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Overview

Impacts of Bed Rest, Exercise and Aging on Dynamic Ventricular-Arterial Coupling (Postdoctoral Fellowship)

Principal Investigator:
Shigeki Shibata, M.D., Ph.D.

Organization:
University of Texas Southwestern Medical Center at Dallas

Exposure to microgravity can result in stiffening of the heart and arteries, leading to orthostatic intolerance (not being able to stand), reduced exercise capacity and decreased blood flow. Research shows that aging and physical inactivity produce similar cardiovascular effects. NSBRI Postdoctoral Fellow Dr. Shigeki Shibata has designed a project to assess the effects of aging and microgravity exposure on the interaction between the heart and the blood vessels. The project will also determine the optimal amount of physical activity to prevent the changes in how much blood the heart pumps and how the blood vessels distribute it to the tissues.

The project uses two different groups of subjects, covering a wide age range, to study the effects of varying amounts of exercise on the stiffening of the heart and arteries. One portion of the study involves healthy young individuals undergoing five weeks of bed rest to simulate the effects of microgravity on the body. The second part of the study involves statistical comparisons of healthy senior citizens over a broad range of age and fitness levels. Findings from this project will determine the effectiveness of exercise to prevent vascular problems related to prolonged microgravity exposure or the deconditioning associated with aging.

NASA Taskbook Entry

Technical Summary

Original Aims
The global objectives of this project were to assess the effects of aging and microgravity exposure on dynamic ventricular-arterial coupling, and to determine the optimal amount of physical activity required to prevent deterioration of the ventricular-arterial coupling of the dynamic Starling mechanism.

Specific Aims

  1. To test the hypothesis that sedentary aging leads to progressive deterioration in dynamic ventricular-arterial coupling, we planned to examine a cross-section of sedentary individuals (20-80 years old).

  2. To test the hypothesis that life-long physical exercise training prevents the deterioration of the dynamic Starling mechanism with aging, we planned to recruit healthy individuals who have consistently trained at two different doses the Surgeon Generals recommended goal of 150 minutes a week (Q3, 4-5 days/week) and a lower, but possibly more realistic, amount of 75-90 minutes (Q2, 2-3 days/week) for at least 25 years and compare these individuals with sedentary elderly (Q1) and Masters athletes (Q4).

  3. To test the hypotheses that prolonged exposure to microgravity in young healthy individuals promotes the deterioration of the dynamic Starling mechanism and that an optimized exercise training program can preserve the dynamic Starling mechanism even after prolonged exposure to microgravity, we planned to perform an exercise countermeasure during five-week six-degree head-down bed rest. We planned to compare pre- and post-bed rest with and without the optimized exercise training.

Key Findings
The dynamic Starling mechanism represents the beat-to-beat modulation of stroke volume (SV) caused by beat-to-beat alterations in left ventricular filling, and reflects the complex interaction between ventricular and arterial stiffness. Spectral transfer function gain between beat-to-beat changes in SV and left ventricular end-diastolic pressure (LVEDP) was used as an index of the dynamic Starling mechanism. A right heart catheter was placed through an antecubital vein into the pulmonary artery. Beat-to-beat pulmonary artery diastolic pressure was used as an index of beat-to-beat LVEDP. Photoplethysmography was used to continuously measure finger arterial blood pressure. Beat-to-beat changes in SV were calculated from finger arterial pressure waveform with the Modelflow method.

  1. Sedentary aging leads to progressive deterioration in dynamic ventricular-arterial coupling. We recruited a cross-section of sedentary individuals (<34 yrs: N=21, 35-44 yrs: N=13, 45-54 yrs: N=10, 55-64 yrs: N=2, >65: N=11, total 57 subjects). We found a linear relationship between the dynamic Starling mechanism index and their age (Index=-0.019xAge+1.71, R=0.594 P=0.002).

  2. Life-long physical exercise training prevents the deterioration of dynamic Starling mechanism with aging. Effects of different levels of life-long exercise training on the dynamic Staling mechanism so far appear to be dose-dependent. The greater the amount of exercise training, the higher the indices of the dynamic Starling mechanism (Q1: 0340.09, Q2: 0.500.24, Q3: 0.770.52, Q4: 0.970.54 ml/mmHg/m^2).

  3. Five-week head-down tilt bed rest promotes the deterioration of the dynamic Starling mechanism. A total of 27 subjects underwent five-week head-down bed rest; nine subjects without an exercise countermeasure (sedentary group) and 18 subjects with an exercise countermeasure (exercise group). Both sedentary and exercise groups showed a significant decrease of the dynamic Starling mechanism after the five-week bed rest while the magnitude of the decrease in the dynamic Starling mechanism was significantly lower in the exercise group than in the sedentary group (Sedentary: -42 percent, Exercise: -12 percent, P=0.04). Based on the relationship between age and the dynamic Starling mechanism, the decrease in the dynamic Starling mechanism in the sedentary group was equivalent to 29 years of aging while that of exercise group was nine years. These findings suggest that microgravity promotes the deterioration of the dynamic Starling mechanism with aging and that this deterioration can be partly prevented by exercise training.

Impact of Findings

  1. The data supports our hypothesis that sedentary aging leads to progressive deterioration in dynamic ventricular-arterial coupling.

  2. The data supports our hypothesis that life-long physical exercise training prevents the deterioration of the dynamic Starling mechanism with aging.

  3. The data support our hypotheses that prolonged exposure to microgravity in young healthy individuals promotes the deterioration of the Starling mechanism with aging and that an optimal exercise training strategy prevents, although it was partially, the deterioration of the dynamic Starling mechanism with five-week head-down bed rest.

Proposed Research for the Coming Year
There have not been major problems for the subjects recruitment, study protocol, and data analysis. Therefore, we plan to recruit eight subjects for the group of 55-64 years old, three subjects for the group of 150 minutes a week (Q3), and five subjects for the group of 75-90 minutes a week (Q2).

Earth Applications

Congestive heart failure is the leading cause of hospitalization in the elderly (>65 years old), and its incidence and prevalence are increasing exponentially. Epidemiologic studies have shown that a large percentage (approximately 50 percent) of patients with congestive heart failure have a preserved ejection fraction (EF>40~50 percent) (CHF-pEF). Although studies addressing the pathophysiology of CHF-pEF are increasing in number with the recognition of the syndrome, its underlying mechanisms are still controversial. Although the mechanism of CHF-pEF has been a matter of vigorous debate, there are two major competing hypotheses that have been advanced to explain CHF-pEF. Both of these suggest static functional impairments in either left ventricular diastolic function or arterial compliance.

In this project, we proposed a novel index called the dynamic Starling mechanism, the beat-to-beat relationship between left ventricular end-diastolic pressure and stroke volume at the respiratory frequency. The dynamic Starling mechanism is likely to unify ventriculararterial compliance reflecting time-varying ventricular-arterial compliance. Furthermore, the Starling mechanism is generally accepted to be a key function pertaining to congestive heart failure. Our previous study showed that CHF-pEF patients have an impaired dynamic Starling mechanism compared with the sedentary elderly as age-matched controls. This finding suggests a novel explanation for the pathophysiology of CHF-pEF, which has never been explained solely by ventricular diastolic function or by arterial stiffness.

Therefore, our finding that exposure to microgravity as well as sedentary aging leads to the deterioration of the dynamic Starling mechanism suggests that physical inactivity is a potential risk factor for the development of CHF-pEF. Moreover, our finding that exercise training prevents the deterioration of the dynamic Starling mechanism with aging and after exposure to microgravity implies that exercise training is a possible preventive strategy for the occurrence of CHF-pEF. As such, our findings will be beneficial for understanding the mechanism underlying cardiovascular diseases and may provide a possible preventive strategy.

This project's funding ended in 2008