Stem Cells and Heart's “Little Brain”

Abstract

Intriguing role of “little brain” neurons of heart in control of myocardium functional state is analyzed with addiction after appearance of this term in the articles by J.A. Armor on the border of the second and third millennia. The “little brain” neural network of heart modifies adrenergic and cholinergic afferent and efferent signals in accordance with functional state of brain, myocardium and heart automation nodes. Thus, the “little brain” of heart is the guarantor of implementation of stochastic principle at the level of key vital organ of mammals. It is advisable to try to find ways to optimize heart activity by influencing the “little brain” neural networks. This idea initiated an attempt by the authors to test the effectiveness of the method of perineural delivery of mesenchymal stem cells (MSCs) to damaged areas of myocardium, including “little brain” structures. First group of male Wistar rats weighing 200-220 g (n=10) was subjected to vagus damage on the right side of neck with subsequent injection of 50000 PKH67-labeled MSCs in 50 µl of phosphate buffer solution into left vagus under ketamine-xylazine-acepromazine (55.6, 5.5 and 1.1 mg/kg, respectively) anesthesia. Only vagus on the right side of neck was damaged in the second group of Wistar rats (n=8) under anesthesia. Heart rate variability disturbances were recorded in rats of both groups on the next day after the operation. Heart rate was analyzed using non-invasive pulse recorder L120E INSELT (USA). One rat from the second group died in two days after the operation, and the heart rate variability was restored in all rats of the first group. Decapitation of three animals from the first group was performed on the third day of observation, horizontal slices of heart (8 µm) were made using a Microm HM525 freezing microtome (Germany). MSCs distribution was visualized using Zeiss AxioVert 200M fluorescence microscope with Zeiss AxioCam HRm CCD camera. The dominant location of MSCs was recorded near sinoatrial and atrioventricular nodes. Ten serial heart slices were taken with the interval of 50 µm and stained in hematoxylin-eosin; structural changes were visualized using MPV-2 microscope (Leitz, Germany) with Leica DC 300F camera (Germany). An accumulation of 10-15 nerve cells, 15-25 µm in size, was found near sinoatrial and atrioventricular nodes. Therefore, experimental simulation of heart rhythm disturbances on rats allowed finding that perineural implantation of MSCs (n.vagus) is one of the ways to correct disturbed heart rhythms. Neurotrophic factors of MSCs are the basis of reparative effects, which is accompanied by an increase in efficiency of corrective action of the “little brain” neurons near sinoatrial and atrioventricular nodes. Implementation of such method in clinical practice will be an alternative or addition to surgical methods in the treatment of patients with cardiac arrhythmias.