Atypical Antiadrenergic Effect of Refralon as a Mechanism of High Antiarrhythmic Effectiveness.

We studied the effect of Refralon on the electrophysiological properties of the supraventricular myocardium against the background of adrenergic (epinephrine) influence in the zone of the pulmonary veins, the area where 50-90% of atrial arrhythmias is triggered. The experiments were carried out on isolated tissue preparations of Wistar rats. The multichannel microelectrode array technique was used to record action potentials simultaneously in the atrium and in the ostium and distal parts of the pulmonary veins. Epinephrine application (12-50 nM) led to depolarization of the resting potential and the conduction block in the distal part of the pulmonary veins. Refralon (30 µg/kg) restored the resting potential in the distal part of the pulmonary veins. Against the background of epinephrine, Refralon did not significantly change the duration of the action potential at 90% repolarization in comparison with control. At the same time, the comparison drug E-4031 against the background of epinephrine significantly increased the duration of action potential in the atrium and in the ostium of the pulmonary veins, and sotalol increased it only in the ostium. Neither E-4031, nor sotalol restored conduction in their distal part. Refralon has a biphasic effect under conditions of adrenergic stimulation: the fast component is responsible for stabilizing the resting potential in the pulmonary vein and reduces the dispersion of action potential duration in the atrium and pulmonary vein and is also quickly washed away, and the slow component is responsible for the increase of the action potential duration and is slowly washed away.

Orbital angular momentum and informational entropy in perturbed vortex beams.

We theoretically and experimentally investigated transformations of vortex beams subjected to sector perturbations in the form of a hard-edged aperture. The transformations of the vortex spectra, the orbital angular momentum (OAM), and the informational entropy of the perturbed beam were measured. We found that relatively small angular sector perturbations have almost no effect on the OAM, although the informational entropy is rapidly increasing due to the birth of new optical vortices caused by diffraction at the diaphragm edges. At large perturbation angles, the uncertainty principle between the angle and OAM involves vortices, with both positive and negative topological charges, so that the OAM decreases to almost zero, and the entropy increases sharply.

[Types of Conduction Disturbances in Pulmonary Veins].

Recently, the notion that in 60-80 % of cases the origin of the pulmonary veins (PV) is the place of origin of atrial fibrillation (AF) has become widespread. It has been shown that in this area, under the action of norepinephrine (HA), in the absence of stimulation, an intrinsic rhythm appears. Using two-channel microelectrode leads (from the mouth and distal part of the PV) in rats weighing 350-450 grams, it was found that: 1) in the distal part of PV there are cells with depolarized resting potential (RP) up to -50 mV, which under normal conditions are not excitable; 2) in 17 experiments out of 23, various blocks of excitation conduction along PV were revealed; 3) in 8 experiments out of 23, a reflected excitation wave - echo from PV - was recorded. Myocardium of PV is an extremely heterogeneous medium with a strong variance in the duration of the action potential and variable rate of conduction, which contributes to the occurrence of different types of conduction blocks and causes echoes and other rhythm disturbances.

[The Myocardial Sleeves of the Pulmonary Veins: Potential Implications For Atrial Fibrillation].

Pulmonary veins (PVs) are thought to play an important role in the initiation of atrial fibrillation. However, systematic microelectrode studies from different regions of the left atria and PV myocardium remain limited. METHODS AND RESULTS: A 2-microelectrode technique was used to characterize electrophysiological properties of rat left atrial and PV myocardium, at baseline and during electrical stimulation. PV myocardium was characterized by prolonged action potential duration (APD) (74+/-2 ms in the PV mouth vs. 59+/-3 ms in the left atriul, p<0.01), high degree of APD alternans, and spontaneous depolarizations of resting membrane potential recorded without electrical stimulation. In the distal part of the PV, we found an unexcitable area which was characterized by a depolarized resting potential (50+/-4 mV vs. 82+/-2 mV in the left atrium, p<0.01) and conduction blocks. CONCLUSION: PV myocardium demonstrates a high degree of action potential duration heterogeneity and conduction discontinuities which may form a functional substrate for reentrant arrhythmias and provoke atrial fibrillation.

[Possible role of autophagy activation in the stimulation of regeneration].

Human cell senescence occurs unevenly and senescent cells in tissues frequently can disturb the function of neighbouring nonsenescent ones. Setting of tissues regeneration can have profound practical significance in medicine, especially in geriatrics. One of the approaches to solve the problem is selective elimination of senescent and damaged cells from the tissues that can be the first phase of the process. During the investigation of the mechanisms of action of the preparation for hair growth stimulation it was discovered that this preparation does not stimulate proliferation of various human cells and does not increase the resistance of cells to stress. On the contrary the preparation becomes cytotoxic at the conditions of oxidative stress although on its own account it did not induce elevation of production of reactive oxygen species. Further investigations showed that the preparation increases transcriptional activity of p53 gene, increase autophagy level and induce weak adipogenic differentiation. The hypothesis of autophagic regeneration is discussed. As a result, the selective autophagic cell death of any senescent and damaged cells that undergoes oxidative stress triggers the regeneration process which can be increased by both the rejuvenation effect of increased autophagy and at the expense of nutrients released during the autophagy.

Evaluation of the greater omentum in the treatment of experimental lymphedema.

Despite advances in microsurgery, the most suitable operation for primary lymphedema remains unclear. A variety of tissue transplants and artificial substances have been used to facilitate drainage of peripheral lymph. The greater omentum, for example, has absorptive lymph draining capability, fights infection, and is expendable for the abdomen. Previous attempts to use the omentum in treatment of clinical lymphedema have, however, been disappointing. This discrepancy between theory and outcome prompted us to reevaluate the role of the omentum in the treatment of chronic lymphedema. In rabbits, mobilization of omentum was carefully examined by three separate techniques and the presence of natural lymph nodal-venous (L-V) shunts determined by an injection of Evans blue into the omentum with sampling later of plasma from the gastroepiploic venous blood. In dogs after promotion of unilateral chronic hindlimb lymphedema by soft tissue excision and sclerosis, the results of four methods of omental transplantation with or without L-V shunt for relief of lymphedema were compared. The results in rabbits suggest that although the greater omentum can be lengthened without jeopardizing its blood supply, it is inappropriate to lengthen it based on blood vascular arcades alone because the omental lymphatics do not strictly follow these arcades in the more distal portion, and with elongation, may be interrupted even though the blood supply remains intact. Moreover, because there is no natural L-V shunt within the greater omentum, the addition of a L-V shunt in dogs in addition to omental transplantation seems to increase effectiveness of the omentum for draining hindlimb lymph after its autotransplantation.

Autotransplantation of the greater omentum in the treatment of chronic lymphedema.

We evaluated the use of transplantation of the greater omentum in the management of chronic lymphedema in 21 patients. The omentum provides a large surface with fluid absorbing capability and potentially therefore is useful in management of patients with primary or hypoplastic peripheral lymphatics. Based on the angio- and lymphangio-architecture of the gastroepiploic architecture, we used large segments of greater omentum as a free autotransplant with microrevascularization to the femoral or axillary artery and vein thereby avoiding technical drawbacks of a pedicle graft with the feeding vessels traversing the abdomen. Elongation of the omentum must be done properly because omental lymphatic arcades do not consistently follow the blood vascular arcades in its more distal part. Accordingly, if not properly mobilized the blood supply may be retained whereas the lymph circulation is interrupted. We combined omental implantation with lymph nodal-venous anastomoses using an omental vein with a nearby systemic venous tributary. In 19 of the 21 patients followed from 3 months to 2 years after operation, remission of lymphedema was good (reduction in swelling more than 50%) in 14 patients and satisfactory in 5 (approximately 25-50% reduction in swelling) with improvement gradually increasing with the passage of time.

Enteromesenteric bridge in the treatment o primary lymphedema--a case report.

Technical details and associated problems of enteromesenteric bridging operation for primary lymphedema (proximal obstructive hypoplasia) are discussed. The short term results are encouraging.