| Arrhythmia is a common cardiovascular disease by a variety of reasons, which areoften considered to be signs of heart disease. Although drug therapy has become themain treatment of arrhythmia in recent years, due to the complicated drugcombination and the strong side effect, drug treatment can not meet the needs of thecommon patient’s medication treatment. Previous studies showed that the vagus nerveplayed an important role in regulating heart rate variability. Vagus stimulation waseffective to regulate the heart rate. Also, it was seemed to be the potential therapeuticmethod to treat tachycardia, atrial fibrillation (AF), myocardial infarction (MI) andangina pectoris. Because of the rapid development of microelectronics technology,implanted microchip that regulates biological function has become an emergingresearch focus. In addition to the common characteristics of other implantablemedical device, the implanted chip system also has some special functions, such as,automatic control, exchanging information with the body, regulating the body’sphysiological functions and communicating with in vitro host. However, at present,most of the implanted microelectronic devices are open-loop control, the human bodyis a complex closed-loop control system, and both the input and output of informationhave a high level of feedback on it. Open-loop control is not safe and reliable toregulate the human system when the body physiological function is defect. Moreover,most of the experiments of heart rate regulation were in acute anesthetic state, therewas no report about implanted closed-loop to regulate the heart rate in chronicconscious animals in our country. Therefore, on the basis of the blood regulation, our lab has transformed the implanted chip system which was invented to regulate theblood pressure. We combined the closed-loop regulation and vagus nerve stimulation,regulated the heart rate of the rabbits in the awake state in long-term.The chip system is mainly composed by two parts: the slave machine and themaster machine. The slave machine is a low-power dissipation and low nosiemicro-processing chip which used to peocess the biomedical signals. It collected theECG (electrocardiography) signals from ECG amplifier circuit, at the same time; thechip gave corresponding frequency of stimulation pluses according to real-timesampling of the ECG signal processing results. The pluse acted on the right vagusnerve to regulate the heart rate. The master machine communicated with the slavemachine via wireless RF (radio frequency) and communicated with the computer bythe USB interface. The master machine transmitted the collected signals to thecomputer and transmitted commands to control the slave machine. The monitoringsoftware was a self-developed MD2000WL data acquisition system (Nanjing MedicalUniversity) which was running on Windows-based PC’s. It can regulate the heart ratein the way of changing the real-time parameters of the chip through the mastermachine.Firstly, we gave the chip basic tests in vitro to comfirm that the system works well.Then, we bagan experiments of the heart rate regulation. The rabbits wereanesthetized with ear vein injection of pentobarbital sodium (1.0g/kg). A middleincision was made on the neck and isolated the right vagus nerve. The slave machinewas implanted into the abdomen. All wires traveling along the subcutaneous tunnels.Meanwhile, the recording electrodes were placed in the chest subcutaneous with oneat the cardiac apex and the other at the cardiac base to record the ECG signals.Ground stimulation was placed between the neck and the chest. After two hours ofrecovery from anesthesia, the rabbits were subjected a chonic experiment. The period of the experiment was one week, and each test animal experienced1-h regulation and1-h recovery. ECG was recorded throughout the experiment to make sure that the chipsystem was reliable and the wireless communication was smooth. The primaryfindings were as follow:1. Chip evaluation: The chip worked well. The ECG signals were successfullyrecorded in one week of HR regulation experiment. The closed-loop systemwas confirmed to be stable.2. Effect of chip system in regulating HR: The chonic experiment data showthat there was significant decreases in HR during the regulation (-24.2±6.5bpm, P<0.01, n=6) compared with the baseline. After the resetting wasstopped, the HR recoverd to normal.The results of this study have shown that the implanted closed-loop chipsystem could work well in conscious animals in vivo without problems. Duringthe regulating period, the chip system could effectively reduce the rabbits’ HR tothe set point, and the HR could restore to the normal level. This study successfullyestablished real-time control physiological functions in cocnsious animals withthe implanted chip system. It has built a good platform for chronic experimentalstudy and clinical application of implanted chips. |
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