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Biomedical subjects

M Zimmermann

Publications and source records attributed to M Zimmermann.

At least 325 records · Page 18Linked to original sources

Calcitonin: brainstem microinjection but not systemic administration inhibits spinal nociceptive transmission in the cat.

In anaesthetized cats, nociceptive responses of lumbar dorsal horn neurons were studied during administration of salmon calcitonin (sCT). Systemic sCT administration (4-95 IU/kg i.v.) produced no change in neuronal responses produced by noxious skin heating or by impulses evoked electrically in afferent C-fibres. Responses to skin heating were reduced during electrical stimulation in the brainstem, but the efficacy of this descending inhibition was not altered by systemic sCT administration. In contrast, noxious heat responses were clearly reduced by microinjection of sCT into the mesencephalic periaqueductal grey or the medullary raphe regions. These results suggest that calcitonin or a related peptide could act at specific brainstem sites to inhibit the spinal transmission of nociceptive information.

Animals↗

Immunoreactive substance P release from skin nerves in the rat by noxious thermal stimulation.

We have examined by radioimmunoassay the substance P (IR-SP) content of superfusate obtained from skin blisters in the anesthetized rat. The blisters were produced on the footpad using a vacuum pump, and the blister base was superfused with tyrode solution. Continuous release of IR-SP was approximately 100 pg/h from the innervated footpad but was considerably reduced when the footpad had been surgically denervated 10-14 days previously. The IR-SP content was markedly increased in the innervated footpad following a local noxious heat stimulus of 50 degrees C applied for 30 s at 5-min intervals for 1 h. The results support the proposal that SP is a mediator of neurogenic inflammation induced by noxious skin heating.

Animals↗

Spinal neuronal inhibition and EEG synchrony by electrical stimulation in subcortical forebrain regions of the cat.

In cats anaesthetized with sodium pentobarbital and 70% N2O, single lumbar dorsal horn neurons were excited by controlled noxious radiant heating of glabrous hindpaw skin. The EEG was recorded from the pericruciate cortex and posterior lateral gyrus. Subcortical forebrain sites where electrical stimulation inhibited dorsal horn neuronal heat-evoked responses contralaterally were identified by mapping the caudate nucleus, internal capsule, septum, nucleus accumbens and basal forebrain regions. Inhibitory sites were mainly located in the ventral forebrain (ventral septum, diagonal band, basal forebrain). The caudate nucleus and internal capsule had a low incidence and effectiveness of inhibitory sites. In the basal forebrain, the incidence and effectiveness of inhibitory sites decreased from caudal to rostral regions. There was a rostral limit of inhibitory sites, both medially and laterally. The magnitude of inhibition increased with graded increases in brain stimulation intensity. The mean incremental increase in inhibition was greater for caudal than for rostral basal forebrain sites. Mean stimulus currents for threshold of inhibition and for inhibition to 50% of control heat responses were lower for caudal than for rostral sites. Responses of the dorsal horn neurons to increasing temperatures of noxious skin heating were monotonic linear functions over the temperature range studied (48-53 degrees C). Stimulation in both rostral and caudal basal forebrain decreased the slope of this stimulus-response function, with a greater decrease for caudal sites. Cortical EEG synchronization was evoked by stimulation in the caudate nucleus and rostral basal forebrain. For both regions, most synchronogenic sites did not produce descending inhibition of dorsal horn neurons. The significance of these findings in relation to descending inhibition from other brain regions and stimulation-produced analgesia is discussed.

Action Potentials↗

Activities of single neurons in midbrain and thalamus of cats during conditioned nocifensive behavior.

Extracellular recordings of neuronal activity were performed in 3 conscious cats in the rostral mesencephalic reticular formation (MRF) and in the nucleus posterior (PO) of the thalamus. The animals were trained by operant conditioning to operate a panel switch with a forepaw to escape a noxious cutaneous heat stimulus. We recorded 12 neurons in the MRF, which responded in association with this nocifensive behavior. Some of the neurons increased their firing rate before the noxious stimulus was terminated, whereas other neurons responded immediately afterwards. The activity of these neurons, however, could be related to the animal's behavior, which was independent of the noxious stimuli. It was found that the neurons showed changes in firing patterns when the animal reacted to a discriminative light stimulus in order to obtain a milk reward. In the PO of the thalamus we did not find any neurons, which could be activated by noxious heating or any nocifensive-related behavior. Modification of the discharge patterns, however, occurred in relation to sensory events and behavioral acts.

Animals↗

Determinants of the spontaneous ectopic activity in repetitive monomorphic idiopathic ventricular tachycardia.

Twenty-four hour ambulatory electrocardiographic tape recordings of 30 patients (16 men and 14 women, mean age 42 +/- 17 years) with repetitive monomorphic idiopathic ventricular tachycardia were analyzed using a new computerized system designed to study 15 RR cycles and mean heart rate of the 3 minutes preceding any defined event. The mean (+/- SD) number of events analyzed per patient in 24 hours was 610 +/- 483 for single premature ventricular complexes, 622 +/- 490 for couplets, 260 +/- 411 for runs of 3 complexes, 186 +/- 476 for runs of 4, 108 +/- 173 for runs of 5, 82 +/- 129 for runs of 6 to 10 and 83 +/- 116 for runs of more than 10 complexes. The heart rate was faster before runs of ventricular tachycardia than before isolated extrasystoles (p less than 0.01) and a positive linear correlation was observed between the mean preceding heart rate and the type of extrasystolic activity, the length of the runs increasing with increasing preceding heart rate (r = 0.98, p less than 0.001). A long RR interval just before the occurrence of runs was present in 77% of the cases (23 of 30) with or without an oscillatory pattern of RR intervals due to bigeminy or trigeminy, and the length of the runs correlated positively with the duration of this long preceding diastole (r = 0.90, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Mechanoreceptors in rat glabrous skin: redevelopment of function after nerve crush.

In the glabrous skin of the rat's hindfoot the same triple set of low-threshold mechanoreceptors is present as has been found in other mammals: slowly adapting (SA), rapidly adapting (RA), and very rapidly adapting Pacinian corpuscle-like (PC) receptors. Their functional characteristics were examined in normal rats and compared with those of sensitive mechanoreceptors found in the glabrous skin of the foot 2-24 wk after crush of the plantar nerves, resulting in regeneration of the transected nerve fibers. After 2 wk of nerve regeneration, low-threshold RA and SA cutaneous mechanoreceptors reappeared in the foot skin. Responses of PC receptors were recorded again after 3 wk, at which time the proportion of fibers that could be identified as low-threshold cutaneous mechanoreceptors had regained control level. Discharge patterns of regenerated cutaneous mechanosensitive receptors were very similar to those of normal skin mechanoreceptors. Their sensitivity to controlled mechanical stimulation was, however, still reduced 4 wk after the lesion. After 8 wk RA and SA receptors had regained their normal dynamic sensitivity, i.e., the responsiveness to the velocity of skin indentation. The static sensitivity of SA receptors, i.e., responsiveness to maintained skin indentation, was not consistently reestablished within 24 wk. No shift in sensitivity could be deduced from tuning curves of PC receptors examined 3-24 wk after nerve crush. In addition to the low-threshold mechanoreceptors, high-threshold (HT) mechanoreceptive fibers were found in controls and in animals with regenerating nerves. This type of fiber was most frequently found 1 wk after the nerve crush, when reinnervation of the foot started. They probably represent fibers not connected to specific mechanoreceptor end organs. Thus, functional restitution of the highly specific cutaneous mechanoreceptors occurs fairly soon after invasion of the original territory by the regenerating nerve. It is assumed that the underlying mechanism is the rapid reconnection of fibers with the end organs that have either survived during the period of denervation or regenerated subsequent to reinnervation of the skin.

Animals↗

[Mechanisms determining sudden death. A cooperative study of 69 cases recorded using the Holter method].

A cooperative study involving 23 centres enabled review of 69 cases of sudden death occurring less than one hour after onset of symptoms recorded by the Holter method and not related to recent, clinically documented myocardial infarction or to class IV cardiac failure. The 15 cases of asystole (22 p. cent) were observed in elderly patients (73.3 +/- 2.7 years) whose known ischaemic heart disease (12/15) was confirmed in 10 cases as the direct cause by the preceding acute ST changes. In 2 cases, death resulted from AV block presumed to be iatrogenic. The 13 episodes of torsades de point (19 p. cent) occurred mainly in younger women (58.8 +/- 6 years) without apparent cardiac disease (8 cases) and were provoked by a Group IA antiarrhythmic drug (7 cases) or by hypokalemia (3 cases). Apart from 1 case of congenital long QT syndrome, slowing of the sinus rhythm was observed (78.3 +/- 2.6 to 60.2 +/- 2.7 bpm, p less than 0.001) in the 3 hours preceding these episodes, and ventricular bigeminy with a long coupling interval was recorded in the lasts seconds before the torsades. The 41 (59 p. cent) cases of ventricular fibrillation (VF) were observed in men aged 64.9 +/- 2 years with coronary artery disease (39/41). However signs of acute ischaemia were only found in 5 cases. The VF was primary in 8 cases and secondary to ventricular tachycardia (VT in 33 cases). An acceleration of the cardiac rhythm (83.3 +/- 3.4 to 90 +/- 4.1 bpm, p less than 0.01) was recorded in the hour preceding VF and other arrhythmias were common: atrial tachycardia (4 cases), atrial extrasystoles (4 cases), a new type of ventricular extrasystoles (VES). The VF and VT were preceded by a long cycle in 17 cases. The first complex was different from previous VES in 10 cases and identical to the previous VES in 16 cases; in 4 cases this feature could not be identified and in 11 cases there were no premonitory VES. The coupling interval of the initial VES was shorter than that of the most premature preceding VES (368 +/- 13 ms vs 442 +/- 19 ms, p less than 0.001), especially in primary VF (335 +/- 9 ms, N = 8) compared to polymorphic VT (360 +/- 12 ms, N = 11) or monomorphic VT (384 +/- 18 ms N = 22).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Determining factors of the repetitive bursts in ventricular tachycardia].

24-h ECG recordings were studied in 60 patients suffering from salvos of repetitive ventricular tachycardia (VT), in order to determine the parameters affecting the repetitive response in ventricular arrhythmias. The tracings were analysed with the use of ATREC II system allowing the systematic study of 15 RR intervals and the heart rate in the 3 min preceding each type of event. The mean number of events taken into account per patient and per 24h of recording amounted to 673 +/- 521 for isolated ventricular extrasystoles, to 568 +/- 461 for paired ventricular extrasystoles and 435 +/- 810 for bursts of VT. The whole group was divided into two groups according to the absence (A) or presence (B) of associated cardiopathy. Group A included 30 patients with a mean age of 42 +/- 17 years, group B included 30 patients with a mean age of 42 +/- 17 years, group B included 30 patients with a mean age of 57.4 +/- 12 years. Three major factors responsible for the repetitive activity could be disclosed: The heart rate preceding isolated ventricular extrasystoles was lower than that preceding the salvos of VT (p less than 0.01) the duration of which increased in a linear way with the sinus rate; Duration of the cycle preceding the last sinus beat before the bursts (long duration in 77% in group A and in 57% in group B). In 60% of cases in group A and 40% in group B the coupling interval was all the more long as the response was repetitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ethical considerations in relation to pain in animal experimentation.

Animal experiments are necessary to better understand the biological mechanisms of pain, and to develop new methods of pain therapy. Therefore, pain has to be produced experimentally in animals. The ensuing moral dilemma requires that the scientists involved have a high level of responsibility for the animal. A set of ethical guidelines has been developed by the International Association for the Study of Pain in order to minimize pain and suffering in such studies. Practically, this may be reached by, e.g. a careful design of the experiment or by analgesic treatment of the animal. The importance of reward in a behavioral paradigm involving pain is emphasized. Animal models of chronic pain will be necessary to understand the mechanisms of chronic pain in man. Observations of the behavior of animal patients should be used to define the species-specific behavioral expression of chronic pain. To observe only one behavioral parameter may be inadequate for the assessment of pain in animals. The training of the young scientist will be crucial to develop his general attitude of great ethical responsibility for the experimental animal and his conceptual and technical capabilities for optimal conductance of experiments. In practice, investigators engaged in research on pain in conscious animals should consider the following guidelines aimed at minimizing the pain in animals. The guidelines have been endorsed by the International Association for the Study of Pain. It is essential that the intended experiments on pain in conscious animals be reviewed beforehand by scientists and lay-persons. The potential benefit of such experiments to our understanding of pain mechanisms and pain therapy needs to be shown. The investigator should be aware of the ethical need for a continuing justification of his investigations. If possible, the investigator should try the pain stimulus on himself; this principle applies for most non-invasive stimuli causing acute pain. To make possible the evaluation of the levels of pain, the investigator should give a careful assessment of the animals's deviation from normal behavior. To this end, physiological and behavioral parameters should be measured. The outcome of this assessment should be included in the manuscript. In studies of acute or chronic pain in animals measures should be taken to provide a reasonable assurance that the animal is exposed to the minimal pain necessary for the purposes of the experiment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Welfare↗

[Late potentials and ventricular arrhythmia].

When electrodes are placed at the surface of the thorax, high-amplification electrocardiography (HA-ECG) combined with signal summation as a function of time provides a non-invasive method for detecting electric potentials occurring after the QRS complex of the clinical electrocardiogram. These potentials are called late, and can probably be likened to the "divided" or "fragmented" potentials recorded directly on the heart or in its ventricles near zones of ischemia, infarction or aneurysm. The prevalence of late potentials of ventricular activation (LPVA) and their association with the occurrence of ventricular arrhythmias seems well established, notably in the presence of ventricular aneurysm and anamnesis of severe ventricular arrhythmia. Some studies have shown that detection of LPVAs is of value in identifying heart patients at risk of ventricular arrhythmia or sudden death. Heart disease aside, the presence of LPVAs has been demonstrated in arrhythmogenic right ventricular dysplasia and reported in Fallot's tetralogy after complete correction. A standardization of recordings and a more precise definition of LPVAs are necessary before HA-ECG can become a routine clinical method. Further, the possibility of "beat by beat" recordings with "spatial" summation will allow detection of LPVAs which vary with time and in nature and hence provide a better understanding of the genesis of ventricular arrhythmias.

Arrhythmias, Cardiac↗

Prognostic significance of ventricular late potentials in coronary artery disease.

By means of high-gain ECG and signal-averaging techniques, we tried to determine the prevalence and prognostic significance of ventricular late potentials (VLPs) in coronary artery disease (CAD). No VLPs were detected in normal subjects (n = 25) or in patients with various noncoronary cardiopathies with sustained ventricular tachycardia and/or fibrillation (VT/VF) (n = 10). Among 92 CAD patients, VLPs were apparent in 35% (32 of 92) at the beginning of the study. The prevalence of VLPs increased to 48% (19 of 40) in the presence of ventricular aneurysm (VA) and to 82% (14 of 17) in the presence of a history of previous sustained VT/VF. To determine the prognostic significance of VLPs, a prospective analysis was conducted during a mean of 7.4 months (range 1 to 22 months). During the follow-up period, 11 patients (12%) presented with an episode of sustained VT/VF, and six of them died from documented VT/VF. Three other patients died from cardiogenic shock. An episode of sustained VT/VF occurred in 31% (10 of 32) of the patients with VLPs vs 2% (1 of 58) of the patients without VLPs (p less than 0.001), and six patients with VLPs died from sustained VT/VF vs none in the group of patients without VLPs (p less than 0.01). This VLP-related increase in arrhythmic risk was still present in the particular subgroup of patients with a history of previous sustained VT/VF (n = 17) and in patients with VA (n = 40). The risk of developing sustained VT/VF was also influenced by the length of the VLP and by a low mean ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗