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Biomedical subjects

J Kohl

Publications and source records attributed to J Kohl.

At least 37 records · Page 2Linked to original sources
PubMed1994

Mechanical respiratory system input impedance during high-frequency oscillatory ventilation in rabbits.

OBJECTIVES: To study the mechanical properties of the rabbit respiratory system during high-frequency oscillatory ventilation by means of mechanical respiratory impedance measurement and to characterize the changes in oscillation mechanics of the respiratory system occurring after bilateral vagotomy. DESIGN: Acute experimental trial. SETTING: Physiology laboratory. SUBJECTS: Ten adult rabbits (mean body weight 3.1 kg). MEASUREMENTS AND MAIN RESULTS: Anesthetized rabbits were exposed to short runs of high-frequency oscillatory ventilation, with stroke volumes of 5.0, 6.6, and 10.0 mL, applied at oscillation frequencies of 10, 15, 20, and 25 Hz before and after vagotomy. Mechanical respiratory input impedance was determined from the pressure and flow signals simultaneously measured at the airway opening and analyzed in terms of its real and imaginary parts. (The real part of respiratory impedance characterizes the resistive property of the lungs and chest wall; the imaginary part of respiratory impedance characterizes the elastic and inertial properties of the lungs and chest wall.) At all stroke volumes and oscillation frequencies studied, vagotomy resulted in a decrease in the real part of respiratory impedance. After vagotomy, the real part of respiratory impedance was stroke volume-independent, and exhibited negative frequency dependency. Vagotomy also led to a decrease in the imaginary part of respiratory impedance, mainly at lower oscillation frequencies, and thus, to a higher resonant frequency of the respiratory system. CONCLUSIONS: Mechanical respiratory impedance measurement proved to be a useful method to study the mechanical properties of the respiratory system during high-frequency oscillatory ventilation. The results suggest that vagally mediated reflex changes in respiratory system mechanics are associated with high-frequency oscillatory ventilation, depending on the ventilatory variables that are used.

Airway Resistance↗
PubMed1994

Delayed treatment with platelet activating factor receptor antagonist web 2086 attenuates pulmonary dysfunction in porcine endotoxin shock.

The triazolodiazepine WEB 2086, a specific platelet activating factor (PAF) receptor antagonist, has previously been shown to prevent pulmonary hypertension, hypoxia, and bronchoconstriction when given before bacterial lipopolysaccharide (LPS). The aim of the present study was to examine whether WEB 2086 reduced these changes even when given after the onset of LPS-induced shock. In a randomized trial LPS was given intravenously (i.v.) in a dose of 1 microgram/kg/h for 8 hours to anesthetized, ventilated pigs. Ten animals received LPS and WEB 2086, 10 mg/kg/h i.v. for 6.5 hours, beginning 1.5 hours after LPS. Ten control animals received LPS and saline. During treatment with WEB 2086, pulmonary hypertension was significantly attenuated compared with the findings in the control group. Gas exchange, airway pressure, extravascular lung water levels, intrapulmonary shunt, and cathepsin B levels in plasma showed a trend toward improvement but the group differences were not statistically significant. These data indicate that the PAF antagonist WEB 2086 can partially block pulmonary dysfunction and enzyme release from inflammatory cells when given during ongoing LPS shock in pigs, and that PAF may be an important mediator of the cardiopulmonary changes seen in septic shock.

Animals↗
PubMed1994

Dextran sulfate activates contact system and mediates arterial hypotension via B2 kinin receptors.

To define some of the mechanisms underlying dextran sulfate (DXS)-induced hypotension, we investigated the effects of either the plasma kallikrein inhibitor des-Pro2-[Arg15] aprotinin (BAY x 4620) or the specific bradykinin B2-receptor antagonist Hoe-140 on the hypotensive response to DXS. In the first study, anesthetized miniature pigs were given DXS alone, DXS plus BAY x 4620 in various doses, or saline. As expected, DXS alone produced a profound but transient systemic arterial hypotension with a concomitant reduction in kininogen. Circulating kinin levels, complement fragment des-Arg-C3a, and fibrin monomer were all increased. Treatment with BAY x 4620 produced a dose-dependent attenuation of these effects with complete blockade of the hypotension as well as the observed biochemical changes at the highest dose (360 mg). In a second study, two groups of pigs were given either DXS alone or DXS plus Hoe-140. DXS-induced hypotension was completely blocked by Hoe-140 pretreatment; however, kininogen was again depleted. We conclude, therefore, that DXS-induced hypotension is produced by activation of plasma kallikrein that results in the production of bradykinin and that liberation of bradykinin and its action on B2 receptors in the vasculature are both necessary and sufficient to produce the observed effects on circulatory pressure.

Animals↗
PubMed1993

The effects of acute altitude exposure in Swiss highlanders and lowlanders.

The functional characteristics at rest in responding to stepwise acute exposure to simulated altitude (6000 m) were compared in 10 acclimatized mountaineers (highlanders), residents of Zermatt (1616 m) working at an altitude up to about 4000 m, and in 11 nonacclimatized control subjects (lowlanders) living and working in Zurich (450 m). In comparison with the lowlanders, the highlanders showed at altitude significantly greater hyperventilation, lower heart rate and systolic blood pressure, smaller haemoconcentration, lower urodilatin secretion and natriuresis, and a preserved neuropsychological ability (attentiveness) and vasomotor tone (diastolic blood pressure); the critical altitude at which hypoxic short-term adaptation became insufficient was 6000 m. The lowlanders, however, manifested reduced tolerance of hypoxia, i.e. insufficient short-term adjustment with subjective and objective distress coinciding with the first signs of hypoxia of the central nervous system, already apparent at and above 4000 m. It was concluded that the functional differences between highlanders and lowlanders in responding to acute gradual hypoxia indicated factors contributing to altitude acclimatization.

Acclimatization↗
PubMed1993

Analysis of co-ordination between breathing and exercise rhythms in man.

1. The purpose of the present study was to analyse the incidence and type of coordination between breathing rhythm and leg movements during running and to assess the effect of co-ordination on the running efficiency, as well as to compare the results with those found during cycling. 2. The experiments were carried out on thirty-four untrained volunteers exercising at two work loads (60 and 80% of subject's physical work capacity 170) on a treadmill. In addition nineteen of the subjects exercised at the same two work loads on a bicycle ergometer. The subjects were running at both work loads in three different modes in randomized order: with normal arm movements, without arm movements and with breathing paced by an acoustic signal which was triggered by the leg movement. 3. Respiratory variables, oxygen uptake and leg movements were continuously recorded and evaluated on-line. The degree of co-ordination was expressed as a percentage of inspirations and/or expirations starting in the same phase of the step or pedalling cycle. 4. The average degree of co-ordination was higher during running (up to 40%) than during cycling (about 20%) during both work loads. The difference in the degree of co-ordination between running and cycling is probably not due to the lack of arm movements during cycling since the degree of co-ordination during running with and without arm movements was the same. 5. The degree of co-ordination during running increased slightly but not significantly with increasing work load and could be increased significantly by paced breathing. 6. The co-ordination between breathing and running rhythms occurred in three different patterns: (a) breathing was co-ordinated all the time with the same phase of step, (b) co-ordination switched suddenly from one phase of step to another and (c) co-ordination ensued alternatively once on the right and once on the left leg movement. During cycling the pattern described in (a) occurred almost exclusively. 7. During running with a high degree of co-ordination, oxygen uptake for a given work load was slightly but significantly lower than during running with weak co-ordination.

Adult↗
PubMed1993

Kinetic aspects of gingival and periodontal ligament fibroblast attachment to surface-conditioned dentin.

An in vitro model has been developed for measurement of initial attachment of 3H-labeled human gingival fibroblasts (HGF) and periodontal ligament cells (HPDL cells) to sieved dentin powder. Reproducible attachment was obtained and was closely related to the number of plated cells, the amount of dentin powder, the temperature, and the time (from 0 to 6 h) of incubation. HGF and HPDL cells had a high affinity for untreated dentin. Heat-denatured BSA coating of the dentin fully inhibited cell attachment, while a fibronectin coating had no significant effect. A surface conditioning of the dentin grains by 3% citric acid or by 2.5% minocycline-HCl increased the initial attachment of HPDL cells significantly (p < 0.05). Minocycline-HCl was more efficient than citric acid in that respect. In addition, HGF attachment to untreated dentin was highly significantly improved (p < 0.005) by a pre-incubation of the cells with 50 micrograms/mL of minocycline, and there was also indication (p = 0.067) of improvement by the presence of minocycline in the attachment medium, with a maximum of efficacy at 110 micrograms/mL. These results suggest that minocycline-HCl directly influenced the attachment properties of fibroblastic cells and that citric acid and minocycline-HCl could act by different mechanisms. HGF and HPDL cells originating from the same patient displayed no significant difference in their attachment to dentin in this model.

Cell Adhesion↗
PubMed1993

Subgingival minocycline hydrochloride ointment in moderate to severe chronic adult periodontitis: a randomized, double-blind, vehicle-controlled, multicenter study.

The safety and efficacy of subgingivally-applied 2% minocycline ointment was evaluated in a randomized, double-blind study of 103 adults with moderate to severe periodontitis. Two groups were compared; one received the test minocycline ointment and the other a vehicle control. Both groups had scaling and root planing at baseline, after which the test or control ointments were applied with an applicator into the periodontal pockets at baseline, and at 2, 4, and 6 weeks. Assessment of clinical response was made by measuring probing depth and probing attachment level and gingival bleeding. These measurements were made at baseline prior to scaling and root planing, and at weeks 4 and 12. Microbiological assessment of the subgingival flora was carried out with DNA probes at baseline, and at weeks 2, 4, 6, and 12 to identify and quantify Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus actinomycetemcomitans. Subgingival minocycline ointment resulted in statistically significantly greater reduction of P. gingivalis at weeks 2, 4, 6, and 12; P. intermedia at weeks 2, 4, 6, and 12; and A. actinomycetemcomitans at weeks 6 and 12. Probing depth reductions were seen for both groups at weeks 4 and 12; however, this reduction was statistically significantly greater in subjects treated with minocycline ointment. Reduction in gingival index and probing attachment gain were seen in both groups, however, the differences between the groups were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1992

Discharge of pulmonary rapidly adapting stretch receptors during HFO ventilation.

High-frequency oscillatory ventilation (HFOV) has been shown to stimulate slowly adapting pulmonary stretch receptors (PSR) and thereby to inhibit spontaneous breathing, i.e. HFOV prolongs expiration or even elicits normocapnic apnea. However, during HFOV respiratory effects possibly mediated by pulmonary rapidly adapting receptors (RAR) have also been observed, e.g., diaphragmatic activation or augmented breaths. Therefore, we analyzed HFOV-induced changes in RAR activity in anaesthetized rabbits by mean of single fibre preparations of vagal RAR afferents. HFOV was applied in several combinations of airway pressure (Paw) and oscillation frequency (fOsc). In the sample of 60 RAR fibres prepared in 20 rabbits we found a wide spectrum of discharge patterns during HFOV. The inspiratory discharge rate during HFOV was increased in 38, decreased in 10, and unchanged in 12 RAR. The expiratory discharge rate was increased in 34, decreased in 17, and unchanged in 9 RAR. The effects of gradually changing Paw or of fOsc during HFOV were different in different fibres. In 17 fibres both inspiratory and expiratory discharge rates rose with increasing Paw during HFOV, whereas 19 fibres were not affected by increasing Paw. In some fibres either the inspiratory (12) or the expiratory (9) activity was inhibited in proportion to increasing Paw. From these results we conclude, that (a) the changes of RAR activity during HFOV are heterogeneous and the reflex effects of RAR stimulation may be balanced by RAR with decreased activity; (b) this heterogeneity of RAR discharge patterns explains the dominancy in the control of breathing during HFOV of the homogeneously stimulated PSR; and (c) depending on HFOV ventilatory parameters used the overall RAR stimulation may be strong enough to overrule the inspiration-inhibiting effects of PSR.

Adaptation, Physiological↗
PubMed1991

Cloning and expression of an HIV-1 specific single-chain Fv region fused to Escherichia coli alkaline phosphatase.

We have constructed a single-chain Fv fragment representing the variable domain of the human monoclonal antibody 3D6, binding specifically to HIV-1 gp41. This gene was fused to the coding region of E. coli alkaline phosphatase (EcPhoA) and expressed in E. coli. The EcPhoA signal peptide was used to direct the recombinant fusion protein to the periplasmic space of the bacteria, from where it was purified by hydrophobic interaction chromatography and gel filtration followed by antigen-affinity chromatography using a synthetic HIV-1 peptide as ligand. The purified fusion protein was bifunctional, showing both phosphatase activity as well as antigen-binding specificity identical to that of the original antibody.

Alkaline Phosphatase↗
PubMed1991

Expression of a human monoclonal anti-HIV-1 antibody in CHO cells.

The cDNA coding for the light and heavy chains, respectively, of the human monoclonal antibody 3D6 (IgG1, kappa), which binds specifically to human immunodeficiency virus-1 (HIV-1) gp41, was inserted into three different mammalian expression vectors and transfected into Chinese hamster ovary (CHO) cells. Transcription was under the control of Rous sarcoma virus long terminal repeat (RSV LTR), human cytomegalovirus major immediate early (CMV IE) promoter, and mouse mammary tumor virus long terminal repeat (MMTV LTR), respectively. Antibody productivity was monitored in the supernatants of selected clones. The binding characteristics of the CHO-derived antibody to HIV-1 gp41 were found to be identical to that of the original antibody produced by hybridoma cells.

Animals↗
PubMed1991

Reflex apnea induced by high-frequency oscillatory ventilation in rabbits.

In rabbits with intact vagus nerves, HFOV applied for 10-20 s caused apnea (i.e., respiratory arrest for as long as HFOV lasted) accompanied by tonic discharges of the diaphragm. To identify the vagal mechanisms involved in this type of apnea, the vagus nerves of anaesthetized rabbits were gradually cooled from 37 degrees C to 0 degree C, i.e., the vagal fibres were, corresponding to their diameter, successively blocked. At each temperature, the effects of HFOV on spontaneous breathing were compared with those of static lung inflation and deflation: Between 20 degrees C and 14 degrees C, the lung inflation reflex (mediated by pulmonary slowly adapting stretch receptors = PSR) was weakened or abolished, whereas the lung deflation reflex (mediated by rapidly adapting stretch receptors = RAR) was reinforced; the HFOV-induced apnea occurred less frequently, however, the accompanying diaphragmatic activity was enhanced. Between 14 degrees C and 5 degrees C, both HFOV and large static inflation caused a slight increase of breathing frequency in the majority of animals. Some animals, however, responded even below 14 degrees C by apnea to both HFOV and inflation, and, under these conditions, both HFOV- and inflation-induced apnea were accompanied by a pronounced tonic diaphragmatic activity. At 5 degrees C, the effects of HFOV as well as of inflation (except in two animals) and deflation were abolished. From the results we conclude that in rabbits the apnea during HFOV is mainly mediated by stimulation of PSR, and the concomitant tonic activity of the diaphragm is mainly due to stimulation of RAR, as it is reinforced with gradual blockade of PSR fibres and abolished when only non-myelinated fibres are intact.

Animals↗
PubMed1991

A triazolodiazepine platelet activating factor receptor antagonist (WEB 2086) reduces pulmonary dysfunction during endotoxin shock in swine.

We wanted to determine the effects of WEB 2086, a platelet activating factor (PAF) antagonist, in lipopolysaccharide (LPS) shock in anesthetized pigs. In a randomized study, LPS from S. abortus equi, 2 micrograms/kg/h was given IV for six hours. Thirteen animals received LPS and WEB 2086, 10 mg/kg/h IV for 6.5 hours, beginning 30 minutes before LPS. Eleven septic controls received saline and LPS, three nonseptic controls received saline and WEB 2086, and three nonseptic controls received saline only. In six animals we investigated the effect of synthetic PAF in doses between 50 and 10,000 ng on arterial (AP) and pulmonary arterial (PAP) pressure before and during infusion of WEB 2086. The LPS-induced rise in PAP was reduced by WEB 2086 (p = 0.01) but not the decrease in AP. The LPS-induced leukopenia, hypoxia, increase in airway pressure, and release of plasminogen activator inhibitor were reduced by WEB 2086. Platelet activating factor produced an increase in PAP and a biphasic response in AP. All PAF dose response curves were shifted to the right by WEB 2086. Platelet activating factor was a pulmonary hypertensive agent and contributed to the LPS-induced respiratory alterations.

Animals↗
PubMed1989

Location of pulmonary stretch receptors in the guinea-pig.

The site of pulmonary slowly adapting stretch receptors (SRs) was investigated in anaesthetized, thoracotomized and artificially ventilated guinea-pigs. The location of SRs within the lungs and airways was determined by analyzing the changes of SR single fibres discharge patterns in response to (a) occlusion of the airways, (b) local probing, and (c) microinjection of the non-diffusible local anaesthetic cinchocaine into the presumed receptor site. The great majority (92%) of the 79 SRs examined was localized in small airways or in lung parenchyma ('peripheral SRs'), whereas only 8% were located in large airways, i.e., in the trachea, main bronchi and lobar bronchi ('central SRs'). The discharge responses to lung inflation and to ammonia inhalation slightly differed between these two SR groups. With the pronounced prevalence of peripheral SRs, the guinea-pig seems to take a unique position among the species examined hitherto.

Administration, Inhalation↗
PubMed1988

Blockade of pulmonary stretch receptors reinforces diaphragmatic activity during high-frequency oscillatory ventilation.

During apneic periods elicited by high-frequency oscillatory ventilation (HFOV) a tonic diaphragmatic activity was observed, contrasting with the absence of diaphragmatic activity during apnea induced by lung inflation. To clarify the mechanism underlying the persistence of the diaphragmatic activity during HFOV-induced arrest of breathing the reflex responses to short periods of HFOV, and to periods of lung inflation with airway pressure (Paw) equal to the mean Paw and/or to maximal Paw during HFOV were examined both before and after the blockade of slowly adapting stretch receptors (SR) by inhalation of sulphur dioxide (SO2) in anaesthetized rabbits. In animals with intact SR, the HFOV-induced reflex apnea lasted longer than that induced by lung inflation, the associated diaphragmatic activity being in the most cases higher than the diaphragmatic activity during quiet expiration; inflation, however, completely inhibited diaphragmatic activity. After blockade of SR, spontaneous breathing continued during periods of lung inflation, i.e., the Hering-Breuer inflation reflex was abolished, whereas HFOV still led to a cessation of spontaneous breathing, the associated diaphragmatic activity even exceeding the level observed during quiet inspiration. From these results we conclude that only one part of the reflex response to HFOV is due to SR-stimulation and that in addition other vagal pulmonary receptors (irritant- and/or C-fibre-receptors) are involved. The stimulation of the latter counterbalances the concomitant stimulation of SR, giving rise to the tonic activity of the diaphragm.

Animals↗
PubMed1986

Location-dependent characteristics of pulmonary stretch receptor activity in the rabbit.

In anaesthetized, thoracotomized and artificially ventilated rabbits, the location of pulmonary stretch receptors (SR) was established by means of local mechanical stimulation as well as by micro-injections of the local anaesthetic cinchocaine. Differences in SR activity were analyzed in relation to the receptor site during specific stimulation by lung inflation, as well as during nonspecific activation by ammonia inhalation. Out of 107 SR, 55% were located in larger airways, i.e., in the trachea, main bronchus and lobar bronchi ("central SR"), whereas 45% were found to lie more peripherally ("peripheral SR"). There were several differences with respect to the discharge pattern evoked by lung inflation and by ammonia inhalation between SR of different locations. The increase of discharge rate evoked by lung inflation and by ammonia inhalation was significantly greater in peripheral than in central SR. Significantly more central than peripheral SR discharged throughout the whole respiratory cycle, i.e., even at end-expiratory lung volume. Furthermore, a delayed inspiratory recruitment as well as a transient cessation of firing after the initial increase of activity, which followed ammonia inhalation, occurred more frequently in central than in peripheral SR.

Ammonia↗
PubMed1985

Effect of coupling the breathing- and cycling rhythms on oxygen uptake during bicycle ergometry.

The influence of the degree of coupling between the breathing and cycling rhythms (K) on oxygen uptake (Vo2) was examined in 30 volunteers. They cycled on an ergometer with a load equal to 50% of their work capacity 170 in two experimental runs with spontaneous breathing rhythm, and in a further two runs with acoustically triggered breathing. K was continuously ascertained. Vo2 and other respiratory parameters were measured by an automatic "breath-by-breath analysis" system. In 16 subjects, Vo2-differences between runs were correlated with the differences in K. In the majority of these subjects (12), Vo2 decreased significantly with increasing K. In 14 subjects, Vo2-and K-variations within individual runs were analyzed. Phases with higher K were regularly accompanied by a decrease in Vo2. It is concluded that coupling the breathing and cycling rhythms reduces Vo2 for a given moderate work load, although the magnitude of the Vo2-reduction varies considerably between individuals.

Adult↗