G. W. Hoffler, M.D.

Robert L. Johnson, M.D.

Lyndon B. Johnson Space Center

 

[227] The Apollo Program was designed to fulfill the specific operational goals of landing man safely on the moon, enabling him to explore the lunar surface, and successfully returning him to Earth. The engineering and operational complexity of this effort necessarily limited inflight physiological studies of man to those measurements considered vital to crew safety and health assessment. Limited availability of astronaut time during busy preflight and postflight periods constrained evaluations significantly; therefore, only examinations believed to have the greatest relevance to the understanding of man's physiological responses to the space flight environment were undertaken.

Reductions in orthostatic tolerance following space flight were first observed with the late flights of Project Mercury. Tilt table tests revealed moderate orthostatic hypotension in the Mercury-Atlas 9 Pilot after only 34 hours of orbital flight. Because of this finding, tilt table tests for orthostatic tolerance were incorporated into routine preflight and postflight evaluations and continued throughout the Gemini Program. The results of these tests confirmed consistent but variable losses of orthostatic tolerance following three- to fourteen-day flights. Elevated heart rate, reduced pulse pressure, and increased pooling of fluid in the lower extremities were found consistently during 70° upright tilts in the early postflight period. Responses to this stress usually returned to normal within 50 hours after splashdown, regardless of flight duration (NASA, 1963; 1967).

The advent of the Apollo Program presented new questions and uncertainties. Fundamental differences in the Apollo spacecraft, in its operational environment, and in program goals were expected to produce physiological responses that differed from those [228] seen after the Gemini flights. The two-gas (oxygen and nitrogen) atmosphere and the capability to move about in the spacecraft led to speculation that returning Apollo crewmen might show little or no change in orthostatic tolerance. On the other hand, there was some concern regarding the ability of the cardiovascular system to withstand acceleration stresses associated with lunar descent and ascent. Headward acceleration (+Gz) was imposed during the Lunar Module descent after three to four days of weightlessness, and a near one-g (+Gz) force was produced by the ascent profile after a day or more of 1/6-g exposure. Also, the results of postflight tests were expected to show important differences in cardiovascular responsiveness between crewmen who walked on the moon and those who remained in weightless flight. These speculations and many other unanswered questions emphasized the need to gain as much understanding as possible about the cardiovascular system and its adaptation, first to zero g and, later, to one g.

For several years before the first manned Apollo flight, investigators had studied the effects on the cardiovascular system of the application of lower body negative pressure (LBNP). Lower body negative pressure involves the application of reduced pressure usually to that portion of the body below the level of the iliac crests. Evaluations of its use as a simulator of orthostatic stress (Samueloff et al., 1966; Brown et al., 1966; Gilbert et al., 1966; Murray et al., 1967) and as a preventer of cardiovascular deconditioning (Stevens et al., 1966a; 1966b) bad been made. Lower body negative pressure, at levels ranging from 40 to 60 mm Hg (-53 x 10² to -80 x 10² N/m²) ) as determined by individual tolerance, produced changes in heart rate and blood pressure similar to those resulting from upright tilting. Clearly, the cardiovascular responses initially induced by either stress procedure depended primarily on displacement of blood, chiefly from central blood volume reservoirs, to the lower extremities.

Although qualitatively alike, differences in the magnitude of cardiovascular compensatory responses induced by LBNP have been reported. Stevens (1966) and Stevens and Lamb (1965) found a greater increase in heart rate during upright tilting than during LBNP adjusted to produce the same cardiac output reduction (-19 percent). Later, Musgrave and co-workers (1969; 1971) reported that even though LBNP at 40 mm Hg (-53 x 10² N/m²) ) and the upright posture displaced essentially equal volumes of blood to the lower extremities, negative pressure levels of -SO mmHg (-67 x 10² N/m²) ) were required to produce equivalent elevations of heart rate. Both groups of investigators attributed the smaller heart rate response during LBNP to the absence of stimulation of carotid and other baroceptors by gravity-induced hydrostatic pressure and flow changes. Further, the absence of hydrostatic pressure gradients along the lower extremities during LBNP caused displaced blood to be distributed differently than during tilt.

In addition to the capability to induce cardiovascular responses similar to those resulting from orthostasis, several advantages over the tilt table test were offered by the LBNP procedure. No movement of the subject was required; therefore, instrumentation was easier to apply and maintain, and physiological signals remained more stable. Stress could be applied at several levels and the magnitude of stress could be adjusted with greater ease and precision with the LBNP procedure. Because it could be used in weightless conditions and tilt table testing could not, LBNP testing of Apollo crewmen [229] furnished a valuable data base for future application to the understanding of Skylab results. LBNP studies were performed for most Apollo crewmen for missions not encumbered by postflight quarantine restrictions. In some instances, a static stand procedure was performed in conjunction with, or instead of LBNP evaluations. Admittedly, these techniques had limitations. The response of the cardiovascular system during weightlessness can only be inferred from studies performed before and after flight. In addition, many variables, including climatic and emotional factors, complicated interpretation of the results (Hoffler et al., 1974).

On the last two Apollo missions, experimental antihypotensive garments were tested. Although the Gemini and earlier Apollo missions revealed no need for such postflight support, planners of the 28- and 56-day Skylab flights envisioned the possible need for such postflight protection. This concern was in part engendered by reports that crewmen of the 18-day Soyuz 9 orbital mission had to be assisted from their spacecraft after flight because of difficulty standing, and that anti-G suits had been provided for Soyuz 11/Salyut crewmen for use following flight if necessary.

In this chapter, the results of the lower body negative pressure and passive stand tests are presented, and the efficacy of the experimental antihypotensive garments is evaluated. Many answers will be required before the entire picture. of man's cardiovascular adaptation to weightlessness can be clarified and understood. The Apollo cardiovascular studies constitute a small but important step in the acquisition of this knowledge.

As noted previously, an LBNP protocol was used in conjunction with missions not encumbered by postflight quarantine restrictions. To assess the comparability of the LBNP and passive stand procedures, both tests were performed on the Apollo 9 crewmen. The passive stand protocol alone was used for evaluating the orthostatic tolerance of the Apollo 10 and 11 crewmen. The Apollo 10 to 14 missions included postflight quarantine, which precluded use of the LBNP. The types and durations of each of the eleven manned Apollo missions and the orthostatic evaluation techniques employed for each are described in table 1. Total mission duration varied from 143 to 302 hours; for the lunar landing missions, the length of crew time in 1/6 g varied from 22 to 75 hours.

The Command Module Pilot (CMP), his backup crewmember, and two control subjects were fitted for Jobst waist-length leotards before the flight of Apollo 16. These garments were to be donned during postflight orthostatic evaluations to assess their antihypotensive effect. A garment employing the capstan principle for the application of lower body positive pressure was designed to be worn by the Apollo 17 CMP during postflight tests.

The following subsections will describe the methodological aspects and conditions affecting orthostatic evaluation with and without the use of countermeasure garments.

Equipment and Measures

Lower Body Negative Pressure Device. The device for accomplishing LBNP consisted of a chamber of sufficient size to accommodate the lower body, an airtight waist seal, and....

[231] ....a regulated vacuum source (Wolthuis et al., 1970; Wolthuis et al., 1972). The LBNP device is shown in figure 1. The type of physiological measurements taken during the LBNP protocol varied slightly from mission to mission. Measurements made in conjunction with the Apollo 7 to 9 missions included continuous axillary and sternal lead electrocardiograms, indirect blood pressure taken every 30 seconds by the Korotkov sound technique [using the NASA Gemini blood pressure measuring system (NASA, 1968)], and changes in calf circumference measured by double-strand, mercury-in-Silastic strain gages.

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For the Apollo 15 to 17 evaluations, the limited two-lead electrocardiogram (ECG) was replaced with a modified Frank lead vectorcardiogram (VCG), and wide-band precordial heart sounds (vibrocardiogram) were recorded with a capacitance microphone system (LTV Research Center, Anaheim, Calif.). The respiration rates of the Apollo 16 and 17 crewmen were measured with a mercury strain gage attached to the lower thorax. The carotid pulse trace was recorded for Apollo 17 crewmen.

Antihypotension Garments. A Jobst waist-length elastic leotard was used in conjunction with the Apollo 16 mission. This garment was designed to produce a pressure [232] at the ankle of 40 to 45 mm Hg (53 x 10² to 60 x 10² N/m²) that decreased linearly to approximately 10 mm Hg (13 x 10² N/m²) ) at the waist. To accommodate the reduction in limb size expected to occur during flight, garments in three separate sizes were made for the CMP. They were, respectively, 0.5, 1, and 1.5 cm smaller in circumference at the calf with proportionate reductions throughout the lower limbs.

A lower body garment using the capstan principle to apply pressure to the lower limbs was designed, fabricated, and sized for the Apollo 17 CMP to use following splashdown. The garment is pictured diagrammatically in figure 2. Capstan pressure was read from an aneroid gage and the capstan was inflated with a hand bulb, both of which were concealed in a zippered pocket. The capstan exerted the pressure of the garment over the skin at the ankle m a 2:1 ratio. This pressure diminished linearly to approximately 10 mm Hg (13 x 10² N/m²) ) at the waist. Preflight testing with pressure sensors between the garment and the skin verified the ratio and the diminishing gradient of pressure from ankle to waist. To accommodate anticipated loss of limb girth, laces were provided for reducing the garment size slightly before stowage in the Command Module. The capstan itself accommodated moderate changes (±2.5 cm) in limb girth.

Physical Examinations

Major medical examinations of space flight crewmembers were performed at approximately 30, 15 and 5 days before flight (F-30, F-15 and F-5, respectively). Orthostatic tolerance evaluations performed as an integral part of these medical examinations provided baseline information for comparison with postflight evaluation results. These preflight orthostatic tolerance evaluations took place at the NASA Lyndon B. Johnson Space Center (JSC) Cardiovascular Laboratory, Houston, Texas, and at the NASA John F. Kennedy Space Center (KSC) Medical Operations Facility, Kennedy Space Center, Florida. As part of the major medical examinations, postflight orthostatic tolerance evaluations were performed shortly after splashdown and at intervals of approximately 24-hours thereafter. The number of postflight evaluations and the time at which they were performed (table 2) were dictated partly by operational constraints and partly by the length of time required for individual crewmembers to regain their preflight status. As indicated in table 2, either two or three postflight orthostatic evaluations were completed on each crewman; a fourth evaluation of the Apollo 15 to 17 crewmembers differed in that it did not necessarily include orthostatic stress tests. Immediately postflight, the first evaluations took place on the recovery ship; subsequent postflight evaluations were performed on the recovery ship, at KSC, or at the JSC Cardiovascular Laboratory.

Control Subjects

To ensure comparability of test conditions and operability of test equipment, several members of the attending support team assigned to each Apollo mission participated in preflight and postflight orthostatic evaluations identical to those used on crewmembers. These control subjects were evaluated a day or two before the Apollo crewmen were evaluated. The data collected helped ensure the validity of postflight changes observed in space flight crewmembers and the operational readiness of test teams and equipment.

Test Protocols

The protocols for the two orthostatic stress procedures are shown in figure 3. The supine LBNP protocol consisted of a five-minute resting control period, a five-minute period at each of three distinct reduced-pressure levels, and a five-minute recovery period. The first five-minute period of reduced pressure included one minute at -8 mm Hg (-11 x 10² N/m²) ) and one minute at -16 mm Hg (-21 x 10² N/m²) ), followed by three minutes at -30 mm Hg (-40 x 10² N/m²) ). The two short-duration, relatively low levels of reduced pressure were adopted to obtain additional information regarding the responsiveness of lower limb capacitance vessels. The three levels of sequentially applied reduced pressure used were chosen on the basis of previous experience in the JSC Cardiovascular Laboratory (Wolthuis et al., 1970). As reported, the use of an incremental LBNP protocol produced physiological responses for each level of reduced pressure [235] applied and ensured a measurable, quantitative stress response in both the normal preflight and the orthostatically intolerant postflight conditions.

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The passive stand protocol consisted of a five-minute resting supine control period followed by a five-minute passive stand. For the passive stand, the subject leaned against a wall in a relaxed manner with his heels spaced 15 cm (6 in.) away from the wall. Physiological measurements made during this protocol included continuous sternal and axillary lead ECG's, and indirect blood pressure taken by the Korotkov sound technique at 30-second intervals.

[236] The Apollo 16 tests, utilizing the Jobst leotard, were performed pre and postflight. Passive stand tests were performed at the F-15 tests on the Command Module Pilot, the backup CMP, and the. two control subjects, and were repeated on the CMP and the controls at their respective recovery day examinations. The tests followed the LBNP test and consisted of a five-minute supine rest period followed by a five minute stand period in the manner of the earlier Apollo passive stand tests. The leotards were then donned, and, after a ten-minute period of supine rest, the stand test was repeated. Blood pressure and heart-rate data were obtained by using the instrumentation of the earlier LBNP test.

Approximately one-half hour before Apollo 17 deorbit, the Command Module Pilot donned but did not inflate the antihypotensive garment. After splashdown, while still reclining in the couch, he inflated the capstan to a pressure of 130 mm Hg (173 x 10² N/m²) ) and, thus, furnished 65 mm Hg (87 x 10² N/m²) ) pressure over the ankle region. This pressure was maintained until a stand test could be performed. The suit was tested by performing a stand test four hours after splashdown and before LBNP testing. Crew time restraints prohibited repetition of the preflight protocol, which included separate tests with and without the garment, each separated by an appropriate recovery period. Therefore, the crewman spent five minutes in the supine position with the capstan inflated, five minutes passive standing with the capstan inflated, five minutes standing with the garment depressurized, and four minutes standing with the capstan reinflated to the original capstan pressure of 130 mm Hg (173 x 10² N/m²) ). The total duration of the continuous stand was 15 minutes, including approximately 45 seconds for reinflation of the capstan. Heart rate was obtained continuously from the VCG; blood pressure was measured every 30 seconds by a Skylab automatic blood pressure measuring system.

Ancillary Indicators of Orthostatic Tolerance

Accessory cardiovascular and related measurements were made in conjunction with orthostatic evaluations. Before orthostatic evaluation of the Apollo 7 to 11 and 15 to 17 crewmen, the circumference of the calf at its maximum girth was measured during supine rest. An assessment of total lower limb volume made on the Apollo 16 and 17 crewmembers consisted of multiple leg circumference measurements at discrete intervals from the ankles to the groin while the crewman was supine with the legs extended and slightly elevated. Limb volume was computed by summing sequential, truncated, assumed circular cones. Standard 1.8-m (6-ft) posterior-anterior chest X-rays were taken of every crewmember at his last major preflight medical examination and first postflight evaluation The cardiothoracic (C/T) ratio was determined by standard clinical methods. The ambient temperature and the oral temperature and body weight of each crewman were recorded at each evaluation.

Ambient Conditions and Other Variables

Ambient temperatures and oral temperatures were recorded during preflight and postflight orthostatic evaluations because sufficiently high temperatures can affect orthostatic tests in an adverse way. While ambient temperatures during preflight orthostatic evaluations were acceptably low, temperatures during the first postflight [237] evaluations were generally markedly higher. Ambient temperatures during orthostatic evaluations for the Apollo 15 Commander are illustrative. During preflight testing, the mean ambient temperature derived from measurements made on three separate days of testing was 297°K (24°C). On the first postflight day, the ambient temperature during orthostatic evaluation was 301°K (28°C). The significant elevation in group mean ambient temperature at the first postflight evaluation reflected the recovery zone climate (usually tropical) and inadequate air conditioning of the recovery ships. Group mean ambient temperatures for subsequent postflight evaluations were not significantly different from preflight temperatures.

Preflight examinations employing the Apollo 16 antihypotensive garment were performed under adequately controlled temperatures of 295° to 296°K (22° to 23°C). However, environmental temperatures during the first and second postflight examinations were the highest of any encountered during the Apollo shipboard tests, ranging from 305° to 306°K (32° to 33°C) during the postflight stand tests of the CMP. Apollo 17 crewmen were exposed to high environmental temperatures during transfer to the recovery vessel and during subsequent ceremonies, but their tests were performed in the air conditioned Skylab Mobile Laboratory at a temperature of 296°K (23°C).

Table 3 is a tabulation of group mean oral temperature. Here, too, the preflight mean was based on three separate determinations, thirty, fifteen and five days before flight. The elevation in this parameter noted at the first postflight evaluation continued for succeeding postflight days.

The effects of elevated ambient and oral temperatures within the postflight evaluation periods may be altered by the presence of certain additional variables. For example, although most Apollo crewmembers reported a normal amount of sleep before each preflight evaluation, there was a significant group mean reduction in the amount of sleep on the night before splashdown. Further, the interval between venipuncture for biochemical analysis (30 to 80 cm³ withdrawn) and time of orthostatic evaluation varied widely (15 minutes to many hours) within preflight and postflight time frames. Finally, the interval between food ingestion and orthostatic evaluation also varied widely (15 minutes to 17 hours).

Data Collection and Reduction

The various physiological measurements were recorded in real time on a strip chart recorder and on frequency modulation magnetic tape. The strip chart data were used for real-time assessment of crewmember well-being and safety. The appearance of presyncopal symptoms in some crewmen during orthostatic stress caused early termination of the procedure. Analog tape data were subsequently converted to digital data and analyzed by specially developed software on a Sigma 3 computer system.

Minute heart rates were derived from an analysis of electrocardiogram or vectorcardiogram R-R intervals; systolic. blood pressure and diastolic blood pressure values were read at the appearance of the first and last Korotkov sounds, respectively, on the calibrated descending arm cuff pressure ramp. Percentage change in calf volume was measured by calculating the change from initial, resting-calf circumference and converting this value to percentage change in calf volume using the method of Eagan (1961) Two....

[239] ...successive heart sound complexes were analyzed from the vibrocardiogram each minute; computation of stroke volume followed the method of Agress and co-workers (1967).

For each crewman evaluation, heart rate, systolic blood pressure, diastolic blood pressure, pulse pressure, and stroke volume values were averaged within each of the five five-minute LBNP periods and within the two five-minute passive stand periods to produce the respective mean values within each of these periods. These mean values for each crewmember, during each period and by each measurement, were subsequently used as the best estimate of measurement within that period in the compilation of data tables. In the case of percentage, maximal calf volume change rather than mean values within each level of LPNP was used.

Data Analysis

Data were analyzed statistically by individual crewmember and by group mean. For individual crewmembers, the mean and the standard deviation of the three preflight values for each measurement in each distinct protocol condition were calculated (preflight summary). From these values, fiducial limits of the normal range at the 95-percent confidence level were determined. Individual postflight values Iying outside these limits were defined as statistically significant changes and are indicated appropriately in the tables. Group means and standard deviations were calculated for each discrete measurement within each protocol condition for every evaluation day and for the preflight summaries. Preflight summary group means were compared with each postflight counterpart by using the independent t-test.

It should be noted that four astronauts flew two Apollo missions each. The Apollo 8 Command Module Pilot (CMP) flew as the Apollo 13 Commander (CDR); the Apollo 9 CMP flew as the Apollo 15 CDR; the Apollo 10 CMP flew as the Apollo 16 CDR; and the Apollo 10 Lunar Module Pilot (LMP) flew as the Apollo 17 Commander.

Heart Rates

Of the various cardiovascular measurements obtained from Apollo crewmembers during their evaluations, heart rate was the most easily measured and yielded the most accurate and predictable values. Table 4 contains heart-rate data on individual crewmembers during three conditions of orthostatic stress evaluations: (1) resting supine control, (2) the highest level of LBNP [-SO mm Hg (-67 x 10² N/m²)], and (3) passive standing. Resting supine heart rate is elevated significantly in 13 of 24 crewmen (54 percent) at the first postflight evaluation; the group response is elevated at the two-percent level of confidence. A trend toward preflight values is subsequently evident. By the third postflight evaluation, only three of fifteen individuals (20 percent) show significant elevations in resting supine heart rate, and the group mean value is not statistically different from the preflight group mean heart rate (n = 15, paired).

Following the same comparisons, the application of -50 mm Hg (-67 x 10² N/m²) LBNP produced significantly elevated heart rates in 14 of 17 Apollo crewmen (82 percent) at the first postflight evaluation, with a group elevation significant at the O.1-percent level. The Apollo 15 LMP experienced presyncope during the last seconds of....