bluuebunny/crossref_metadata_2025 huggingface dataset:
Operation Everest II: structural adaptations in skeletal muscle in response to extreme simulated altitude
Authors: MacDOUGALL J. D. , GREEN H. J. , SUTTON J. R. , COATES G. , CYMERMAN A. , YOUNG P. , HOUSTON C. S.
Published: December 2008

Alterations in skeletal muscle structure were investigated in 6 male subjects who underwent 40 days of progressive decompression in a hypobaric chamber simulating an ascent to the summit of Mount Everest. Needle biopsies were obtained from vastus lateralis of 5 subjects before and immediately after confinement in the chamber, and were examined for various structural and ultrastructural parameters. In addition, total muscle area was calculated in 6 subjects from CT scans of the thighs and upper arms. Muscle area at these sites was found to decrease significantly (by 13 and 15%) as a result of the hypobaric confinement. This was substantiated by significant (25 %) decreases in cross sectional fibre areas of the Type I fibres and 26% decreases (non significant) in Type II fibre area. Capillary to fibre ratios remained unchanged following hypoxia as did capillary density although there was a trend (non significant) towards an increase in capillary density. There were no significant increases in mitochondrial volume density or other morphometric parameters. These data indicate that chronic, severe hypoxia on its own does not result in an increase in absolute muscle capillary number or a de nova synthesis of mitochondria. The trends toward an increase in capillary density and mitochondrial volume density were interpreted as being secondary occurrences in response to the pronounced muscle atrophy which occurred.
Myocardial blood flow and lactate metabolism at rest and during exercise with reduced arterial oxygen content
Authors: GRUBBSTRÖM J. , BERGLUND B. , KAIJSER L.
Published: December 2008

The effect of a reduction in arterial oxygen content, equivalent to acute exposure to an altitude of 2300 metres above sea level, on myocardial blood flow and oxygen and lactate exchange was studied by coronary sinus catheterization in 12 healthy men. Measurements were made at rest, during atrial pacing and during submaximal and maximal exercise both breathing air and breathing 15% oxygen (hypoxia). Coronary sinus blood flow was measured by thermodilution and the possibility of a simultaneous uptake and release of lactate by the heart was calculated using intravenous infusion of 14C lactate. At all levels of cardiac power output myocardial oxygen consumption was the same during hypoxia as during air breathing. At rest this was achieved entirely by a more complete extraction of oxygen from the coronary blood, during maximal exercise entirely by a greater coronary sinus blood flow, while at intermediate levels of cardiac power output a combination of these mechanisms prevailed. At rest and during submaximal work myocardial lactate extraction was lower with hypoxia than air breathing suggesting a change in myocardial redox state, while the 14C lactate data suggested no significant lactate release or possibly limited areas with some lactate production. During maximal exercise, however, there was no difference in myocardial lactate net extraction between hypoxia and air breathing, which together with the greater blood flow suggests that the heart has a ‘coronary flow reserve’ permitting maximal exercise at moderate altitude without anaerobic myocardial metabolism.
Plasma levels of endothelin‐1 and atrial natriuretic peptide in men during a 2‐hour stay in a cold room
Authors: HASSI J. , RINTAMÄKI H. , RUSKOAHO H. , LEPPÄLUOTOT J. , VUOLTEENAHO O.
Published: December 2008

Male volunteers were exposed to +10° C ambient temperature for 2 hours while they were sitting undressed. The levels of endothelin‐1 and atrial natriuretic peptide were determined by radioimmunoassays. Control samples were obtained at thermoneutrality. The cold exposure resulted in lowering of the mean skin temperature (from 31.2± 0.3°C‐22.6 ± 2.5°C, mean ± SEM), which indicates that a marked vasocon‐striction took place, as well as a decrease of the body heat content (by 11.2 ± 0.7 kJ kg‐1). However, plasma endothelin‐1 levels did not change significantly during the exposure. Thus circulating endothelin‐1 does not seem to be responsible for the vasoconstriction associated with cold air exposure. The plasma atrial natriuretic peptide levels exhibited a slight increase towards the end of the cold exposure. This finding is in accord with the notion that atrial natriuretic peptide might contribute to the diuresis frequently observed in the cold.
Galanin and neuropeptide Y in chromaffin granules from the guinea‐pig
Authors: FRIED G. , WIKSTRÖM L.‐M. , FRANCK J. , RÖKAEUS Å.
Published: December 2008

We have examined the subcellular distribution of galanin‐like immunoreactivity, neuropeptide Y‐like immunoreactivity and the catecholamines noradrenaline and adrenaline in the adrenal medulla from guinea‐pigs. By differential centrifugation of the adrenal medulla homogenate the neuropeptides as well as the catecholamines sedimented in a 10000 g pellet. This pellet was resuspended and further examined in discontinuous and continuous density gradients. In the discontinuous gradient the catecholamines peaked in the heavy bottom fraction, assumed to contain chromaffin granules. Galanin‐like immunoreactivity and neuropeptide Y‐like immunoreactivity were also enriched in this fraction. However, both neuropeptides showed high levels of sedimentable material also in a fraction of intermediate density. In the continuous density gradient, the sum of sedimentable and soluble catecholamines showed peak values in two fractions corresponding to 1.07 and 1.47m sucrose, respectively. The NA peak in the denser fraction was more pronounced than the corresponding A peak. Galanin‐like immunoreactivity showed only one peak, in the fraction corresponding to 1.07 M sucrose. The data suggest that galanin‐like immunoreactivity and neuropeptide Y‐like immunoreactivity are partly stored with catecholamines in chromaffin granules. However, galanin‐like immunoreactivity and neuropeptide Y‐like immunoreactivity was also found in fractions lighter than those containing the bulk of the catecholamines.
In vitro steroid production by follicles of frog Rana esculenta: mammaIian gonadotropin‐releasing hormone effects
Authors: ZERANI M. , GOBBETTI A. , POLZONETTI‐MAGNI A.
Published: December 2008

The effects of mammalian gonadotropin‐releasing hormone on ovarian release of progesterone, androgens and estradiol‐17β were studied in vitro by a superfusion system carried out on follicles of adult female Rana esculenta, collected at different periods of the annual reproductive cycle.

The follicles were superfused with medium alone, pituitary, mammalian gonadotropin‐releasing hormone, or pituitary plus mammalian gonadotropin‐releasing hormone. For follicles obtained in the prereproductive period, pituitary plus mammalian gonadotropin‐releasing hormone increased the estradiol values much more than pituitary alone. In the reproductive period, pituitary alone increased the estradiol values much more than pituitary plus mammalian gonadotropin‐releasing hormone. For follicles obtained in the recovery period, mammalian gonadotropin‐releasing hormone alone stimulated the highest estradiol production, and pituitary plus mammalian gonadotropin‐releasing hormone increased the estradiol values much more than pituitary alone.

The results reported here suggest that mammalian gonadotropin‐releasing hormone and/or pituitary have a direct effect on ovarian estradiol secretion, and that this effect varies with the annual reproductive cycle.
Gut blood flow in the estuarine crocodile,Crocodylus porosus
Authors: AXELSSON M. , FRITSCHE R. , HOLMGREN S. , GROVE D. J. , NILSSON S.
Published: December 2008

Simultaneous recordings of blood flow in the right and left aorta and carotid and coeliac artery were made in the crocodile,Crocodylus porosusat rest and during various stimuli. In resting animals the right aorta and carotid artery flow profiles resembled the recordings obtained in the caiman (Axelssonet al. 1989 a), with an anterograde blood flow throughout the cardiac cycle. As in the caiman, the left aorta flow profile was complex with both anterograde and retrograde blood flow during the cardiac cycle, and a net left aorta blood flow near zero at rest.

The coeliac artery blood flow profile did not show the complex pattern seen in the upper aorta, immediately suggesting that most of the coeliac artery blood originates elsewhere. We believe that coeliac artery blood flow in the resting animal derives from the right aorta via the abdominal anastomosis between the two aortas. Feeding induced an increase in the coeliac artery and left aorta blood flow, probably due to a decrease in visceral vascular resistance, and hence coeliac arterial and the left aorta blood pressure, which facilitates blood flow (from right to left aorta) through the foramen of Panizza.

During short ‘fright dives’, heart rate fell and there was a decrease in the recorded blood flows: carotid artery blood flow did not decrease to the same extent as the RAo and coeliac artery flow, indicating some capacity for redistribution of blood to the cephalic circuits during diving. Similarly, a near‐unimpaired carotid artery blood flow was maintained after adrenaline injection.

Substance P increased the coeliac artery blood flow and produced a right‐to‐left cardiac shunt, probably by construction of the pulmonary vasculature.
Haemodynamic and humoral responses to repeated hypotensive haemorrhage in conscious sheep
Authors: HJELMQVIST H. , ULLMAN J. , GUNNARSSON U. , LUNDBERG J. M. , RUNDGREN M.
Published: December 2008

Haemodynamic and humoral responses to two subsequent hypotensive haemorrhages, separated by 3 hours and each followed by retransfusion, were studied in unanaesthetized sheep. Haemorrhage was induced by removal of blood from a jugular vein at a rate of 0.7 ml kg‐1 min‐1 until the mean systemic arterial pressure suddenly decreased by 35 mmHg or more.

In addition to the mean systemic arterial pressure, the cardiac output, the mean pulmonary arterial pressure, the central venous pressure and the pulmonary capillary wedge pressure decreased in response to each haemorrhage. The recovery of the systemic and pulmonary arterial pressure was slower and/or less efficient after the second haemorrhage, due to a less pronounced increase of the vascular resistance. Relative bradycardia, in association with the abrupt fall of the mean systemic arterial pressure, was more apparent during the first haemorrhage.

The plasma levels of vasopressin, renin activity and angiotensin II were increased by each blood removal, but the vasopressin response to the second haemorrhage was significantly reduced. The plasma noradrenaline concentration was slightly and transiently elevated only in response to the second haemorrhage. The concentration of neuropeptide Y‐like immunoreactivity in plasma was unaffected by both haemorrhages.

It is suggested that the reduced and delayed increase in the systemic vascular resistance, accompanied by impaired recovery of the arterial pressure, and the relative absence of ‘bleeding bradycardia’, during the second haemorrhage, were due to the diminished vasopressin response.
Influence of α‐adrenergic receptor stimulation on splanchnic intravascular volume in conscious humans
Authors: BELL L. , ZARET B. L. , RUTLEN D. L.
Published: December 2008

The influence of selective α‐adrenergic receptor stimulation on total splanchnic intravascular volume and blood volume in individual splanchnic organs in humans has not been previously examined. The present study employed a previously validated quantitative radionuclide imaging technique, involving a gamma camera and Tc‐99m labeled erythrocytes, to measure changes in total splanchnic, hepatic, splenic, and extrahepatosplenic volume during a 20‐minute phenylephrine infusion (30–120 μ min‐1 iv). Changes in total splanchnic volume were estimated from changes in total splanchnic radioactivity, blood radioactivity, and estimated in vivo tissue attenuation. Radionuclide‐estimated total splanchnic volume increased 477±96 ml (P < 0.0003) at the end of phenylephrine infusion. Hepatic volume increased 25±5% (P < 0.0003), splenic volume decreased 46±7% (P < 0.0003), and extrahepatosplenic volume decreased 15±2% (P < 0.0003). Systolic and diastolic arterial pressures increased from 119±4 to 138 ± 5 mmHg (P < 0.0003) and from 83+1 to 96 ± 2 mmHg (P < 0.0003), respectively. Heart rate decreased from 62±2 to 51±3 bpm (P < 0.0003). Thus, in man, selective α‐adrenergic receptor stimulation is associated with an increase in splanchnic intravascular volume that is due to an increase in hepatic volume and occurs despite decreases in splenic and extrahepatosplenic volumes. This increase in total splanchnic volume would be associated with a decrease in venous return from the splanchnic vasculature to the right heart which would act to decrease cardiac output.
Effects of alpha2‐adrenoceptor blockade and thyrotropin‐releasing hormone (TRH) on the cardiovascular system in the rabbit
Authors: SELIGSOHN E. E. , KOSKINEN L.‐O. D.
Published: December 2008

The effects of two different doses of thyrotropin‐releasing hormone on regional blood flows were studied in urethane‐anaesthetized rabbits pretreated with the α2adrenergic antagonists yohimbine and idazoxan. The effects of yohimbine were also studied using unanaesthetized rabbits. Blood flow measurements were performed using the tracer microsphere method. Thyrotropin‐releasing hormone was injected i. v. at a dose of either 0.1 mg kg‐1or 2.0 mg kg‐1. Yohimbine and idazoxan did not modify the effect of thyrotropin‐releasing hormone on mean arterial blood pressure. In the anaesthetized animals, blockade of the α2adrenoceptors resulted in a vasoconstriction in several peripheral organs and the vasoconstriction increased after thyrotropin‐releasing hormone administration. Pretreatment with yohimbine reduced total cerebral blood flow moderately and in such animals thyrotropin‐releasing hormone elicited only minor cerebral blood flow effects. Pretreatment with idazoxan did not reduce the total cerebral blood flow and in such animals it increased from 53± 1 to 75±4 g min‐1100 g‐1(P< 0.01) after the administration of the lower dose of thyrotropin‐releasing hormone and from 64±5 to 112±17 g min‐1100 g‐1(P< 0.01) after the higher dose.

In the conscious animals, yohimbine caused an increase in mean arterial blood pressure and heart rate. Vascular resistance increased in several organs. The cerebral blood flow decreased in white matter (P<0.05) and the caudate nucleus (P< 0.05).

The results indicate that there is a yohimbine‐sensitive mechanism involved in the cerebrovasodilating effect of thyrotropin‐releasing hormone in anaesthetized rabbits. There is also an activation of the sympathetic nervous system by thyrotropin‐releasing hormone which results in increased vascular resistance and mean arterial blood pressure. Its effect on the vascular resistance may be enhanced by α2adrenoceptor blockade. In conscious animals, there seems to be a yohimbine‐sensitive mechanism involved in the control of cerebral blood flow.
Interstitial lactate, inosine and hypoxanthine in rat kidney during normothermic ischaemia and recirculation*
Authors: EKLUND T. , WAHLBERG J. , UNGERSTEDT U. , HILLERED L.
Published: December 2008

The aim of this study was to determine the potential value of extracellular fluid (ECF) lactate, inosine and hypoxanthine for monitoring the disturbance in energy metabolism associated with kidney ischaemia and recirculation, using intrarenal microdialysis as sampling technique. Normothermic ischaemia was produced in rats by clamping of the left renal pedicle. Microdialysis probes were implanted into the renal cortex and the medulla, respectively. Dialysates were collected in 10‐minute fractions before, during 20 (Group A) or 40 minutes (Group B) ischaemia and 2 hours of recirculation. Samples were analysed by HPLC for lactate, inosine and hypoxanthine. Ischaemia caused a dramatic increase of extracellular fluid lactate, inosine and hypoxanthine in both groups, reflecting the disturbance of energy metabolism. The basal extracellular fluid level of lactate as well as that during ischaemia was markedly higher in the medulla compared to cortex, whereas the relative change in lactate concentration was similar (i. e. about 4‐fold). In group A all three metabolites returned to the pre‐ischaemic level within 20 minutes after reperfusion. However, while inosine and hypoxanthine returned promptly to base line in Group B, recovery of lactate varied dramatically between animals suggesting a persistent metabolic disturbance in some rats.

Our results indicate that extracellular fluid lactate, inosine and hypoxanthine, measured by intrarenal microdialysis, may be useful for monitoring of the energy state of the kidney during normothermic ischaemia and that extracellular fluid lactate may be a sensitive indicator of post‐ischaemic disturbances in energy metabolism.
A study on the renal synthesis of dopamine in aged rats
Authors: SOARES‐DA‐SILVA P. , FERNANDES M. H.
Published: December 2008

The present study has examined the synthesis of dopamine froml‐DOPA in kidney slices and in kidney homogenates of 3‐ and 24‐month‐old rats. The deamination of newly‐formed dopamine into 3,4‐dihydroxyphenylacetic acid (DOPAC) was also studied. The assay ofl‐DOPA, dopamine, noradrenaline and DOPAC was performed by high pressure liquid chromatography with electrochemical detection. Incubation of renal slices and homogenates of whole kidney with exogenousl‐DOPA (0.1–100μm) resulted in a concentration‐dependent formation of both dopamine and DOPAC. At 50 and 100μml‐DOPA, but not at lower concentrations (10 and 25μM), the total amounts of dopamine and DOPAC formed were significantly greater in kidney slices obtained from 3‐month‐old rats. By contrast, the total amount of dopamine and DOPAC formed was greater in homogenates of renal tissues from aged rats than from young animals; this was particularly evident at 5.0 and 10.0μml‐DOPA in the incubation medium. However, the DOPAC/dopamine ratios, both in kidney slices and kidney homogenates, were found to be higher in young rats than in old rats. The present results suggest an impairment in the formation of dopamine and of its deamination into DOPAC in renal tissues of aged rats; however, the reduced synthesis of dopamine does not appear to be the result of a decreased activity of the enzyme aromaticl‐amino acid decarboxylase.
Spatial distribution of motor unit fibres in fast‐and slow‐twitch rat muscles with special reference to age
Authors: ANSVED T. , WALLNER P. , LARSSON L.
Published: December 2008

The spatial arrangement and morphometrical properties of the muscle fibres within single motor units (motor unit fibres) were studied in fast‐twitch units of the tibialis anterior (TA) and in slow‐twitch units of the soleus, using a computer‐assisted model. The motor unit fibres were identified by the glycogen‐depletion technique and the position of each fibre was defined by (x, y)‐coordinates. The distance between each fibre and the nearest motor unit fibre (nearest‐neighbour distance), and the distance between each fibre and each of the other fibres in the unit (interfibre distance), was calculated and plotted. Comparisons were made between young adult (3–6 months) and old (20–25 months) rats. In old animals, the motor units of TA and the soleus were larger (P < 0.05 and P < 0.01), contained an increased number of muscle fibres (P < 0.01) and covered a larger portion of the muscle cross‐section (P < 0.01 and P < 0.1). These changes indicate the presence of an age‐related denervation‐reinnervation process in both types of muscles. In the young adult group, the fast‐twitch motor unit fibres of TA were non‐randomly arranged (P < 0.05–0.01) whereas the fibre arrangement within the slow‐twitch motor units of the soleus was not significantly different from random. In old animals, the fibre arrangement was non‐random in both fast‐ and slow‐twitch motor units. In TA, the distribution of nearest‐neighbour distances showed an increased (P < 0.05) proportion of short distances in old age, whereas the distribution of interfibre distances was unchanged. In the soleus, the distribution of interfibre distances showed an age‐related displacement to the left at short distances (P < 0.05) and to the right at long distances (P < 0.01), but the distribution of nearest‐neighbour distances was not significantly altered. It is concluded that motor unit fibres are non‐randomly arranged in the fast‐twitch motor units studied and that a non‐random rearrangement of motor unit fibres takes place in both fast‐ and slow‐twitch units during the ageing process. This age‐related rearrangement is secondary to a denervation‐reinnervation process and it appears as if different types of reinnervation predominate in fast‐ and slow‐twitch units.
Acetyl group accumulation and pyruvate dehydrogenase activity in human muscle during incremental exercise
Authors: CONSTANTIN‐TEODOSIU D. , CARLIN J. I. , CEDERBLAD G. , HARRISt R. C. , HULTMAN E.
Published: December 2008

The changes in the muscle contents of CoASH and carnitine and their acetylated forms, lactate and the active form of pyruvate dehydrogenase complex were studied during incremental dynamic exercise. Eight subjects exercised for 3–4 minutes on a bicycle ergometer at work loads corresponding to 30, 60 and 90% of their V02max Muscle samples were obtained by percutaneous needle biopsy technique at rest, at the end of each work period and after 10 minutes of recovery. During the incremental exercise test there was a continuous increase in muscle lactate, from a basal value of 4.5 mmol kg‐1 dry weight to 83 mmol kg‐1 at the end of the final period. The active form of pyruvate dehydrogenase complex increased from 0.37 mmol acetyl‐CoA formed per minute per kilogram wet weight at rest to 0.80 at 30% V02max1.28 and 1.25 at 60 and 90% V02max respectively. Both acetyl‐CoA and acetylcarnitine increased at the two highest work loads. The increase of acetyl‐CoA was from 12.5 μmol kg‐1 dry weight at rest to 27.3 after the highest work load and for acetylcarnitine from 6.0 mmol kg‐1 dry weight to 15.2. The CoASH and free carnitine contents fell correspondingly. There was a close relationship between acetyl‐CoA and acetylcarnitine accumulation in muscle during exercise, with a binding of ˜ 500 mol acetyl groups to carnitine for each mole of acetyl‐CoA accumulated. The results imply that the carnitine store in muscle functions as a buffer for excess formation of acetyl groups from pyruvate catalyzed by the pyruvate dehydrogenase complex.
Mechanics and Ca2+‐sensitivity of human detrusor muscle bundles studiedin vitro
Authors: MALMQVIST U. , ARNER A. , UVELIUS B.
Published: December 2008

Mechanical properties of isolated smooth muscle strips from human urinary bladder were investigatedin vitro. Bladder tissue was obtained from tumour‐free wall regions of bladders from male patients undergoing cystectomy for bladder carcinoma. In intact muscle strips, activated with high‐K+solution, half‐maximal force occurred at about 0.9 mm extracellular [Ca2+]. The length‐active force relation was determined and the muscle strips were fixed for light and electron microscopy at optimal length for active force (Io). The maximal active force per unit smooth muscle cross‐sectional area was 208±49 mN/mm2,n= 6. Chemically skinned preparations were obtained by treatment with triton X‐100. These preparations had a steep [Ca2+]‐force relation in the micromolar range which was influenced by calmodulin. The skinned preparations could be maximally activated by irreversible thiophosphorylation of the regulatory light chains. The force‐velocity relation was determined in the maximally activated skinned muscle at 22 °C at 0.5 1o. When the muscle was shortened by 10%, force was reduced by 35% whereas the maximal shortening velocity was little affected.
Effect of diffusion distance on measurement of rat skeletal muscle glucose transport in vitro
Authors: HENRIKSEN E. J. , HOLLOSZY J. O.
Published: December 2008

The relationships between muscle size, diffusion distance, and glucose uptake were studied using the Type II b epitrochlearis (13 ± 1 mg intact), Type I soleus (25± 1 mg), and mixed Type II a/II b extensor digitorum longus (25 ± 1 mg) from 60–70 g rats. Using intact muscles, the relative rates of 3‐O‐methyl‐glucose uptake in response to 2 mUml‐1 insulin were soleus = epitrochlearis > extensor digitorum longus, a finding inconsistent with the fibre‐type compositions and the relative GLUT‐4 protein levels (soleus > extensor digitorum longus > epitrochlearis). To test whether these results were influenced by substrate diffusion limitations in the tubular muscles, soleus and extensor digitorum longus were split longitudinally from tendon to tendon into strips of comparable size (13 ± 1 mg) to the epitrochlearis. Insulin‐stimulated rates of 3‐O‐methyl‐glucose uptake were significantly enhanced in the split soleus (+120%) and split extensor digitorum longus (+200%), but not in the epitrochlearis, with the relative rates being soleus > extensor digitorum longus > epitrochlearis. Diffusion distances of the split soleus and extensor digitorum longus, as reflected by [14C]mannitol space equilibration time, were markedly enhanced (by at least 50%) relative to the intact muscles, and were comparable to that of the epitrochlearis. These results indicate that when muscles of different size and/or shape are used for in vitro measurement of glucose transport, the muscle preparations used must have similar diffusion distances for physiologically meaningful comparisons to be made.
Differential bronchial and pulmonary vascular responses to vagal stimulation in the pig
Authors: MATRAN R. , ALVING K. , LUNDBERG J. M.
Published: December 2008

The pulmonary and bronchial vascular responses and changes in bronchial tone upon vagal stimulation (240 impulses at 2 Hz or 10 Hz) were studied in anaesthetized pigs paralyzed with pancuronium. The acetylcholine‐evoked vasodilatation in the tracheobronchial circulation had the same magnitude when using pancuronium or succinylcholine as skeletal muscle relaxants. Atropine‐sensitive bradycardia, hypotension and bronchoconstriction were observed upon vagal stimulation. A vasoconstrictor response in the pulmonary vascular bed and clear‐cut vasodilatation in the bronchial circulation supplied by the bronchial artery also occurred upon vagal stimulation. The vagallyevoked increase in pulmonary vascular resistance was markedly reduced after atropine while the bronchial vasodilatation was unchanged. This suggests that the vagallyinduced increase in bronchial blood flow was not secondary to changes in the pulmonary circulation. Furthermore, the pulmonary vasoconstrictor response caused by vagal stimulation under control conditions is probably explained by reflex sympathetic activation due to the fall in systemic blood pressure. These data indicate selective vagal non‐cholinergic influence of blood flow in the bronchial vascular bed compared to the pulmonary circulation.
Sympathetic nerve stimulation influences mucociliary activity in the rabbit maxillary sinus
Authors: CERVIN A. , LINDBERG S. , MERCKE U.
Published: December 2008

The effect of preganglionic sympathetic nerve stimulation on mucociliary activity in the rabbit maxillary sinus was investigated in vivo. Response to nerve stimulation was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity prior to stimulation.

Nerve stimulation (15 V, 5 ms) for 60 s at 2, 10 and 20 Hz stimulated mucociliary activity, the maximum increase being 21.1 ±1.3% at 20 Hz, an increase that pretreatment with the cholinergic antagonist atropine reduced to 14.5±2.4%, suggesting that part of the response involves cholinergic mechanisms. Nerve stimulation (10 Hz) of animals pretreated with the β‐adrenoceptor antagonist propranolol reversed the mucociliary response from an increase to a decrease (‐10.6± 1.6%), indicating the involvement of β‐receptors in the nerve‐evoked increase. Pretreatment with the α‐adrenoceptor antagonist phentolamine had no effect on response to nerve stimulation. Rabbits given a combined atropine, propranolol and phentolamine blockade manifested decreased mucociliary activity in response to nerve stimulation (‐ 10.6± 2.1 %). Guanethidine pretreatment blocked the effect of nerve stimulation on mucociliary activity, including the observed decrease after combined blockade, indicating the effect to be mediated via sympathetic nerve fibres.

The decrease in mucociliary activity in response to nerve stimulation after combined cholinergic‐, β‐, and α‐adrenoceptor blockade suggests the presence of a nonadrenergic, non‐cholinergic inhibitory mechanism. It is possible that this effect is mediated by release of neuropeptide Y, as intraarterial injections of neuropeptide Y reduce mucociliary activity in the rabbit maxillary sinus, and as neuropeptide Y is released in the upper airways upon sympathetic nerve stimulation.
Intravenous bilirubin infusion causes vacuolization of the cytoplasm of hepatocytes and canalicular cholestasis
Authors: VEEL T. , VILLANGER O. , HOLTHE M. R. , SKJØRTEN F. S. , RÉDER M. G.
Published: December 2008

To examine whether intravenous bilirubin infusion causes cholestasis and impairs liver metabolism, bile secretion and ethanol clearance were measured in 34 anaesthetized pigs before and after intravenous infusion of 0.5 μmol kg‐1 min‐1 bilirubin for 4.5 hours. Bilirubin infusion increased plasma bilirubin to 556±76 μmol l‐1 and hepatic tissue bilirubin to 3.5 ± 1.3 mmol kg tissue weight‐1. Bilirubin infusion depressed bilirubin secretion and net hepatic uptake of cholate and taurocholate, and caused a 86±6% reduction of cholate‐induced bile secretion. Bilirubin caused formation of large cytoplasmic vacuoles in hepatocytes and dilatation of bile canaliculi. Ethanol clearance and secretin‐dependent ductular bile secretion were unaffected by bilirubin. We conclude that intravenous infusion of unconjugated bilirubin causes accumulation of bilirubin in the liver, vacuolization of the hepatocyte cytoplasm and canalicular but not ductular cholestasis. The canalicular cholestasis is not due to impaired hepatic mitochondrial energy metabolism, but may be due to inhibition of a common pathway for lipid, bilirubin and bile salt secretion from hepatocytes.
Pain threshold changes by skin vibratory stimulation in healthy subjects
Authors: ZOPPI M. , VOEGELIN M. R. , SIGNORINI M. , ZAMPONI A.
Published: December 2008

The purpose of this research is to evaluate the changes of cutaneous pain threshold induced by vibratory stimuli applied to the skin. The pain threshold was tested by means of electrical stimuli using the method of limits. Both vibratory stimuli (conditioning stimuli) and electrical stimuli (test stimuli) were driven by a computer. The experiments were carried out on the dorsal surface of the second phalanx of the index finger in the dominant hand of 34 healthy subjects (18 males and 16 females). The conditioning stimuli were sinusoidal waves (250 microm peak to peak) at a rate of 30 and 300 Hz. During the experiment (6 min of vibration and 9 min after) the cutaneous temperature of the stimulated area was recorded. Both vibratory rates induced significant increases of the pain threshold but the 30 Hz vibrations were the more effective. After stimulation the pain threshold lowered to a steady value which was higher than before the start of vibrations. Such threshold changes showed no correlation throughout the experiment with changes in skin temperature. We therefore advance the hypothesis that the main factors which modulate the pain threshold are neuronal connections between tactile and pain pathways.
An isolated perfused rat kidney preparation designed for assessment of glomerular permeability characteristics
Authors: JOHNSSON E. , HARALDSSON B.
Published: December 2008

The aim of the present investigation was to modify the widely used isolated perfused rat kidney preparation to make it more suitable for studies of glomerular permeability to macromolecules. Both kidneys were perfusedin situusing separate pumps in two of each other independent systems with Tyrode‐solution containing human serum albumin (18.2 g 1‐1). Sodium nitroprusside was administered to induce dilatation and to maintain constant vascular resistance (PRU100) during the experiments. The addition of sodium nitroprusside decreased vascular resistance from 0.17 ± 0.05 to 0.09 ± 0.02 mmHg min‐l100 g‐1ml‐1and increased urine flow and glomerular filtration rate. The temperature of the perfusate was reduced from 37°C to 8°C to inhibit tubular reabsorption of protein and fluid, resulting in a urine to plasma concentration ratio of [51Cr]EDTA of 1.26 ± 0.07. Furosemide reduced the urine to plasma concentration ratio for [51Cr]EDTA further to 1.15 ± 0.02 and increased glomerular filtration rate. Moreover, by performing the studies at low temperatures (8°C) in the presence of sodium nitroprusside and furosemide it was possible to achieve low and stable albumin fractional clearance values close to those prevailingin vivo. Thus, the described technique, allowing simultaneous perfusions of both kidneys with different solutions, pressures and flows, seem to be well suited for studies of macromolecular transport across glomerular capillaries.
Growth inhibition of human hepatoma cells (HepG2) by polyunsaturated fatty acids. Protection by albumin and vitamin E
Authors: HØSTMARK A. T. , LYSTAD E.
Published: December 2008

Albumin carries fatty acids and has also been suggested to act as an antioxidant. In the present work, polyunsaturated fatty acids (linoleic, arachidonic, eicosapentaenoic and docosahexaenoic acids) ‐ but not palmitic and oleic acid ‐ inhibited growth of human hepatoma cells in low albumin concentration (0.5%). Growth inhibition by polyunsaturated fatty acids was prevented by albumin in a dose‐related manner in the range 0.7–5.0%. Albumin also protected against growth inhibition following catabolism (by lipoprotein lipase) of very low density lipoproteins. Vitamin E strongly counteracted the inhibitory effect of polyunsaturated fatty acids. Vitamin E and albumin appeared to have additive effects in protecting against growth inhibition by polyunsaturated fatty acids. Indomethacin did not greatly modify the polyunsaturated fatty acids effect. Growth inhibition by polyunsaturated fatty acids, as well as the level of thiobarbituric acid reacting substances (a measure of lipid peroxidation) in growth media, increased with increasing number of fatty acids double bonds. Vitamin E and albumin prevented both thiobarbituric acid reacting substances formation and growth inhibition by polyunsaturated fatty acids. The results suggest that the concentrations of albumin and vitamin E in the incubation medium are essential when studying polyunsaturated fatty acids effects on cell growth.
Neutrophil influx into guinea‐pig airway lumen during cholinergic and non‐cholinergic bronchoconstriction
Authors: LÖTVALL J. , RABE K. , TOKUYAMA K. , LÖFDAHL C.‐G , BARNES P. J. , CHUNG K. F.
Published: December 2008

Sensory nerve activation will produce adherence of neutrophils to tracheobronchial microvessels. The aim of the present study was to investigate whether this adherence would lead to an influx of neutrophils into the airway lumen. To do this, we studied the effects of 20 minutes of vagal stimulation (1 Hz, 5 ms, 5 V) in anaesthetized and tracheostomized guinea‐pigs on both lung resistance, and the cell picture in bronchoalveolar lavage. Any changes were compared to those of intravenous methacholine influsion, producing similar changes in lung resistance. Since high pressure ventilation could produce lung damage, we also studied the effects of ventilation through an extracorporeal resistor, producing a similar change in transpulmonary pressure (45 ± 2 cmH2O) as vagal stimulation (42 ± 4 cmH2O). The total number of cells recovered in the lavage was not increased by vagal stimulation, methacholine influsion or the extracorporeal resistor. However, both vagal stimulation and methacholine influsion significantly increased the relative number of neutrophils in the lavage compared to sham stimulated animals (21 ± 11%, 13 ± 4% and 4±1% respectively), but the extracorporeal resistor had no effect (4 ± 2%). Our data suggests that prolonged bronchoconstrictionper semay induce an influx of neutrophils into the airway lumen of the guinea‐pig.
Is the motor unit uniform?
Authors: LARSSON L.
Published: December 2008

Single motor units in the fast‐twitch tibialis anterior muscle were functionally isolated by stimulation of microdissected ventral root filaments. The muscle fibres of 35 fast‐twitch single motor units (motor unit fibres), 18 units from 3 to 6–month‐old and 17 units from 20 to 24–month‐old male rats, were identified by glycogen depletion. Measurements were made of staining intensities for intermyofibrillar succinate dehydrogenase, using microphotometric techniques, and of cross‐sectional areas of the motor unit fibres. The average coefficients of variation for succinate dehydrogenase activity of the muscle fibres within each unit, between the different units and for repeated measurements of the same fibre in 10 consecutive cross‐sections stained on different glasses were 26, 72 and 14%, respectively. The average coefficients of variation for cross‐sectional fibre areas within each unit, between the different units and for repeated measurements were 21, 53 and 774, respectively. Further, the succinate dehydrogenase activity of muscle fibres within the motor unit differed significantly depending on the position of the fibre along the superficial‐deep axis of the muscle. The average succinate dehydrogenase activity in the 35 motor units was 21% lower (P < 0.001) in the superficial as compared with the deep motor unit fibres. In order to eliminate the influence of altered motoneurone properties related to a transformation process or an age‐related motoneurone dysfunction as indicated by a non‐homogeneous myosin heavy chain composition in motor unit fibres, cross‐sectional fibre areas and enzyme activities were also compared in motor units with a uniform myosin heavy chain composition in young animals. However, the same regional differences were observed in these 16 units as when all the 35 units were pooled together. Thus, in conformity with previous reports, the variability in enzyme activities within single motor unit fibres is small but too Iarge for a motor unit homogeneity to be accepted. In addition, the present results demonstrate that the systematic differences in succinate dehydrogenase activities of motor unit fibres along the superficial‐deep axis of the tibialis anterior muscle represent a biological rather than a methodological phenomenon.
Chloride‐selective channels of large conductance in bovine aortic endothelial cells
Authors: OLESEN S.‐P. , BUNDGAARD M.
Published: December 2008

Single‐channel currents of an anionic channel in the plasma membrane of cultured bovine aortic endothelial cells have been recorded with the patch‐clamp technique. The channel is selective for chloride over cations, and has an average single channel conductance of 382 picosiemens in symmetric 140 millimoles of chloride. In addition to the main conductance state it shows well‐defined subconductance states of about 50, 100, 150 and 200 picosiemens. The channel is very active at membrane potentials close to 0 mV, but steps to either positive or negative membrane potentials above ± 20 millivolt lead to a rapid inactivation of the channel. Changes in the concentrations of free calcium or andenosine tri‐phosphate on the cytosolic surface do not influence channel activity. The chloride channel rarely opens at resting membrane potential, but it may help repolarize endothelial cells following depolarizing stimuli.
Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium‐derived nitric oxide
Authors: EKELUND U. , BJÖRNBERG J. , GRANDE P.‐O. , ALBERT U. , MELLANDER S.
Published: December 2008

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium‐derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium‐derived nitric oxide blockade by the specific inhibitors NG‐monomethyl‐l‐arginine or NG‐nitro‐l‐arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium‐derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium‐derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large‐bore arterial resistance vessels > 25 μm, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium‐derived nitric oxide blockade suggested that endothelium‐derived nitric oxide released in vivo acts as a ‘metabolic’ factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium‐derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium‐derived nitric oxide. Nor did, endothelium‐derived nitric oxide seem to play a role as a ‘metabolic’ mediator of the functional hyperaemia response to muscle exercise, since the magnitude of this response was the same in the absence and presence of endothelium‐derived nitric oxide blockade.
Galanin receptors and their second messengers in the lumbar dorsal spinal cord
Authors: BEDECS K. , LANGEL Ü. , BARTFAI T. , WIESENFELD‐HALLIN Z.
Published: December 2008

The ligand binding properties of galanin receptors were examined in crude synaptosomal fraction preparations of lumbar dorsal spinal cord, using chloramin‐T mono‐iodinated porcine Tyr26 galanin as ligand.

The equilibrium binding of [125I]galanin showed the presence of a single population of high‐affinity binding sites with KD= 0.6±0.2 nM in a concentration of 55±15 fmol mg‐1 protein (Bmax.

The N‐terminal fragments galanin (1–16) and galanin (1–12) fully displaced specific [1251]galanin binding from membranes with IC50 values 6 nM and 4 μM, respectively. The C‐terminal fragment galanin (17–29) did not displace [125I]galanin when applied in the concentration range 10‐11–10‐4 M. GTP inhibited the specific binding of [125I] galanin in a concentration dependent manner, with 54% inhibition at 1 mM, suggesting that the galanin receptor found in lumbar dorsal spinal cord is G‐protein coupled.

Second messenger systems, through which the galanin receptor in lumbar dorsal spinal cord may exert its effect, were also studied. A galanin (10,μm) produced inhibition (58%) of the depolarization induced cGMP increase was found, whereas galanin (10 μM) did not inhibit the noradrenalin (100 μM) activated CAMP synthesis or phosphoinositide turnover in tissue slices of the spinal cord.

Bilateral transection of the sciatic nerve at midthigh level 14 days prior to the binding experiment was performed, a treatment which is known to cause a dramatic increase of galanin‐like immunoreactivity in the superficial layers of the dorsal spinal cord, dorsal root ganglion and in galanin mRNA levels, but no significant effect on Bmax or KD of the galanin receptor was found.
Myosin heavy chain isoform transition in ageing fast and slow muscles of the rat
Authors: SUGIURA T. , MATOBA H. , MIYATA H. , KAWAI Y. , MURAKAMI N.
Published: December 2008

Sugiura, T., Matoba, H., Miyata, H., Kawai, Y. & Murakami, N. 1992. Myosin heavy chain isoform transition in ageing fast and slow muscles of the rat. Acta Physiol Scand144, 419423. Received 26 August 1991, accepted 3 December 1991. ISSN 0001–6772. Laboratory of Biomechanics and Physiology, Faculty of Liberal Arts, Yamaguchi University, Yamaguchi, Faculty of Integrated Arts and Sciences, Tokushima University, Tokushima, and Department of Physiology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.

Using gradient sodium dodecyl sulphate‐polyacrylamide gel electrophoresis, myosin heavy chain (MHC) isoforms were studied in the extensor digitorum longus (EDI,) and the soleus muscles of male Wistar rats at different ages (5, 10, 20 weeks, 1 and 2 years). In the EDL muscle, four types of MHC isoforms were observed in all age groups. There was an increase in the percentage of HCIId and a concomitant decrease in the percentage of HCIIb with increasing age. No significant difference was observed in the percentages of HCI and HCIIa isoforms in all the age groups. In contrast, the soleus muscle contained two MHC isoforms, HCI and HCIIa. There was an increase in the percentage of HCI and a concomitant decrease in the percentage of HCIIa with increasing age. These results suggest that age‐related changes in the MHC isoforms in both the fast‐twitch EDI, and the slow‐twitch soleus muscles are one factor underlying the age‐related decrease in the speed of muscle contraction.
The importance of frequency and amount of electrical stimulation for contractile properties of denervated rat muscles
Authors: GUNDERSEN K. , EKEN T.
Published: December 2008

Soleus (SOL) and extensor digitorum longus (EDL) muscles were denervated and directly stimulated for 23–69 days through implanted electrodes employing three different patterns. The stimulation was delivered in impulse trains where the pulse frequency differed (20, 75, and 150 Hz), while the train duration (0.3 s) and train repetition rate (1 min‐1) were identical. Consequently, the number of pulses varied such that higher frequency was combined with a higher amount of stimulation. In both SOL and EDL the high‐frequency pattern resulted in shorter twitch time‐to‐peak, greater post‐tetanic potentiation, and greater tetanic force than the low frequency. Isotonic shortening velocity was increased to the same extent by all the patterns in SOL whereas in EDL fast intrinsic shortening velocity was maintained by the low‐frequency pattern while it was decreased by the high‐frequency pattern. We attribute this unexpected effect on the EDL to the larger number of pulses in the high‐frequency pattern. By combining the present findings with previous data on directly stimulated rat muscles we conclude: in SOL the twitch duration is influenced by both the frequency and the amount of impulse activity, higher frequencies and smaller amounts leading to faster twitches. The EDL twitch duration is similarly dependent on the amount of activity, but the role of frequency is more unclear. In both SOL and EDL the isotonic shortening velocity is reduced by increasing amounts of activity and there is no evidence that impulse frequency plays a role. In EDL force output is strongly influenced by the impulse frequency, low frequencies resulting in low force outputs irrespective of the amount of activity.