Search PubMed⌕ Search

Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 307 records · Page 17Linked to original sources
PubMed1988

Inhibition of nociceptive responses of lumbar dorsal horn neurones by remote noxious afferent stimulation in the cat.

In cats anaesthetized with nitrous oxide and sodium pentobarbital, multireceptive lumbar dorsal horn neurones excited by controlled noxious radiant heating of glabrous hind paw skin were recorded by extracellular microelectrodes. These noxious heat responses were inhibited by concomitant noxious stimulation of the ipsilateral forepaw or pinna, or repetitive electrical stimulation of the ipsilateral forelimb deep radial nerve. Similar extents of inhibition were produced by noxious peripheral stimulation and by deep radial nerve stimulation in repetitive trains at intensities sufficient to excite small myelinated fibres or unmyelinated fibres. A greater inhibitory effect was produced by continuous repetitive high-intensity stimulation of the deep radial nerve. With a constant frequency (5 Hz) of continuous deep radial nerve stimulation, graded increases in stimulation intensity revealed the threshold for inhibition in the small myelinated fibre range, and an additional increment of the inhibitory effect when unmyelinated fibres were also activated. When suprathreshold for unmyelinated fibres, the efficacy of continuous deep radial nerve stimulation increased with graded increases in stimulation frequency, with a threshold frequency for inhibition between 0.5 and 1 Hz and maximal effect at 5 Hz. Two nociceptive-specific neurones studied were also inhibited by deep radial nerve stimulation. The results indicate that 'diffuse noxious inhibitory controls' (DNIC) occur in the cat and can be activated by remote electrical or natural noxious stimulation.

Animals↗
PubMed1988

Vasovagal syncope during rectosigmoidoscopy: report of a case.

Cardioinhibitory vasovagal syncope with sinus arrest and asystole of 28 seconds' duration occurred during rectosigmoidoscopy in a patient with frequent previous symptoms and a syncopal episode. A ventricular inhibited pacemaker was implanted and the patient has remained asymptomatic for 18 months.

Adult↗
PubMed1988

Colocalization and coprecipitation of ankyrin and Na+,K+-ATPase in kidney epithelial cells.

Interactions between integral proteins of the plasma membrane and the cytoskeleton may be important for localizing certain membrane proteins in a nonrandom fashion at specialized domains of the cell surface. Here, we show that ankyrin, the key protein for the linkage of the erythrocyte anion exchanger (band 3) to the spectrin-based membrane cytoskeleton, is also present in kidney distal tubular cells where ankyrin is precisely colocalized with Na+,K+-ATPase. Both proteins are confined to the basolateral plasma membrane and are absent from the apical membrane, the junctional complex and the membrane surface that contacts the basal lamina. Purified Na+,K+-ATPase of sheep and pig kidney contains a binding site for erythrocyte ankyrin as demonstrated by immunoprecipitation experiments. A band 3-like binding site for ankyrin is likely, since binding of ankyrin to Na+,K+-ATPase could be inhibited in a competitive fashion by the isolated cytoplasmic domain of erythrocyte band 3.

Animals↗
PubMed1987

Hepatic microsomal N-demethylation of N-methylbenzamidine. N-dealkylation vs N-oxygenation of amidines.

The microsomal oxidative N-demethylation of N-methylbenzamidine, a model compound for active substances containing the basic amidine function, was investigated. N-Methylbenzamidine was converted into benzamidine and formaldehyde by aerobic incubation with non-induced microsomal fractions of rabbit liver homogenates and NADPH. The formation of benzamidine in the incubation mixtures under widely differing conditions was assayed using a newly-developed, high-performance, ion pair, reverse-phase partition chromatographic method. Optimal reaction conditions were determined. The benzamidine formation in the incubation mixture followed Michaelis-Menten kinetics and required the presence of molecular oxygen and NADPH. The effects of the inducer phenobarbital, methylcholanthrene, ethanol and N-methylbenzamidine itself on the activity were studied. Neither superoxide anion nor hydrogen peroxide was directly involved in the demethylation reaction. The direct involvement of cytochrome P-450 in this reaction is supported by the observation that the presence of inhibitors of cytochrome P-450, in particular of carbon monoxide, markedly decreased the rate of N-demethylation. This N-demethylation of N-methylbenzamidine proves the hypothesis that benzamidines with hydrogen atoms in the alpha-position to the amidine nitrogen atoms are N-dealkylated instead of N-oxygenated by the microsomal mixed function oxidase system.

Amidines↗
PubMed1987

Ouabain-binding site of (Na+ + K+)-ATPase in right-side-out vesicles has not an externally accessible SH group.

The fluorescing sulfhydryl reagent N-(7-dimethylamino-4-methylcoumarinyl)maleimide (DACM) inactivates purified (Na+ + K+)-ATPase at 20 microM. This inactivation results in a decrease of the ouabain-binding capacity of the enzyme. Treatment of (Na+ + K+)-ATPase, embedded in right-side-out-oriented vesicles, by DACM does not affect ouabain binding to the enzyme. Incorporation of DACM into the alpha subunit of (Na+ + K+)-ATPase embedded in right-side-out vesicles is also not affected by the presence or absence of 100 microM ouabain. It is therefore concluded that a sulfhydryl group does not reside within the ouabain-binding site of (Na+ + K+)-ATPase.

Animals↗
PubMed1987

Raphe magnus-induced descending inhibition of spinal nociceptive neurons is mediated through contralateral spinal pathways in the cat.

In anesthetized cats, extracellular recordings were made from lumbar spinal dorsal horn neurons, driven by noxious radiant skin heating. Heat-evoked responses were inhibited during electrical stimulation in the medullary nucleus raphe magnus (NRM). To identify the spinal pathways mediating this descending inhibition, reversible blocks in the spinal cord white matter were produced by microinjection of the local anesthetic lidocaine. Descending inhibition from the NRM was significantly reduced during blocks in the dorsal and medial, but not ventral parts of the contralateral lateral funiculus (LF). Blocks at any site in the ipsilateral LF failed to affect NRM-induced descending inhibition. These results indicate that NRM-induced inhibition of nociceptive dorsal horn neurons is conveyed primarily in fibers descending in the contralateral spinal white matter.

Animals↗
PubMed1987

Diffuse noxious inhibitory controls of lumbar spinal neurons involve a supraspinal loop in the cat.

In anesthetized cats, lumbar dorsal horn neurons were excited by brief noxious radiant heating of glabrous hindpaw skin. These nociceptive responses were inhibited by concomitant repetitive electrical stimulation of the ipsilateral deep radial nerve. Noxious heat responses were linearly correlated with skin temperature during heating. The slope of this stimulus-response function was decreased, and the response threshold increased, by deep radial nerve stimulation. Microinjection of lidocaine into the medullary raphe attenuated the inhibition induced by deep radial nerve stimulation. The results indicate that in the cat, 'diffuse noxious inhibitory controls' (DNIC) involve medial medullary regions.

Action Potentials↗
PubMed1987

Frequency of ventricular late potentials and fractionated right ventricular electrograms after operative repair of tetralogy of Fallot.

This study was conducted to assess the incidence of abnormalities of ventricular depolarization in sinus rhythm after repair of tetralogy of Fallot and their relation to spontaneous ventricular arrhythmias. Forty-four patients were studied, 10 before surgery (mean age 6.9 years) and 34 after repair (mean age 8.1 years, mean age at surgery 6.5 years, mean interval between surgery and evaluation 11 months). Evaluation was performed by means of body surface and intracavitary signal-averaging techniques, by recording local right ventricular (RV) electrograms at several sites and by 24-hour Holter monitoring (n = 28). No electrophysiologic abnormality was observed in children before surgery. Ventricular late potentials were detected in 18 patients (53%) after repair. Body surface detection of ventricular late potentials was frequently masked by the postoperative right bundle branch block pattern. Local RV electrograms were fractionated in 11 cases (32%) (mean duration 103 +/- 33 ms), most often in the RV outflow tract (n = 9), but no relation was found between fragmentation of RV electrograms and the presence of ventricular late potentials. Spontaneous ventricular arrhythmias occurred in 12 children after repair (43%), but were complex in only 4 patients (14%). There was no correlation between spontaneous ventricular arrhythmias and the presence of ventricular late potentials, presence of fractionated RV electrograms, presence of a proximal right bundle branch block or postoperative hemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1987

Substance P modulates the release of locally synthesized nerve growth factor from rat saphenous nerve neuroma.

In saphenous nerve neuromata of adult rats a long-term increase of immunoreactive nerve growth factor (irNGF) was detected after nerve transection. The occurrence of messenger RNA encoding NGF (NGF mRNA) in these proximal nerve stumps indicates local biosynthesis of NGF. In situ superfusion of neuromata revealed a constant release of irNGF which was significantly reduced by substance P (SP) but not affected by calcitonin gene related peptide (CGRP). We therefore suggest that SP may modulate the availability of NGF in the microenvironment of the regenerating nerve fiber endings.

Animals↗
PubMed1987

The use of local anaesthetic microinjections to identify central pathways: a quantitative evaluation of the time course and extent of the neuronal block.

The time course and extent of local anaesthetic blocks within the spinal cord of cats were evaluated. A monopolar stimulation electrode with the tip lowered into the dorsal columns (DC) 1000 microns below cord surface was used to activate antidromically DC fibers at the T13 level and evoke cord dorsum potentials at the level of the lumbar spinal cord. The amplitude of the negative deflection, the N-wave, was determined for various stimulation intensities (stimulation-response-function, SRF). Lidocaine (1%) was microinjected in volumes of 0.5 or 1.0 microliter into the DC from a glass micropipette 1 mm caudal to the stimulation site. Conduction block was characterized by a reversible shift of the SRFs to higher stimulation intensities. The diameter of the blocked area in the transverse plane was evaluated from threshold intensities and was found to be 0.9 +/- 0.1 mm 4 to 30 min after the injection of 0.5 microliter lidocaine and 1.6 +/- 0.36 mm 10 to 45 min after the injection of 1.0 microliter lidocaine. In the sagittal plane, the diameter of the blocked area following 1.0 microliter lidocaine was found to be up to 2.8 mm. The DC-block was reversible within 92 min following injection of 1.0 microliter and 69 min after the injection of 0.5 microliter lidocaine. The application of the present findings for blocks in other CNS structures is discussed.

Anesthetics, Local↗
PubMed1987

Pentobarbital, in subanesthetic doses, depresses spinal transmission of nociceptive information but does not affect stimulation-produced descending inhibition in the cat.

The present study evaluates the effect of systemic pentobarbital on the spinal transmission of nociceptive information and on stimulation-produced descending inhibition in the deeply anesthetized, paralyzed cat. Single neuronal responses to noxious skin heating were recorded extracellulary in the lumbar dorsal horn and found to be depressed by pentobarbital at subanesthetic doses (4.0, 8.0, 17.0 and 24.5 mg/kg) in a dose-dependent manner. At 0.5 and 1.5 mg/kg, depression by pentobarbital was positively correlated with the depth of the recording site in the spinal cord (laminae IV-VI), i.e., neurons in deeper laminae (V-VI) were attenuated, while neurons in lamina IV were unaffected. At all doses tested, pentobarbital failed to affect stimulation-produced descending inhibition from either the midbrain periaqueductal gray or the medullary nucleus raphe magnus. The present data furnish evidence for the antinociceptive potency of pentobarbital, they do not support the view that a 'partial pharmacological spinal cord transection' would attenuate stimulation-produced descending inhibition of nociceptive dorsal horn neurons.

Animals↗
PubMed1987

Effects of midbrain stimulation and iontophoretic application of serotonin, noradrenaline, morphine and GABA on electrical thresholds of afferent C- and A-fibre terminals in cat spinal cord.

We have used the single-fibre excitability testing method to investigate whether electrical stimulation in midbrain periaqueductal gray or lateral reticular formation, as well as intraspinal iontophoretic application of the suspected inhibitory neurotransmitters serotonin (5-hydroxytryptamine), noradrenaline, the opiate morphine, or gamma-aminobutyric acid (GABA), exert presynaptic actions at the central terminals of cutaneous afferent unmyelinated or myelinated fibres. Thresholds to antidromically excited 42 single unmyelinated and 18 myelinated fibres in the sural nerve by intraspinal microstimulation were determined before and during periaqueductal gray or lateral reticular formation stimulation (3 100 ms trains/s at 100 Hz; 100-900 microA) or intraspinal iontophoretic application (40-300 nA) of 5-hydroxytryptamine, noradrenaline, morphine or GABA from a multibarrel micropipette. Periaqueductal gray or lateral reticular formation stimulation had mixed effects on unmyelinated and myelinated fibre thresholds, with most threshold measurements within +/- 10% of control. There was a tendency for thresholds to increase more during periaqueductal gray than lateral reticular formation stimulation. Thresholds of unmyelinated fibres were predominantly raised during iontophoretic application of 5-hydroxytryptamine (20/29 fibres), noradrenaline (10/13) and morphine (15/21), while GABA had mixed effects; thresholds of nearly all myelinated fibres were raised by each drug. Both periaqueductal gray or lateral reticular formation stimulation and application of 5-hydroxytryptamine, noradrenaline or morphine tended to raise thresholds in the majority of the 53 unmyelinated and myelinated fibres tested. Methodological problems in interpreting the physiological significance of these results for presynaptic modulation are discussed.

Animals↗
PubMed1987

Exercise test: arrhythmogenic or antiarrhythmic? Rate-dependency vs. adrenergic-dependency of tachyarrhythmias.

The arrhythmogenic effects of exercise tests are often unpredictable, sometimes paradoxical, and usually poorly reproducible. This explains why they are rather neglected by rhythmologists in studying the mechanisms of arrhythmias and the effects of antiarrhythmic drugs and why their prognostic value is a matter of controversy. At the same time the induced, supposedly ischaemia-related arrhythmias are usually not prevented by revascularization procedures. All these discrepancies are probably explained by the complex interactions between the time-limited stimulation of the sympathetic drive and the arrhythmia mechanisms. During the exercise test the sympathetic drive is increased via the neurogenic and humoral routes, and the post-exercise period is characterized by a vagally-induced deceleration of the heart rate which intervenes in the setting of a persistent high level of sympathetic activity. The arrhythmia components formed by potential triggers (isolated premature beats) and substrates (repetitive activity) do not react in the same way to those different phases. Extrasystoles are mainly rate-dependent, so that they often tend to disappear as the sinus rate accelerates. The repetitive ventricular activity directly depends on the sympathetic drive, but necessitates the presence of the trigger to become manifest. Conceivably, many different situations may result from the complex interplay between these distinct parameters, so that the apparent clinical effect of exercise may be either arrhythmogenic or antiarrhythmic in apparently identical diseases, or even in the same patients.

Arrhythmias, Cardiac↗
PubMed1987

Spinal pathways mediating tonic or stimulation-produced descending inhibition from the periaqueductal gray or nucleus raphe magnus are separate in the cat.

1. The spinal pathways for tonic and stimulation-produced descending inhibition of spinal nociceptive neurons were investigated in anesthetized paralyzed cats. Reversible circumscribed blocks were produced at various depths in the lateral funiculi (LF) at L1-L2 using the microinjection of the local anesthetic lidocaine. The total amount of tonic descending inhibition in the absence of LF blocks was evaluated by monitoring the spinal neuronal activity during reversible spinalization by cold block and compared with the activity of the same neuron during LF blocks. Stimulation-induced descending inhibition of neuronal responses to noxious skin heating was produced by bipolar focal electrical stimulation in the periaqueductal gray (PAG) or nucleus raphe magnus (NRM) and compared with the inhibition of the same neurons during LF blocks. The relative significance of ipsi- and contralateral pathways in the dorsal, medial, or ventral aspects of the lateral funiculi for these types of descending inhibition are quantitatively described. 2. All 35 lumbar spinal dorsal horn neurons studied responded to noxious and innocuous mechanical and noxious thermal stimuli applied within the receptive fields on the glabrous skin of the hindlimb. Responses to noxious skin stimuli (50 degrees C, 10 s at 3-min intervals) were constant over time and served as a parameter to evaluate tonic and stimulation-produced descending inhibition. All neurons also responded to electrical stimulation of hindlimb cutaneous nerves supramaximal for the activation of A-beta-, delta-, and C-fibers. Neurons were located in laminae I-VI of the dorsal horn at L5-L7 levels. LF blocks were produced by the microinjection of 1 microliter lidocaine at each of one to six sites in the ipsilateral and/or contralateral LF 500, 1,500, and/or 2,500 microns below cord surface. 3. LF blocks ipsilateral to the recording sites in the cord significantly reduced tonic inhibition, with blocks in the dorsal part of the LF [i.e., the dorsolateral funiculus (DLF)] being equally effective to complete LF blocks. Stimulation-produced inhibition from PAG or NRM was, however, not significantly affected by ipsilateral LF blocks. 4. Contralateral LF blocks significantly reduced stimulation-produced descending inhibition and failed to affect tonic descending inhibition. Ventral LF blocks attenuated inhibition from the PAG but not from NRM, whereas DLF blocks were more effective on inhibition from the NRM. 5. Bilateral LF blocks significantly reduced tonic as well as stimulation-produced descending inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Characteristics of the microsomal N-hydroxylation of benzamidine to benzamidoxime.

1. A simple and fast h.p.l.c. analysis of benzamidoxime formed by microsomal N-hydroxylation of benzamidine is presented which is well suited for the determination of the N-oxygenation activity of microsomal enzymes. 2. Optimal reaction conditions were determined. The apparent Km and Vmax values were, respectively, 1.61 mM and 0.38 nmol benzamidoxime/min per mg protein. 3. The effects of the inducers phenobarbital, 3-methylcholanthrene and benzamidine itself on hepatic benzamidine metabolizing activity in rabbits were determined. 4. Neither superoxide anion nor hydrogen peroxide is directly involved in the N-hydroxylation reaction. 5. The direct involvement of cytochrome P-450 in the N-hydroxylation of benzamidine is supported by the observation that inhibitors of cytochrome P-450, in particular carbon monoxide, markedly decreased the rate of N-oxygenation.

Amidines↗