Effect of body posture on stability and balance of occlusal contacts.

OBJECTIVE: To evaluate the effect of body posture on occlusal contact. METHODS: A total of 30 healthy subjects were evaluated. T-Scan™ III was used to analyze the center of occlusal force (COF) and occlusal force distribution while subjects remained supine (SP), upright sitting with the head fixed (UP-HFI), upright sitting with the head free (UP-HFR), and natural standing (NS). RESULTS: The total trajectory length of COF was significantly longer in NS than in SP, UP-HFI, and UP-HFR. The COF area was significantly larger in UP-HFR than in SP and UP-HFI and also significantly larger in NS than in SP, UP-HFI, and UP-HFR. The anteroposterior occlusal force distribution (AOD) in NS shifted significantly forward, compared to SP, UP-HFI, and UP-HFR. AOD in UP-HFI and UP-HFR shifted significantly forward, compared to the SP position. CONCLUSION: Changes in body posture affect the stability and anteroposterior balance of occlusal contacts.

Anti-ulcer agent teprenone inhibits hepatitis C virus replication: potential treatment for hepatitis C.

BACKGROUND: Previously we reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, inhibited hepatitis C virus (HCV) RNA replication. Furthermore, recent reports revealed that the statins are associated with a reduced risk of hepatocellular carcinoma and lower portal pressure in patients with cirrhosis. The statins exhibited anti-HCV activity by inhibiting geranylgeranylation of host proteins essential for HCV RNA replication. Geranylgeranyl pyrophosphate (GGPP) is a substrate for geranylgeranyltransferase. Therefore, we examined the potential of geranyl compounds with chemical structures similar to those of GGPP to inhibit HCV RNA replication. METHODS: We tested geranyl compounds [geranylgeraniol, geranylgeranoic acid, vitamin K(2) and teprenone (Selbex)] for their effects on HCV RNA replication using genome-length HCV RNA-replicating cells (the OR6 assay system) and a JFH-1 infection cell culture system. Teprenone is the major component of the anti-ulcer agent, Selbex. We also examined the anti-HCV activities of the geranyl compounds in combination with interferon (IFN)-α or statins. RESULTS: Among the geranyl compounds tested, only teprenone exhibited anti-HCV activity at a clinically achievable concentration. However, other anti-ulcer agents tested had no inhibitory effect on HCV RNA replication. The combination of teprenone and IFN-α exhibited a strong inhibitory effect on HCV RNA replication. Although teprenone alone did not inhibit geranylgeranylation, surprisingly, statins' inhibitory action against geranylgeranylation was enhanced by cotreatment with teprenone. CONCLUSIONS: The anti-ulcer agent teprenone inhibited HCV RNA replication and enhanced statins' inhibitory action against geranylgeranylation. This newly discovered function of teprenone may improve the treatment of HCV-associated liver diseases as an adjuvant to statins.

Oxidative stress induces anti-hepatitis C virus status via the activation of extracellular signal-regulated kinase.

UNLABELLED: Recently, we reported that beta-carotene, vitamin D(2), and linoleic acid inhibited hepatitis C virus (HCV) RNA replication in hepatoma cells. Interestingly, in the course of the study, we found that the antioxidant vitamin E negated the anti-HCV activities of these nutrients. These results suggest that the oxidative stress caused by the three nutrients is involved in their anti-HCV activities. However, the molecular mechanism by which oxidative stress induces anti-HCV status remains unknown. Oxidative stress is also known to activate extracellular signal-regulated kinase (ERK). Therefore, we hypothesized that oxidative stress induces anti-HCV status via the mitogen activated protein kinase (MAPK)/ERK kinase (MEK)-ERK1/2 signaling pathway. In this study, we found that the MEK1/2-specific inhibitor U0126 abolished the anti-HCV activities of the three nutrients in a dose-dependent manner. Moreover, U0126 significantly attenuated the anti-HCV activities of polyunsaturated fatty acids, interferon-gamma, and cyclosporine A, but not statins. We further demonstrated that, with the exception of the statins, all of these anti-HCV nutrients and reagents actually induced activation of the MEK-ERK1/2 signaling pathway, which was inhibited or reduced by treatment not only with U0126 but also with vitamin E. We also demonstrated that phosphorylation of ERK1/2 by cyclosporine A was attenuated with N-acetylcysteine treatment and led to the negation of inhibition of HCV RNA replication. We propose that a cellular process that follows ERK1/2 phosphorylation and is specific to oxidative stimulation might lead to down-regulation of HCV RNA replication. CONCLUSION: Our results demonstrate the involvement of the MEK-ERK1/2 signaling pathway in the anti-HCV status induced by oxidative stress in a broad range of anti-HCV reagents. This intracellular modulation is expected to be a therapeutic target for the suppression of HCV RNA replication.

The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication.

Cellular responses to DNA damage are crucial for maintaining genome integrity, virus infection, and preventing the development of cancer. Hepatitis C virus (HCV) infection and the expression of the HCV nonstructural protein NS3 and core protein have been proposed as factors involved in the induction of double-stranded DNA breaks and enhancement of the mutation frequency of cellular genes. Since DNA damage sensors, such as the ataxia-telangiectasia mutated kinase (ATM), ATM- and Rad3-related kinase (ATR), poly(ADP-ribose) polymerase 1 (PARP-1), and checkpoint kinase 2 (Chk2), play central roles in the response to genotoxic stress, we hypothesized that these sensors might affect HCV replication. To test this hypothesis, we examined the level of HCV RNA in HuH-7-derived cells stably expressing short hairpin RNA targeted to ATM, ATR, PARP-1, or Chk2. Consequently, we found that replication of both genome-length HCV RNA (HCV-O, genotype 1b) and the subgenomic replicon RNA were notably suppressed in ATM- or Chk2-knockdown cells. In addition, the RNA replication of HCV-JFH1 (genotype 2a) and the release of core protein into the culture supernatants were suppressed in these knockdown cells after inoculation of the cell culture-generated HCV. Consistent with these observations, ATM kinase inhibitor could suppress the HCV RNA replication. Furthermore, we observed that HCV NS3-NS4A interacted with ATM and that HCV NS5B interacted with both ATM and Chk2. Taken together, these results suggest that the ATM signaling pathway is critical for HCV RNA replication and may represent a novel target for the clinical treatment of patients with chronic hepatitis C.

HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A.

Cyclosporine A (CsA) is a well-characterized anti-HCV reagent. Recently it was reported that the genotype 2a JFH-1 strain was more resistant than genotype 1 HCV strains to CsA in a cell culture system. However, the JFH-1 responsible region for the resistance to CsA remains unclear. It was also demonstrated that in genotype 1b HCVs, NS5B interacts with cyclophilin (CyP). To clarify whether or not NS5B of JFH-1 is significant for CsA resistance, we developed a chimeric replicon with NS5B of JFH-1 in the genotype 1b backbone. The chimeric replicon was more resistant to CsA than the parental genotype 1b replicon. Furthermore, reduction of CyPA had a greater effect on HCV RNA replication and sensitivity to CsA than reduction of CyPB. Here, we demonstrated that NS5B of JFH-1 contributed to this strain's CsA-resistant phenotype. NS5B and CyPA are significant for determining HCV's sensitivity to CsA.

Development of a hepatitis C virus relapse model using genome-length hepatitis C virus ribonucleic acid-harboring cells possessing the interferon-alpha-resistance phenotype.

AIM: The cure rate of current interferon (IFN) therapy is limited to approximately 50% and most of the relapses after therapy are caused by genotype-1. To develop a relapse model in cell culture, we attempted to obtain genome-length hepatitis C virus ribonucleic acid (HCV RNA) harboring cells possessing the IFN-alpha-resistance phenotype from previously established OR6 cells, which enabled the luciferase reporter assay for monitoring of HCV RNA replication. METHODS: The IFN-alpha-resistant HCV RNA-harboring cells and control cells were obtained by the treatment of OR6 cells with and without IFN-alpha, respectively. Then, we examined the relapse of HCV in IFN-alpha-resistant HCV RNA-harboring cells. RESULTS: Only type I IFN (alpha and beta) showed significantly different anti-HCV activity between IFN-alpha-resistant HCV RNA-harboring cells and control cells. There was no significant difference in the anti-HCV activity of IFN-gamma, fluvastatin, or cyclosporine A between the two types of cells. Furthermore, we showed that fluvastatin or cyclosporine A in combination with IFN-alpha could prevent the relapse after therapy in the IFN-alpha-resistant HCV RNA-harboring cells. CONCLUSION: We developed a HCV relapse model in cell culture using IFN-alpha-resistant HCV RNA-harboring cells. Thus anti-HCV reagents, which have a mechanism different from IFN-alpha, were shown to be useful for preventing a relapse of IFN-alpha-resistant HCV.

New efficient replication system with hepatitis C virus genome derived from a patient with acute hepatitis C.

We report for the first time a new RNA replication system with a hepatitis C virus (HCV) strain (AH1) derived from a patient with acute hepatitis C. Using an HCV replicon RNA library constructed with the AH1 strain (genotype 1b), we first established a cloned cell line, sAH1, harboring the HCV replicon. Cured cells obtained with interferon treatment of sAH1 cells were used for transfection with genome-length HCV RNA possessing four mutations found in sAH1 replicon. Consequently, one cloned cell line, AH1, supporting efficient replication of genome-length HCV RNA was obtained. By the comparison of AH1 cells with the O cells supporting genome-length HCV RNA (HCV-O strain) replication, we found different anti-HCV profiles of interferon-gamma and cyclosporine A between AH1 and O cells. Reporter assay analysis suggests that the diverse effects of interferon-gamma are due to the difference in HCV strains, but not the cellular environment.

DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication.

DDX3, a DEAD-box RNA helicase, binds to the hepatitis C virus (HCV) core protein. However, the role(s) of DDX3 in HCV replication is still not understood. Here we demonstrate that the accumulation of both genome-length HCV RNA (HCV-O, genotype 1b) and its replicon RNA were significantly suppressed in HuH-7-derived cells expressing short hairpin RNA targeted to DDX3 by lentivirus vector transduction. As well, RNA replication of JFH1 (genotype 2a) and release of the core into the culture supernatants were suppressed in DDX3 knockdown cells after inoculation of the cell culture-generated HCVcc. Thus, DDX3 is required for HCV RNA replication.

A new living cell-based assay system for monitoring genome-length hepatitis C virus RNA replication.

We previously developed a cell-based luciferase reporter assay system for monitoring genome-length hepatitis C virus (HCV) RNA replication (OR6 assay system). Here, we aimed to develop a new living cell-based reporter assay system using enhanced green fluorescent protein (EGFP). Genome-length HCV RNAs encoding EGFP were introduced into a subline of HuH-7 cells and G418 selection was performed. One cloned cell line, OGF7, was successfully selected from among the several G418-resistant cell lines obtained, and the robust expression of HCV RNA and proteins in OGF7 cells was confirmed. The fluorescent intensity of OGF7 cells was decreased by interferon-alpha treatment in a dose-dependent manner, and it correlated well with the HCV RNA concentration. We demonstrated that the interferon-alpha sensitivity in the OGF7 assay system measuring the fluorescent intensity was equivalent to that of the OR6 assay system, and that the OGF7 assay system was useful for quantitative evaluation of anti-HCV reagents. The OGF7 assay system is expected to be the most time-saving and inexpensive assay system for high-throughput screening of anti-HCV reagents.

Serum-free cell culture system supplemented with lipid-rich albumin for hepatitis C virus (strain O of genotype 1b) replication.

HuH-7 is a highly differentiated hepatoma cell line and the only cell line that supports robust RNA replication of the hepatitis C virus (HCV). HuH-7 cells cause cell death in serum-free culture condition. However, the effect is reversed by supplementation with selenium. Serum-free cell cultures are advantageous for vaccine development and experimental reproducibility. However, HCV RNA replication in HuH-7 cells in serum-free medium had not yet been achieved. Therefore, we tried to develop a system for robust HCV RNA replication in a serum-free cell culture. Although HuH-7 cells grew in serum-free medium in the presence of selenium, HuH-7 cells under these conditions did not support HCV RNA replication in long-term culture. Among the supplements tested, serum-free medium with lipid-rich albumin (LRA) was found to yield robust HCV RNA replication. HCV proteins were detected for more than 9 months in serum-free medium supplemented with LRA. This is the first report to demonstrate a long-term, serum-free cell culture that successfully maintained robust HCV RNA replication. This cell culture system is expected to be a useful tool for vaccine development, as well as for further investigation of cellular factors that are essential for HCV RNA replication.

Cell culture-adaptive NS3 mutations required for the robust replication of genome-length hepatitis C virus RNA.

We recently established a genome-length HCV RNA-replicating cell line (O strain of genotype 1b; here called O cells) using cured cells derived from sO cells, in which HCV subgenomic replicon RNA with an adaptive NS5A mutation (S2200R) is replicated. Characterization of the O cells revealed a second adaptive NS3 mutation (K1609E) required for genome-length HCV RNA replication. To clarify the role of adaptive mutation in genome-length HCV RNA replication, we newly established one and three kinds of genome-length HCV RNA-replicating cell lines possessing the cell background of sO and O cells, respectively, and found additional adaptive NS3 mutations (Q1112R, P1115L, and E1202G) required for the robust replication of genome-length HCV RNA. We further found that specific combinations of adaptive NS3 mutations drastically enhanced HCV RNA replication, regardless of the cell lines examined. These findings suggest that specific viral factors may affect the replication level of genome-length HCV RNA.

cDNA microarray analysis of lactoferrin expression in non-neoplastic human hepatocyte PH5CH8 cells.

Lactoferrin (LF), a milk protein belonging to the iron transporter transferrin family, is known as a primary defense protein against pathogenic microorganisms. Previously, we found that bovine and human LFs prevented hepatitis C virus infection in cultured human hepatocytes by a direct interaction with the virus. Since LF is proposed to have transcriptional regulatory activity in addition to its antimicrobial function, we sought to identify the target genes that these two types of LF have in common. To this end, we were the first to perform microarray analysis (9970 genes) using human hepatocytes that expressed bovine or human LF by retrovirus-mediated gene transfer. In the results, LF could give a variety of expression profiles in the human hepatocytes, and showed that 9 and 19 genes were commonly up-regulated (more than 2.0-fold) and down-regulated (less than 0.50-fold), respectively, in both bovine and human LF-expressing cells compared with control cells. Among these genes, we found that gamma-aminobutyric acid (GABA)-B receptor 2 was transcriptionally down-regulated by bovine and human LFs, but not by human transferrin. Furthermore, we obtained the suggestive result that LF may modulate the level of intracellular cAMP. This modulation is one of the cellular responses that the GABA-B receptor modifies. This is the first report of microarray analysis applied to search inclusively for the target genes of LF.

Indirect flow rate estimation of the NEDO PI Gyro pump for chronic BVAD experiments.

In totally implantable ventricular assist device systems, measuring flow rate of the pump is necessary to ensure proper operation of the pump in response to the recipient's condition or pump malfunction. To avoid problems associated with the use of flow probes, several methods for estimating flow rate of a rotary blood pump used as a ventricular assist device have been studied. In the present study, we have performed a chronic animal experiment with two NEDO PI gyro pumps as the biventricular assist device for 63 days to evaluate our estimation method by comparing the estimated flow rate with the measured one every 2 days. Up to 15 days after identification of the parameters, our estimations were accurate. Errors increased during postoperation days 20 to 30. Meanwhile, their correlation coefficient r was higher than 0.9 in all the acquired data, and estimated flow rate could simulate the profile of the measured one.

cDNA microarray analysis to compare HCV subgenomic replicon cells with their cured cells.

The hepatitis C virus (HCV) replicon system carrying autonomously replicating HCV subgenomic RNA in human hepatocyte cells is a potent tool for basic studies of HCV, such as viral replication and drug development. Recently, we developed two HCV subgenomic replicons (50-1 and 1B-2R1) derived from two HCV strains, 1B-1 and 1B-2, respectively. Since the expression of HCV proteins is thought to affect the host cells' gene expression profiles, we attempted to identify target genes of HCV proteins using microarray analysis (9970 genes) by comparing 50-1 and 1B-2R1 replicon cells with their "cured cells", from which the replicons had been eliminated by prolonged treatment with interferon-alpha. The results showed that HCV replicons could have a variety of expression profiles in human hepatocytes. The results also showed that 2 and 6 genes were commonly up-regulated (more than 2.0-fold) and down-regulated (less than 0.50-fold), respectively, in both 50-1 and 1B-2R1 replicon cells compared with their cured cells. The differential expression profiles of genes selected by the microarray analysis were confirmed with standard RT-PCR and real-time LightCycler PCR. It was noteworthy that the commonly down-regulated genes contained large multifunctional proteases 2 and 7, which are known as catalytic subunits of immunoproteasome, and serine proteinase inhibitor clade C. Our microarray analysis demonstrated that HCV subgenomic replicons can change the gene expression profiles of host cells, and it allowed us to compile the first list of genes that the replicons transcriptionally regulate.

Non-linear dynamic analysis of hemodynamic behavior during virtual reality immersion.

Several years ago, a famous accident occurred in Japan. Hundreds of children, who were watching a cartoon on television, suddenly complained of spasms and vertigo, and were taken to hospital. In this study, the autonomic nervous system was evaluated during audiovisual stimulation with three dimensional Virtual Reality (VR) imaging. In our previous studies, we designed the diagnosis machine for an autonomic function using multi-parameters, including electrocardiography, arterial blood pressure, respiration and stroke volume as detected by ultrasonic cardiography. Healthy adult volunteers were used in this experiment with their satisfactory informed consent. The three-dimensional content for VR included dinosaur images in a pre-historic scene. The content was projected on a wide screen and volunteers watched an audiovisual screen for about 20 minutes and the 3-D and 2-D images were compared. There was no significant arrhythmia during experiments in both images. No significant alteration was observed in the quantified hemodynamic data during the experiment. Spectral analysis was performed to evaluate the heart rate variability (HRV) during the experiment. LF, HF and LF/HF of HRV were calculated. However, there were no significant changes during the experiment. Significant change was observed in the fractal dimension of the stroke volume during 2-D and 3-D image VR immersion. Our results suggest that a significant response was observed in the autonomic function according to the 2-D or 3-D images. Our study, which aims at safe audiovisual stimulating equipment, must be developed.

Can personality traits predict pathological responses to audiovisual stimulation?

The "Pockemon shock" is the most famous accident in the history of the broadcasting industry in Japan. Based on the experiences of this unfortunate accident from famous animation program "Pocket Monster", this study focused on the psychology and psychosomatics of the patients. A head-mounted display was used as the three-dimensional image presentation device and "Descent", a free software shooting game, was used as the software. Ten healthy adult male volunteers were used in this experiment after obtaining their informed consent. The oxygen metabolic change in the anterior lobe of the brain was measured by near infrared spectroscopy and recorded on an electrocardiogram. The mental scaling tendency of the object was analyzed using the type A behavior pattern and the hostility scaling. The Cook and Medley hostility (HO) scale from the Minnesota multiphasic personality inventory (MMPI) was also used in this experiment. From this scaling methodology, the paranoid scale, cynicism scale, lie scale, social support quality and social support quantity were calculated. All measured time series data were kept in the normal range, and no fatal arrhythmia or epilepsy were observed during experiments. In some cases, the brain oxygen metabolism may completely differ for the objects of Type A and Type B behavior patterns. On the whole, correlation did not become significant in type A scaling and hostility scaling. In a comparison of the percent changes of the HF in HRV with lie scaling, significant negative correlation was observed. The social support quantity was calculated from Cook and Medley, and significant negative correlations were observed with percent changes of LF/HF in HRV. The lie scale and social support quantity are opposite scaling. The sympathetic nervous system and parasympathetic nervous system have an opposite function also. Therefore, our results showed an interesting phenomenon, when considering the relationship between the autonomic function and the pathophysiological reaction to the audiovisual stimulations. As for the photo sensitive epilepsy, it was reported to be only 5-10% for all patients. Therefore, 90% or more of the cause could not be determined in patients who started a morbid response. The results in this study suggest that the autonomic function was connected to the mental tendency of the objects. By examining such directivity, it is expected that subjects, which show morbid reaction to an audiovisual stimulation, can be screened beforehand.

Artificial myocardium with an artificial baroreflex system using nano technology.

Where is the place which should be helped in a patient with congestive heart failure? The answer may be contraction of the heart. At Tohoku University, development research of "the artificial myocardium" has been conducted, using a ball screw type electromagnetic motor. Furthermore, super-miniaturization is being attempted at present. Thus, a system with shape memory alloy is being developed. The cooling speed problem was solved by the application of the Peltier element. A drive at a speed equal to that of a heartbeat was realized by the application of this system. At present, a ventricular assist device is used for patients waiting for a heart transplant in Japan. An air driven type system disturbs a patient's QOL remarkably because it is connected to the drive device. With our concept, energy is provided by using the electromagnetic force from outside of the body by the use of transcutaneous energy transmission system. Magnetic shielding by amorphous fibers was used at Tohoku University to improve the total efficiency. A natural heart can alter the cardiac output corresponding to the demand. Artificial internal organs must participate in the system of the living body, too. Tohoku University has developed a resistance based artificial heart control algorithm, which simulated a baroreflex system to cope with every demand. Nano level sensing equipment is now under development at Tohoku University. At present, development is being conducted aiming at an "intelligent artificial myocardium".

Fluctuations of the Hemodynamic Derivatives During Left Ventricular Assistance Using Oscillated Blood Flow.

To analyze the autonomic nervous system during left heart bypass with a vibrating flow pump (VFP), fluctuations in hemodynamic derivatives were evaluated by the spectral analysis method using fast fourier transform methodology. After the left pleural cavity was opened through the fourth intercostal space under general anesthesia, a VFP was implanted as the left heart bypass device in chronic animal experiments using 3 healthy adult goats. Hemodynamic parameters with and without VFP assistance were recorded on magnetic tape in awake animals and were analyzed by computer through an analog to digital convertor. Power spectral analysis was performed on a beat-to-beat basis for the evaluation of the fluctuations. During left heart bypass with the VFP, Mayer wave fluctuations were decreased significantly although respiratory waves were not changed significantly. These results suggest that sympathetic nervous system modulation was changed under the influences of the left heart bypass with VFP. By using this analysis methodology, truly physiologic ventricular assistance may be achieved.

Sensorless estimation of pressure head and flow of a continuous flow artificial heart based on input power and rotational speed.

The present study has proposed a new method for estimating the pressure head (P(t)[mm Hg]) and flow (Q(t)[L/min]) of a centrifugal pump on the basis of voltage (V(t)[V]), current (I(t)[A]), and rotational speed (N(t)[k(rpm)]) of the DC motor for a pump without any additional sensors. In the proposed estimation method, two auto-regressive exogenous (ARX) models are employed. One ARX model has an output, P(t) or Q(t), and three inputs, VI(t) = V(t)I(t) and N(t) and the steady state gain (K) of the system from VI(t) to N(t). It can be assumed that K may include the information on viscosity of blood. The coefficient parameters of this ARX model are identified in an off-line fashion before implantation of the pump. After implantation, P(t) or Q(t) is estimated by the same ARX model with the already identified parameters. The other ARX model is used to identify Kon the basis of VI(t) and N(t) in an on-line fashion every time the viscosity of blood may change. In the experiment, a mock circulatory system consisting of a centrifugal pump and a reservoir with 37% glycerin or water was employed. The root mean square error between measured Q(t) and its estimate obtained from the proposed method was 1.66L/min. On the other hand, a different method based on a single ARX model with inputs of VI(t) and N(t), but without the additional input of K, yielded the corresponding estimation error of 2.22L/min. This means that the proposed method can reduce its estimation error by about 25% in comparison with a method that cannot cope with the change in blood viscosity.

Recording vagal nerve activity for the control of an artificial heart system.

Monitoring cardiovascular control system information is important in considering the quality of life (QOL) of patients with artificial hearts. Natural heart circulation is controlled by an autonomic nervous system. Therefore, it is desirable to record autonomic nerve activity for the control of artificial heart systems. We directly recorded vagal nerve activity in long-term animal experiments. Six healthy adult goats were anesthetized with halothane inhalation, and thoracotomy was performed with the fourth rib resection during mechanical ventilation. Arterial blood pressure and right and left atrial pressures were continuously monitored with an inserted catheter. Cardiac output was measured by an electromagnetic flow meter attached to the ascending aorta. After the chest was closed, an incision was made in the left neck, and the left vagal nerve was separated. Stainless steel electrodes were inserted into the vagal nerve and fixed by a plasticizer. After the incision was closed, the goats were transferred to a cage and extubated after waking. Vagal nerve activity was measured using hemodynamic parameters when the animals were awake. Our results show that clear observation of autonomic nerve discharge was made through this experimental system for over 1 month. The tonus of the vagal nerve was significantly altered before body motion with hemodynamic changes, suggesting the possibility of prediction. These results suggest that information from autonomic nerves may help to control implantable artificial hearts or ventricular assist devices.