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Effect of left ventricular assistance on sympathetic tone.

To determine the effect of left ventricular assist device (LVAD) pumping on sympathetic tone, renal sympathetic nerve activity (RSNA) was detected in acute animal experiments. Our TH-7B pneumatically driven, sac-type ventricular assist device was used in 7 adult mongrel dogs. RSNA was detected by the use of bipolar electrodes attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator circuit. The area of the integrated nerve discharge per unit time was calculated in the computer system and expressed as RSNA per unit time. During LVAD pumping, RSNA decreased with increase in blood pressure, with an increase in pulmonary artery flow, and with a decrease in left atrial pressure. These data suggest that LVAD has an effect on the sympathetic nervous system which is mediated by the aortic and cardiopulmonary baroreflex system.

Fundamental Rhythm of Sympathetic Nerve Discharges in Animals with Total Artificial Hearts

To evaluate the effect of total artificial heart replacement on the autonomie nervous system, sympathetic neurograms were analyzed by power spectrum and coherence function. Two pneumatically driven, sac type ventricular assist devices were implanted as biventricular bypasses (BVB) in adult, mongrel dogs. After initiation of BVB pumping, the natural heart was electrically fibrillated to form a BVB TAH model. Renal sympathetic nerve activity (RSNA) was recorded using a bipolar electrode attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator. Power spectra of the RSNA and values of squared coherence between the arterial pressure wave form and the RSNA were calculated by computer. In animals with total artificial hearts (TAHs), coherence at the cardiac rhythm frequency was decreased, and coherence at the TAH pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed in TAH animals contributed to the sympathetic neurogram.

Estimation of the following Cardiac Output Using Sympathetic Tone and Hemodynamics for the Control of a Total Artificial Heart

A sympathetic neurogram is potentially useful for the development of a real time total artificial heart (TAH) control system. We used sympathetic tone and hemodynamic derivatives to estimate the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was employed as a parameter of sympathetic tone. Equations for the following cardiac output were calculated using multiple linear regression analysis of the time series data. A significant correlation was observed between the estimated and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system.

Chaotic behavior of hemodynamics with ventricular assist system.

In order to analyze hemodynamic parameters during left ventricular assistance as an entity and not as decomposed parts, non-linear mathematical techniques were utilized. Pneumatically actuated ventricular assist systems (VAS) were implanted as left heart bypasses in acute animal experiments, using healthy adult mongrel dogs. By the use of the non-linear mathematical technique, the arterial blood pressure waveform (AP) was embedded into the four-dimensional phase space and projected into the three-dimensional phase space. The Lyapunov numerical method was used as an adjunct to the graphical analysis of the state space. The phase portrait of the attractor showed a complex structure; a three dimensional solid torus with a screw type structure as a part, suggesting deterministic chaos in the AP without left ventricular assistance. Positive lyapunov exponents confirmed the existence of chaos. During counterpulsation mode left ventricular assistance, the phase portrait of the attractor showed a more complex structure, and positive Lyapunov exponents suggested a greater dimensional deterministic chaos. However, non-structured patterns were seen in the phase space during internal mode VAS driving, suggesting the possibility of dissipative dynamics in the four dimensional phase space. These results suggest that the cardiovascular system with counterpulsation mode VAS driving is in a homeochaotic state, which is thought to be a flexible and intelligent control system. And there is greater dimensional complex dynamics in the circulatory regulatory system with VAD during internal mode assistance.

DEVELOPMENT OF INTRACORONARY LOCAL ADHESIVE DELIVERY TECHNIQUE

Acute coronary occlusion may occur in weak coronary atherosclerotic lesions, including dissection, ulceration or thrombus. In some cases of occlusion “bail-out” is performed by using recently developed New Devices. However, these have not yet completely solved the problem to this end, we designed a new method of coronary revascularization, the Intracoronary Local Adhesive Delivery Technique, utilizing antithrombotic and absorbable adhesive injected locally into the fragile and morbid arterial wall using a drug delivery PTCA catheter more flexible than the existing New Devices. This adhesive strengthened and hardened the lesions. In this study, we examined the efficacy of making an adhesive cylinder in arteries of similar size to the coronary, through acute animal experiments using the existing clinical adhesives and drug delivery PTCA catheters and 12 femoral arteries of adult goats. We were successful in forming firm tunnels along the inside of six arteries, infused with approximately 0.04 ml Cyanoacrylate. These tunnels were observed with intravascular ultrasound (IVUS) imaging and evaluated microscopically. These results suggest the feasibility of this method as a new approach for making synthetic resinous stents.

Cardiac-related sympathetic nerve activity during circulation with only the left ventricular assist device.

Circulatory maintenance with a left ventricular assist device (LVAD) alone during cardiac arrest until heart transplantation has been evaluated. To assess the effect on the autonomic nervous system, the sympathetic neurogram was analyzed by power spectrum and coherence function. LVAD were inserted between the left atrium and the descending aorta in seven adult mongrel dogs and ventricular fibrillation was induced electrically. Renal sympathetic nerve activity (RSNA) was detected by bipolar electrodes attached to the left renal sympathetic nerve. Values of squared coherence between the arterial pulse wave and RSNA were calculated. Under the condition of circulatory maintenance with only LVAD, coherence at the cardiac rhythm frequency was decreased, and coherence at the LVAD pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed during maintenance of the circulation with only LVAD contributed to the sympathetic neurogram.

Micro-Pressure Sensor for Continuous Monitoring of a Ventricular Assist Device

We have been involved in the development of a clinical ventricular assist device (VAD) system. Here, we report our investigation of in vitro and in vivo stability and sensibility of pressure microsensors. The sensors were mounted in the inflow and outflow cannulae wall to measure the left atrial and aortic pressures during VAD pumping. The pressure sensitive surface of the piezoresistive effect absolute pressure sensor was coated with a thromboresistant polymer, as was the inner surface of the cannulae of the VAD. In the in vitro and chronic animal experiments which were of more than a month duration, reliable stability and sensitivity, without any thrombus formation on the blood contacting surface of the sensors, and high sensitivity were observed. After chronic experiments, the sensitivity of sensors was reevaluated in the mock circulatory system as compared to reference values. The relationship between the output of the micro-sensors and the reference value was linear and correlated well.

DEVELOPMENT OF VIBRATING FLOW PUMP FOR LEFT VENTRICULAR ASSIST CIRCULATION

Vibrating flow pump (VFP) can generate high frequency oscillated blood flow within 1040 Hz. In this study, new type VFP was developed as a ventricular assist device. Left Ventricular assist circulation using VFP were performed as aseptic animal experiments using goats, hemodynamic parameters were recorded continuously at awaked state. Driving frequency of VFP was 25 Hz and pump flow rate was controlled to approximately 2 l/min. Frequency of VFP was 25 hz and pump flow rate was controlled to approximately 2 L/min. Frequency analysis method was used for analyzing hemodynamics. The peak of power was observed at 25 Hz from the Fourier transformation of blood flow waveform. Systemic vascular resistance was decreased by the start of left ventricular assistance using oscillated blood flow. No fatal arrhythmia was osberved during this study. As the conclusion, new type VFP has a sufficient performance for left ventricular assistance. Small size blood pump may be enabled by the oscillated blood flow because VFP is driven at high frequency moving with short stroke volume.

Mayer waves in dogs with total artificial heart.

To assess the effect of a total artificial heart (TAH) on the autonomic nervous system a power spectral analysis of the hemodynamics in a TAH animal was done by the maximum entropy method. Two pneumatically driven sac-type ventricular assist devices were implanted as total biventricular bypass (BVB) in adult mongrel dogs to compare the differences between natural heart and TAH. Once the BVB was pumping, the natural heart was electrically fibrillated to constitute the BVB-type TAH model. In the arterial pressure waveform in animals with TAH, respiratory waves were not changed (97.7±24.6%) though Mayer waves were significantly decreased (47.5 ± 22.6%) compared with the animal with a natural heart. These results suggest that prosthetic hemodynamics in the TAH animal affect fluctuations in the cardiovascular system.

The prospective control of a total artificial heart using sympathetic tone and hemodynamic parameters

In order to develop the real-time control system of a total artificial heart (TAH), we use the sympathetic tone and the hemodynamic parameters. Moving averages of the mean left atrial pressure and mean aortic pressure were used as the parameters of the preload and the afterload in the circulatory system. Also, renal sympathetic nerve activity (RSNA) was utilized as the parameter of the sympathetic tone. A functional formula which prospectively indicated cardiac output, was calculated using the multiple regression analysis of the time series data in the acute animal experiments using adult mongrel dogs. Also, a functional formula which prospectively indicated heart rate was determined through the time series data of the RSNA.