Simultaneous Control of Venous Reservoir Level and Arterial Flow Rate in Cardiopulmonary Bypass With a Centrifugal Pump.

Cardiopulmonary bypass (CPB) is an indispensable technique in cardiac surgery, providing the ability to temporarily replace cardiopulmonary function and create a bloodless surgical field. Traditionally, the operation of CPB systems has depended on the expertise and experience of skilled perfusionists. In particular, simultaneously controlling the arterial and venous occluders is difficult because the blood flow rate and reservoir level both change, and failure may put the patient's life at risk. This study proposes an automatic control system with a two-degree-of-freedom model matching controller nested in an I-PD feedback controller to simultaneously regulate the blood flow rate and reservoir level. CPB operations were performed using glycerin and bovine blood as perfusate to simulate flow-up and flow-down phases. The results confirmed that the arterial blood flow rate followed the manually adjusted target venous blood flow rate, with an error of less than 5.32%, and the reservoir level was maintained, with an error of less than 3.44% from the target reservoir level. Then, we assessed the robustness of the control system against disturbances caused by venting/suction of blood. The resulting flow rate error was 5.95%, and the reservoir level error 2.02%. The accuracy of the proposed system is clinically satisfactory and within the allowable error range of 10% or less, meeting the standards set for perfusionists. Moreover, because of the system's simple configuration, consisting of a camera and notebook PC, the system can easily be integrated with general CPB equipment. This practical design enables seamless adoption in clinical settings. With these advancements, the proposed system represents a significant step towards the automation of CPB.

Construction of a detachable artificial trachea model for three age groups for use in an endotracheal suctioning training environment simulator.

Tracheal suctioning is an important procedure to maintain airway patency by removing secretions. Today, suctioning operators include not only medical staff, but also family caregivers. The use of a simulation system has been noted to be the most effective way to learn the tracheal suctioning technique for operators. While the size of the trachea varies across different age groups, the artificial trachea model in the simulation system has only one fixed model. Thus, this study aimed to construct multiple removable trachea models according to different age groups. We enrolled 20 patients who had previously received proton beam therapy in our institution and acquired the treatment planning computed tomography (CT) image data. To construct the artificial trachea model for three age groups (children, adolescents and young adults, and adults), we analyzed the three-dimensional coordinates of the entire trachea, tracheal carina, and the end of the main bronchus. We also analyzed the diameter of the trachea and main bronchus. Finally, we evaluated the accuracy of the model by analyzing the difference between the constructed model and actual measurements. The trachea model was 8 cm long for children and 12 cm for adolescents and young adults, and for adults. The angle between the trachea and bed was about 20 degrees, regardless of age. The mean model accuracy was less than 0.4 cm. We constructed detachable artificial trachea models for three age groups for implementation in the endotracheal suctioning training environment simulator (ESTE-SIM) based on the treatment planning CT image. Our constructed artificial trachea models will be able to provide a simulation environment for various age groups in the ESTE-SIM.

Hemodialysis efficiency management from the viewpoint of blood removal pressure.

Degradation of dialysis efficiency during hemodialysis, caused by incompatible indwelling needle size or increase in hematocrit, is a serious problem that can threaten a patient's life. This study aims to derive a quantitative index for determining the indwelling needle diameter that can maintain an appropriate blood flow rate, and presents an effective method to prevent a decrease in the actual blood flow rate. The relationships between the set flow rate and various parameters such as indwelling needle diameter, blood viscosity, and arterial line pressure are analyzed. A simple and reliable method for estimating the actual blood flow rate is derived from these relationships. A correlation between viscosity and actual blood flow rate is estimated adequately by regression analysis using a least-squares method. The relationship between Reynolds number and the flow rate reduction ratio is also evaluated. A new parameter (simple estimation method for actual blood flow) is derived by measuring the blood removal pressure. A pump control approach that uses blood removal pressure is suggested, which can be a future research direction in the field of hemodialysis.

Effective Catheter Manoeuvre for the Removal of Phlegm by Suctioning: A Biomechanical Analysis of Experts and Novices.

Purpose: The aim of this study was to determine the effective biomechanical technique for suctioning phlegm. Methods: A novel tracheal suctioning simulator combined with a motion capture system was used to calculate the amount of simulated phlegm suctioned and the biomechanical parameters of the associated suctioning manoeuvre. A laboratory study, including 12 nurses with > 3 years of suctioning experience and 12 nursing students without any clinical suctioning experience, was conducted. The amount of phlegm suctioned, the maximum length of catheter insertion, and the biomechanical parameters of hand movement were calculated. Results: The mean amount of phlegm suctioned per second was significantly larger in the experienced group than in the non-experienced group. The amount of phlegm suctioned correlated positively with the length of the vertical path of motion of the wrist and forearm, and with the angular velocity of thumb rotation in both the groups. Conclusion: Greater vertical motion of the wrist and thumb rotation improved the effectiveness of phlegm suctioning and prevented the need for deep suctioning, which is unsafe.

Relationship Between Tracheal Suctioning Catheter Motion and Secretion Amount Based on Viscosity.

BACKGROUND: To provide safe tracheal suctioning, the American Association of Respiratory Care guideline discusses the length of suctioning catheter, but the most effective tracheal suctioning catheter technique is still unknown. OBJECTIVE: The aim of this study is to compare the amount of simulated secretion produced by five different handlings of a catheter at two different viscosities and in two different models to discover the most effective suctioning maneuver in the various mucus conditions. DESIGN: In vitro experimental design. METHODS: The amount of secretion aspirated by our researcher's manipulation of a suctioning catheter was measured. The tip of the catheter was recorded using a high-speed video camera to visualize the secretion motion. RESULTS: The most effective suctioning technique differed depending on the viscosity of the secretion. There were no significant differences between five suctioning methods applied to high-viscosity phlegm in a tracheal membrane model, but the flexion technique was the most efficient for low-viscosity secretion. CONCLUSIONS: Our results imply that the flexion technique was reasonably safe and the most effective of these five methods for low-viscosity secretion.

Thiamine tetrahydrofurfuryl disulfide promotes voluntary activity through dopaminergic activation in the medial prefrontal cortex.

A physically active lifestyle is associated with better health in body and mind, and it is urgent that supporting agents for such lifestyles be developed. In rodents, voluntary locomotor activity as an active physical behavior may be mediated by dopaminergic neurons (DNs). Thiamine phosphate esters can stimulate DNs, and we thus hypothesized that thiamine tetrahydrofurfuryl disulfide (TTFD), a thiamine derivative, promotes locomotor activity via DNs in rats. Acute i.p. administration of TTFD enhanced rat locomotor activity in a normal cage. In vivo microdialysis revealed that TTFD-enhanced locomotor activity was synchronized with dopamine release in the medial prefrontal cortex (mPFC). Antagonism of the dopamine D1 receptor, but not D2 receptor, in the mPFC fully suppressed TTFD-enhanced locomotor activity. Finally, we found a TTFD dose-dependent increase in voluntary wheel running. Our findings demonstrate that DNs in the mPFC mediates TTFD-enhanced locomotor activity, suggesting the potential of TTFD to induce active physical behavior.

PET Imaging Analysis of Vitamin B1 Kinetics with [11C]Thiamine and its Derivative [11C]Thiamine Tetrahydrofurfuryl Disulfide in Rats.

PURPOSE: Thiamine is an essential component of glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is better absorbed than readily-available water-soluble thiamine salts because it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions have not yet been clarified. C-11-labeled thiamine and TTFD were recently synthesized by our group. In this study, to clarify the differences in pharmacokinetics and metabolism of these probes, a quantitative PET imaging study and radiometabolite analysis of C-11-labeled thiamine and TTFD were performed in the rat heart. PROCEDURES: Positron emission tomography (PET) imaging with [11C]thiamine and [11C]TTFD was performed in normal rats to determine the pharmacokinetics of these probes, and the radiometabolites of both probes from the blood and heart tissue were analyzed by thin-layer chromatography. RESULTS: Accumulation of [11C]TTFD was significantly higher than that of [11C]thiamine in the rat heart. Moreover, as a result of the radiometabolite analysis of heart tissue at 15 min after the injection of [11C]TTFD, thiamine pyrophosphate, which serves as a cofactor for the enzymes involved in glucose metabolism, was found as the major radiometabolite and at a significantly higher level than in the [11C]thiamine-injected group. CONCLUSIONS: PET imaging techniques for visualizing the kinetics and metabolism of thiamine using [11C]thiamine and [11C]TTFD were developed in this study. Consequently, noninvasive PET imaging for the pathophysiology of thiamine-related cardiac function may provide novel information about heart failure and related disorders.

Synthesis of (11)C-Labeled Thiamine and Fursultiamine for in Vivo Molecular Imaging of Vitamin B1 and Its Prodrug Using Positron Emission Tomography.

To enable in vivo analysis of the kinetics of vitamin B1 (thiamine) and its derivatives by positron emission tomography (PET), (11)C-labeled thiamine ([(11)C]-1) has been synthesized. This was carried out via a rapid, multistep synthesis consisting of Pd(0)-mediated C-[(11)C]methylation of a thiazole ring for 3 min and benzylation with 5-(bromomethyl)pyrimidine for 7 min. The [(11)C]-1 was also converted to (11)C-labeled fursultiamine ([(11)C]-2), a prodrug of vitamin B1, by disulfide formation with S-tetrahydrofurfurylthiosulfuric acid sodium salt. Characterization of [(11)C]-1 and [(11)C]-2 showed them to be suitable for use as PET probes for in vivo pharmacokinetic and medical studies. The total durations of the preparations of [(11)C]-1 and [(11)C]-2 were shorter than 60 and 70 min, respectively. The [(11)C]CH3I-based decay-corrected radiochemical yields of [(11)C]-1 and [(11)C]-2 were 9-16% and 4-10%, respectively. The radioactivities of the final injectable solutions of [(11)C]-1 and [(11)C]-2 were 400-700 and 100-250 MBq, respectively. The radiochemical purity of both [(11)C]-1 and [(11)C]-2 was 99%, and the chemical purities of [(11)C]-1 and [(11)C]-2 were 99% and 97-99%, respectively. In vivo PET imaging of normal rats was illustrated by the distribution of [(11)C]-1 and [(11)C]-2 following intravenous injection.

An educational training simulator for advanced perfusion techniques using a high-fidelity virtual patient model.

The operation of cardiopulmonary bypass procedure requires an advanced skill in both physiological and mechanical knowledge. We developed a virtual patient simulator system using a numerical cardiovascular regulation model to manage perfusion crisis. This article evaluates the ability of the new simulator to prevent perfusion crisis. It combined short-term baroreflex regulation of venous capacity, vascular resistance, heart rate, time-varying elastance of the heart, and plasma-refilling with a simple lumped parameter model of the cardiovascular system. The combination of parameters related to baroreflex regulation was calculated using clinical hemodynamic data. We examined the effect of differences in autonomous-nerve control parameter settings on changes in blood volume and hemodynamic parameters and determined the influence of the model on operation of the control arterial line flow and blood volume during the initiation and weaning from cardiopulmonary bypass. Typical blood pressure (BP) changes (hypertension, stable, and hypotension) were reproducible using a combination of four control parameters that can be estimated from changes in patient physiology, BP, and blood volume. This simulation model is a useful educational tool to learn the recognition and management skills of extracorporeal circulation. Identification method for control parameter can be applied for diagnosis of heart failure.

Evaluation of basic perfusion techniques, ECCSIM-Lite simulator.

Although serious accidents during extracorporeal circulation are infrequent, potential adverse events with both equipment and operation do still occur and require immediate and well-coordinated responses. Hence, perfusionists need to be well trained in both standard and emergency procedures, and this would be aided by the establishment of an official education and training curriculum. In particular, the establishment of a simulator-based educational program and corresponding evaluation methods will spur development of increasingly medical simulators. ExtraCorporeal Circulation SIMulator (ECCSIM-Lite) was used during repeated sessions of undergraduate students (n = 12) using a simple training scenario. Trainees aimed to maintain reservoir volume around a constant mean, and increase or decrease the arterial flow avoiding rapid variations, and their performance was monitored. Ability to prevent backflow was also recorded as a measure of accomplishment. Skills in performances were evaluated by using a scoring system based on task accomplishment. Accomplishment score was improved in all participants after 1 week of training. Accomplishment scores reflecting ability to maintain flow improved to an average of 78%; in the third and final practice session backflow was prevented in 100% of cases. The average reservoir level maintenance score in the flow-up phase was 75%, in the flow-maintenance phase was 92%, and in the flow-down phase was 58%. During skill training, in which trainees learn methods of avoiding adverse events, the use of simulators combined with tractable skills scores can ease the transition from training session to clinical practice. Use of these training scenarios within a perfusion education system also has the advantage of providing an index of trainees' current proficiency and improvement by providing tractable skill scores. In conclusion, the use of ECCSIM-Lite simulations, together with evaluation of task accomplishment over repeated training sessions, is an effective method of basic skill training for perfusionists.

Analysis of flow patterns in a ventricular assist device: a comparative study of particle image velocimetry and computational fluid dynamics.

In order to develop a diaphragm-type ventricular assist device (VAD), we studied the flow field change following structural modifications. We devised a center flow-type pump by putting a small projection on the center of the housing and/or diaphragm to provide a center in the flow field, and examined the following four types of VADs: N type without a projection, D type with a projection on the diaphragm, H type with a projection on the housing, and DH type with projections on both the diaphragm and housing. Computational fluid dynamics (CFD) was used for flow simulation. Particle image velocimetry (PIV) was also used to verify the reliability of the CFD method and to determine how the flow field changes in the presence of a projection. The results of the PIV and CFD analyses were comparable. The placement of a projection on the housing was most effective in rectifying the flow field.

Virtual patient simulator for the perfusion resource management drill.

Perfusionists require a detailed understanding of a patient's physiological status while comprehending the mechanics and engineering of the cardiopulmonary bypass system, so it is beneficial for them to obtain relevant practical skills using extracorporeal circulation technology and educational physiological simulators. We designed a perfusion simulator system (ECCSIM: Extracorporeal Circulation SIMulator system) based on a hybrid of a simple hydraulic mock circulation loop linked to a computer simulation model. Patient physiological conditions (height, weight, and cardiac indices) were determined by a parameter estimation procedure and used to accurately reproduce hemodynamic conditions. Extracorporeal circulation trainees in pre-clinical education were able to maintain venous oxygen saturation levels above 50%, except during cardiac standstill and a brief resumption of pulsation. Infant amplitudes of reservoir volume oscillation and flow rate were greatly increased compared with adult cardiovascular parameters, this enabled the instructor to control the difficulty level of the operation using different hemodynamic variations. High-fidelity simulator systems with controllable difficulty levels and high physiological reproducibility are useful in constructing a perfusion resource management environment that enable basic training and periodic crisis management drills to be performed.

Quantitative evaluation of hand cranking a roller pump in a crisis management drill.

The heart-lung machines for open-heart surgery have improved over the past 50 years; they rarely break down and are almost always equipped with backup batteries. The hand-cranking procedure only becomes necessary when a pump breaks down during perfusion or after the batteries have run out. In this study, the performance of hand cranking a roller pump was quantitatively assessed by an objective method using the ECCSIM-Lite educational simulator system. A roller pump connected to an extracorporeal circuit with an oxygenator and with gravity venous drainage was used. A flow sensor unit consisting of electromagnetic sensors was used to measure arterial and venous flow rates, and a built-in pressure sensor was used to measure the water level in the reservoir. A preliminary study of continuous cranking by a team of six people was conducted as a surprise drill. This system was then used at a perfusion seminar. At the seminar, 1-min hand-cranking drills were conducted by volunteers according to a prepared scenario. The data were calculated on site and trend graphs of individual performances were given to the participants as a handout. Preliminary studies showed that each person's performance was different. Results from 1-min drills showed that good performance was not related to the number of clinical cases experienced, years of practice, or experience in hand cranking. Hand cranking to maintain the target flow rate could be achieved without practice; however, manipulating the venous return clamp requires practice. While the necessity of performing hand cranking during perfusion due to pump failure is rare, we believe that it is beneficial for perfusionists and patients to include hand-cranking practice in periodic extracorporeal circulation crisis management drills because a drill allows perfusionists to mentally rehearse the procedures should such a crisis occur.

Development of an educational simulator system, ECCSIM-Lite, for the acquisition of basic perfusion techniques and evaluation.

A training system with quantitative evaluation of performance for training perfusionists is valuable for preparation for rare but critical situations. A simulator system, ECCSIM-Lite, for extracorporeal circulation (ECC) training of perfusionists was developed. This system consists of a computer system containing a simulation program of the hemodynamic conditions and the training scenario with instructions, a flow sensor unit, a reservoir with a built-in water level sensor, and an ECC circuit with a soft bag representing the human body. This system is relatively simple, easy to handle, compact, and reasonably inexpensive. Quantitative information is recorded, including the changes in arterial flow by the manipulation of a knob, the changes in venous drainage by handling a clamp, and the change in reservoir level; the time courses of the above parameters are presented graphically. To increase the realism of the training, a numerical-hydraulic circulatory model was applied. Following the instruction and explanation of the scenario in the form of audio and video captions, it is possible for a trainee to undertake self-study without an instructor or a computer operator. To validate the system, a training session was given to three beginners using a simple training scenario; it was possible to record the performance of the perfusion sessions quantitatively. In conclusion, the ECCSIM-Lite system is expected to be useful for perfusion training, since quantitative information about the trainee's performance is recorded and it is possible to use the data for assessment and comparison.

Development of a new pulsatile ventricular assist device.

We developed a small, lightweight, low-cost implantable ventricular assist device (VAD) for use in smaller Japanese subjects. The major advantage of this pump is the simplicity of its fabrication. Most parts of the pump were shaped from a transparent acrylic block by a turning process, and the diaphragm was made from a silicon sheet. Since this method of construction did not require any complex processes, we could manufacture many pumps of various shapes. We determined the -most efficient shape for the Ebacor VAD using the flow visualization technique. The pump showed an output above 6 liters/min under a driving pressure of 300/-100 mmHg. The pump performance of current VADs is superior to that of the Ebacor VAD, because these pumps are larger. Since the Ebacor VAD is small in size, it can be driven by the driving system of a normal IABP control unit, which many hospitals already have in place. During a 30-day continuous driving performance test of this pump, no problems like performance decrements or water and air leakage were observed.

Effect of simultaneous administration of vitamin C, L-cysteine and vitamin E on the melanogenesis.

The effect of simultaneous administration of vitamin C (ascorbic acid), L-cystein (Cys) and vitamin E (tocopherol) on the melanogenesis in vivo and in vitro was studied. Forty-eight brownish guinea pigs were divided into 4 groups as follows: VC group, VC+Cys group, VC+Cys+VE group and control group. They were given these vitamins by oral administration every day. UV-B exposure (0.384 J/cm2) on their depleted back skin was done at the day 8, 10, 12, 15 17 and 19. After UV-B irradiation, vitamins were administrated further 3 weeks. The luminosity score was measured using a Color Reader CR-11 (Minolta, Co) and the numbers of DOPA-positive melanocytes of their back skin were counted. B16 melanoma cells were incubated with VC, N-acetyl cystein (NAC) and VE. After 4 days of incubation, cells were harvested. The melanin contents and the tyrosinase activities in cells were measured. The luminosity score in the VC+VE+Cys group was higher than those in the other groups. The numbers of DOPA-positive melanocytes of guinea pigs treated with VC, VE and Cys were significantly decreased compared with those in VC group. In B16 melanoma cells, simultaneous treatment of VC, VE and NAC was the most effective to decrease the melanin contents and to inhibit tyrosinase activity.