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Biomedical subjects

F Lind

Publications and source records attributed to F Lind.

15 recordsLinked to original sources

Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study.

Sixteen patients, 12 with episodic and four with chronic cluster headache (CH) according to the International Headache Society criteria (1), participated in the study. They were randomly selected to start with one out of two different hyperbaric treatments in a double-blind, placebo-controlled, cross-over study design. Both gases were administered by mask inside a multiplace hyperbaric chamber for 70 min at 250 kPa (2.5 ATA) in two sessions 24 h apart. Active treatment was 100% oxygen (HBO treatment), while placebo treatment was 10% oxygen in nitrogen (hyperbaric normoxic placebo = sham treatment) corresponding to breathing air at sea level. All patients were decompressed on air. The patients documented the number of headache attacks and their degree of severity according to a modified VAS scale (level 0-4, where level 0 = no headache and level 4 = very severe headache). A headache index (HI = sum of (number of attacks times degree of severity)) was calculated for the run-in week prior to and the week after each separate treatment. A treatment was regarded as effective if it reduced the HI by>50%. Blood samples were taken from the external jugular vein before and during hyperbaric treatment (after 30 and 70 min), 1 day and 1 week after each treatment for analyses of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) and in a few patients also endotheline and nitrate. No difference between HBO and sham treatment on the HI or the prophylactic effect was observed in our study. However, 83% of the episodic CH patients and 25% of the chronic ones responded to either of the two treatments with at least 50% reduction of HI or remission for shorter or longer periods. This response rate exceeds an expected high placebo response due to the study procedure. Two episodic CH patients still experienced remission on follow-up 1 year after sham treatment. Five patients reported mild or moderate CH attacks during the sham treatment, and none during the HBO treatment. Changes in neuropeptides, endotheline and nitrate levels did not differ systematically when comparing the two different hyperbaric treatments or with respect to responders and non-responders. We conclude that two HBO sessions were not more effective than two sham treatments in reducing the HI and interrupting the CH period when given in a well-established cluster period or in chronic CH. The hyperbaric condition itself seems effective in reducing the HI, at least in patients with episodic CH, although a powerful placebo response can not be ruled out.

Adult↗

Effects of acute hypobaric hypoxia on regional cerebral blood flow distribution: a single photon emission computed tomography study in humans.

Single Photon Emission Computed Tomography (SPECT) and radiopharmaceutical stabilizing agents allowed us to investigate regional cerebral blood flow (CBF) distribution in six resting healthy subjects during acute laboratory hypobaric hypoxic conditions. In the hypobaric experiment stabilized 99mTc-D, L-hexamethyl-propylene amine oxime was injected 40 min after reaching hypoxic conditions corresponding to an altitude of 5500 m above sea level. Arterial blood sample was taken after five additional minutes. Mean arterial oxygen pressure and haemoglobin saturation were 28 mmHg and 56%, respectively. The control experiment was performed similarly, apart from barometric pressure and blood gas analysis. We analysed CBF distribution in 12 regions of functional interest bilaterally in frontal, parietal, temporal, occipital cortex, in the hippocampus, in the basal ganglia and other central structures of brain. No overall effect of hypoxia on normalized regional CBF distribution in the considered regions was found. Motor cortex (Brodmann 4) and basal ganglia were the only regions in which hypobaric hypoxia significantly increased relative distribution of the radiopharmaceutical [F(1,5)=18.30; P < 0.008 and F(1,5)=10.85; P < 0.022, respectively]. Despite severe hypoxia, we did not observe any major regional CBF redistribution. We found a small relative increase in blood flow to the motor cortex and the basal ganglia, at rest after 40 min of hypobaric hypoxia, suggesting a preferential compensatory mechanism of these functional regions of brain.

Acute Disease↗

Hyperbaric bradycardia and hypoventilation in exercising men: effects of ambient pressure and breathing gas.

We sought to determine whether hydrostatic pressure contributed to bradycardia and hypoventilation in hyperbaria. Eight men were studied during exercise at 50, 150, and 250 W while breathing 1) air at 1 bar, 2) helium-oxygen (He-O(2)) at 5.5 bar, 3) sulfur hexafluoride-oxygen (SF(6)-O(2)) at 1.3 bar, and 4) nitrogen-oxygen (N(2)-O(2)) at 5.5 bar. Gas densities were pairwise identical in 1) and 2), and 3) and 4), respectively. Increased hydrostatic pressure to 5.5 bar resulted in a modest but significant relative bradycardia on the order of 6 beats/min, in both the absence [1) vs. 2), P = 0. 0015] and presence [3) vs. 4), P = 0.029] of gases that are both denser than normal and mildly narcotic. In contrast, ventilatory responses appeared not to be influenced by hydrostatic pressure. Also, the combined exposure to increased gas density and mild-to-moderate inert gas narcosis at a given hydrostatic pressure [1) vs. 3), 2) vs. 4)] caused bradycardia (P = 0.032 and 0.061, respectively) of similar magnitude as 5.5-bar hydrostatic pressure. At the same time there was relative hypoventilation at the two higher workloads. We conclude that heart rate control, but not ventilatory control, is sensitive to relatively small increases in hydrostatic pressure.

Adult↗

Ion secretion and isotonic transport in frog skin glands.

The aim of this study was to clarify the mechanism of isotonic fluid transport in frog skin glands. Stationary ion secretion by the glands was studied by measuring unidirectional fluxes of 24Na+, 42K+, and carrier-free 134Cs+ in paired frog skins bathed on both sides with Ringer's solution, and with 10(-5) M noradrenaline on the inside and 10(-4) M amiloride on the outside. At transepithelial thermodynamic equilibrium conditions, the 134Cs+ flux ratio, JoutCs/JinCs, varied in seven pairs of preparations from 6 to 36. Since carrier-free 134Cs+ entering the cells is irreversibly trapped in the cellular compartment (Ussing & Lind, 1996), the transepithelial net flux of 134Cs+ indicates that a paracellular flow of water is dragging 134Cs+ in the direction from the serosal- to outside solution. From the measured flux ratios it was calculated that the force driving the secretory flux of Cs+ varied from 30 to 61 mV among preparations. In the same experiments unidirectional Na+ fluxes were measured as well, and it was found that also Na+ was subjected to secretion. The ratio of unidirectional Na+ fluxes, however, was significantly smaller than would be predicted if the two ions were both flowing along the paracellular route dragged by the flow of water. This result indicates that Na+ and Cs+ do not take the same pathway through the glands. The flux ratio of unidirectional K+ fluxes indicated active secretion of K+. The time it takes for steady-state K+ fluxes to be established was significantly longer than that of the simultaneously measured Cs+ fluxes. These results allow the conclusion that - in addition to being transported between cells - K+ is submitted to active transport along a cellular pathway. Based on the recirculation theory, we propose a new model which accounts for stationary Na+, K+, Cl- and water secretion under thermodynamic equilibrium conditions. The new features of the model, as compared to the classical Silva-model for the shark-rectal gland, are: (i) the sodium pumps in the activated gland transport Na+ into the lateral intercellular space only. (ii) A barrier at the level of the basement membrane prevents the major fraction of Na+ entering the lateral space from returning to the serosal bath. Thus, Na+ is secreted into the outside bath. It has to be assumed then that the Na+ permeability of the basement membrane barrier (PBMNa) is smaller than the Na+ permeability of the junctional membrane (PJMNa), i.e., PJMNa/PBMNa > 1. The secretory paracellular flow of water further requires that the Na+ reflection coefficients (sigmaNa) of the two barriers are governed by the conditions, sigmaBMNa > 0, and sigmaBMNa > sigmaJMNa. (iii) Na+ channels are located in the apical membrane of the activated gland cells, so that a fraction of the Na+ outflux appearing downstream the lateral intercellular space is recirculated by the gland cells. Based on measured unidirectional fluxes, a set of equations is developed from which we estimate the ion fluxes flowing through major pathways during stationary secretion. It is shown that 80% of the sodium ions flowing downstream the lateral intercellular space is recycled by the gland cells. Our calculations also indicate that under the conditions prevailing in the present experiments 1.8 ATP molecule would be hydrolyzed for every Na+ secreted to the outside bath.

Amiloride↗

Trapping of 134CS+ in frog skin epithelium as a function of short circuit current.

In the sodium/potassium pump of the isolated frog skin epithelium, 134CS+ can to a certain degree replace potassium. If 134CS+ in almost a carrier-free amount is added to the solution bathing the inside of the frog skin in an Ussing chamber, there will be an uptake of 134 CS+ into the epithelium cells which is proportional to the short circuit current. Transepithelial flux of 134CS+ in leaky epithelia, for instance small intestine and frog skin glands, indicates a paracellular pathway. The consequences of these findings for the recycling-theory are discussed.

Animals↗

Relative narcotic potency and mode of action of sulfur hexafluoride and nitrogen in humans.

Impairments of psychomotor, perceptual, and cognitive abilities were determined in nine male subjects exposed to inhaled SF6 partial pressures of 0, 52, 104, and 156 kPa and to inhaled N2 partial pressures of 103, 575, 825, and 1,075 kPa. Also data from a previous study with inhaled N2O partial pressures of 0, 13, 26, and 39 kPa were included. With the highest gas concentrations, performances were reduced by 41-57%. Effective doses for a 20% performance impairment were 830, 97, and 21.5 kPa for N2, SF6, and N2O, respectively, yielding relative narcotic potencies of 1.0:8.5:39. The order of narcotic potencies is the same as for the lipid solubility of the three gases. In contrast, the order of increasing tendency for hydrate formation (decreasing hydrate dissociation pressure) for the three gases is N2, N2O, and SF6. Thus, mild to moderate inert gas narcosis in humans shows the same positive relationship to lipid solubility as was shown in previous animal models that utilized much deeper levels of anesthesia.

Adult↗

Effects of sulphur hexafluoride on psychomotor performance.

The narcotic influence of sulphur hexafluoride on mental and psychomotor performance has been studied in 9 subjects at normal atmospheric pressure. Control experiments were performed with air and with nitrous oxide. Psychomotor, perceptual and cognitive abilities were assessed using a computerized test battery. Subjects were exposed to air and six different normoxic gas mixtures: 13, 26, and 39% N2O, and 39, 59, and 79% SF6. Significant performance impairments were found with 13% N2O and gradual further impairment with 26, and 39% N2O. During exposure to 39, 59, and 79% SF6 over-all performance was impaired by 5, 10, and 18%, respectively. Impairment was significant with 59 and 79% SF6. The results indicate that the relative narcotic potency of SF6: N2O is about 1:4 in humans. It is concluded that a normoxic SF6-O2 mixture can be inhaled for lung function studies without any harmful effects and that the short-lasting narcotic effect, although detectable with a test battery, would not impair the ability of the subject to perform simple breathing procedures.

Adult↗

Significance of airway resistance for the pattern of breathing and lung volumes in exercising humans.

The effects of increased airway resistance on lung volumes and pattern of breathing were studied in eight subjects performing leg exercise on a cycle ergometer. Airway resistance was changed 1) by increasing the density (D) of the respired gas by a factor of 4.2 and changing the inspired gas from O2 at 1.3 bar to air at 6 bar and 2) by increasing airway flow rates by exposing the subjects to incremental work loads of 0-200 W. Increased gas D caused a slower and deeper respiration at rest and during exercise and, at work loads greater than 120 W, depressed the responses of ventilation and mean inspiratory flow. Raised airway resistance induced by increases in D and/or airway flow rates altered respiratory timing by increasing the ratio of inspiratory time (TI) to total breath duration. Furthermore, analyses of the relationships between tidal volume and TI and between end-inspiratory volume and TI revealed elevation of Hering-Breuer inspiratory volume thresholds. We propose that this elevation, and hence exercise-induced increases of tidal volume, can largely be explained by previous observations that the threshold of the inspiratory off-switch mechanisms depends on central inspiratory activity (cf. C. von Euler, J. Appl. Physiol. 55: 1647-1659, 1983), which in turn increases with airway resistance (Acta Physiol. Scand. 120: 557-565, 1984).

Airway Resistance↗

Human skeletal muscle function and metabolism during intense exercise at high O2 and N2 pressures.

The maximal contractile force (peak torque) of the quadriceps femoris was studied during 60 repeated unilateral dynamic knee extensions in nine subjects under three different conditions, viz., during air breathing at normal (1 ATA) and raised (6 ATA) ambient pressures and during O2 breathing at 1.3 ATA. In six subjects the electromyographic (EMG) activity of the working muscle was recorded. Muscle biopsies were obtained from the vastus lateralis before, immediately after, and 1 min after exercise. Tissue specimens were subsequently assayed for various muscle metabolites. Peak torque, as an average of the 60 knee extensions, was higher (P less than 0.05) at 1.3 ATA than at 6 or 1 ATA. Peak torque of the exercising muscle declined more rapidly at 1 ATA than at 1.3 ATA, differing in the final 24 contractions by 14%. At 6 ATA peak torque of the initial 12 contractions was 6% lower (P less than 0.05) than at 1 ATA but equaled 1-ATA values in the latter third of the exercise bout. Although the EMG activity at 1 ATA increased relative to that at 6 ATA as exercise proceeded, the rate of force decline was greater at 1 ATA. Despite greater total work produced at 1.3 ATA than at 1 ATA, the metabolic response to exercise was not substantially altered at increased O2 pressure. However, the restitution rate of energy-rich phosphagens and the elimination of lactate during recovery were greater (P less than 0.05) at 1.3 ATA. These results suggest that hyperoxia may enhance the rate of energy release, whereas high N2 pressure and/or high hydrostatic pressure seem to interfere with neuromuscular activity.

Adenosine Triphosphate↗

Effects of blood volume distribution on ventilatory variables at rest and during exercise.

Ventilatory variables and heart rate (HR) were investigated in eight supine subjects during dynamic leg exercise at 0 and 100 W with and without the lower portion of the body exposed to a pressure of -50 mmHg (lower body negative pressure, LBNP). Resting values of inspired minute volume (V1), and respiratory drive in terms of mouth occlusion pressure (P0.1) were unchanged, whereas HR was higher during LBNP than in the control condition. Exercise values for HR in steady state were not affected by LBNP, whereas V1 was 15 and 11% lower and P0.1 was 20 and 11% lower in this condition at the 0 and 100 W workload levels, respectively. Time courses for V1 at the onset of 100 W exercise were similar with and without exposure to LBNP, indicating that the sudden increase in venous return occurring upon onset of pedalling during LBNP affords no significant stimulus in the initial development of exercise hyperpnoea. That exercise ventilation and P0.1 in steady state were reduced by LBNP suggests diminished humoral and/or locally induced chemical drive due to improved blood flow in exercising muscles resulting in reduced production of muscle metabolites or facilitation of their removal.

Adult↗

Breathing pattern and lung volumes during exercise.

The interrelationships of ventilation (V), tidal volume (VT), inspiratory (T1), expiratory (TE) and total breath (Ttot) durations, mean inspiratory (VT/TI) and expiratory (VT/TE) flows, and lung volumes were studied in normal subjects at rest and during exercise on a cycle ergometer. The ergometric load was increased by 10 W every minute, from zero W to 200 W. The TI/Ttot ratio increased with V in the range 15 to 60 1 X min-1, indicating that with increasing V the rate of increase of VT/TI decreased whereas that of VT/TE increased. Possible mechanisms responsible for the difference in behaviour of VT/TI and VT/TE are discussed. The VT-TI and VT-TE relationships both displayed three ranges with breakpoints at tidal volumes of about 1.4 and 2.4 1. The relations of TI and TE to end-inspiratory volume were approximately linear over the entire VT range studied, whereas the relations of TI and TE to end-expiratory volume showed three ranges with different characteristics. We conclude that the termination of inspiration during cycle exercise is dependent on volume-related afferent feedback from the lungs and/or chest walls, not only in the high but also in the low volume range.

Adult↗

Role of airway resistance in the control of ventilation during exercise.

To analyze the interdependence of respiratory drive, ventilation and airway resistance during exercise, mouth occlusion pressure (P0.1), minute ventilation (V) and mean inspiratory flow (VT/TI) were studied in eight normal subjects performing cycle-ergometer exercise at loads ranging from 0 W to 200 W under two different ambient conditions: 1) during oxygen breathing at 1.3 ATA, and 2) during air breathing at 6 ATA (PO2 = 1.3 ATA). Comparison of measurements at 6 ATA with those at 1.3 ATA indicated that a 4.2-fold increase in respired gas density (D) had little or no influence on the V and VT/TI responses whereas P0.1 at any given VT/TI was increased by a factor of 1.9. In both conditions, P0.1 increased at a faster rate than VT/TI as the work load increased. At loads higher than 40 W, the relationship between P0.1, D and VT/TI was found to approximate the equation P0.1 = K X D0.5(VT/TI)1.4, where K is a constant that varies among subjects. The results indicate that the ratio P0.1/(VT/TI), an estimate of respiratory impedance, increased with both D and VT/TI. Evidence is presented that the respiratory drive was reflexly enhanced in response to loading as airway resistance increased with D and/or VT/TI. We conclude that neural mechanisms compensating for internal flow-resistive loading play an important role in the control of ventilation during exercise, both at normal and at raised air pressures.

Adult↗

Breathing pattern and occlusion pressure during moderate and heavy exercise.

We studied changes in breathing pattern and mouth occlusion pressure (P0.1) in 11 healthy subjects performing graded steady-state exercise on a cycle ergometer up to the maximal load sustainable for 4 min. With increasing work intensity both the tidal volume (VT) and end-inspiratory volume relations to inspiratory (TI) and expiratory (TE) durations were linear in the moderate work load range; in the high load range VT and end-inspiratory volume tended to plateau with further decreases in TI and TE. The ratio of TI to total breath duration (TI/Ttot) increased with work intensity. Intraindividual coefficients of variation for VT, breathing frequency (f), mean inspiratory flow (VT/TI), and other respiratory variables decreased with increasing work intensity, indicating that breath-to-breath variations in breathing pattern became smaller as the level of ventilation increased. P0.1 rose with VT/TI as a power function with an exponent averaging 1.5 (range 1.3-1.9), indicating that the ratio P0.1/(VT/TI), an index of respiratory system impedance, increased with VT/TI and work intensity. We conclude that in moderate and heavy exercise the work of inspiration at a given ventilation is reduced because of the increase in TI/Ttot, the impedance of the respiratory system increases with work intensity because of both an increase in f and a flow-dependent rise in airway resistance, and the neuromuscular inspiratory activity is reflexly augmented because of internal flow-resistive loading.

Adult↗

Ventilatory and occlusion-pressure responses to incremental-load exercise.

Mouth occlusion pressure (P0.1), minute ventilation (V), and mean inspiratory and expiratory flows were studied in eight normal subjects at rest and during exercise on a cycle ergometer, the load of which was increased in steps of 10 W every minute. All four variables rose curvilinearly as the load was increased from 0 to 200 W. The ratio of P0.1 to mean inspiratory flow, like the ratio P0.1/V, increased with work load in the range 40-200 W, indicating that P0.1 increased considerably faster than mean inspiratory flow and V at rates higher than about 0.7 L X sec-1 and 15 L X min-1, respectively. Evidence is presented that the progressive divergence of the P0.1 and ventilatory responses was a result of raised respiratory impedance consequent to increasing respiratory frequency and resistance, and that, concurrently, the respiratory drive as assessed by P0.1 was enhanced because of an active load-compensating response. In this way, the respiratory drive increased with work load in a self-adjusting fashion, compensating for the impedance-dependent alterations in ventilatory responses. We also conclude that in moderate and heavy exercise P0.1 is a more representative index of the respiratory drive than are V and mean inspiratory flow.

Adult↗

Dose-dependent hyperbaric oxygen stimulation of human fibroblast proliferation.

Diabetic wounds are characterized by a prolonged wound healing process with insufficient formation of granulation tissue. Systemic hyperbaric oxygen therapy has been observed to improve the healing of these wounds. However, the mechanism(s) responsible for these findings are not yet fully elucidated. In the present study we have studied the in vitro effects of hyperbaric oxygen on proliferation of human fibroblasts from normal skin and from chronic foot ulcers in non-insulin-dependent diabetics. A 1-hour exposure to hyperbaric oxygen at oxygen pressures between 106 and 300 kPa (795 to 2250 mm Hg) increased the proliferation in both diabetic and normal fibroblasts. The stimulatory effect was dose-dependent, with a peak increase in cell proliferation at 250 kPa and 200 kPa for normal and diabetic cells, respectively. The effects were not due to hydrostatic pressure per se. These results suggest that hyperbaric oxygen could stimulate fibroblast activity in the diabetic wound, a finding that could explain the enhanced formation of granulation tissue seen clinically in wounds treated with hyperbaric oxygen. We also speculate that mechanisms other than just increased oxygen availability may be responsible for our findings.

Journal Article↗