Some aspects of the pathogenesis of multiple sclerosis

The key mechanism of the pathogenesis of multiple sclerosis (MS) is demyelination and the associated impairment of axonal impulse conduction. This disease is genetically determined to a certain extent.

Di-4-ANEPPS Modulates Electrical Activity and Progress of Myocardial Ischemia in Rabbit Isolated Heart

AimsAlthough voltage-sensitive dye di-4-ANEPPS is a common tool for mapping cardiac electrical activity, reported effects on electrophysiological parameters are rather. The main goals of the study were to reveal effects of the dye on rabbit isolated heart and to verify, whether rabbit isolated heart stained with di-4-ANEPPS is a suitable tool for myocardial ischemia investigation.Methods and ResultsStudy involved experiments on stained (n = 9) and non-stained (n = 11) Langendorff perfused rabbit isolated hearts. Electrophysiological effects of the dye were evaluated by analysis of various electrogram (EG) parameters using common paired and unpaired statistical tests. It was shown that staining the hearts with di-4-ANEPPS leads to only short-term sporadic prolongation of impulse conduction through atria and atrioventricular node. On the other hand, significant irreversible slowing of heart rate and ventricular conduction were found in stained hearts as compared to controls. In patch clamp experiments, significant inhibition of sodium current density was observed in differentiated NG108-15 cells stained by the dye. Although no significant differences in mean number of ventricular premature beats were found between the stained and the non-stained hearts in ischemia as well as in reperfusion, all abovementioned results indicate increased arrhythmogenicity. In isolated hearts during ischemia, prominent ischemic patterns appeared in the stained hearts with 3–4 min delay as compared to the non-stained ones. Moreover, the ischemic changes did not achieve the same magnitude as in controls even after 10 min of ischemia. It resulted in poor performance of ischemia detection by proposed EG parameters, as was quantified by receiver operating characteristics analysis.ConclusionOur results demonstrate significant direct irreversible effect of di-4-ANEPPS on spontaneous heart rate and ventricular impulse conduction in rabbit isolated heart model. Particularly, this should be considered when di-4-ANEPPS is used in ischemia studies in rabbit. Delayed attenuated response of such hearts to ischemia might lead to misinterpretation of obtained results.

Cardiac macrophages prevent sudden death during heart stress

Cardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and β-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death.

Substantiation of the use of indices of the heart rate variability in predicting the development of polyneuropathies in workers of coal enterprises

Introduction. One of the most common forms of occupational diseases of the peripheral nervous system is autonomic-sensory polyneuropathy. For Kuzbass, which is one of the leaders in coal mining, the problem of early diagnosis and prevention of polyneuropathies is the most urgent.The purpose of this study was to determine autonomic disorders and their role in the development of occupational polyneuropathy in workers of coal enterprises in Kuzbass.Material and methods. 72 male miners aged from 40 to 64 years with working experience from 15 to 36 years were examined. The control group consisted of 18 subjects of the same age, engaged in light physical or mental work that had no occupational risk factors. To assess the degree of peripheral nerve damage electroneuromyography was performed in all cases; indices of spectral and nonlinear heart rate variability were used to determine the state of autonomic regulation.Results. No signs of polyneuropathy were detected in 20 subjects of the examined workers of coal enterprises according to electroneuromyography data. The miners with diagnosed polyneuropathy were divided into 3 groups according to the severity of the lesion of the impulse conduction along the peripheral nerves. In the miners with no signs of polyneuropathy, who exposed to harmful production factors, a statistically significant decrease in the power of high-frequency oscillations of the heart rate variability spectrum was determined. The subjects with initial disorders of the impulse conduction showed a progressive decrease in high-frequency oscillations, with moderate signs of polyneuropathy, there were a sympathetic predominance and increased influence of suprasegmental autonomic centers. In the development of severe disorders of the impulse conduction along the peripheral nerves, depression of oscillations in all frequency ranges and rigidity of the heart rate are characteristic.Conclusion. The obtained data confirm the influence of autonomic dysfunction on the development of occupational polyneuropathy. The analysis of heart rate variability is an important tool for evaluating autonomic regulation and can be used in mass medical examinations. A decrease in spectral and nonlinear parameters in coal-mining workers is an early sign of the disorder of autonomic regulation, which allows predicting the occurrence and development of peripheral nerve damage.