A ventricular assist device powered by conditioned skeletal muscle.

BACKGROUND: We are developing and testing a new ventricular assist device (VAD) to be powered by conditioned skeletal muscle. METHODS: To evaluate the VAD hardware and to develop a muscle training regimen, 8 calves have been used in studies in which the right latissimus dorsi muscle was employed. The experiments were carried out to an approximately 4-month duration. RESULTS: There was significant conversion of type II (fast twitch) to type I (slow twitch) muscle fibers. This did not correlate well, however, with device performance. The device stroke volumes ranged from approximately 17 to 90 cc. This variability of outcome occurred despite the fact that identical hardware, surgical procedures, and training regimens were employed. CONCLUSIONS: The results from the first eight studies lead us to speculate that perfusion may be important even when the muscle is working at pressures much lower than systemic blood pressure levels. In an attempt to augment tissue perfusion, we plan to investigate thermally induced angiogenesis as a possible mechanism for increasing blood flow to the tissue.

An infection inhibiting urinary catheter material.

Catheter associated bacteriuria is a common infection in hospitals and nursing homes. An infection inhibiting catheter material for fabricating urinary catheters is being developed. The material consists of silicone rubber elastomer compounded with chlorhexidene gluconate (CHG) matrix. The antibiotic is released in sustained fashion over at least 4 weeks. A method was established for adding CHG to silicone rubber. To protect the CHG, it is suspended in a water soluble wax that also modulates CHG release from the elastomer. It was found that CHG is randomly dispersed in the elastomer and that the primary release mechanism is by diffusion. The antibacterial activity of the material with a range of 0.1 to 5% CHG by weight was examined using in vitro zone inhibition testing. The new material demonstrated significant inhibitory activity against three pathogens tested (Escherichia coli, Proteus mirabilis and Staphylococcus epidermidis.). The release rate of CHG was measured in vitro using high performance liquid chromatography (HPLC). With 5% CHG loading, the antibiotic was released at a steady rate of approximately 8.4 mg/cm2/day for periods extending beyond 4 weeks. This new material for urinary catheters has the potential to provide protection against infection and surface colonization.

Microencapsulated vaccines to provide prolonged immunity with a single administration.

Vaccines that provide lasting immunity with a single administration of the antigen can reduce the cost of routine immunization programs while increasing their efficacy by lessening the need for patient compliance. The authors have been developing methods for using biodegradable polymer microspheres to encapsulate vaccines. These microcapsules are designed to provide timed release of the antigen on a schedule that mimics conventional booster shots. The microspheres are made from poly-DL-lactide-co-glycolide. The rate of biodegradation of this polymer is controllable by varying the molar ratio of the monomers. High performance liquid chromatography was used to measure release kinetics in vitro, and a process was developed for the encapsulation of water soluble protein antigens. This process then was used to prepare a microencapsulated vaccine for type A botulism made using a recombinant C fragment antigen. A series of 27 adult C57BL/6J mice were used to study the efficacy of this vaccine. Six mice injected with saline filled microspheres served as a control group. Plasma samples were taken weekly to measure antibody levels using enzyme linked immunosorbent assay. At 14 weeks, 21 immunized mice and six control subjects were used for an aerosol challenge test with botulinum toxin. All control subjects died within 72 hrs. Fifteen (71%) of the immunized mice survived.

Effects of intraoperative hyperthermia on canine sciatic nerve: histopathologic and morphometric studies.

Failure to achieve local control in the treatment of pelvic and retroperitoneal tumours results in a high rate of recurrences. The objective of intraoperative hyperthermia (IOHT) is to enhance the effect of intraoperative radiation therapy and to increase local tumour control. The tolerance of peripheral nerves to heat may limit the heat dose that can be applied to tumours. Histopathologic and histomorphometric changes of canine sciatic nerve after 60-min IOHT were studied in three groups of five dogs each for temperatures of 43, 44 and 45 degrees C. IOHT was performed using a water-circulating hyperthermia device with a multichannel thermometry system on surgically exposed sciatic nerve. Histopathologic and histomorphometric studies were done immediately, 3 weeks and 12 months after IOHT. Histologic changes observed immediately after treatment were minimal but at 3 weeks following 60-min 45 degrees C IOHT both axon and myelin loss and an increase in endoneurial fibrous tissue were observed. Twelve months after treatment a statistically significant decrease in axon, myelin and small vessel percentages as well as an increase in endoneurial and epineural connective tissue were observed for dog treated to 45 degrees C. Dog treated to 44 degrees C for 60 min had similar statistically significant but less severe changes. Twelve months after 43 degrees C IOHT for 60 min, nerve fibres appeared normal and endoneurial connective tissue was only increased mildly around small and medium-sized vessels. These results suggest that temperatures to the peripheral nerve > 44 degrees C for 60 min are likely to cause significant histopathologic changes that can be found 12 months after treatment. A hypothesis of the mechanism of heat injury to peripheral nerves was developed.

The effects of radiation therapy on the tissue capsule of soft tissue implants.

A prosthesis has been developed for cosmesis after lumpectomy surgery for breast carcinoma. The device is saline filled and percutaneously adjustable in volume to permit an optimal cosmetic result after surgical wound healing. A series of 24 studies of 18 weeks' duration using the adult rabbit animal model were first used to study tissue capsule formation around textured versus smooth surface control implants and to evaluate the effects of volume adjustments on the tissue capsule. Single or multiple adjustments of implant volume had no effect on tissue capsule thickness or morphology. Because lumpectomy surgery is invariably followed by radiation therapy, a series of six studies was then conducted to determine the effects of a typical course of radiation therapy on tissue capsule formation. One week after device implantation, a 4 x 4 cm field including the implant was irradiated with 5,000 rad (200 rad/day x 5 days/week x 5 weeks). The animals were maintained for a 6 week period after radiation treatment. After sacrifice, the implants were removed, and the tissue capsules studied using conventional histologic techniques, including scanning and transmission electron microscopy. There was no statistically significant difference in tissue capsule thickness compared to nonirradiated controls. Tissue capsule morphology, however, differed markedly. Radiation therapy decreased angiogenesis, cellularity, and the inflammatory cell response to the implants. Qualitatively, radiation treatment seemingly improved rather than compromised the connective tissue response to the implants.

Development of a magnetically operated artificial urethral sphincter. Chronic effects of compression on the skin structure and blood flow.

The artificial urethral sphincter (AUS) has been in clinical use for more than 20 years. Currently available AUS devices, however, are difficult to use and not entirely reliable. A magnetically operated AUS is currently under the development. Although the skin between the magnets will be compressed all day long, little information exists on the effects of chronic pressure on the skin structure and blood flow. In five miniature pigs, two internal magnets and one control metal disk were implanted subcutaneously at three different positions, and external magnets with differing magnetic forces were applied to the skin overlying the internal magnets for six weeks. In four pigs, the skin blood flow was measured by a laser Doppler flow meter applying different pressures. Compression of 10 mmHg preserved normal skin morphology in all but one animal where blood flow had not recovered 2 weeks after surgery. Compression of 20 mmHg for 6 weeks, however, produced pressure ulcers in all five cases (p < 0.05 vs. 10 mmHg group). The skin blood flow declined for pressures exceeding 20 mmHg (0 mmHg: 4.3 +/- 1.2, 10 mmHg: 4.3 +/- 3.3, 20 mmHg: 2.6 +/- 2.7 ml/min/100 g). We concluded that the magnetically operated AUS should use a magnetic coupling with a pressure less than 10 mmHg exerted on the interposing skin.

A new finger joint prosthesis.

A new finger joint prosthesis is being developed for the proximal and distal interphalangeal positions. Currently available "joint spacer" prostheses provide relief from pain and cosmetic improvement, but relatively poor long-term function. The new prosthesis employs a mechanical hinge at the joint. It is fabricated from titanium alloy (6A14V). The hinge mechanism avoids direct metal to metal contact by using high density polyethylene bearings. In vitro tests of the hinge mechanism have passed 75 million cycles of continuous flexure without failure (n = 12). The hinge also incorporates a mechanical limit stop to prevent hyperextension. The hinge mechanism is enclosed in a sealed elastomeric jacket that isolates the hinge from connective tissue ingrowth. The jacket, equivalent to an artificial synovial membrane, has an integrally textured exterior surface designed to promote tissue attachment to the implant to stabilize tissue capsule formation around the joint. To test the in vivo efficacy of the new design, a series of 12 devices were implanted in the knee joint position of adult rabbits. A jacketed prosthesis was implanted on one side, whereas 2 weeks later an unjacketed control was implanted contralaterally. The animals then were maintained for an 8 week period. At sacrifice, the implants were removed, and the response of the surrounding tissues was studied histologically. At the time of implantation, the range of motion of the joints was approximately 100-105 degrees. There was a progressive loss in range of motion observed in both groups. The fibrous tissue capsule around the jacketed implants, however, was significantly reduced in thickness compared with the controls (mean thickness, 1.5 mm vs. 4.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic in vivo function of a new ventricular assist device: the extracorporeal pulsatile assist device (EPAD).

An extracorporeal pulsatile assist device (EPAD) is a valveless, single-chambered, pneumatically-actuated blood pump composed of a graft conduit, connecting ring, bladder, and blowmolded housing. This allows a simple and quick surgical procedure and is easily actuated with a conventional intraaortic balloon pumping console if desired. To evaluate in vivo pump functions, the EPAD was tested in calves as a left ventricular assist device for 6-24 days. The EPAD was well synchronized to the natural heart beat up to 130 bpm in the counterpulsation mode with mild systemic heparinization (active clotting time: 200-250 seconds). Heart rate, coronary flow and cardiac output were not significantly changed by on-off testing. However, the pump showed promising diastolic augmentation (10.8% increase in the diastolic pressure time index) in these chronic animal experiments.

A new, all silicone rubber small vessel prosthesis.

A new small vessel prosthesis composed entirely of silicone rubber was developed. The new prosthesis has a trilaminar wall structure consisting of: 1) a porous blood contacting layer designed to promote the deposition of a pseudoneointima (PNI) from blood flowing over the surface; 2) a solid middle layer the thickness of which is adjusted to provide approximately the same radial compliance as the host artery; and 3) a porous outer layer that promotes connective tissue attachment to the exterior of the prosthesis to limit tissue capsule formation around the implant and preserve its compliance after healing of the perigraft tissues. The new graft also has excellent suture retention in addition to its other desirable physical characteristics. The mechanical integrity of the textured surfaces was first evaluated in vitro with cyclic flexure testing at a 20-30% strain. Grafts of 4 mm inside diameter by 5 cm length were then implanted in the left carotid artery of adult dogs for an 8 week period. Seven animals were studied. Platelet inhibitors were administered postoperatively. The patency rate was 86% (six of seven); all grafts except the first remained widely patent. After the animals were killed, the grafts were surgically exposed, and compliance was measured directly. The PNI from the grafts was then studied with light and scanning electron microscopy, and morphometric measurements were made of PNI thickness over the length of the graft. Overall, the grafts retained 80% of their preimplant compliance (n = 5); however, in the absence of any postoperative complications such as hematoma or infection, the grafts remained essentially isocompliant with the host artery during the duration of this study.

An electromagnetic pneumatic blood pump driver.

An electromagnetic pneumatic pump driver has been developed with the goals of enhanced mechanical reliability and simplicity of operation. The new driver eliminates failure prone components such as solenoid valves or pressure regulators common to conventional pneumatic drive systems, has only a single moving part, and provides for closed-loop operation in which stroke volume and dP/dT are controlled on each beat in real time. Power is provided by a high force (178 N) electromagnetic linear actuator. This assembly uses a high energy density neodymium-iron-boron permanent magnet, low loss vanadium alloy pole pieces, and an energized moving coil. The nominal stroke length of the actuator is 1.7 cm. During operation, the moving coil always remains within a fixed annular air gap, resulting in a measured force output versus applied power linearity of better than 92% over its stroke range. The coil is directly attached to the free end of a 10 cm diameter, 21 convolution, welded titanium metal bellows that forms the gas containing element of the system. The comparatively low pressure gradients across the bellows in this application result in a predicted life for the bellows in excess of 10(9) cycles. Bellows position and internal pressure are monitored continuously to control the pneumatic output. The linear actuator total excursion and velocity are adjusted on each beat using a closed-loop servo system. This results in a pump driver with no operator required adjustment of drive pressure. Instead, there are user selected settings of stroke volume, operating mode, and fill sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved textured surfaces for implantable prostheses.

Textured surfaces have been shown to reduce scar tissue formation around implanted prostheses compared with identical smooth surface controls in applications such as compliance chambers for artificial heart systems. The authors have developed and evaluated alternative textured surfaces to the polyester velour surface that has been used on those devices. These new textured surfaces are fabricated with materials known to provoke a diminished tissue response compared with polyester fibers. Two new textured surfaces have been examined: a surface composed of extruded 25 micron diameter polyurethane fibrils (PF) woven into a fabric, and an integrally textured silicone rubber surface (TS) with nonfibril geometry applicable to silicone rubber implants such as mammary prostheses. In both cases, tissue fixation to the textured surface depends primarily on mechanical interdigitation with the complicated surface morphology of the implant rather than on chemical bonding. Two types of control were employed: polyester velour fabric (PV) as a textured surface, and smooth silicone rubber (SS). Each surface was first characterized with scanning electron microscopy (SEM), and test specimens consisting of 1 cm diameter by 1 mm thickness disks were then prepared and implanted subcutaneously in a series of 16 adult New Zealand white rabbits. After 8 weeks the samples were explanted and histologic sections prepared for analysis. In all cases a thin, organized tissue capsule surrounded the implant. While the tissue capsule on average was thinner surrounding the textured surface implants, variations in the individual host response were more significant. Tissue attachment was minimal with SS, present with PF, and greatest with TS and PV.(ABSTRACT TRUNCATED AT 250 WORDS)