Susceptibility to experimental autoimmune myasthenia gravis (EAMG) was found to decrease with aging in both Lewis and Brown Norway (BN) rats. In this study, the difference in susceptibility between young and aged Lewis and BN rats was used to analyze factors determining the clinical severity of EAMG. The incidence and severity of muscular weakness did not correlate with acetylcholine receptor (AChR) loss nor with the ability of antibodies to interfere with AChR function. Aged rats showed significantly lower anti-rat AChR antibody titers than young rats and developed less severe or no clinical signs of disease. In individual young or aged rats, however, no significant correlation was found between the clinical signs of disease and anti-rat AChR titer. Neuromuscular transmission was found to change with aging as measured by single-fiber electromyography (SFEMG). In aged BN rats, increased jitter and blockings were found even before EAMG induction. Despite this disturbed neuromuscular transmission, these aged BN rats were clinically resistant against induction of EAMG. The results of this study indicate that the age-related susceptibility to EAMG is influenced by factors determined by the immune attack as well as mechanisms at the level of the neuromuscular junction.
In the present study we have investigated the correlation between hyperpolarization-activated current (1(h)) and menthol-activated current (I(TRPM8)) in rat dorsal root ganglion (DRG) neurons. We showed that I(h) is present in 89% of menthol-sensitive neurons which makes its presence reliable, though not absolute, criterion for pre-selection of such neurons. Endogenous I(h) recorded from different neurons exhibited variable density and activation kinetics. Based on the analysis of I(h) activation kinetics we hypothesize that the population of hyperpolarization-activated channels in menthol-sensitive DRG neurons is mainly represented by HCN1, HCN2 and HCN3 channels. The expression of HCN4 isoform in these cells is very low.
Competitive rhythmic sportive gymnastics have been accused of promoting an unphysiologic weight reduction which may progress to manifest anorexia nervosa. In this study, eight young female gymnasts who represented Norway in the European Championships in Rhythmic Sportive Gymnastics 1982 were examined for evidence of malnutrition. Ten girls, matched for age and height, served as controls. The examination included registration of anthropometric data (height, weight, and body-mass index), motor and sensory neurography and biopsies of the vastus lateralis muscle with exact measurements of muscle fibre areas on sections stained for myofibrillar ATPase activity. The mean body weight of the gymnasts did not differ from that of the control group or of a large series of age matched Norwegian females. This finding excludes the possibility of general malnutrition among the examined gymnasts. Muscle fibres of both types 1 and 2 were found to be smaller in the gymnasts than in the controls, with values of 3,404 microns2 vs 3,811 microns2 for type-1 fibres and 2,985 microns2 vs 3,942 microns2 for type-2 fibres respectively. Although contradictory to most previous reports, this finding suggests that the reduction in fibre size among the gymnasts might be an effect of physical training. There were some differences in neurographic parameters between the groups, but the mean values were all within normal ranges. The motor nerve conduction velocity in the proximal segments of the median and ulnar nerves was significantly slower in the gymnasts and, as a possible consequence of smaller muscle fibres, the motor responses were generally less in this group.
The present article reviews pertinent contributions from the Montreal Heart Institute, Montreal, Quebec, to the understanding of the mechanisms and treatment of atrial fibrillation. The article discusses the usefulness of anticoagulant therapy, antiarrhythmic drug therapy for sinus rhythm maintenance, the electrophysiological basis of atrial fibrillation and the investigation of new energy sources for catheter ablation. Future directions at the Montreal Heart Institute are also briefly addressed.
During recent years, the exploration of different aspects of atrial fibrillation (AF) has become increasingly interesting. Thus, knowledge about basic underlying mechanisms, consequences and different modes of treatment has rapidly expanded. At a meeting in Lund, Sweden, in 1993, scientists within different fields of AF research gathered for the exchange of information. This paper is a short summary of some topics discussed at the Lund meeting and some suggestions as to how further research in this field may help to improve our understanding of this arrhythmia and the treatment of patients suffering from it. Underlying pathoelectrophysiological mechanisms in AF have been explored in experimental models in animals and by direct recordings of different atrial myocardial electrophysiological variables both in the catheter laboratory and during open heart surgery in man. Some findings illustrate possible generalized atrial myocardial mechanisms, whilst other findings clearly indicate the possibility of localized pathoelectrophysiological mechanisms. The generally accepted hypothesis that AF is perpetuated by multiple re-entry mechanisms is, thus, both verified and modified by recent studies. In addition to subjective symptoms and well identified thromboembolic consequences, accumulating evidence tells us that AF may precipitate a myocardial dysfunction which may be misinterpreted as an underlying factor initiating the arrhythmia. Today's treatment of AF includes several newer antiarrhythmic drugs, different ablation techniques, the application of different electrical devices as well as different surgical methods. New, improved and simplified methods are expected. Atrial fibrillation is the single most important supraventricular arrhythmia needing substantial further exploration of mechanisms, consequences and treatment. The Lund symposium contributed to this process by defining the state of knowledge in 1993 and outlining the need for the years to come.
Radiofrequency ablation of atrioventricular nodal reentrant tachycardia is commonly guided by slow and sharp bipolar potentials of the atrioventricular slow nodal pathway. We optimized the morphology of the guiding potential by unipolar mapping of the slow nodal pathway. We identified a novel unipolar dual-component atrial electrogram at the anterior limb of the coronary sinus ostium. The first component was a positive delta-wave type that corresponded to the isoelectric phase on a bipolar electrogram. The second component had fast biphasic morphology and corresponded to the R wave on a bipolar atrial electrogram. Of 104 consecutive patients with typical atrioventricular nodal reentrant tachycardia, 51 were treated with ablation guided by the novel potential, and 53 underwent ablation using the conventional technique. There was no recurrence of tachycardia in any of these patients. In those treated by the novel potential, there was significantly less radiofrequency power applied and a shorter duration of application than in patients treated by the traditional approach. The novel approach to mapping and ablation of the slow nodal pathway in atrioventricular nodal reentrant tachycardia guided by unipolar recording was safe and effective, and comparable to the traditional technique.
A form of autosomal recessive spastic ataxia unique to the Charlevoix-Saguenay area was clinically identified 20 years ago in patients from that region. This region of Québec, Canada, was once considered a genetic isolate. First noted at gait initiation, signs of ataxia slowly progress along with spasticity of the four limbs, slurred speech, and followed by distal amyotrophy. Early diagnosis relies on the presence of prominent myelinated fibers embedding retinal blood vessels at funduscopy and marked saccadic alteration of ocular smooth pursuit. Imaging of the posterior fossa shows cerebellar vermis atrophy and nerve conduction studies reveal loss of sensory and reduced motor conduction velocities. The clinical features are consistent with a developmental defect in myelination of both retinal and peripheral nerve fibers. The cause of this defect and the progressive axonal degeneration in the corticospinal and spinocerebellar tracts, as well as in the peripheral nerves is still unknown. Results of recent molecular genetic linkage analysis have located the gene locus to chromosome 13q12. Further research is needed to define where this hereditary spastic ataxia stands in the classification of the early onset spinocerebellar degenerations.
The membrane properties of short type blowfly photoreceptors (R1-6) were investigated in dark and light adaptation with single electrode current and voltage clamp techniques. The impedance of the cells was defined in frequency domain by using discontinuous current clamp and white-noise-modulated current injection. We found that the slow activation and relaxation of the voltage-dependent K+ conductance transform the photoreceptor membrane effectively into a band-pass filter. This behaviour could be observed under current clamp as voltage-dependent outward and inward rectification of the membrane. The voltage-dependent band-pass filtering is likely to be present in all neurons with graded potentials and voltage-dependent membrane conductances.