Various artificial heart control algorithms have been proposed. 1–3 Before designing an automatic control system for an artificial heart system, it is necessary to determine the target cardiac output for the artificial heart. 1–3 For this purpose, information from the circulatory regulatory system is necessary. 4–9 Prediction of the hemodynamic parameters is desirable because the biologic system always alters over time. 10–15 Many regulatory systems in the circulation influence cardiac output. 13–17 The autonomic nerve system is a particularly important factor. 13–16 The natural heart is controlled by both sympathetic and parasympathetic nerves. This study examines the parasympathetic nervous system. This nerve is so important that many researchers have attempted to evaluate it; however, few researchers directly recorded this nerve. There are no published articles on the direct recording of vagal nerve activity in a wakeful condition except in our previous article. 17
In this study, direct recording of vagal nerve activity was attempted with hemodynamic parameter measurement in a wakeful condition. Time series data of hemodynamic derivatives and vagal nerve discharge were recorded and evaluated in consideration of an artificial heart automatic control algorithm.
Materials and Methods
Figure 1 shows the experimental preparation. In six healthy adult goats weighing 48 to 72 kg, the left pleural cavity was opened through the fourth intercostal space under mechanical ventilation after anesthesia was induced with halothane inhalation. 5–7 Electrodes for monitoring the electrocardiogram were positioned, and arterial blood pressure (BP) and left atrial pressure (LAP) were monitored continuously with catheters inserted into the artery and left atrium through the left femoral artery and left atrial appendage, respectively. After the chest was closed, the skin of the left side of the neck was incised. The left carotid artery and left vagal nerve were then exposed. Stainless steel bipolar electrodes were inserted into the vagal nerve trunk. They were then fixed to the surrounding connective tissues using plastics.
The goats were moved to a cage after the skin was closed and extubated after waking. Time series data of hemodynamic parameters and vagal nerve discharge were recorded onto the magnetic tape data recorder (TEAC RD232C, Tokyo, Japan). All data were input into a personal computer system through an analog-digital (A-D) converter. Quantitative evaluation, statistical handling, and nonlinear mathematical analysis were performed. For the dimensional analysis of the time series data using a nonlinear mathematical analyzing technique that includes chaos and fractal theory, a box-counting algorithm was used in this experiment.
Figure 2 shows an example of the time series data of the vagal nerve activity and the hemodynamic parameters recorded in a long-term animal experiment using a healthy adult goat. Burst discharge that coincided with the respiratory cycle was observed. Homonymic alteration was induced by drug administration. Figure 2 shows that methoxamine, which increases peripheral vascular resistance, was injected intravenously.
Blood pressure increased significantly, and vagal nerve discharge significantly increased. Heart rate significantly decreased according to the increase in BP. These results show the response of the central nervous system through the autonomic nervous system.
As shown in Figure 2, recording vagal nerve activity was achieved even in a wakeful condition. However, noise contamination sometimes occurred when the experimental goats moved their necks and pushed their necks against the cage bars. While the goats were standing or sitting in a resting position, a clear, stable vagal nerve activity recording with hemodynamic parameters was possible. Two of the goats’ autonomic nerve discharge were recorded for over 1 month. However, recording of the nerve discharge was terminated within 1 month in four of the goats because of excessive noise.
Figure 3 shows the alteration in the autonomic nervous system and hemodynamic parameters during changes in body position. Before one of the goats started to stand, burst discharges of the autonomic nerve was observed. Unfortunately, however, it was difficult to observe this phenomenon because of noise contamination induced by the electrodes being scratched against the cage.
We observed alteration in the autonomic nervous system before body motion. This result indicates that it possible to predict hemodynamic alteration in the next moment. The results of this study suggest the possibility of nervous control of artificial heart systems if noise contamination is reduced. In Tohoku University, we recorded autonomic nerve discharge until 1987 and succeeded in the first recording of sympathetic nerve activity while using a left ventricular assist device. Subsequent examination, including research by the National Cardiovascular Center in which renal sympathetic nerve activity was recorded, was conducted after our reports that recorded renal sympathetic nerve discharge with ventricular assistance. 1,14 Unfortunately, these reports were based on only short-term animal experiments, and few reports show autonomic nerve discharge in long-term animal experiments. In a wakeful condition, long-term animal experiments for vagal nerve recordings were successful in this study by using stainless steel electrodes attached to the vagal nerve trunk.
However, noise contamination is significant when considering the stable automatic control of artificial heart systems. We recorded the vagal nerve at the neck. In this position, the electrodes were unfortunately scratched against the cage. Thus, we plan to record the autonomic nerve in another position. Further investigation is necessary, especially into ways of avoiding noise contamination. We will continue this research aimed at nervous control of artificial heart systems.
This work was partly supported by a 21 COE program of Biomedical Engineering based on bionano technology in Tohoku University; Health and Labor Sciences Research Grants of Research on Advanced Medical Technology (H14-Nano-020); Grant-in-Aid for Scientific Research (11480253, 14657315) from the Ministry of Education, Science, Sports and Culture; and a Research Grant for Cardiovascular Diseases from the Ministry of Health and Welfare and Program for Promotion of Fundamental Studies in Health Science of Organizing Drug ADR Relief, R&D Promotion, and Product Review of Japan. The authors thank Mr. Kimio Kikuchi for the experimental preparation and kind cooperation, and Miss Yoko Itoh and Mrs. Hisako Iijima for their excellent technical assistance and kind cooperation.
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