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Cardiovascular and Metabolic Consequences of Circadian Misalignment (Postdoctoral Fellowship)

Principal Investigator:
Christopher J. Morris, Ph.D.

Brigham & Women’s Hospital and Harvard Medical School

Astronauts are frequently exposed to sudden changes in their sleep/wake cycles (slam shifting) in order to perform mission tasks “around the clock”. Slam shifting can cause problems for astronaut performance during a space mission and can open the door for possible health problems. Dr. Christopher J. Morris is conducting a project to study slam-shifting effects on the human body’s cardiovascular system; and, in particular, to determine if slam shifting makes the cardiovascular system more susceptible to disease. Dr. Morris will also seek to determine if humans are able to adapt to repeated exposure to slam shifting.

NASA Taskbook Entry

Technical Summary

The risk of adverse cardiac events has been listed as a major priority in the NASA Human Research Program Integrated Research Plan. "Slam shifts," which entail rapidly changing an individual's sleep/wake cycle, are frequently performed by astronauts. For example, in 2,043 days of International Space Station operations between 2000 and 2006, slam shifts occurred on 13 percent of these days. Moreover, it should be noted that the effects, of slam shifting, such as fatigue, can persist for many days after a slam shift has been undertaken.

Epidemiological research indicates that slam shifting is associated with adverse endocrine, inflammatory and cardiovascular function. The possible adverse cardio-metabolic consequences of slam shifts could significantly harm an astronaut's performance and, therefore, the likelihood of mission success. The association between slam shift work and health problems may be due to circadian misalignment. However, the limitation of any epidemiological study is that the underlying mechanisms cannot be deduced with any degree of certainty. In particular, there is no separation of the effect of circadian misalignment, per se, and differences in individual characteristics, socioeconomic status, and life-style factors, such as alcohol, caffeine, nicotine and eating habits. Thus, this calls for an experimental study to investigate the effect of circadian misalignment and to assess in detail potential underlying mechanisms for the increased health risk with slam shift work.

This project's primary aim is to determine the effect of simulated slam shift work on physiological changes that increase susceptibility to the development of cardiovascular disease. This will be accomplished by comparing cardio-metabolic, vascular, endocrine and inflammatory changes when subjects are scheduled to a three-day simulated slam shift schedule versus a three-day simulated day shift schedule.

To address the question whether or not individuals adapt to repeated slam shift exposures, the researchers aim to study a control group of day workers and a group of chronic slam shift workers in an identical experimental. The independent variables include: a) circadian alignment (misaligned [slam shift] vs. aligned [day shift]); b) shift duration (first day vs. third day on slam shift or day shift); and, c) chronic slam shift workers vs. non-slam shift workers. Our dependent variables include: a) cardiac and autonomic nervous system measures (catecholamines, sympatho-vagal balance, baroreceptor sensitivity and blood pressure); b) peripheral vascular endothelial function (flow-mediated vasodilatation, augmentation index); c) insulin sensitivity and release measured in response to a mixed meal; and, d) inflammatory markers -- CRP, IL-6, TNF-alpha, MCP-1.

In the near future, it is likely that humans will return to the moon and undertake missions to Mars and other destinations in our solar system. Thus, it is vital that humans understand the adverse health effects of spaceflight (e.g., circadian misalignment caused by slam shifts). This will ensure that countermeasures are developed to limit or alleviate the adverse health consequences of spaceflight and thus ensure mission success. Moreover, approximately 8.6 million Americans undertake some type of slam-shift work, and consequently, the findings from this project will be applicable to ground-based people as well as astronauts. Research plan for the coming year: Due to study being 'up and running', we believe we can complete the study of another 12 subjects over the next year in addition to the two subjects that have already completed the study. This will be achieved by increasing recruitment effort and training more staff to work on the project.

Key findings
To date, the researchers have successfully completed the study of two subjects that each undertook two eight-day in-laboratory stays separated by two to 12 weeks. Thus, at this stage of the project, there are no findings to present.

Earth Applications

Approximately 8.6 million Americans undertake shift work routines similar to those experienced by astronauts on the ISS. Thus, the findings regarding adverse effects of shift work on cardiovascular and metabolic factors from the current project are applicable to both astronauts and people on Earth.

This project's funding ended in 2012