intervention studies have shown that reducing the proportion of infants sleeping prone was followed by a reduction in cot deaths. There is also evidence that overheating is a risk factor for SIDS. In one British study it was found that infants who died of SIDS had more clothes on, and blankets covering them, and that both prone position and overheating were independently associated with SIDS. A possible mechanism is that overheating interferes with respiratory control. Although we do not completely understand the mechanisms underlying the links between SIDS and the prone position, the epidemiological evidence and the evidence from intervention are now so strong that it is fully justified to advice against the general use of the prone sleeping position for babies.

Australia↗

PubMed1992

Dietary omega-3 fatty acid supplementation and naproxen treatment in patients with rheumatoid arthritis.

In a controlled, double blind, clinical trial we tested the effect of dietary omega-3 fatty acid supplementation with and without naproxen and placebo, respectively, in 67 patients with active rheumatoid arthritis. The patients were randomized into 3 groups that received the following treatment: Group 1, corn oil ("placebo omega-3 fatty acids"), 7 g/day for 16 weeks, and naproxen, 750 mg/day for 10 weeks followed by a stepwise reduction to 0 mg/day during the following 3 weeks; Group 2, omega-3 fatty acids, 3.8 g of eicosapentaenoic acid plus 2.0 g of docosahexaenoic acid, and naproxen, 750 mg/day for 16 weeks; and Group 3, omega-3 fatty acids as Group 2 and naproxen as Group 1. At the end of the trial, patients in Group 2 had improved with respect to duration of morning stiffness and global assessment by physician and patient. In Groups 1 and 3 there was a significant deterioration for most of the variables measured. However, for duration of morning stiffness the deterioration was significantly less pronounced in Group 3 compared with Group 1. These effects might be ascribed to the dietary omega-3 fatty acid supplementation.

Adult↗

PubMed1991

Hypocapnia and cerebral ischaemia in hypotensive newborn piglets.

This study tested the hypothesis that hypocapnia superimposed upon hypotension produces a further reduction in cerebral blood flow velocity (CBFV). In 12 newborn piglets, CBFV was measured continuously by Doppler ultrasound through an artificial fontanelle. Hypotension was induced by removing 30 ml/kg of blood. Increasing the ventilator rate reduced the average arterial carbon dioxide tension from 5.5 to 2.0 kPa. When mean arterial pressure (MAP) was held steady at 45 mm Hg or above, hypocapnia produced a substantial drop in CBFV but, in all the piglets with MAP below 38 mm Hg, hypocapnia failed to change CBFV by 10%. Hypocapnia produced an increase in lactate in sagittal sinus blood but cerebral venous hypoxanthine concentrations were not affected by hypocapnia. Hyperventilation (without haemorrhage) produced a significant drop in MAP, preventable by infusing colloid. Hypocapnia itself does not further reduce CBFV in the hypotensive piglet. However, the pressure effect of hyperventilation may significantly impair the cerebral circulation.

Animals↗

PubMed1984

Atlanto-axial subluxation in rheumatoid arthritis. A study of 104 hospital patients.

Arthritic affection of the upper cervical spine is relatively common in rheumatoid arthritis (RA). Atlanto-axial subluxations are also reported to occur frequently, but it seems that neurological symptoms due to the subluxations seldom occur. We have studied 104 consecutive in-patients. In a group of 50 non-arthritics we have measured the distance from dens to the anterior arch of the atlas, and from dens to the foramen magnum line. By means of percentile-estimate we have defined values at risk for having pathological values for the measured distances. In 104 rheumatoid arthritis patients we found that 45% of the patients had values at risk, but only one of the patients had medullary neurological signs. A planned follow-up study will show if oncoming neurological symptoms due to subluxations will occur in the risk-group or in the group now defined as having normal values.

Adolescent↗