Key words: neurology, cardiology, stimulator, defibrillator, ICD, biomaterial, tech support
OST performs safety studies on medical devices intended for implant in electrically-excitable tissues of the heart and nervous system. This work applies to a large number of devices that include cardiac defibrillators (both implanted and external), brain stimulators, spinal cord stimulators, peripheral nerve stimulators, and a new series of implants which require nerve growth onto bio-active surfaces. The classic devices use electrical stimulation to restore function or treat symptoms. OST work concentrates on the possible deleterious effects of these devices upon live cells and how these harmful effects can be avoided.
Over the past fiscal year work focused primarily on the safety of electroshock from cardiac defibrillators. One reason for this focus was the release in April 1997 of the first finding (in the controlled "AVID" clinical study by the National Heart Lung and Blood Institute) that implanted cardioverter-defibrillators (ICDs) reduce death by 38% more than conventional drug therapy. This finding was interpreted by CDRH as a justification for greatly expanding the clinical indications for ICDs. This expanded the patient population that is now eligible to receive ICDs and resulted in an increase in concerns about the patient safety issues that must be addressed in all IDEs and PMAs for implantable defibrillators. The specific safety concerns require further OST investigation of the conditions under which ICD therapy produces deleterious effects to relatively intact heart tissues.
OST studies involving isolated heart cells have demonstrated electroshock-induced changes associated with calcium ion elevation in heart cells. Such cellular changes are related to the production of secondary arrhythmias seen clinically following defibrillator shocks. During FY 97 OST scientists focused on the mechanisms by which calcium becomes elevated in heart cells after defibrillation pulses. By employing a high-time resolution intracellular calcium imaging system, studies revealed that the calcium elevation is caused by both intracellular release and extracellular entry. Excised heart cells were maintained in culture, stained with a calcium-sensitive dye and shocked with defibrillation pulses. A low-noise, cooled CCD camera recorded the calcium-related intracellular fluorescence changes. The experiments suggest that much of the extracellular entry is through the same calcium channels on which many anti-arrhythmic drugs operate. Researchers therefore hypothesized that there are interactions between electric shock therapy for arrhythmias and pharmacotherapy. These results served in establishing review criteria for a number of medical devices, were presented during safety analyses at FDA Advisory Panel meetings, and were used in formulating a guidance document on the regulation of implanted cardioverter-defibrillators.
Another area of investigation is a proactive study of tissue-engineered surfaces for neural growth. A new generation of implantable medical devices will use coatings and surfaces designed to promote interaction with the nervous system. Such implants have potential uses for neurodegenerative disorders of the large aging population in the United States and for developmental disorders in children. As a result, OST scientists are performing a collaborative study with the National Institutes of Health that involves the growth and survival of explanted neurons from mouse brain on surfaces coated with the laminin biopolymer. This coating is useful in medical devices for obtaining nerve growth across injury sites and for obtaining infiltration into the devices to help restore neural function. Certain nerve cell types grow well on this bio-polymer while other types do not grow well and die. Studies revealed that the surface coating affects selectivity for neural survival and growth, and this selectivity is regulated by intracellular calcium modulators. These studies support the reviews of investigational devices which involve nerve cell growth.