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U.S. Department of Health and Human Services

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FY 2000 Artificial Organ Replacements And Assists


Advances in the development of artificial organs will be driven by the continuing dearth of natural donor organs. The products in this category are among the most complex that the Center evaluates, and their public health significance is often profound. OST’s projects are directed toward elucidating the underlying mechanisms by which this technology interacts with the body so as to identify key questions early for CDRH. Projects also include development of meaningful test methods. In FY 2001, OST investigated a number of issues related to the successful use of artificial organs and organ assists including 1) cavitation damage to prosthetic heart valves, 2) damage to blood components following implant surgery, 3) test methods for implantable infusion pumps, 4) blood flow thru implants, and 5) issues related to neural stimulation. In each case, the goal is to develop information that will assist Center decision-making in the timely assessment of manufacturers' submissions. The on-going work in the areas of heart valves, blood damage, and hemodialysis is directly coupled into regulatory guidance and standards-setting activities. For example, there are on-going validation round-robin experiments involving both manufacturers and FDA in the area of heart valves. These experiments have grown out of the experimental work conducted in the area by OST over a number of years. This program also provided input to the development of ANSI and ISO standards on refractive implants and multifocal IOLs. Laboratory work on electrical stimulation was used to help formulate a guidance document for spinal cord stimulators, and in the revision process for national standards for nerve stimulators. Additionally, this research served as a basis for the premarket review of a number of investigational sense-organ replacement devices.

A New Flow Visualization System for Quantifying Flow in Artificial Organs
Key words: flow visualization, DPIV validation model, and standard test method

A new Digital Particle Image Velocimetry (DPIV) flow visualization system was developed this year incorporating a state-of-the-art dual pulsed YAG laser and fiber optic link. This new tool quantifies flow patterns from artificial organs such as heart valves, vascular grafts, artificial hearts, blood pumps, etc. It can identify aberrant flow patterns which may cause blood damage and device failure. When blood flow is too slow, dangerous blood clots can form; when blood flow gradients are too high, red blood cells are destroyed.

A block diagram of this system is shown in the figure below. The system uses two laser flashes to freeze the motion of particles seeded in the moving fluid. A high-speed digital camera captures the images produced by the laser pulses. A computer calculates fluid velocity by correlating particle positions in the two images.

This graphics shows the Dual Pulsed YAG laser/Fiber DPIV System
Figure 1. This system was validated and used to measure flow through a
St. Jude mechanical heart valve. The figure below showsa sample
measurement obtained with the DPIV system that demonstrates
the tri-jet flow pattern for this triple orifice valve.

This graphic shows the Tri-Jet DPIV vector plot for St. Jude 19 mm heart halve at valve openings and leaflets vertical. The verticle axis is in 0 to 1 cm and the horizontal axis has Valve openings foFigure 2

Ophthalmic Implants
Key words: intraocular lenses, refractive implants, standards, technical support

OST continues to participate in the Center's enforcement program for intraocular lens implants (IOL's) by developing and using test methods to assess IOL optical properties, such as refractive power and resolution. During FY 2000, several samples of IOLs were tested in the OST laboratory. Staff scientists are also participating in voluntary standards activities for IOLs on the ANSI Z80 subcommittees for optical engineering issues. The present ANSI Z80.7 standard for Intraocular Lenses is in the process of being harmonized with the ISO 11979 series. Additionally, there are two new IOL standards being developed in ANSI Z80 - Z80.12 (Multifocal Intraocular Lenses), and Z80.13 (Refractive Implants). These standards have also been accepted by the International Standards organization (ISO) for consideration as international standards. In the first half of FY 2001, OST will participate in a ring-test on Modulation Transfer Function (MTF) calculations (computer modeling) for a number of multifocal IOL designs.

Safety of High-Rate Nerve Stimulation
Key words: neuron, computer simulation, cochlear implant, spinal cord stimulator, brain

This project assesses the safety of rapid-rate nerve electrical stimulation at rates higher than nerve impulses can follow. This simulates the energy delivered by new-generation neurological implants. OST scientists examined the physiological effects of such stimulation in real and computer-simulated nerve cells. As pulse-rate is increased, nerve firing followed the stimulation. Then, as the rate increased further, the firing decreased, increased and finally (at highest pulse-rates) the nerve stopped firing and became refractory to stimulation. Even when pulses are subthreshold, rapid-rate pulses alter neural excitability. This work, for the first time, gives quantitative measures of nerve stimulation efficiency. It forms the basis of questions in regulatory reviews and improves the design of rapid-rate stimulation.

Figyue 3 consists of two graphs as described below. The Rabbit graphic has Action potential in mV on the verticle axis. The Simulation graph has the same verticle axis, but has time in ms for the horizontal axis
Figure 3: Action potential in real rabbit myelinated axon (left trace)
as compared to computer-simulated rabbit axon (right trace, the solid bar in each
trace represents a 2 millisecond, 0.2 nanoampere stimulation pulse).

Figure 4 as described below as AP firing rate in HZ for the verticle axis going from 0 to 200 and Stimulation rate in pps for the horizontal axis going from 0 to 2000
Figure 4: Relationships between stimulation rate and action potential (A.P.) firing rate.

Examination of Mechanical Prosthetic Heart Valve Closing Sounds for High Frequency Acoustic Energy as a Signature of Cavitation
Key words: cavitation, acoustic, heart valves

Transient cavitation has been observed near operating mechanical heart valves. This cavitation, the formation and very rapid collapse of tiny bubbles, can cause valve damage or influence the hemolysis associated with these valves. FDA requires the manufacturers of mechanical heart valves under review to test for the presence of induced cavitation. OST is currently examining the available tests for cavitation. Previous studies to develop an acoustic technique detecting cavitation in and around mechanical prosthetic heart valves encountered a new problem. Not only does the collapse of cavitation bubbles causes high frequency noise; the mechanical action of valve closing, as well as the pump used to actuate the valves, also causes a broad band high frequency signal. In an attempt to distinguish cavitation noise from irrelevant sources, more data from different types of mechanical valves were taken. Spectra from time windows offset with varying time delays from valve closing were also captured to try to separate valve noise from cavitation noise. These data are currently being analyzed. Also, a new system using a sensor resonant at very high frequency (2 MHz) was put in place, and data will be taken at a higher frequency range for the universe of valves being studied.

Simplified Bernoulli Relation and Artificial Heart Valves
Key words: Bernoulli, heart valves, pressure drop.

Clinicians utilize Doppler ultrasound devices to determine the blood velocity near heart valves. A theoretical relationship, the Simplified Bernoulli equation (P = 4V2), is then commonly used to calculate the transvalvular pressure gradient, an important indicator of valve performance. A study has begun in OST to determine how well this relation applies to currently marketed prosthetic heart valves, since prior studies have shown that the Bernoulli constant of 4 is not always appropriate. In vitro test data reported to the FDA by valve manufacturers shows a range of 1.5-8.0 for the constant. With data taken for the entire range of valves available for implantation, the current study is designed to resolve whether the variation is a real effect or primarily due to measurement error. The study comes as the ISO 5840 international heart valve standard and FDA heart valve guidance are under revision.

Blood Flow and Pressure Transducer Protectors in Hemodialysis Machines
Key words: hemodialysis, transducer protector, pressure

In May 1999, FDA issued a Safety Alert in conjunction with a manufacturer’s recall of hemodialysis blood tubing sets due to blood contamination within the tubing’s pressure line transducer protectors. Due to the large number of people undergoing hemodialysis in this country (approximately 250,000), OST began a study as to how blood contacts the pressure line transducer protectors in hemodialysis machines. Blood contact may prevent accurate pressure monitoring and lead to contamination of the machine’s internal tubing. The blood level may rise in the bubble traps due to air leaks in the pressure lines, air entrainment in the flowing blood, air-blood mixing causing foaming, and air compression due to increased flow resistance. Air leaks are especially serious since they can allow blood to contact the transducer protectors without activating the pressure alarms.

Neurological CSF Shunts
Key words: neurological shunts, CSF shunts, hydrocephalus, in vitro performance testing

Testing has been underway to address problems associated with neurological shunts used to treat hydrocephalus. Currently, there exists an ASTM standard for these devices. However, this standard has been criticized as not being predictive of in vivo performance. Preliminary test results from this shunt evaluation have shown variable performance that does not match data provided by the manufacturer. In order to further understanding of CSF shunt performance, several shunt models from different manufacturers have been acquired in larger numbers and will be evaluated using the ASTM standard. This will allow a better statistical determination of shunt performance in vitro and will enhance understanding of the suitability of the ASTM standard to currently marketed shunt designs. This may ultimately lead to the development of more appropriate test methodologies for CSF shunts.

Large Animal Models of Vascular Disease and Therapeutic Device Interventions
Key words: minimally invasive techniques, vascular disease, angioplasty, radiofrequency ablation, re-clinical animal models

CDRH has established a large animal cardiovascular research program to develop and study models of cardiovascular disease and therapeutic device interventions. OST scientists are studying the effects of gender and hormone state on the response of the coronary and carotid arteries to initial balloon angioplasty injury and then to subsequent re-intervention with angioplasty or stents for the treatment of restenosis. OST is also examining the biophysics of radiofrequency ablation for the treatment of hepatic tumors. The relationship of ablation volume to blood flow is being investigated along with the electrical properties of tissue. The research goals include improved understanding of both the mechanisms of action and the failure modes for these interventions.