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Copyright notice: This article is available for free from pubmedcentral.nih.gov RADIOISOTOPE POWERED CARDIAC PACEMAKERS Fred N. Huffman, Ph.D., Joseph J. Migliore, M.D., William J. Robinson, B.S. and John C. Norman, M.D. Over 100,000 implantable cardiac pacemakers are currently being used to rehabilitate patients with heart block. The chemical batteries powering these pacemakers usually fail within a few years. A variety of nuclear batteries with the potential of providing long-lived (10-20 years) pacemaker power, are under development. This paper reviews the status of this development. Nuclear powered pacemakers have reached the stage of clinical evaluation. Their cost, although initially high, is not prohibitive. In our institution, third party insurance carriers have assumed their cost. The primary concern of widespread application is the maintenance of fuel capsule integrity under all credible conditions. PACEMAKER ENERGY SOURCES A wide variety of chemical, biologic and nuclear energy sources have been explored to power cardiac pacemakers. Almost all currently implanted pacemakers utilize primary batteries. Formerly, mercury-zinc cells and electrodes produced an average pacemaker longevity of under two years. Contemporary electrodes require significantly lower energy input to produce consistent pacing. As a result of reduced battery drain and improved circuits, commercially available pacemakers using primary batteries are expected to average three to five years of longevity.' Since the average patient is 72 years at implantation, primary batteries are likely to be adequate for the majority of clinical situations. Solid state lithium-halide batteries2'3 offer potential longevities significantly greater than zinc-mercury cells. Although the first clinical application of an implantable cardiac pacemaker4 used a nickel-cadmium battery, there has been only limited clinical use of rechargeable systems due to operational complexity, patient anxiety and lack of cells that would operate at body temperature. Recently, Fishell et al.5 addressed the latter problem and developed a rechargeable pacemaker with an estimated lifespan of 20 years (Pacesetter Systems Inc.). Other investigators have sought to develop biogalvanic systems7'8 using body fluids as well as biological fuel cells.9 While biological fuel cells should provide adequate power for pacing, no such unit has reached prototype evaluation. In addition to anxiety and expense, pacemaker replacement constitutes a small but definite risk of infection and prolonged hospitalization. As a result, batteries using the energy of radioisotope decay to provide longlived (10-20 year) pacemaker power are being developed internationally. A genealogy of the more highly developed nuclear-to-electric conversion techniques is included in Fig. 1. These conversion techniques can be grouped into two types: thermal and non-thermal. The thermal converters (whose output power is a function of a temperature differential) include thermoelectric and thermionic generators. The non-thermal converters From the Cardiovascular Surgical Research Laboratories, Texas Heart Institute, of St. Luke's Episcopal and Texas Children's Hospitals, Texas Medical Center, Houston, Texas; The Thermo Electron Research and Development Center, Waltham, Massachusetts, and the Cardiovascular Division, Sears Surgical Research Laboratories, Harvard Medical School, Boston, Massachusetts. 52 (whose output power is not a function of a temperature difference) extract a fraction of the incident energy as it is being degraded into heat rather than using thermal energy to run electrons in a cycle. < ATOMIC ENERGY RESEARCH ESTABLISHMENT Figure 1. Genealogy of Cardiac Pacemaker Power Sources 53 THERMAL CONVERTERS Both thermionic and thermoelectric converters have been evaluated for pacemaker application. A thermionic converter,10 (Fig. 2), consists of a hot electrode which thermionically emits electrons over a space charge barrier to a cooler electrode, producing a useful power output. Cesium vapor is used to optimize the electrode work functions and provide an ion supply (by surface contact ionization) to neutralize the electron space charge. A thermoelectric converter" connects thermocouples in series. Each thermocouple (Fig. 3) is formed by the junction of two dissimilar materials, one of which is heated and the other cooled. Metal thermocouples have low thermal-to-electrical efficiency. However, the carrier density and charge can be adjusted in semiconductor materials such as bismuth telluride and silicon germanium to achieve much higher conversion efficiencies. A block diagram for thermoelectric and thermionic systems is shown in Fig. 4. Effective thermal insulation is essential to minimize heat loss with attendant reductions in fuel inventory, radiation exposure and expense. Both fiber and vacuum foil insulations are being used. Vacuum foil insulation, consisting of multiple layers of thin foils separated in a vacuum by oxide particles, provides lower thermal losses in a more compact unit than does fiber insulation. The dc-to-dc power conditioner is optional depending on the output potential of the converter. In principle, the voltage required (typically, about five volts) can be obtained by connecting in series adequate numbers of thermocouples or thermionic diodes. In practice, fabrication is often simplified by designing the converter for a low voltage output (approximately 0.5 volts) and subsequently employing a dc-to-dc circuit to transform the converter output voltage to the level required by the pacemaker electronics. The subsystem combinations are evident from Fig. 1. The Isomite thermionic converter'2 developed by McDonnell Douglas has been discontinued for pacemaker application. ARCO Nuclear'3 uses 528 metal (CupronTophel) thermocouples in conjunction with vacuum foil insulation to obtain a high output voltage that can power a pacemaker without a dc-to-dc converter. However, the low efficiency of the metal thermocouple results in a relatively high fuel loading. The development of this pacemaker has been sponsored by the USAEC. CIT-Alcatel14 in France, the Atomic Energy Research Establishment15 in Great Britain, and the Gulf Energy and Environmental Systems Company in the United States all use low voltage bismuth telluride modules in combination with fiber insulations and dcto-dc power conditioner units which decrease the relatively high thermoelectric conversion efficiencies. Nuclear Battery Corporation'6 uses a similar system, with the exception that vacuum foil insulation is substituted for fiber insulation. Their Atomcell has the lowest fuel loading (0.120 gram) of the thermal conversion systems. Siemans AG17 in West Germany vapor deposit 1420 bismuth telluride couples on a polyimide substrate to obtain a high potential thermopile. The thermocouples are connected electrically in two series strings. Syncal Corporation18 is working on a high potential silicone germanium module in which all thermocouples are connected in series-parallel. 54 COOL COLLECTOR HOT EMITTIER kCOLLECTOR I EMITTER9 CESIUM / AI/ VAPOR EL VL _-VL_ F,L////-// Figure 2. HOT JUNCTION Thermionic Converter with Potential Diagram. COLD JUNCTION HOT JUNCTION COLD JUNCTION rfl_ HEAT IN EL. Ipu EL. HEAT OUT Figure 3. Thermocouoe with Potential Diagran. _ HEAT PATH TISSUE --ELECTRICAL PATH THERMAL Figure 4. RADIOISOTOPE POWERED PACEMAKER Block Diagram of Radioisotope-Fueled Thermoelectric and Thermionic Systems. 55 NON-THERMAL CONVERTERS Non-thermal converters extract a fraction of the nuclear energy as it is being degraded into heat. Their outputs are not functions of temperature differences as are thermoelectric and thermionic converters. Non-thermal generators can be grouped into three classes. The primary generators consists of a condenser19 which is charged by the current of charged particles from a radioactive layer deposited on one of the electrodes. Spacing can be either vacuum or dielectric. Negatively charged beta particles or positively charged alphas, positrons or fission fragments may be utilized. Although this form of nuclear-electric generator dates back to 1913, few applications have been found for the extremely low currents and inconveniently high voltages provided by direct charging generators (Fig. 5). The betavoltaic cell is the most successful of several generators that rely on secondary electronic excitation. One of the oldest is the ionic or contact potential battery which dates back to 1924 (Fig. 6). Two electrodes of dissimilar work function enclose a gas. Any source of ionizing radiation can generate ion pairs in the gas, which are collected by the electric field set up by the contact potential owing to the dissimilar work function electrodes. The currents of oppositely charged particles flowing in opposite directions add and may be passed through an external load to deliver an electrical output. The U. S. Army sponsored work on this concept in the early fifties at Ohmart Corporation and Tracerlab. Its drawbacks were poor efficiency, instability and low power density. The irradiated P-N junction20 is a solid state analog of the ionic battery (Fig. 7). Incident radiation (e.g. light, X-rays, alpha or beta particles) ionize hole-electron pairs. Minority carriers near the junction are collected and constitute a current through an external load. Compared to the ionic battery, efficiency is high, conversion volume is small and output is stable. Beta radiation of the P-N junction is the most practical. RCA was responsible for most of the early work on this betavoltaic generator. More recently, McDonnell Douglas2' has significantly improved the efficiency and power output. Their betavoltaic unit is termed the "Betacel". COLLECTOR CHARGED PARTICLE F.L. DECAY ISOTOPE / EMITTER COLLECTOR VL BETA EMITTER F L. VACUUM OR DIELECTRIC + V - L Figure 5. Direct Charging Generator with Potential Diagram 56 IONIZING RADIATION 3 LOW WORK HIGH WORK FUNCTION ELECTRODE t o A_ | FUNCTION ELECTRODE HIGH# E)---w ARGON o_@ F.L. 4 YL F- - VL Figure 6. Work Function Battery with Potential Diagram. ..p.. I "N". opts , CZ I I I I IONIZING RADIATION " N" CONDUCTION I I 177 7 7 7EL F.L.7p vm VALENCE BAND VL Figure 7. Irradiated P-N Junction Battery with Potential Diagram. IONIZING RADIATION | PHOTOVOLTAIC CELL Figure 8. Radioisotope-PhosphorliPhotovoltaic-Generator 57 The phosphor-photovoltaic generator22 is an example of a dual conversion nuclear battery (Fig. 8). First, the radioactive energy is converted into light by a scintillating phosphor. Second, the photovoltaic cell converts the light into an electrical output. Theoretically, the phosphor-photovoltaic generator has the potential of higher power density than the betavoltaic generator. In practice, phosphor degradation has limited its application. RADIOISOTOPE FUELS Plutonium-238 (Pu-238) is the unanimous choice of thermoelectric pacemaker developers while most betavoltaic converters have utilized Promethium-147 (Pm-147). Plutonium-238 has a long half-life (89 years), reasonable power density (3.5 watts/cm3), low radiation output, established containment technology and low cost. Since Pu-238 is primarily an alpha emitter, its decay builds up a helium pressure inside the sealed fuel capsule. Most thermoelectric power sources (see Table 1) use a plutonium oxide fuel form. This refractory material (melting point of 4050°F) is chemically and biologically inert. To minimize the probability of particulate inhalation if the encapsulation is compromised, the fuel pellet is pressed and sintered. The dose rate can be further reduced by using high purity "medicalgrade"' Pu-238 oxide23 enriched with Oxygen-16. The high energy and mass of the Pu-238 alpha particles would rapidly degrade a P-N junction. Consequently, a low energy and mass beta particle is used for radiating a P-N junction to obtain an electrical output. Most betavoltaic investigations have used the inexpensive Promethium-147 (Pm-147) beta emitter which has a half-life of only 2.62 years. Unfortunately, there does not appear to be a radioisotope with the requisite combination of beta energy, half-life and low dose rate that can be produced economically to take full advantage of this conversion technique. Although tritium24 and Nickel-63 have been considered, the beta range of the former is quite short (resulting in excessive source absorption), while the latter is too expensive. Both give a drastically reduced electrical power density relative to the Pm-147 fueled betavoltaic converters. McDonnell-Douglas projects a useful lifetime of 7 to 10 years for their Pm-147 fueled Betacel units. Betavoltaic converters do not appear to have the potential for extended life (up to 20 years) of the Pu-238 thermoelectric generators. In the case of either the Pu-238 or Pm-147 units, the integrity of the fuel containment under all credible conditions is the primary design consideration. NUCLEAR BATTERY COMPARISON Of the many nuclear conversion methods investigated for powering pacemakers, only thermoelectric and betavoltaic systems have been applied clinically and are commercially available. The subsystem combinations of these power sources have been identified in Fig. 1. With a single exception, all thermoelectric generators use semiconductor thermocouples to achieve a higher conversion efficiency than metal thermocouples. A summary of the fuel, pacemaker electronics, cost and evaluation status is given in Table 1. The tabulated nuclear power sources are comparable in size and weight 58 to chemical batteries. The fuel loadings of the semiconductor thermoelectric generators range from 0.120 to 0.200 gram of Pu-238; The ARCO Nuclear unit uses lower efficiency metallic thermocouples and requires a higher fuel inventory. The Nuclear Battery Corporation Atomcell is the most efficient of the batteries, since it uses vacuum foil insulation as well as bismuth telluride thermocouples. The radiation dose rates from all the nuclear batteries are less than 20 mrem/hr at contact and less than 0.5 mrem/hr at 5 cm. Based on continuing studies in our laboratories, the somatic effects to the patient from these dose rates should not be a deterrent to clinical use. Effects on canines25 implanted with 16- and 24-watt Pu-238 sources (two orders of magnitude larger than those contained in nuclear-powered cardiac pacemakers) have been benign except for minor pathological alterations in tissues within 6 mm of these sources. Radiation equivalent sources simulating the dose rate fields of 50 gram Pu-238 sources, but with negligible thermal outputs, have been implanted in dogs26 for periods up to four years with similar results. The whole body, time averaged dose rate from a typical nuclear pacemaker is approximately 0.5 rem/year compared to the whole body occupational exposure limit of 5 rem/year recommended by the National Committee on Radiation Protection. To date most nuclear pacemakers have been implanted in younger patients. At our institution, two ARCO Nuclear and four Medtronic (Laurens-Alcatel battery) nuclear pacemakers are being clinically evaluated. There have been no unusual results from these studies. In summary, nuclear-powered cardiac pacemakers have reached the stage of clinical evaluation. Such pacemakers have the potential of long life. Their cost, although initially high, is not prohibitive. Animal studies indicate that the somatic and genetic radiation effects from a sealed source should not preclude clinical use.The primary concern of widespread application is the maintenance of the fuel capsule integrity under all credible conditions. TABLE I SUMMARY OF PRINCIPAL NUCLEAR PACEMAKERS Fuel Radioisotope Loading Pacemaker Ev,aluation Status Facility Nation ARCO Nuclear U. S. Pu-238 Oxide "Atomcell" (,Nuclmear Battery Corp.) U. S. Pu-238 Oxide 0.120 (0- 16 Enriched) - $ 2500/ Batte ry Animal Evaluation ost efficient of available n-clear bvatteri,s Atomic Energy Research Estab. (AERE) Great Britain Pu-238 Nitride 0. 180 - _ -80 Clinical Cases Based on "Btacel 400" (McDonnell Douglas U. S. Pm- 147 Oxide 0. 105 Gulf Energy and Environmental Systemls U. S. Pu-238 Oxide 0. 180 CIT-Alcatel France Pu-238/ Sc Alloy 0. 160 Siemens AC. West Pu-238 Oxide 0.200 Pu-238 Oxide - Fuel (GM) Electronics Cost $ 5000/ 0.410 ARCO (0-16 Enriched) C.mn,, nts 42 Clinical Cases Pacemaker Biotronik IF;P- S1; I USAEC sS Z:0oo/ Animal B3attery 5000/ Medtronics $ Model 9000 Psac-mak- - - Fsaluati.n U. S. Clinical C- First pa-a 17k,r to e used linically e1 ap-)at. d tEin-filn, - rototype under t, st 59 that Basi-Ily if 1ential to AFb th - ha >a tt,- ry 400 Germany Sync,al RIPPLE techn7,l7gy ( 2375/ 60 Clinical Ca.sc 1'otential life 1 I P'a emas.k" r)f P'l- Z 38 unit, - (0- 16 Enriched) Developnunt sponsored by th-n-pil- rmopile Direct highi -ol.tage -ith siIico:n-gern,.niu., th--r,).pil,- REFERENCES 1. Furman S: Cardiac Pacing-An Endless Frontier. Medical Instrumentation 7:169, 1973 2. Greatbatch W, Lee JH, Mathais W, et al: The Solid State Lithium Battery: A new improved chemical power source for implantable cardiac pacemakers. IEEE Trans. Biomed. Eng.BME-18 5: 317, 1971 3. Fester K, Doty RL: Solid-state batteries for cardiac pacemakers. Medical Instrumentation 7:172, 1973 4. Greatbatch W, Chardack W: A transistorized implantable pacemaker for the long-term correction of complete atrio-ventricular block. Proc New England Research and Eng Meeting (NEREM) 1:8, 1959 5. 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Huffman FN, Molokhia FA, Norman JC: Thermal and radiation effects of Pu-238 fuel capsules in dogs and primates. Trans. American Nuclear Society 14: 510, 1971 26. Sandberg GW, Huffman FN, Norman JC: Experimental observations of intracorporeal Strontium-90-Americium 241 Beryllium sources simulating radiation fields from nuclear powered artificial hearts. Annals of Thoracic Surgery 9: 401-409, 1970 27. Norman JC, Sandberg GW, Huffman FN: Current concepts. Implantable nuclear-powered cardiac pacemakers. N Engl J Med 283:1203-1206, 1970 60 VISIT www.prutchi.com for more information and pictures on implantable devices