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K Overgaard

Publications and source records attributed to K Overgaard.

At least 19 recordsLinked to original sources
PubMed2006

D-amphetamine improves cognitive deficits and physical therapy promotes fine motor rehabilitation in a rat embolic stroke model.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D-amphetamine (D-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats. METHODS: Seventy-four rats were trained in appropriate cognitive and motor behaviours. Thirteen animals were sham-operated and fifty-nine animals were embolized in the right carotid territory. Animals were randomly assigned to five groups: 1) SHAM (non-embolized, saline), 2) CONTROL (embolized, saline), 3) D-AMPH (embolized, D-amph), 4) THERAPY (embolized, saline + physical therapy) and 5) D-AMPH + THERAPY (embolized, D-amph + physical therapy). Rats of the groups 4-5 underwent d-amph or saline treatment on days 1, 3, 5 and 7 after surgery and were re-trained for 1 h starting 60 min after each treatment. During this time, rats were allowed to voluntarily engage in suitable cognitive or motor behaviours in order to obtain food. Animals from all groups were re-tested during days 21-28 after surgery. RESULTS: No differences in infarct volumes were observed between the groups of embolized animals. When evaluating performances on days 21-28 after surgery, rats of the SHAM and THERAPY groups had better fine motor performance than those of the CONTROL (P < 0.05), whereas rats of SHAM and D-AMPH groups achieved better cognitive performance than CONTROL rats (P < 0.05). No significant differences were observed between any groups regarding gross motor performance. CONCLUSIONS: After embolization, physical therapy improved fine motor performance and D-amph accelerated rehabilitation of cognitive performance as observed in the rats of the THERAPY and D-AMPH groups. As a result of the administration of a high dose of D-amph, the rats of the D-AMPH + THERAPY combination group failed to engage in physical therapy during D-amph intoxication, thereby limiting any promotion of rehabilitation by combining physical therapy and D-amph.

Animals↗
PubMed2004

Evidence that the Na+-K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch muscles.

AIM: Muscles containing predominantly fast-twitch (type II) fibres [ext. dig. longus (EDL)] show considerably lower contractile endurance than muscles containing mainly slow-twitch (type I) fibres (soleus). To assess whether differences in Na+-K+ fluxes and excitability might contribute to this phenomenon, we compared excitation-induced Na+-K+ leaks, Na+ channels, Na+-K+ pump capacity, force and compound action potentials (M-waves) in rat EDL and soleus muscles. METHODS: Isolated muscles were mounted for isometric contractions in Krebs-Ringer bicarbonate buffer and exposed to direct or indirect continuous or intermittent electrical stimulation. The time-course of force decline and concomitant changes in Na+-K+ exchange and M-waves were recorded. RESULTS: During continuous stimulation at 60-120 Hz, EDL showed around fivefold faster rate of force decline than soleus. This was associated with a faster loss of excitability as estimated from the area and amplitude of the M-waves. The net uptake of Na+ and the release of K+ per action potential were respectively 6.5- and 6.6-fold larger in EDL than in soleus, which may in part be due to the larger content of Na+ channels in EDL. During intermittent stimulation with 1 s 60 Hz pulse trains, EDL showed eightfold faster rate of force decline than soleus. CONCLUSION: The considerably lower contractile endurance of fast-twitch compared with slow-twitch muscles reflects differences in the rate of excitation-induced loss of excitability. This is attributed to the much larger excitation-induced Na+ influx and K+ efflux, leading to a faster rise in [K+]o in fast-twitch muscles. This may only be partly compensated by the concomitant activation of the Na+-K+ pumps, in particular in fibres showing large passive Na+-K+ leaks or reduced content of Na+-K+ pumps. Thus, endurance depends on the leak/pump ratio for Na+ and K+.

Action Potentials↗
PubMed2003

Thrombolytic and anticoagulation treatment in a rat embolic stroke model.

OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilaterally and assigned to: (i). controls, (ii). rt-PA 6 mg/kg, (iii). PENTA 0.5 mg/kg, (iv). PENTA 0.5 mg/kg and rt-PA 6 mg/kg. After 2 days animals were killed, the brains removed and evaluated microscopically. RESULTS: The median infarct size measured in percentage of the affected hemisphere was 25% in the control group, 4% (P < 0.01, Mann Whitney) in group 2, 19% (n.s.) in group 3, and 10% (P < 0.05) in group 4. rt-PA, and rt-PA combined with PENTA also promoted functional recovery. CONCLUSION: The present study found no effect of 0.5 mg/kg PENTA treatment. Compared with rt-PA treatment alone, 0.5 mg/kg PENTA alone or combined with rt-PA did not significantly increase mortality or tendency for hemorrhage.

Angiography↗
PubMed2002

The course of blood pressure in acute stroke is related to the severity of the neurological deficits.

OBJECTIVES: To evaluate how soon after stroke the diagnosis of hypertension could be established. METHODS: In a prospective study including 1192 patients with acute stroke within 6 h, blood pressure was measured serially at 2-h intervals during the first 24 h. Results are presented as mean arterial blood pressure (MAP). The Scandinavian Stroke Scale (SSS) assessed the neurological deficit. RESULTS: In 779 patients with mild to moderate ischaemic stroke or transient ischaemic attack (TIA) and SSS > 25, MAP was 118 mmHg (CI 95%: 116-119 mmHg) on admission and 109 mmHg (CI 95%: 108-110 mmHg) 4 h later (paired t-test, P < 0.001). No such early decrease was observed in 228 patients with severe cerebral infarction (CI). In mild to moderate ischaemic stroke or TIA, MAP at 24 h was not different from MAP at 3 months in paired t-test. CONCLUSIONS: Blood pressure 24 h after admission in patients with mild to moderate CI or TIA was representative of the patient's blood pressure 3 months after stroke. A diagnosis of arterial hypertension can be established a few days after stroke.

Aged↗
PubMed2001

Protective effects of lactic acid on force production in rat skeletal muscle.

1. During strenuous exercise lactic acid accumulates producing a reduction in muscle pH. In addition, exercise causes a loss of muscle K(+) leading to an increased concentration of extracellular K(+) ([K(+)](o)). Individually, reduced pH and increased [K(+)](o) have both been suggested to contribute to muscle fatigue. 2. To study the combined effect of these changes on muscle function, isolated rat soleus muscles were incubated at a [K(+)](o) of 11 mM, which reduced tetanic force by 75 %. Subsequent addition of 20 mM lactic acid led, however, to an almost complete force recovery. A similar recovery was observed if pH was reduced by adding propionic acid or increasing the CO(2) tension. 3. The recovery of force was associated with a recovery of muscle excitability as assessed from compound action potentials. In contrast, acidification had no effect on the membrane potential or the Ca(2+) handling of the muscles. 4. It is concluded that acidification counteracts the depressing effects of elevated [K(+)](o) on muscle excitability and force. Since intense exercise is associated with increased [K(+)](o), this indicates that, in contrast to the often suggested role for acidosis as a cause of muscle fatigue, acidosis may protect against fatigue. Moreover, it suggests that elevated [K(+)](o) is of less importance for fatigue than indicated by previous studies on isolated muscles.

Animals↗
PubMed2001

Activity-induced recovery of excitability in K(+)-depressed rat soleus muscle.

Increased extracellular K(+) concentration ([K(+)](o)) can reduce excitability and force in skeletal muscle. Here we examine the effects of muscle activation on compound muscle action potentials (M waves), resting membrane potential, and contractility in isolated rat soleus muscles. In muscles incubated for 60 min at 10 mM K(+), tetanic force and M wave area decreased to 23 and 24%, respectively, of the control value. Subsequently, short (1.5 s) tetanic stimulations given at 1-min intervals induced recovery of force and M wave area to 81 and 90% of control levels, respectively, within 15 min (P < 0.001). The recovery of force and M wave was associated with a partial repolarization of the muscle fibers. Experiments with tubocurarine suggest that the force recovery was related to activation of muscle Na(+)-K(+) pumps caused by the release of some compound from sensory nerves in response to muscle activity. In conclusion, activity produces marked recovery of excitability in K(+)-depressed muscle, and this may protect muscles against fatigue caused by increased [K(+)](o) during exercise.

Animals↗
PubMed2000

The role of K+ channels in the force recovery elicited by Na+-K+ pump stimulation in Ba2+-paralysed rat skeletal muscle.

The present experiments were performed to assess the role of K+ channels in hormonal stimulation of the Na+-K+ pump and to determine the contribution of Na+-K+ pumps to the recovery of excitability and contractility in depolarized skeletal muscle. In soleus muscle, Ba2+ (0.02 and 1 mM) was found to inhibit 42K+ efflux and 42K+ influx. Both in the absence and the presence of Ba2+ (1 mM), salbutamol and calcitonin gene-related peptide (CGRP) induced a marked decrease in intracellular Na+ and stimulation of 42K+ uptake. In soleus muscles Ba2+ (0.1 and 1.0 mM) decreased twitch and tetanic force. Subsequent stimulation of the Na+-K+ pumps by salbutamol, CGRP or repeated electrical stimulation produced a highly significant restoration of force development, which was suppressed by ouabain, but not by glibenclamide. Also, in extensor digitorum longus muscles Ba2+ (0.1 mM) produced a considerable force decline, which was partly restored by salbutamol and CGRP. The area of compound action potentials (M-waves) elicited by indirect stimulation was decreased by Ba2+ (0.1 mM). This was associated with a concomitant decrease in tetanic force and depolarization. Salbutamol, CGRP or repeated electrical stimulation all elicited marked recovery of M-wave area, force and membrane potential. All recordings showed close correlations between these three parameters. The data add further support to the concept that due to its electrogenic nature and large transport capacity, the Na+-K+ pump is a rapid and efficient mechanism for the maintenance of excitability in skeletal muscle, acting independently of Ba2+- or ATP-sensitive K+ channel function.

Albuterol↗
PubMed2000

Influence of different fixation procedures on the quantification of infarction and oedema in a rat model of stroke.

In pharmacodynamic studies using focal ischaemia models, the size of the infarct measured by quantitative histology is the most important outcome measure. Precise, unbiased and reproducible assessment of infarct volume is of foremost importance. A frequent problem in interventional stroke models is the evaluation of infarcts in animals found dead, where instant post-mortem fixation of the brain cannot be performed. The purpose of this study was to investigate possible bias from perfusion, immediate and 3-h post-mortem delayed immersion fixation on the measured volumes of cerebral infarction, oedema and hemispheres in a rat embolic stroke model. Thirty-six male Sprague-Dawley rats were thromboembolized into the internal carotid artery. After survival for 24 h, the animals were divided into three groups: group 1 - immediate perfusion fixation; group 2 - immediate immersion fixation of the brain; and group 3 - animals left dead for 3 h at room temperature before removal of the brain for immersion fixation. Following histological preparation and evaluation, the volumes of the hemispheres and infarction were measured by quantitative histology and planimetry. Brains fixed by immersion were 7% larger than the perfusion-fixed brains. Delaying the immersion fixation for 3 h may increase hemisphere volume by a further 12%. Independent of the fixation procedure, the size of infarction was approximately 40% of the ipsilateral hemisphere, and the oedema was approximately 11% of the size of the infarct. The used planimetric technique was accurate with measured values within +/- 2% of the factual value. In conclusion, sizes of hemispheres, infarction and oedema in absolute volume measures are influenced by the effect of unwanted variation of brain size caused by biological factors and artificial shrinkage caused by fixation, dehydration and heat treatment of the specimens. Infarction and oedema expressed relatively in per cent of hemisphere and infarct, respectively, are robust measures independent of the investigated fixation procedures.

Animals↗
PubMed1999

Relations between excitability and contractility in rat soleus muscle: role of the Na+-K+ pump and Na+/K+ gradients.

1. The effects of reduced Na+/K+ gradients and Na+-K+ pump stimulation on compound action potentials (M waves) and contractile force were examined in isolated rat soleus muscles stimulated through the nerve. 2. Exposure of muscles to buffer containing 85 mM Na+ and 9 mM K+ (85 Na+/9 K+ buffer) produced a 54% decrease in M wave area and a 50 % decrease in tetanic force compared with control levels in standard buffer containing 147 mM Na+ and 4 mM K+. Subsequent stimulation of active Na+-K+ transport, using the beta2-adrenoceptor agonist salbutamol, induced a marked recovery of M wave area and tetanic force (to 98 and 87% of the control level, respectively). Similarly, stimulation of active Na+-K+ transport with insulin induced a significant recovery of M wave area and tetanic force. 3. During equilibration with 85 Na+/9 K+ buffer and after addition of salbutamol there was a close linear correlation between M wave area and tetanic force (r = 0.92, P < 0.001). Similar correlations were found in muscles where tetrodotoxin was used to reduce excitability and in muscles fatigued by 120 s of continuous stimulation at a frequency of 30 Hz. 4. These results show a close correlation between excitability and tetanic force. Furthermore, in muscles depressed by a reduction in the Na+/K+ gradients, beta-adrenergic stimulation of the Na+-K+ pump induces a recovery of excitability which can fully explain the previously demonstrated recovery of tetanic force following Na+-K+ pump stimulation. Moreover, the data indicate that loss of excitability is an important factor in fatigue induced by high-frequency (30 Hz) stimulation.

Action Potentials↗
PubMed1999

Effects of citicoline combined with thrombolytic therapy in a rat embolic stroke model.

BACKGROUND AND PURPOSE: We sought to evaluate the effects of the combination of cytidine-5'-diphosphocholine (citicoline) and thrombolysis on infarct size, clinical outcome, and mortality in a rat embolic stroke model. METHODS: Eighty-three Sprague-Dawley rats were embolized in the carotid territory with a single fibrin embolus and randomly assigned to the following treatment groups: (1) control (saline), (2) citicoline 250 mg/kg, (3) citicoline 500 mg/kg, (4) recombinant tissue plasminogen activator (rtPA) 5 mg/kg, (5) rtPA 5 mg/kg plus citicoline 250 mg/kg, and (6) rtPA 5 mg/kg plus citicoline 500 mg/kg. rtPA was administered as a continuous intravenous infusion over 45 minutes starting 45 minutes after embolization; citicoline was given intraperitoneally 30 minutes and 24, 48, and 72 hours after embolization. At 96 hours, the brains were fixed and stained by hematoxylin-eosin, and infarct volumes were measured. Neurological scores were determined daily. RESULTS: The median infarct size, measured as percentage of the affected hemisphere, in the control group was 37% (interquartile range, 26% to 69%) compared with 22% (5% to 52%; P=NS) in group 2, 11% (5% to 34%; P=NS) in group 3, 24% (12% to 31%; P=NS) in group 4, 11% (3% to 22%; P=0.02) in the combined group 5, and 19% (9% to 51%; P=NS) in group 6. The infarct size was significantly reduced in the combined citicoline+rtPA-treated groups to a median of 13% (5% to 30%; P<0.01). Citicoline 500 mg/kg and citicoline combined with rtPA also promoted functional recovery. CONCLUSIONS: These results demonstrate that the combination of low-dose citicoline and rtPA significantly reduced infarct size in this focal ischemia model.

Animals↗
PubMed1998

The Na+,K+ pump and muscle excitability.

In most types of mammalian skeletal muscles the total concentration of Na+,K+ pumps is 0.2-0.8 nmol g wet wt(-1). At rest, only around 5% of these Na+,K+ pumps are active, but during high-frequency stimulation, virtually all Na+,K+ pumps may be called into action within a few seconds. Despite this large capacity for active Na+,K+ transport, excitation often induces a net loss of K+, a net gain of Na+, depolarization and ensuing loss of excitability. In muscles exposed to high [K+]o or low [Na+]o, alone or combined, excitability is reduced. Under these conditions, hormonal or excitation-induced stimulation of the Na+,K+ pump leads to considerable force recovery. This recovery can be blocked by ouabain and seems to be the result of Na+,K+ pump induced hyperpolarization and restoration of Na+,K+ gradients. In muscles where the capacity of the Na+,K+ pump is reduced, the decline in the force developing during continuous electrical stimulation (30-90 Hz) is accelerated and the subsequent force recovery considerably delayed. The loss of endurance is significant within a few seconds after the onset of stimulation. Increased concentration of Na+ channels or open-time of Na+ channels is also associated with reduced endurance and impairment of force recovery. This indicates that during contractile activity, excitability is acutely dependent on the ratio between Na+ entry and Na+,K+ pump capacity. Contrary to previous assumptions, the Na+,K+ pump, due to rapid activation of its large transport capacity seems to play a dynamic role in the from second to second ongoing restoration and maintenance of excitability in working skeletal muscle.

Animals↗
PubMed1998

Cerebral blood flow measurement during embolization of the rat brain using the xenon injection method.

The purpose of this study was to investigate if cerebral blood flow (CBF) was influenced by the volume of the bolus using the intracarotid 133Xenon method in anesthetized rats, and to evaluate the effect of intracarotid embolization on hemispheric CBF. In 18 male Sprague-Dawley rats hemispheric CBF was calculated from recorded clearance of an intracarotid injected 50 microliters bolus of 133Xenon. A second clearance recording was done after the injection of a 200 microliter bolus of 133Xenon. Then the 18 animals were divided in 3 subsets each of 6 animals. In the first subset of 6 animals a bolus of 200 microliters 133Xenon was given, clearance was recorded before and after the injection of a suspension of microemboli. In all the above experiments within 90 sec after the initial bolus of 133Xenon, 20 microliters 133Xenon remaining in the carotid catheter was flushed into the brain by saline or the suspension of emboli. In the second subset of 6 rats the distribution of 133Xenon in various parts of the brain and head was examined after killing the animals 35 sec after injection of a 200 microliter bolus of 133Xenon. The third subset of 6 rats was treated as the second subset, except for the size of the bolus which was 50 microliters of 133Xenon. The calculated CBF values were independent of the volume of the bolus. At the post-mortem examination 76% of the radioactivity was located in the right hemisphere and majority of the remainder in the head outside the brain. The clearance curve was not monoexponential, but flattened out within the initial 30 sec when clearance from areas with CBF dominated the initial 15-second period, then clearance form areas with lower CBF values were more prominent in the following 15-second period. Embolization significantly reduced right hemispheric CBF to 0.26 (0.09-0.50) of the value immediately before embolization. The findings demonstrate applicability of CBF measurements using the intra-arterial 133Xenon injection method during embolization of the rat brain, provided a second bolus of 133Xenon is given before the embolization.

Animals↗
PubMed1998

[Can acute stroke be treated with hypothermia?].

In animal stroke models, treatment with mild hypothermia (30-34 degrees C) for 3-4 hours may reduce the size of cerebral infarction if started within three hours of the initiation of cerebral ischaemia. The mechanism by which hypothermia exerts its neuroprotective effect is unknown, but experimental studies have shown the release of neurotoxic excitatory amino acids and free oxygen radicals to be reduced during hypothermic ischaemia. In patients with acute stroke, body temperature above 37.5 degrees C are associated with poor outcome, and temperatures below 36.5 degrees C with improved outcome, compared to normothermic patients. Due to the unpleasantness of cooling and side effects as shivering, hypothermia may not be tolerated by stroke patients without sedation of light anaesthesia which may increase the risk of hypotension and respiratory complications. However, lowering body temperature by 1-2 degrees C may suffice to improve functional outcome in acute stroke patients, and such mild hypothermia should be tested in randomized controlled clinical trials.

Acute Disease↗
PubMed1997

Effects of reduced electrochemical Na+ gradient on contractility in skeletal muscle: role of the Na+-K+ pump.

Continued excitation of skeletal muscle may induce a combination of a low extracellular Na+ concentration ([Na+]o) and a high extracellular K+ concentration ([K+]o) in the T-tubular lumen, which may contribute to fatigue. Here, we examine the role of the Na+-K+ pump in the maintenance of contractility in isolated rat soleus muscles when the Na+, K+ gradients have been altered. When [Na+]o is lowered to 25 mM by substituting Na+ with choline, tetanic force is decreased to 30% of the control level after 60 min. Subsequent stimulation of the Na+-K+ pump with insulin or catecholamines induces a decrease in [Na+]i and hyperpolarization. This is associated with a force recovery to 80-90% of the control level which can be abolished by ouabain. This force recovery depends on hyperpolarization and is correlated to the decrease in -Na+-i (r = 0. 93; P<0.001). The inhibitory effect of a low -Na+-o on force development is considerably potentiated by increasing [K+]o. Again, stimulation of the Na+-K+ pump leads to rapid force recovery. The Na+-K+ pump has a large potential for rapid compensation of the excitation-induced rundown of Na+, K+ gradients and contributes, via its electrogenic effect, to the membrane potential. We conclude that these actions of the Na+-K+ pump are essential for the maintenance of excitability and contractile force.

Animals↗
PubMed1997

Bone metabolism following bladder substitution with the ileal urethral Kock reservoir.

OBJECTIVES: To assess bone metabolism following bladder substitution with the ileal Kock reservoir. PATIENTS, SUBJECTS AND METHODS: The investigation comprised two separate studies, one with baseline measurements before and after surgery, and the second after surgery only, of bone mass, made using single-photon absorptiometry and dual-energy X-ray absorptiometry, biochemical variables of bone turnover, plasma analyses and measurements of renal calcium and phosphate excretion. After inclusion, both groups of patients were observed longitudinally for 2 years. The post-surgery study included 25 patients who had undergone bladder substitution (median age 67 years, range 44-75), with a median post-operative follow-up of 1.0 year (range 0.3-3.7), and 16 control subjects (either healthy or with other minor urological complaints; median age 62 years, range 34-80), and the pre-surgery study comprised seven patients who had undergone bladder substitution (median age 57 years, range 42-68). RESULTS: Total body, forearm and spinal bone mineral contents were similar in patients with an ileal bladder substitute measured 1 year after surgery and in control subjects. There were equivalent significant changes in both the patients and control subjects during the 2-year observation period, with a 2-3% decrease in total body and forearm bone mineral content. The values were similar in patients with and without a mild metabolic acidosis. Plasma calcium, phosphate, total alkaline phosphatase, intact parathyroid hormone, vitamin D and osteocalcin were normal in both patients and control subjects. Renal excretion of calcium and phosphate was also similar in patients and in control subjects. CONCLUSIONS: Ileal urethral Kock bladder substitution does not lead to accelerated bone mineral loss in elderly men, despite a mild metabolic acidosis in half of the patients.

Absorptiometry, Photon↗
PubMed1996

Comparison of bone densitometry of the phalanges, distal forearm and axial skeleton in early postmenopausal women participating in the EPIC Study.

We present baseline bone densitometry from the Early Postmenopausal Interventional Cohort study (EPIC, sponsored by Merck, Sharp & Dohme) for the first time, in which 1609 women from England, Oregon, Hawaii and Denmark are participating to investigate the efficacy of daily oral alendronate to prevent early postmenopausal bone loss. We compared radiographic absorptiometry (RA) of the phalanges for bone mineral density (BMD) measurement with single-energy X-ray absorptiometry (SXA) of the distal forearm, and dual-energy X-ray absorptiometry (DXA) of the lumbar spine, proximal femur and distal forearm. In a random subgroup of 308 women, aged 45-60 years, on average 6 years since menopause (YSM), bone densitometry was measured once at baseline by RA of the phalanges besides the mandatory measurements by DXA. Bone densitometry was furthermore measured by SXA at the Danish site (89 women). Sixty-eight of the women had duplicate measurements performed within 1-3 weeks to evaluate the short-term precision error (CV%). One hundred and one healthy premenopausal women, aged 25-48 years, were recruited at the Danish and Hawaiian sites to establish a reference group. The precision error was 1.5% for RA of the phalanges and in the range 1.0-2.2% for SXA and DXA. BMD by RA correlated with BMD measured by SXA and DXA in the range 0.45 < r < 0.72 (p < 0.001). In conclusion, bone densitometry by RA of the phalanges is highly correlated with bone densitometry by SXA and DXA. RA of the phalanges has a short-term precision error comparable to that of SXA and DXA.

Absorptiometry, Photon↗