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Biomedical subjects

W J Weiss

Publications and source records attributed to W J Weiss.

28 records · Page 2Linked to original sources

Comparative in vitro and in vivo activities of piperacillin combined with the beta-lactamase inhibitors tazobactam, clavulanic acid, and sulbactam.

Tazobactam (YTR-830H), a novel beta-lactamase inhibitor, was compared with clavulanic acid and sulbactam for enhancement of the activity of piperacillin against beta-lactamase-producing, piperacillin-resistant clinical isolates. Piperacillin MICs were determined in media containing a fixed concentration of 2 or 4 micrograms of the inhibitors per ml. The higher concentration was generally more effective. Tazobactam was superior to sulbactam in enhancing the spectrum and potency of piperacillin. Although the calvulanic acid combination was more potent, tazobactam was effective for a similar spectrum of resistant gram-negative clinical isolates containing beta-lactamase. MICs were reduced to the susceptible range for Escherichia coli, Klebsiella pneumoniae, Proteus spp., Salmonella spp., and Shigella spp. Combinations with tazobactam and sulbactam, but not clavulanic acid, were effective against Morganella spp. Some antagonism of the activity of piperacillin was observed with clavulanic acid but not with tazobactam or sulbactam. The inhibitors were similarly effective with piperacillin against beta-lactamase-positive Staphylococcus spp. and the Bacteroides fragilis group. Piperacillin-tazobactam was more effective against a broader spectrum of gram-negative enteric bacteria than ticarcillin plus clavulanic acid was. Combinations with tazobactam or clavulanic acid had a broader spectrum of activity than combinations with sulbactam against bacteria that produce characterized plasmid-mediated enzymes of clinical significance. In particular, piperacillin with tazobactam or clavulanic acid, but not with sulbactam, inhibited TEM-1, TEM-2, and SHV-1 enzymes. In vitro activity was reflected in vivo. Tazobactam and clavulanic acid were superior to sulbactam in enhancing the therapeutic efficacy of piperacillin in mice infected with beta-lactamase-positive E. coli, K. pneumoniae, Proteus mirabilis, and Staphylococcus aureus. Only combinations with tazobactam and sulbactam were effective against the Morganella infection. Tazobactam has a good potential for enhancing the clinical efficacy of piperacillin.

Animals↗

In vivo performance of a transcutaneous energy transmission system with the Penn State motor driven ventricular assist device.

A transcutaneous energy transmission system (TETS) has been used to power the Penn State motor driven ventricular assist device in nine calf experiments, for a total of 316 days of cumulative in vivo experience. This is seen as an important step toward a completely implantable ventricular assist system and total artificial heart. The TETS converts an external 12 volt DC source via inductive coupling to a regulated 14 volt output voltage for use by the motor controller. A maximum output power of 70 watts is available. In calf experiments, the TETS output power averaged between 8 and 12 watts. The motor controller was not implanted in these experiments, awaiting further development of the miniaturized electronics. The TETS output was returned percutaneously to the external motor controller, allowing the TETS output to be monitored directly. System efficiency, from DC source to DC output, and including losses in 12 feet of cable, ranged from 55% to 70%, depending upon supply voltage, motor load, and degree of coil coupling. The subcutaneous coil was well tolerated, demonstrating only temporary, mild, superficial induration.

Animals↗

Recent improvements in a completely implanted total artificial heart.

The total artificial heart under development by the Pennsylvania State University and 3M Health Care has undergone a number of design improvements to improve reliability, manufacturability, implantability, and performance. These improvements are nearing completion in preparation for formal durability testing. The redesigned implanted electronics canister, consisting of a welded titanium shell with hermetic connectors, contains the control, telemetry, and energy transmission electronics, as well as a 9 cell, 800 mAhr Ni-Cd battery pack. Functional changes include a reduction in the battery recharge time from 14 hours to 4 hours, and a new inductive telemetry system. The energy transmission system operating frequency has been increased from 160 kHz to 200 kHz. Electromagnetic interference filters and a more efficient control mode have also been implemented. The energy converter has been modified to incorporate a new motor with integral Hall effect position sensors, and new cable, and compliance chamber conduit fittings. High flex life cable is now used for the motor and coil cables. Two prototype durability mock circulatory loops have been built and are being tested. Substantial progress has been made in the completion of manufacturing documentation, and in the implementation of a quality system.

Animals↗

In vivo observation of cavitation on prosthetic heart valves.

In this study, a method to determine the existence of prosthetic heart valve cavitation in vivo is presented. Pennsylvania State University Left Ventricular Assist Devices (LVADs) were implanted in two separate calves for this study. Björk-Shiley Monostrut (Irvine, CA) 27 mm and 25 mm valves with Delrin occluders were used in the mitral and aortic positions, respectively. A high fidelity, piezoelectric pressure transducer was mounted approximately 1.25 cm proximal to the mitral valve and measured the high frequency pressure fluctuations caused by cavitation bubble formation and collapse after valve closure. The root mean square (RMS) value of the mitral pressure signal during a 5 ms interval after valve closure was used as a measure of cavitation intensity. The pressure signals observed in vivo were similar to ones observed in vitro with the same type of pressure transducer and were associated with the visually observed cavitation. The percentage of beats with cavitation increased from 20.3% to 67.7% when pump filling was decreased by increasing beat rate. A blood test conducted during post-operative days 1-3 showed a significant increase in plasma hemoglobin during the low filling condition. However, blood tests conducted later (post-operative days 7-44) did not show a significant change in plasma hemoglobin during low filling conditions.

Animals↗

Postoperative pulmonary complications in calves after implantation of an electric total artificial heart.

In long-term studies testing the Penn State Total Artificial Heart involving 30 calves, seven calves died of pulmonary complications within 2 weeks after receiving the implant (Group 1 [G1]) and seven calves survived from 2 weeks to 3 months without infection (Group 2 [G2]). Comparative studies were performed using multiple variables: cardiopulmonary bypass (CPB) time, cardiac index, central venous pressure, leukocyte count, hematocrit, total protein, albumin, serum glutamic oxaloacetic transaminase (GOT), creatinine, water balance, and transfused blood volume. In G1, CPB time was longer than in G2 (182 +/- 19 vs 156 +/- 17 minutes, respectively, p = 0.018). Postoperative minimum total protein and albumin in G1 were lower than those in G2 (56.5% +/- 6.0% and 59.0% +/- 5.5% of preoperative values vs 68.4% +/- 8.5% and 67.8% +/- 6.1%, respectively, p = 0.011 and 0.015). Water balance in G2 was more positive than in G1 (11.7 +/- 6.8 vs 1.4 +/- 8.3 L, respectively, p = 0.020). Other variables showed no significant differences. Microscopic findings of the lung in G1 were congestion, hemorrhage, aggregation of neutrophils, and proteinaceous material within the interstitial tissues and alveoli.

Animals↗

Steady state hemodynamic and energetic characterization of the Penn State/3M Health Care Total Artificial Heart.

Total Artificial Heart (TAH) development at Penn State University and 3M Health Care has progressed from design improvements and manufacturing documentation to in vitro and in vivo testing to characterize the system's hemodynamic response and energetic performance. The TAH system is completely implantable and intended for use as an alternative to transplantation. It includes a dual pusher plate pump and rollerscrew actuator, welded electronics and battery assembly, transcutaneous energy transmission system, telemetry, and a compliance chamber. In vitro testing was conducted on a Penn State mock circulatory loop with glycerol/water solution at body temperature. Tests were performed to characterize the preload and afterload response, left atrial pressure control, and power consumption. A sensitive preload response was demonstrated with left atrial pressure safely maintained at less than 15 mm Hg for flow rates up to 7.5 L/min. Variations in aortic pressure and pulmonary vascular resistance were found to have minimal effects on the preload sensitivity and left atrial pressure control. In vivo testing of the completely implanted system in its final configuration was carried out in two acute studies using implanted temperature sensors mounted on the electronics, motor, and energy transmission coil in contact with adjacent tissue. The mean temperature at the device-tissue interface was less than 4 degrees C above core temperature.

Animals↗

Testing of a 50 cc stroke volume completely implantable artificial heart: expanding chronic mechanical circulatory support to women, adolescents, and small stature men.

The development of a completely implanted total artificial heart at our institution has progressed to successful in vivo and in vitro testing of a device that is nearing clinical testing. This system consists of a 70 cc stroke volume pump originally designed to be used in men of average stature. Implantation of this system remains limited by patient size; hence, many women and adolescent patients will likely be precluded from support because of their smaller stature. A system similar in design, but with a 50 cc stroke volume pump has been developed. The first in vivo study of this device has been undertaken. A calf was supported for 33 days. The animal was extubated and ambulatory within the first 6 hours of implantation, and remained healthy until the thirty-third postoperative day when it suffered an embolic neurologic event. The pump and operating system worked flawlessly throughout the period of support. Further in vivo and in vitro testing will be undertaken. Development of a scaled down total artificial heart system expands this type of circulatory support to those critically ill patients previously deemed poor candidates because of their smaller body habitus.

Adolescent↗

In vivo testing of a completely implanted total artificial heart system.

The authors performed 14 implants of a completely implanted total artificial heart (TAH) system in calves. The system consisted of a dual pusher plate rollerscrew energy converter, two sac type blood pumps, an implanted electronic control and battery package, and a transcutaneous energy transmission system. Ten of the implants included a percutaneous lead for monitoring of the implant; the remainder made use of wireless two way telemetry between the implant and the outside. Three animals survived the perioperative period. These calves survived for 98 to 118 days, and one was still alive at 150 days. Causes for termination of the 98 and 118 day cases were abdominal pocket sepsis originating at a monitoring line, and systemic sepsis acquired perioperatively. Death or termination in the shorter cases was mainly due to respiratory complications or bleeding. The TAH system proved capable of providing adequate cardiac outputs at modest atrial pressures. Wireless monitoring and wireless intervention for weaning from cardiopulmonary bypass were readily achieved. All organ systems functioned normally in the presence of the device. Once recovery from implantation in these very young animals was achieved, the system proved its ability to reliably support these animals until body mass exceeded its cardiac output capabilities.

Animals↗

A completely implanted left ventricular assist device. Chronic in vivo testing.

A completely implantable left ventricular assist device (LVAD) designed for permanent circulatory support has recently been tested in animals without the use of percutaneous leads, using transcutaneous energy transmission and wireless telemetry. The LVAD consists of a brushless DC motor and rollerscrew energy converter, a pusher plate actuated blood pump with a seamless segmented polyurethane blood sac, Bjork-Shiley Delrin disk monostrut valves, an implanted compliance chamber, an implanted electronic controller and battery, and a transcutaneous energy transmission system. The blood pump/energy converter assembly weighs 565 g and displaces 295 cc. The dynamic stroke volume is 60 ml, and the maximum output is 9 L/min. Pump output is automatically controlled to maintain full stroke volume as preload varies. Hall effect sensors for detecting rotary position of the motor are the only sensors used. Six bovine implants were performed, with durations of 84, 208, 244, 130, 70 (ongoing), and 15 (ongoing) days. Four animals used two-way telemetry, whereas the remaining two used one-way (outgoing) telemetry. These first chronic in vivo tests with the Penn State completely implanted LVAD system have demonstrated that it is a feasible solution to long-term ventricular support.

Animals↗