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Biomedical subjects

N D Bishop

Publications and source records attributed to N D Bishop.

7 recordsLinked to original sources

Altered voltage sensitivity of mutant OmpC porin channels.

Single OmpC porin channels have been reconstituted in planar bilayer membranes. Wild-type OmpC forms trimers which are largely insensitive to voltages below 250 mV.A single-point mutation of the ompC gene has been prepared resulting in replacement of Trp56 by Cys in the eyelet region of the channel wall in a highly conserved segment of the polypeptide. The monomeric channels of which the trimer is composed have smaller conductivity in 1 M NaCl (400 +/- 20 pS, mean and S.E.M., n=30) and increased voltage sensitivity by comparison with the wild-type under similar conditions, whereas other (Dex) mutants form larger channels and display different behaviour. Further, by treatment in SDS solutions at different temperatures, the W56C mutant has been shown to be less stable than either the wild-type or the Dex mutants.

Amino Acid Sequence

Elastomeric valves, a new design.

The convex bileaflet valve replaces the flat biflap inflow valve designed by Long Sheng Yu and the tricusp semilunair outflow valve. One reason is easier manufacturing. Convex bileaflet valves are developed for the 11, 20, 40, 70 and 140cc ventricles. Testing included curves (Cardiac Output versus Venous Pressure, Cardiac Output versus Heart rate), flow visualization studies, paint and bloodbag studies. The curves and flow visualization were done by connecting ventricles to one of our standard mock circulations. Paint and bloodbag studies were done by connecting the hearts to a bloodbag, but the bag was filled with water for the paint studies. The curves show high cardiac output, even with pumping at high heart rates (150 BPM+). The flow visualization shows a good stream through the sinus Valsalvae. No stagnating flow is visible. The bloodbag studies which provoke thrombosis show it on the edges of the heart valves, and little in the groove between the valve and the sinus Valsalvae. Heparninzation prevents the thrombosis. Results of our tests were good. The convex bileaflet valve seems to have good future.

Biocompatible Materials

Characterisation of the porin of Rhodobacter capsulatus 37b4 in planar lipid bilayers.

The outer membrane of Gram-negative bacteria contains aqueous channels, porins, which aid the diffusion of small hydrophilic molecules across it. Escherichia coli, as enteric bacteria, are able to survive a hostile environment of proteases, surfactants, and drastic changes of osmotic pressure. Rhodobacter capsulatus is not an enteric bacterium and as such has not evolved to resist the same challenges. Porins, which have molecular weight of approximately 35 kDa, form trimeric channels with a solute exclusion limit of about 600 Da. Most of them open and close in a controlled manner as a function of p.d. This function is little understood at present. The functional properties of single trimers of the major porin of Rhodobacter capsulatus 37b4 have been investigated in planar artificial bilayers. On application of a suitable p.d. the observed trimer closes in approximately three equal steps. The behaviour is completely symmetrical as regards closure in response to p.d.'s of opposite polarity and is strongly cation selective.

Electric Conductivity

Muscle- and pneumatic-powered counterpulsating LVADs: a pilot study.

There is a worldwide interest in supporting the failing heart with a skeletal muscle by either wrapping it around the natural heart (dynamic cardiomyoplasty) or by constructing a skeletal muscle ventricle (SMV) used for counterpulsation. Conventional cardiomyoplasty in many clinics carries an operative mortality rate of 15-20% partly because it requires 6 weeks to train the muscle to contract continually. A flexible, pear-shaped blood pump with an inflatable air chamber was designed and made around which a muscle can be wrapped. The advantage of our design is that it can also be driven by pneumatic power, immediately supporting the circulation of a seriously ill patient while that patient is still on the operating table. After a period of time to allow for revascularization and the subsequent training of the muscle, the external pneumatic power can be gradually discontinued. Then the assisted patient becomes tether-free. If, at any time, the muscle power fails, the pneumatic-powered mechanism can be reactivated. In the preferred approach, the blood pump is connected to the aorta for diastolic counterpulsation. A muscle can either be wrapped around the blood pump directly, or around one of two separate muscle pouches connected to the blood pump. To facilitate surgery, a large pouch is inserted under the musculus latissimus dorsi, which is connected to a blood pump. When stimulated, the muscle will contract over the pouch compressing it and providing power to the blood pump. If it is found that the pressure generated in the pouch cannot meet the aortic blood pressure, it can be augmented by using a pressure amplifier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Concept of a soft, compressible artificial ventricle under evaluation.

This study was designed to compare the relative merits of soft and rigid artificial ventricles. A cascade mock circulation was used to measure cardiac output under different circumstances. The data show that these soft air driven ventricles show a Starling's-like response over a wider range of filling pressures than identical, but rigid, ventricles. Compression of soft ventricles by high intrathoracic pressures was simulated in vitro. Air pressures up to +20 mm Hg did not seriously affect soft ventricles. Cardiac tamponade was simulated by compressing the ventricle in a closed fluid compartment. Tamponade became severe when volume reduction of the ventricle rose to 60 ml. Hemolysis caused by soft and rigid ventricles was tested in a blood bag set-up and was 48-82% higher in the rigid ventricle, depending on the driving conditions. Possibly, this could be explained by the authors' finding that rigid ventricles showed a 20% higher intraventricular dP/dtmax value than soft ventricles. Soft ventricles were implanted in three calves as a total artificial heart (TAH). Implantation without quick connectors was easy because the surgeon could easily fold and compress the ventricles. No physiological complications of softness were observed. Blood damage in the animals was low (less than 5 mg/dl). The authors conclude that soft ventricles show distinct surgical and functional advantages over rigid ventricles.

Animals

Development of a new inflow valve for a 20cc semisoft ventricle: preliminary results.

We remodeled and tested our semisoft 20cc ventricle and made a new bileaflet flap inflow valve. Housings, bases, outflow valve, and a newly designed diaphragm were all made by vacuum forming and put together by radiofrequency welding or glue. In vitro, the ventricle produced a cardiac output of 2.5 to 3.0 L/min and showed reliable durability results. Hematological testing showed no important thrombogenicity of the new valve. Cardiac output was higher than expected for the volume of the ventricle, perhaps because of stretching or flow through. Animal experiments with the left ventricular assist device (LVAD) version was done at Ohio State University. Earlier in Utah, we did 20 cc total artificial heart (TAH) implantations and LVAD experiments in lambs and recently in calves with the 60cc TAH version. A soft ventricle is easy to implant and low in production costs.

Animals

The development of a valveless cardiac assist device attached to the ventricular apex.

Konstantinov et al, in October, 1991, published a novel way to bridge a patient for heart transplantation. They proposed to cut off both ventricles high under the atrioventricular groove, leaving the atria, aorta, and pulmonary artery and their valves intact and to attach pneumatically driven, valveless pulsating pouches to assist the heart until a donor could be found. The removal of the ventricles just below the atrioventricular groove is called the "high cut"; it, however, destroys the chordae tendineae rendering the mitral and tricuspid valves insufficient. These have to be replaced by tissue inflow valves. We chose to cut off the ventricles at a lower level (the "low cut") to leave the papillary muscles on both sides intact, thereby saving the integrity of the mitral and tricuspid valves. Pulsating pouches were made to fit the heart at this lower level. They can be easily connected to the remaining heart after a specially disigned cuff has been sutured over the ventricular stumps. The pouches were pumped during the systole of the natural heart, but the myocardium may have to be electrically stimulated during systole to prevent undue distension. If the turgor is too weak to prevent distension, a sleeve over the ventricles is provided. To find the best location for these pouches, human cadaver implantations were done and the pre peritoneal cavity was found to be the most suitable. In vitro testing to determine how much flow could be pumped was done by attaching the pouches to fresh pig hearts and connecting them to a double sided mock circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output