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Biomedical subjects

J F Chen

Publications and source records attributed to J F Chen.

106 records · Page 6Linked to original sources
PubMedDate not supplied

Hemodynamic changes with posture in calves with total artificial heart.

Hemodynamic changes with posture, sitting versus standing, were analyzed in five Holstein calves with the Cleveland Clinic-Nimbus TAH. This total artificial heart (TAH) has a left master alternate control mode that adjusts the pump rate and consequently pump flow proportional to the pulmonary venous return to the left pump (AUTO period). However, in this series of experiments, the pump reached its maximum beat rate within 1-5 days post operatively, after which pump flow could not increase (MAX period). Hemodynamic parameters (RAP, LAP, PAP, AoP, and pump flow) were obtained every 15-20 min throughout the experiments for as long as 120 days and averaged for each posture for each period. During the AUTO period, the flow while standing was significantly higher than that while sitting (standing: 8.7 +/- 0.2 L/min; sitting: 7.5 +/- 0.4 L/min; p < 0.05), and the systemic vascular resistance (SVR) was significantly lower (standing: 895 +/- 93 dyne.sec.m-5; sitting: 1,041 +/- 124 dyne.sec.m-5; p < 0.05). During the MAX period, the AoP and SVR standing were significantly lower than those sitting (AoP standing: 91 +/- 7 mmHg; AoP sitting: 98 +/- 7 mmHg; p < 0.05; SVR standing: 652 +/- 75 mmHg; SVR sitting: 730 +/- 96 mmHg; p < 0.05). The Cleveland Clinic-Nimbus TAH responded well to these changes in position, increasing pump flow and maintaining the AoP during the AUTO period.

Animals↗
PubMedDate not supplied

Adaptation of tissue to a chronic heat load.

Determination of the chronic effect of heat on tissue is one of the important issues facing mechanically actuated total artificial heart (TAH) development. In an effort to characterize this effect, implantations of heating devices producing constant heat fluxes of 0.04 watts/cm2, 0.06 W/cm2, and 0.08 W/cm2 were performed in 11 calves (H-series). Heated disks were implanted adjacent to lung and muscle tissue for a period of 7 weeks. Temperature sensors were placed at the surface as part of the heater assemblies. The results showed that initially, temperature elevations above body temperature (delta T) were 6.4 +/- 0.6 degrees C, 4.5 +/- 0.2 degrees C, and 1.8 +/- 0.5 degrees C at the muscle heater surface for 0.08, 0.06, and 0.04 W/cm2, respectively. At 2 weeks after implant delta T values changed to 5.5 +/- 0.6 degrees C, 3.4 +/- 0.2 degrees C, and 1.8 +/- 0.2 degrees C, respectively. Seven weeks after implant, delta T values decreased to 3.7 +/- 1.2 degrees C, 2.8 +/- 0.1 degrees C, and 0.8 degrees C for 0.08, 0.06, and 0.04 W/cm2, respectively. The authors think this change is attributable to an adaptive response of the tissue to increase heat dissipation through angiogenesis. Results from three TAH cases indicated that at two measured tissue interfaces, delta T decreased by 1 degrees C during a 15 day period. At the same time, the waste heat (volts x current in-flow x afterload to the blood) remained constant at 11.1 +/- 0.5 W during this period. This decrease in delta T corresponded to that observed for the H-series experiments at the higher heat fluxes. Thus, it appears that adaptation observed in the H-series experiments also is seen for tissues surrounding heat sources such as the TAH.

Adaptation, Physiological↗
PubMedDate not supplied

Anatomic fitting studies of a total artificial heart in heart transplant recipients. Critical dimensions and prediction of fit.

Anatomic fitting studies of the Cleveland Clinic-Nimbus total artificial heart were performed in 33 patients undergoing heart transplantation. The pump fit in the pericardial space in 20 men (80%) and 4 women (50%). There was no significant difference between the Fit and Non-Fit groups in external chest dimensions. Among 42 intrathoracic dimensions, the distance from the center of the mitral valve to the diaphragm (Fit: 5.6 +/- 2.2 cm, Non-Fit: 3.6 +/- 0.4 cm, p < 0.00001) and the distance from the caudal end of the pulmonary valve to the diaphragm (Fit: 9.4 +/- 1.6 cm, Non-Fit: 6.3 +/- 0.8 cm, p < 0.0001) were the most critical. To predict anatomic fit, an index (A x B x C) was obtained from chest X-ray measurements (A, the craniocaudal distance from the dorsal region of the 8th left rib to the left diaphragm; B, the maximum left chest width; and C, the maximum anteroposterior sternum-vertebrae dimension). The pump fit in 88.5% of the patients with an index above 1200 cm3, whereas it fit in only 14.3% of the patients with an index below 1200 cm3 (p < 0.001). This index was an easily obtainable, good predictor of anatomic fit.

Diaphragm↗
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In vitro evaluation of automatic control performance of a total artificial heart with changes in pump orientation.

Unlike in animal experiments, the pump orientation of a total artificial heart (TAH) can change remarkably in humans with the recipient's posture (upright, supine, or prone), thus affecting its filling characteristics. The left master alternate control mode of the Cleveland Clinic-Nimbus (CC-N) TAH adjusts beat rate by maintaining the left pump at 90% filling, producing a Frank-Starling like preload sensitivity. In order to verify that the CC-N TAH functions properly regardless of the gravity effects on pump filling, the preload sensitivity curves of the CC-N TAH were evaluated on a mock circulatory loop with the simulated supine (right pump up) and prone (left pump up) positions in humans. The right preload sensitivity was slightly higher when the right pump was up versus down, and likewise the left preload sensitivity was higher when the left pump was up versus down. Despite these gravity effects on pump filling, right and left preload sensitivity remained within physiologic range and the automatic control of the CC-N TAH functioned properly without significant postural effects.

Animals↗
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Optimization of pacing parameters for conditioned latissimus dorsi muscle in cardiomyoplasty.

Synchronous paced contractions of latissimus dorsi muscle pedicle (LDM) around the heart improve ventricular function in dynamic cardiomyoplasty. To optimize assistance and prolong pacemaker battery life, the LDM should be stimulated with the lowest energy pacing parameters (PP) that will produce maximal muscle contraction. Muscle fractional shortening (FS) and duration of contraction (CT) were studied in conditioned, fatigue-resistant LDM of six goats. Fractional shortening and CT were determined at increasing amplitude, (A, 1-6v); pulse width, (PW, 60-450 musec); and frequency, (F, 5-130 Hz). Maximal rate of contraction was determined by pacing at higher rates. Maximal FS plateaued after V, 2.4 +/- .6v; PW, 125 +/- 47 musec; and F, 36 +/- 9 Hz. Mean CT for all PP was significantly longer (p less than or equal to 0.001) than the burst length (185 msec). Increasing F resulted in CT, which peaked at 460 +/- 59 msec. Increasing rate of contraction demonstrated that over 87 beats per minute the muscle fails to achieve complete relaxation, and, therefore, maximal FS.

Animals↗
PubMedDate not supplied

Anatomic study for in vivo evaluation of a total artificial heart in calves.

A poor fit will negate any physiologic evaluation of an implantable total artificial heart (TAH). Fifteen Holstein calves (weight, 65-111 kg) were used to measure intrathoracic dimensions for TAH design, to find correlations between intrathoracic and external parameters for preoperative animal selection, and to suggest minor modifications for fitting a TAH in calf chests. The following dimensions were found to be critical to avoid compromising venous return: 1) mitral annulus center (MVC)-sternum, 10.4 +/- 1.0 cm; 2) tricuspid annulus center (TVC)-sternum, 9.8 +/- 1.6 cm; 3) MVC-TVC, 5.5 +/- 0.4 cm; 4) MVC-diaphragm, 3.4 +/- 0.8 cm; 5) MVC-left chest wall, 4.5 +/- 0.9 cm; and 6) TVC-right chest wall, 4.5 +/- 1.0 cm. These dimensions had no statistically significant correlation with body weight, but three of them did with the following external parameters: 1) bronchial carina-sternum on chest radiograph, p less than 0.05; 2) dorsoventral dimension at xiphoid, p less than 0.05; and 3) circumference at the caudal end of the scapula, p less than 0.05. Based on these results, the port orientation of the left housing of this electrohydraulic TAH designed for humans was modified for in vivo evaluation in calves. No other pump features required change. These data should prove useful to others involved in TAH development.

Animals↗
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Development of an epicardial circulatory assist device.

The overall purpose of this project was to develop a circulatory assist device that could be used as a bridge to heart transplantation. Although heart muscle damage was one of the disadvantages with the original epicardial assist devices, as long as no bleeding occurs, such trauma would be of secondary importance in this particular application. The development of the proposed epicardial circulatory assist device (ECAD) was evolutionary in nature, with the second prototype design based on the lessons learned from that of the first. In vivo results from both phases of the project are reported. ECAD prototype 1 (ECAD-1) was composed of a flexible outer housing and two driving balloons. Fixation to the heart was adjustable for various heart sizes using Velcro fasteners. The design of the ECAD prototype 2 (ECAD-2) was based on the results of ECAD-1. Fixation to the heart was accomplished by suturing the outer housing onto the heart along the anterior descending artery and at the posterior atrioventricular groove. Each device was tested in five dogs. ECAD-1 was able to maintain the systemic circulation for 5 hours. However, unstable fixation and myocardial damage due to rubbing were the major problems. ECAD-2 passive effects on natural heart filling were acceptable. Under conditions of severe heart failure, a flow of more than 85% of control was obtained with a driving rate of 90-110 beats/min and 30% systole. The longest pumping was conducted for 8 hours. The ECAD was demonstrated to be a device useful in assisting the failing heart for short periods. Proper design will play a fundamental role in successful extended use.

Animals↗
PubMedDate not supplied

Renal effects of a pyridoxalated-hemoglobin-polyoxyethylene conjugate solution as a blood substitute in exchange transfusions.

With PHP as an oxygen carrier, histologic studies in ET showed changes of renal tubular epithelial cells at 2 weeks post ET, with normal structure by 3-12 months post ET. The renal functional effects of PHP were evaluated by ET (30%, N = 3; 50%, N = 1; 80%, N = 3) in seven healthy mongrel dogs. Blood, urine, and renal biopsy specimens were taken pre ET and at 0, 1, and 2 days, 2, 4, and 6 weeks, and 3, and 6 months post ET. Data were compared to modified criteria of acute tubular necrosis. All dogs tolerated the procedure well and survived for 1 year. Urine output was normal with elevation during the first 2 days in the 50 and 80% ET, followed by stable output by 2 weeks, ranging from 12 to 60 ml/kg/day. Blood urea nitrogen (BUN) and serum creatinine (SCr) were normal. BUN/SCr was normal. The urine to plasma osmolality ratios were 2.6 to 8.3 (normal greater than 1), and fractional percent excretions of sodium (FES) were stable throughout. No existence of broad granular pigmented casts (BGPC) in urine sediment were noted. Renal histologic evaluation of vacuolization in the renal tubules were seen to be dose-dependent and transient, with normal histology by 3-6 months post ET. Dose-dependent vacuole formation observed in the early weeks post ET with PHP showed no renal functional changes. Based upon the modified criteria for acute tubular necrosis, no histologic abnormalities were noted.

Animals↗
PubMedDate not supplied

Flow visualization in an artificial heart using diffuse and planar laser lighting.

The purpose of the study was to characterize flow properties within a clinical pusher plate type artificial heart. Dual camera video tape and synchronized still photographs were used to study flow patterns. Diffused light and a planar laser source provided illumination. The laser light was turned into a plane of light with a thickness varying from 0.1 to 10 mm, and magnesium oxide and Amberlite particles were used as tracers. Qualitative and quantitative analyses were performed by the examination and digitization of flow patterns. Inflow, outflow, pneumatic drive and after-load pressure, diaphragm motion, cardiac output, and heart rate were measured and recorded. An electrical circuit was developed to synchronize pump diaphragm motion with captured images of flow trajectories. Trajectories were then digitized, and velocities, turbulence, and shear stresses were calculated. As the result of these experiments, disturbed, recirculating, and stagnation zones were identified and global and local turbulence values were determined. Simultaneous turbulence, stasis, recirculation, and laminar flow patterns were observed during most phases of the pumping cycle. Velocities obtained varied from 2 cm/sec to 145 cm/sec; total local shear stresses of 12 to 897 dynes/cm2 were seen.

Blood Flow Velocity↗
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Development of a completely implantable total artificial heart.

In conjunction with engineering and physiologic requirements, anatomic fit is a fundamental problem that must be carefully addressed in the design of a truly feasible implantable total circulatory support system. To facilitate the conceptualization, a three-dimensional anatomic model of an average adult thorax was developed from a data bank of 14 human cadavers, 100 radiographs, 18 computerized tomographs, 4 nuclear magnetic resonance (NMR) studies, and 31 cineangiograms. The location and orientation of the valves, the atrial chambers, venae cavae, and pulmonary hili were found to be the most critical information. As a result, configuration of a one piece, completely implantable total artificial heart (E4T system) with the hydraulic actuator placed between the two ventricles was defined and sized to provide an output of 8 L/min at 120 beats/min. The device was designed to be positioned through a midsternotomy similar to the natural ventricles (in the pericardial sac toward the left chest cavity), and the ports were carefully designed to eliminate the risk of compression of critical cardiovascular structures. Validation of the design was conducted with an E4T model implanted in three human adult cadavers, two of which were submitted to NMR imaging after the device was implanted and the incision closed. Excellent fit was observed in all cadavers, and analysis of the several sagittal, transverse, and coronal NMR images showed no compression of the natural internal structures.

Heart, Artificial↗
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Continuing development of the Cleveland Clinic-Nimbus total artificial heart.

A completely implanted total artificial heart (TAH) is under development by Nimbus, Inc., and the Cleveland Clinic Foundation (CCF). Key features of the system include an electrohydraulic energy converter, an automatic control system that produces a Frank-Starling response, and dual ventricles composed of graphite-epoxy and titanium with gelatin blood contacting surfaces. The system is controlled by a single substrate, hybridized microcircuit (the hybrid). Fabrication of the TAH control hybrid has recently been completed and testing begun. Its design emphasizes simplicity, reliability, and efficiency. Particular attention was given to optimizing thermal management. Externally controlled TAH systems have been used in eight in vivo experiments of up to 120 days' duration. In the last two of these experiments, a variable volume device was also implanted with excellent results. In vivo use of the system has demonstrated the Frank-Starling pump response, but the systems quickly reach maximum output with the bovine animal models. Human fitting studies, including adult patients undergoing heart transplantation, demonstrated satisfactory fit of the pump within the pericardium without compression of the vascular structures or chest wall. Measurements of chest circumference, plain chest films, and transesophageal echocardiograms should provide reliable predictions of pump fit in the majority of patients.

Animals↗
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Effects of a total artificial heart right stroke volume limiter on left-right hemodynamic balance.

In a completely implantable total artificial heart (TAH), the left-right flow difference attributable to higher volumetric efficiency of the right pump and bronchial artery shunting has always been a significant problem. The automatic control of the Cleveland Clinic-Nimbus TAH accommodates for the left-right flow difference when the beat rate is below maximum (AUTO range). However, at its maximum beat rate (MAX), high left atrial pressure (LAP) (greater than 25 mmHg) with relatively low right atrial pressure (RAP) (less than 8 mmHg) were observed both in vitro and in vivo, suggesting the need for a stroke volume limiter (SVL) of the right pump. In vitro volume loading tests showed 10%, 15%, and 20% SVLs prevented a disproportionate increase of LAP. In vivo studies in five Holstein calves also showed a balanced LAP-RAP relationship with 10% and 15% SVLs at MAX. The left pump flow was not affected by this range of SVLs either in vitro or in vivo. Pulmonary function was maintained with either size SVL, with autopsies revealing absence of pulmonary congestion and minimal pleural effusions in two calves surviving for more than 1 month. Although additional studies are needed to determine the appropriate size of the SVL, both 10% and 15% SVLs were effective in maintaining left-right hemodynamic balance in this TAH.

Animals↗
PubMedDate not supplied

Progress in Cleveland Clinic-Nimbus total artificial heart development.

A totally implantable, Cleveland Clinic-Nimbus total artificial heart (TAH) uses electrohydraulic energy conversion and an automatic left master-alternate mode control scheme, with a filling sensitivity of 1.0 l/min/mmHg and a maximum output of 9.5 l/min. The TAHs were tested in 12 calves for 1-120 days with normal major organ and blood cell function. Post-operative suppression of platelet aggregation recovered by the second post-operative week. The gelatin-coated pump surface generally was clean without any anticoagulants and free from infection. Embolism, which occurred in two cases, was caused by complications attributable to fungal infection in a Dacron graft and by thrombus formed around a jugular vein catheter. A system with a hybridized microcircuit controller in the interventricular space has been tested successfully in the three most recent cases, with a peak device surface temperature elevation of 6.5 degrees C. Heat effects were confined to the tissues immediately adjacent to the hottest spots. The carbon fiber-reinforced epoxy housing and 60 ml butyl rubber compliance chamber showed good tissue compatibility with a thin, fibrous tissue capsule. The transcutaneous energy transmission system and the internal battery functioned well as designed in the most recent animal implant.

Animals↗