Biomedical Instrumentation in Space Medicine

biomedical instrumentation in space medicine by Robert F. Shaw, MD

W

hile at one time considerable discussion was devoted to the question of whether America's program of space exploration could best be implemented by instrumented satellites and space probes or by manned space flights, it is now well established and accepted that man will play the central and primary role in future space exploration. Space missions are enormous ventures. Each mission brings together the extensive planning of many groups, the labors of hundreds of thousands of individuals. Missions are not only extraordinarily expensive and ambitious beyond anything man has ever attempt.ed before but. are highly complex and demand the highest degree of precise performance for their successful completion. At t.he center of each vast. and COlTIpIe x space syst.em are the few individuals who are key components of t.hese systems- the spaceborne astronauts . Since they play the central and primary role, success of these missions depends upon t.heir ability to maintain a high level of performance when subjected to the severe stresses of sust.ained space flights. Any physiologic degradations they suffer place these entire missionsand indeed the future of interplanetary explorat.ion and manned space flightin jeopardy. Experience in the comparatively brief space flights to date suggests that during these missions no severe physiological degradation attended launching, short-term flight, orbiting and re-entry. But as space flights become more ambitious, flight profiles more complex, flight periods more sustained and flight distances from the earth greater, astronaut personnel will be subjected to stresses never before encountered and, in fact, only incompletely defined and underst.ood. As the severity of the stresses increase, so will grow the demands for precise performance and the stake of all

* Adapted from presentation to industrial pharmacy section at the annual meeting of the AMERICAN PHARMACEUTICAL ASSOCIATION in New York City, August 4, 1964. 370

•-\merica in the success of these missions. This is a st.ake not only of dollars and cents but. of human and mat.erial resources, of nat.ional purpose. Assurance that the key components of t.hese vast systems will suffer no deg radat.ions in t.heir abilit.y to function and perform optimally becomes vital. The game is much t.oo big for gambling. Bioinstrument.ation monit.ors critical physiologic funct.ions t.o assure n()

Traversing the United States are the ideas of Robert Francis Shaw, MD, as he directs the biomedical engineering laboratory of Columbia University in New York City and the technical development laboratory of the Institute of Medical Sciences at the Presbyterian Med ical Center in San Francisco, California. Shaw, who has been a consultant to the National Aeronautics and Space Administration and to the United States Army, earned his MD from Western Reserve University after completing his surgical internship and residency at Columbia University. A postdoctoral research fellow of the National Heart I nstitute, he specialized in cardiovascular and respiratory physiology.

Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION

impairment. of physiologic performance . Bioinst.rumentation of space medicine has as it.s objective the acquisition of reliable and critical data regarding human physiologic performance. By st.udying the effect upon physiologic fu nction of t.he various actual and pot.ential st.resses of space flight, signifi.can t stresses can be iden tifted and quant.itat.ed and engineering solut.ions to eliminate or minimize them can be sough t . Classic in such studies are t.he well-known experiments on t.he human centrifuge relating body posit.ions to t.he abilit.y t.o withstand the effects of gloading forces. From such studies the design specificat.ions regarding orient.at.ion and configurat.ion of spacecraft and astronaut flight couches with respect to the forces of launching and reentry were specified. Similar t.ypes of st.udies are examining the eiTects upon body physiology of various st.resses t.hat can be simulat.ed upon eart.h such as vibrat.ions, heat, noise, radiat.ion, al ternative gaseous environments, immobilit.y and isolation. St.ill other st.udies will have to be conducted during actual space flight.s, for some potential stresses cannot be simulat.ed upon earth as , for example, zero gravit.y, absence of t.he earth's magnet.ic field, heavy primary cosmic rays and still others of which we are unaware. Bioinstrument.ation has a further important role to play during t.he actual conduct of space flight missions . Ult.imately such inst.rument.ation should be able to acquire sufficiently meaningful and reliable data not only to evaluate the state of astronaut well-being but to permit diagnosis of the cause or causes of physiologic degradat.ion should they occur. Corrective actions then may be initiated wherever possible or decisions made regarding assumption of spacecraft control by ground-based personnel in the event physiologic degradations advance to a point of astronaut disablement. Since bioinstrumentation for space medicine is designed to acquire signifi' cant and reliable data concerning human physiologic performance, it is not

generically diffe rent fro m the bioinstrumentation of clinical medicine or m edical research . Space medicine bioin strumentation , h owever , does have certain restraints imposed upon it by the operati onal condition s under which it m ust be u sed . In general devices mu st be entirely ext ernal , be comfortable, be insen sitive t o m otion artifact , have stable operating characteristics requiring infrequ ent adjustments and m u st be of overall size and power requirements consist ent with spacecraft opera tions. ~The re these devices are t o be used for simulation studies in terrestriallaboratories, some restraints can be relaxed . Unfortunately within the confin es of these restraints appropri at e general purpose bioinstrumentation cannot be selected and m odified for space medicine usc. Th e field of m edical bioinstrumentation is relatively YO llng and , at the current st ate of its art , an a bun dance of reliable general pur pose instruments fo r m easuring critical ph ysiologic phenom ena sim ply does not exist . As a con sequence, space m edicine and the Space Admini stration , in particul ar ,

has fo und itself in the ra ther anom alous position of h aving to support development of basic biomedical instrumentation fo r its own u sage . Since such instrumentation is of fund2.m ental importance t o the en tire m edical field, both clinical and research , such de velopment s represent unanticipa ted but outstandin g "spin-off " benefit s from the nation 's space program . Because of this paucity of appropri ate instrumentation for m easurin g critical physiological phenom ena, the physiologic param et ers m easured thu s fa r in the m an-in-s pace program h ave been the time-h onored " vital signs" of medi cal practice- temperature, pulse rate, respiratory rate and blood pressure. These m easurem ents have enj oyed wide u sage for a very long time becau se of the ease with which they can be ob tained. There has thus accrued a large body of clinical experience regarding the ran ge of " normal-values" for the "vital signs" and they are exce1lent screening paramet ers. The Gemini flight series will continue to record "vital sign s" as the M ercury series before it. Fi gure I illu strates

t he bioin strumentat ion for the Gemill i mission in place on a n astronau t. Temperature will he m onitored by an oral thermi ster thermometer , pul se rate will be deri ved from EKG signds sensed by chest e1C'ctrodes and respira tor y rate will be monitored by an impedan ce pneum ogra ph detectin g t he phasic respira tion varia tion in impedance between the t wo EKG electrodes on either side of th e chest wall . Blood pressure will also be intermittentl y determined in Gemini by means of a sphygmoma nometer cuff upon the upper arm and a small recording microphone overlyin gthe brachial arter}r. If you can never run out of gas, a fuel gauge is unnecessary. If we could be certain that every thin g would always go well with the astronauts, then even the simple bi oin strumentation u sed t() obtain the " vital signs" would not he required . But , if things ca n go wron g, then th e instrumentation should be adequa te to reveal what is ha ppenin g. The question is, " \Vhich physiological param eters are critical and sh ould he measured ?" Any a nswer to this qu estion must address itself to two considerations- '

Figure I - In place on an astronaut is the bioinstrumentation as it was used f or the Gemini fli g ht.

Vol. NS5, No . 7, July 1965

371

TOTAL

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Figure 2-0n this chart is shown the interplay of the various factors responsible for the integrated performance of the cardiovascular and respiratory systems.

How important is any particular physiologic phenomena (parameter) to the operational integrity of the astronaut? 2. How likely is it that circumstances encountered during space flight will impair the physiologic phenomena (parameter) under consideration? 1.

Having decided what phenomena should be measured, it is then necessary to establish whether and how such measurements can be appropriately, accurately and reliably aceomplished. While all of man's physiological systems are important to his wellbeing, three systems are of particular and continuous importance to astronaut performance. These are the cardiovascular, the respiratOlY and the sensory-neuro-motor system. In our own laboratories we have been especially concerned with the cardio-

vascular and respiratory systems which are not only critical to physiologic performance, in general, but are especially sensitive to the deleterious influence of zero gravity, excessive g-forces, artificial gaseous environments, immobility and other aspects of space flight. A summary representation of the integrated performance of the cardiovascular and respiratory systems is shown in Figure 2. These two systems are primarily directed toward furnishing an adequate quantity of oxygen and other metabolites to each of the cells, tissues and organs of the body and toward removing the metabolic waste products. Both the cardiovascular system and the respiratory system must be performing satisfactorily to fulfill the vital func tions of tissue oxygenation and carbon dioxide excretion. The cardiovascular system meets its

3-This schematic presentation shows the two-transducer pulsed-Doppler configuration for contin uous mom ent-by-moment determination of volumetriC blood flow rate.

Figure

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SURFACE A (VESSEL WALL)

372

Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION

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responsibility by maintaining an adequate volumetric circulation of blood, the cardiac output (Figure 2). The respiratory system fulfills its function by adequately oxygenating the blood pumped to it by the heart and clearing this volume of blood of sufficient but not excessive carbon dioxide. If these two systems are performing satisfactorily, cardiac output, the level of blood oxygen and the level of carbon dioxide in the blood will all be normal. These three physiologic parameters are in turn affected by the interplay of other physiologic phenomena. But if cardiac output, blood oxygen and blood carbon dioxide are normal, then cardiorespiratory function is normal even though measured values for such parameters as heart rate, blood pressure, respiratory rate and tidal volume may be abnormal. Or, conversely, if cardiac output, blood oxygen level and blood carbon dioxide levels are abnormal, then the cardiorespiratory system is performing abnormally even though the individual values for heart rate, blood pressure, respiratory rate and tidal volume among other parameters may be normal. The measurement of critical physiologic parameters not only assesses the level of performance and well-being but permits diagnosis of the mechanisms or causes of degradations should they occur. It is possible to develop biomedical instrumentation for measurements of critical parameters such as these although such developments may be difficult technical undertakings. Since identical bioinstrumentation is of considerable significance and importance to the general medical community, it is to the considerable credit of the Space Administration that some of the most significant bioinstrumentation developmental programs are being conducted under its auspices. Perhaps it is a reflection of the general awareness within the Space Administration of the paramount importance of technological advances and a willingness to tackle difficult technical problems. Two such programs now being conducted in our own laboratories in New York and San Francisco are directed toward measuring the two more important of the three critical cardiovascular - respiratory parameters just discussed-cardiac output and blood oxygenation. The first of these programs is developing instrumentation for measuring cardiac output and blood flow in individual particular blood vessels from completely external transducers while automatically tracking the movements of blood vessels that occur with cardiac contractions, breathing and extreme activity. Figure 3 is a schematic presentation of a two-transducer pulsed-Doppler con(continued on page 379)

ballistic missiles, air craft and submarines. The pulse mode transducer (}'igure 3, above, page 372) "acquires" and "tracks" the blood vessel of interest, while measuring its cross-sectional dimneter from moment to moment. The Doppler mode transducer (Figure 3, below, page 372) measures blood flow velocity in the vessel by detennining the Doppler shift in pulse repetition frequency caused by blood flow. Figure 4 illustrates the idealized waveforms for the pulse mode transducer and the Dop-

biomed ica I i nstru mentation (continued from page 372)

figuration for measurement of volumetric blood flow. The instrumentation employs ultrasonic traveling waves which are modulated in a pulse mode. The signal modulation concepts and information extraction methods utilized in this system are nlethods that have been developed and successfully employed in modern radar and sonar systems for detecting and tracking

Figure 4- This diagram shows idealized waveforms for the (a) "pulse mode" transducer and (b) Doppler mode transducer. The "pulse mode" transducer "acquires" and "tracks" the blood vessel of interest while measuring blood vessel diameter from moment to moment. The Doppler mode transducer measures blood flow velocity . From the two transducers volumetric blood flow is computed automatically from moment to moment.

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Figure 5-This roentgenogram of a Rhesus monkey was prepared for continuous measurement of cardiac output, electrocardiogram, respiratory rate and effort and electroencephalogram.

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9

pharmaceuticals in space (continued from preceding page)

toxic in protective doses and have given variable response. Further work is certainly indicated in this area. In the re-entry and recovery phase an timotion sickness drugs and the antifatigue drugs may prove to be useful, particularly if we continue our sea landings. Early studies with the Gemini spacecraft have been quite efIective in producing motion sickness with the spacecraft in the water. The postflight orthostatic hypotension and bone demineralization may lend themselves to amelioration through drug therapy. This should certainly be in vestiga ted. In the current drug climate one cannot help but worry about exactly

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what drugs do and particularly about efIects of which we may not be aware . It is imperative that if we do something with drugs, it must be for the good and betterment of the flight crew and not something harmful. Every attempt must be made to know the actual effect of the drugs, their mode of action, any side effects and the effect on performance of man in the space situation or, at least, space simulated situation. Our medical selection and maintenance program with the preventive medicine activities has precluded generally the development of in-flight ills. We still tend to feel that a carefully selected and trained astronaut would better accomplish his mission without the use of drugs, thereby adhering to the natural man theory. However, as we look forward to more prolonged

pIer mode transducer. From the output of these two transducers volumetric blood flow is computed automatically. Such a device will find general medical usefulness not only in evaluating and managing patients with cardiac and vascular disease but in ra pidl y, (continued on page 380)

mISSIons, it is obvious that man will need assistance and he might obtain this through a careful choice of drugs . • references 1.

2.

3.

4.

5. 6.

Cutting, W .C., Guide to Drug Hazards in Aviation 111 ed., Fed. Aviation Agency, Aviation Med. Serv., Washington, D .C., U.S. Govt. Printing Office (1962). Berry, C.A., "Aeromedical Preparations ," .11 ercury Proj . Sum. including R esults of the Fourth AI anned Orbital Flight, JI ay 15 and May 16, 1963, NASA Manned Spacecraft Center, 199. BetTY, C.A., Space Aled. Expel'. and Applications to Apollo, presented at Amer. Astronautical Soc. meeting , New York, N.Y., May 1964. Freedman, T., and Linder , G .S., Can A1an Be Modified?, pt'esented at 17th annual Amer. Rocket Soc. meeting, Los Angeles, Calif., Nov. 13-18, 1962. Berry, C.A. , "l\Ian, Drugs and Spaceflight," A nnals of Otology, Rhinology and Laryngology, 70, 418 (June 1961) . l\IcGuire, T . , and Leary, F.J., "Tmnquilizing DI-ugs and StJ-ess Tolerance ," WADC Tech. Rpt., Wright Patterson AFB, 58 (Oct. 1958).

Vol. NS5, No.7, July 1965

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safely and painlessly screening large populations for the presence of disease . The great majority of individuals who suffer coronary occlusions, for example, do not have symptoms of reduced coronary blood flow prior to their thrombotic episode and consequently are not receiving therapy. Once the coronary occlusions and strokes have occurred, the damage suffered is irreversible within minutes of the event. The device I have described should make it possible to detect and quantitate compromised blood flow in coronary and cerebral blood vessels before such tragic events so that suitable preventive therapy can be instituted before coronary occlusions and strokes occur. The second instrument development is a device for determining accurately and reliably the oxygen content of the arterial blood from a dime-sized external transducer positioned on any skin surface. This device is being developed under the auspices of the manned spacecraft center. It will make use of solid-state photometric cells and injection laser diodes to measure the amount of optical energy backscattered from blood within the skin at. highly selected and refined spectral bands. In the general medical sphere, this device will find widespread usefulness as a hypoxia warning device in surgical operating rooms and recovery rooms . It gives promise of preventing an estimated 35,000 hospital deaths each year from accidental hypoxia- twice the annual toll from carcinoma of the lung. These examples from our own laboratory are but two of the many programs that are currently in progress

and will in the near future furnish better bioinstrumentation for assessing physiologic performance and well-being of astronauts. Other similar bioinstrumentation development programs are in progress elsewhere. To mention some of t.hese in t.he cardiovascular and respirat.ory fields, for exam ple , a device for measuring the third of t.he three critical cardiorespiratory parameters, the carbon dioxide level of blood, is being refmed by the Beckman Corporation . Completely external continuous blood pressure sensors are under de velopment at the Stanford Research Institut.e , the Lear-Sigler Corporation and the Du Pont Corporat.ion. The usefulness of vibrocardiography as a cardiovascular paramet.er is being investigated at the Lovelace Foundation. Pulse wave velocit.y is being similarly investigat.ed at t.he Edwards Air Force Base and in our own laboratory. At Baylor University the impedance pneumograph is undergoing further development and t.his device is being refined commercially by a number of instrument companies. The Beckman Corporation is investigating the u sefulness and applicability of collecting and analyzing salivary samples for long-term monitoring of body fluid chemistry. In the field of EEG measurements and interpret.at.ion, both t.he Brain Research Institute at UCLA and Baylor University are conducting pertinent programs for the Space Administration. Another family of bioinstruments may be of special interest to investigators in the pharmaceut.ic31 industry and in the field of pharmacology. These are the surgically implant.able

psychopharmacology in space m iss ion s (continued from page 365)

might not exert its influence through raising the level of alertness and interest. Recovery in these studies includes bicycle pumping, pursuit tracking and psychomotor tasks. maintenance Any discussion of maintenance must acknowledge drugs which overcome environmental and other forces tending to degrade performance. Thus, motion sickness preventives are of interest when they protect with some sedation or protect without any impairment. 1o With benzedrine's history in recovery from fatigue it is not surprising to find the drug equally effective in maintaining performance by earlier administration. This includes tracking abilityll, CFF, hearing, vision and memory functions 12 and ability to "fortify most persons for a long period 380

of mental effort. and psychomotor output. "13 Again we :find another promising drug, mephentermine , maintaining tracking or piloting performance. Deterioration of piloting performance also was delayed for about four hours through administration of dexedrine which appears to be working through the CNS14 in contrast to benzedrine's apparent avenue.

en hanceme nt In the absence of better measures of current physiological state, establishment of true enhancement is difficult. However, enough such evidence exists to encourage belief that man's "normal" ability represents much less than full capability. Maybe full realization of that capability is denied by biochemical or nutrit.ion lacks, by stress

Journal of the AMERICAN PHARMACEUTICAL ASSOCIATION

biosensors appropriate for chronic con tinuous monitoring of physiologic phenomena in experimental animals. These are included in the general class of space medicine bioinstruments for many of them have been developed for possible use in experimental animal orbital and simulation space studies. In actual fact, this family of biosensors is somewhat more advanced than the external transducers for use on humans . This consideration, plus the great.er suitability of experimental animals for dangerous studies and studies of severe stresses, is t.he chief rationale for an experinlental animal program in space medicine (Figure 5). Space medicine has also played a role in t.he field of biomedical instrumentation, for biomedical instrumentation is, in fact, an infant science. And b:cause of the part.icular needs and resources of the man in space program, space medicine has not insignificantly nourished and nurtured t.he growing infant. In the pharmaceutical industry there are various ways particular bioinstruments can contribute to drug evaluat.ion and development but there is another possible role for the pharmaceutical industry in luedical bioinstrumentation. The pharmaceutical industry is directly concerned with medical diagnostic and therapeutic agents. It is directly responsible for the vast and varied armamatarium that. we in modern American medicine now enjoy. Might it not be true that the pharmaceutical industry should be nourishin g and nurturing this infant science we have been talking about.? It needs all the su stenance it can get for t.his infant. will grow to be a giant in the medical field . •

or lack of interest or concentration. \Yhatever the cause, psychopharmacology affords means for tapping the poten tiaI. The a venues of two drugs already ha,"e been mentioned. Another, pregnenolone, is claimed by some to be an enhancer 14 and by others to work only when there is an element of st.ress to be redllced Y>

persona li ty Drug reactions differ according to the personality of the subject in the test situation. 16 This thesis should have received more consideration in view of the drug action which can reduce inhibition and provide an outlet for underlying personality patterns. Thus when seconal and benzedrine subjects feel less tension, show less leadership but more activity and have nonaggressi ve "good times," 17 one wonders what the original point of departure