Michael W. Bungo

Echocardiographic Evaluation of the Cardiovascular Effects of Short-Duration Spaceflight

Results are presented of echocardiographic investigations and hemodynamic measurements performed on 24 astronauts before and after short-duration (4-5 days) spaceflight, including data on the heart rate, blood pressure, and cardiac volumes. Cardiovascular changes which were found to occur after 4-5 day long spaceflight included decreased the left ventricular end-diastolic volume and the stroke volume indices, with a compensatory increased heart rate and the cardiac output being maintained; in addition, altered total peripheral vascular resistance was found to occur, with an apparent reduction in the ability to augment the peripheral vascular tone upon assuming the standing position. These cardiovascular characteristics normalized within 48 hrs of landing.

Real-Time 12-Lead High-Frequency QRS Electrocardiography for Enhanced Detection of Myocardial Ischemia and Coronary Artery Disease

Several studies have shown that diminution of the high-frequency (HF; 150-250 Hz) components present within the central portion of the QRS complex of an electrocardiogram (ECG) is a more sensitive indicator for the presence of myocardial ischemia than are changes in the ST segments of the conventional low-frequency ECG. However, until now, no device has been capable of displaying, in real time on a beat-to-beat basis, changes in these HF QRS ECG components in a continuously monitored patient. Although several software programs have been designed to acquire the HF components over the entire QRS interval, such programs have involved laborious off-line calculations and postprocessing, limiting their clinical utility. We describe a personal computer-based ECG software program developed recently at the National Aeronautics and Space Administration (NASA) that acquires, analyzes, and displays HF QRS components in each of the 12 conventional ECG leads in real time. The system also updates these signals and their related derived parameters in real time on a beat-to-beat basis for any chosen monitoring period and simultaneously displays the diagnostic information from the conventional (low-frequency) 12-lead ECG. The real-time NASA HF QRS ECG software is being evaluated currently in multiple clinical settings in North America. We describe its potential usefulness in the diagnosis of myocardial ischemia and coronary artery disease.

The mystery of sudden death: Mechanisms for risks

This review addresses the possible overlapping mechanisms that may apply to the risk of sudden unexpected death occurring in epilepsy and in cardiac disease. It explores the interaction between the central and peripheral autonomic nervous systems and the cardiopulmonary systems. Included is a discussion of the potential interactive role of genetically determined subtle cardiac risk factors for arrhythmias with a predisposition for seizure-related cardiac arrhythmias. We address the possible mechanisms that are operant in producing both epileptogenic and cardiogenic arrhythmias. Finally, we speculate about potential preventive measures to minimize the risk of both sudden unexpected death in epilepsy and sudden cardiac death.

Acute Hemodynamic Responses to Weightlessness in Humans

As NASA designs space flights requiring prolonged periods of weightlessness for a broader segment of the population, it will be important to know the acute and sustained effects of weightlessness on the cardiovascular system since this information will contribute to understanding of the clinical pharmacology of drugs administered in space. Due to operational constraints on space flights, earliest effects of weightlessness have not been documented. We examined hemodynamic responses of humans to transitions from acceleration to weightlessness during parabolic flight on NASAs KC‐135 aircraft. Impedance cardiography data were collected over four sets of 8–10 parabolas, with a brief rest period between sets. Each parabola included a period of 1.8 Gz, then approximately 20 seconds of weightlessness, and finally a period of 1.6 Gz; the cycle repeated almost immediately for the remainder of the set. Subjects were semi‐supine (Shuttle launch posture) for the first set, then randomly supine, sitting and standing for each subsequent set. Transition to weightlessness while standing produced decreased heart rate, increased thoracic fluid content, and increased stroke index. Surprisingly, the onset of weightlessness in the semi‐supine posture produced little evidence of a headword fluid shift. Heart rate, stroke index, and cardiac index are virtually unchanged after 20 seconds of weightlessness, and thoracic fluid content is slightly decreased. Semi‐supine responses run counter to Shuttle crewmember reports of noticeable fluid shift after minutes to hours in orbit. Apparently, the headword fluid shift commences in the semi‐supine posture before launch,1 is augmented by launch acceleration, but briefly interrupted immediately in orbit, then resumes and is completed over the next hours.

Acute and Intermediate Cardiovascular Responses to Zero Gravity and to Fractional Gravity Levels Induced by Head‐Down or Head‐Up Tilt

Determination of early cardiovascular responses to simulated gravity levels between 0 and 1 G will add knowledge of cardiovascular responses to space flight. Cardiovascular responses to 6 hours in a −5° head‐down bedrest model of weightlessness (0 G) were compared to those in head‐up tilts of +10°, +20°, and +42° (1/6, 1/3, and 2/3 G, respectively). Six healthy young adult males experienced the four angles on separate days. Impedance cardiography was used to measure thoracic fluid index, cardiac output, stroke volume, and peak flow. Although much intersubject variation occurred, the mean thoracic fluid content at −5° decreased during the first hour and remained decreased; 6‐hour values were similar to + 10° and +20°. Heart rate decreased the first 2 hours for all angles, then increased, converging at 3–4 hours, and reached control by hour 6. Stroke volume decreased for the first 3 hours at −5°, +10°, +20°; values at all four angles converged at hour 3 and increased in unison thereafter. Cardiac output and peak aortic flow reflected the angle at start of tilt; values at all angles converged by the second hour, decreased through the third hour, and increased thereafter. Pulse pressure decreased for the first 3 hours for angles −5°, +10°, and +20°, converged at the fourth hour, and returned to control. Peak flow at +42° was constant for the first 3 hours and increased thereafter. Blood pressure decreased for the first 2 hours, although the greatest decrease occurred at −5° and +42°; thereafter, values at all angles increased in unison and converged at the fourth hour. Total peripheral resistance increased during the first hour at −5° and +20° and decreased from hour 3 to hours 5–6 at the +42° angle. Cardiovascular values were related to tilt angle for the first 2 hours of tilt, but after hour 3 values at all four angles began to converge, suggesting that cardiovascular homeostatic mechanisms seek a common adapted state regardless of effective gravity level (tilt angle) up to 2/3 G.

Pharmacology in space. Part 1. Influence of adaptive changes on pharmacokinetics

The topic of pharmacology in space, i.e. the administration of drugs during space flight and the subsequent pharmacokinetic handling of the pharmaceuticals, is a new field about which little is known. In a two-part series, Claire Lathers and colleagues highlight some of the current questions in this field. In this first article the physiological and biochemical changes associated with weightlessness in space are discussed. These changes induce adaptive alterations which may influence the pharmacokinetic properties of drugs. The cardiovascular system is of particular relevance here. Also discussed are the classes of pharmacological agent that are most likely to be used during space flight for medical problems and thus, by necessity, will become drugs to be examined in space to determine whether their pharmacokinetic and pharmacodynamic properties are altered. Therapy of the most common spaceflight ailment-motion sickness-will be considered next month in Part 2.

Pharmacologic considerations for Shuttle astronauts

Medication usage by crewmembers in the preflight and inflight mission periods is common in the Shuttle Program. The most common medical reports for which medication is used are: space motion sickness (SMS), sleeplessness, headache, and backache. A number of medications are available in the Shuttle Medical Kit to treat these problems. Currently, astronauts test all frequently used medications before mission assignment to identify potential side‐effects, problems related to performance, personal likes/dislikes, and individual therapeutic effect. However, microgravity‐induced changes in drug pharmacokinetics, in combination with multiple operational factors, may significantly alter crew‐member responses inflight. This article discusses those factors that may impact pharmacologic efficacy during Shuttle missions.

Cardiovascular physiology in space flight

The effects of space flight on the cardiovascular system have been studied since the first manned flights. In several instances, the results from these investigations have directly contradicted the predictions based on established models. Results suggest associations between space flights effects on other organ systems and those on the cardiovascular system. Such findings provide new insights into normal human physiology. They must also be considered when planning for the safety and efficiency of space flight crewmembers.

Orthostatic function during a stand test before and after head-up or head-down bedrest

Astronauts may exhibit orthostatic dysfunction upon returning to 1 g after space flight Understanding cardiovascular changes at 0 G will provide insights into the mechanisms of the loss of orthostatic tolerance, whether due to space flight or bedrest. Bedrest is one model used to produce cardiovascular changes that are associated with space flight. In the current study, young male adults were placed at −5°, +10, +20, or +42° bedrest (0, 1/6, 1/3, and 2/3g, respectively) for 6 hours on 4 different days. This was preceded and followed by a stand test: 5 minutes in the supine position, and then 5 minutes in the standing position, with the feet 9 inches apart and 6 inches from the wall. Cardiovascular values were measured at 1‐minute intervals. Systolic and diastolic pressures were measured using an automated blood pressure device; mean arterial pressure (MAP; mm Hg) was calculated. Heart rate (bpm) and cardiac parameters were measured with a thoracic impedance device. Minute 3, 4, and 5 values were used to determine whether there were time or angle effects. Of six subjects, one reported nausea upon 3 minutes of standing after 6 hours of bedrest at −5°. The same subject was lightheaded in the first minute of standing after 6 hours of bedrest at +10°. Mean heart rate pre‐bedrest in the supine position was 63 and increased by 24 bpm on standing. Heart rate post‐bedrest in the supine position was 65 and increased by 35 bpm on standing; standing heart rate increased 11 bpm after −5° bedrest. The increases after +10°, +20°, and +42° tilts were 4,3, and 4 bpm, respectively. Changes in the mean arterial blood pressure were minimal. Results from the stand test pre‐ and post‐ 6 hours of bedrest at −5° but not at +10°, +20°, or +42° are similar to those after space flight.

Echocardiograms during six hours of bedrest at head-down and head-up tilt and during space flight

Left ventricular end‐diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6‐hour bedrest model of 0 gravity (G; 5° head‐down tilt) were compared with those of fractional gravity loads of 1/6G, 1/3G, and 2/3G by using head‐up tilts of 10°, 20°, and 42°, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two‐dimensional and M‐mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P < .05) for all tilt angles when compared with control. Ejection fraction (EF) at −5° was greater than at +20° and +42° (not significant); EF at +10° was greater than at +42° (not significant). For the tilt angles of −5°, +10°, and +20°, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20°) by 6 hours (not significant). At the +42° angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle. Left ventricular end‐diastolic volume did not change significantly with time or tilt angle, but there was a trend to a decrease by hour 2. Left ventricular end‐systolic volume was increased at hour 2 (not significant) and at hour 4 (not significant) for subjects at −5°. Systolic blood pressure did not change significantly. Left ventricular end‐diastolic volume, left ventricular end‐systolic volume, stroke volume, ejection fraction, heart rate, and cardiac output were at control values by hour 6 for all tilt angles. The lack of a significant immediate change in left ventricular end‐diastolic volume despite decrements in stroke volume (P < .05) and heart rate (not significant) suggests that multiple factors may play a role in the adaptation to simulated hypogravity. The data indicate that no angle of tilt, whether head‐down or head‐up for 4 to 6 hours, mimicked exactly the changes in cardiovascular function recorded after 4 to 6 hours of flight. Thus space and bedrest changes in left ventricular end‐diastolic volume may be similar but possess a different time course. Nevertheless, head‐down tilt at 5° for 6 hours mimics some (stroke volume, systolic and diastolic blood pressure, mean arterial blood pressure, total peripheral vascular resistance), but not all, of the changes occurring in an equivalent time of space flight.