The effects of spaceflight microgravity on the musculoskeletal system of humans and animals, with an emphasis on exercise as a countermeasure: a systematic scoping review.

The purpose of this systematic review is twofold: 1) to identify, evaluate, and synthesize the heretofore disparate scientific literatures regarding the effects of direct exposure to microgravity on the musculoskeletal system, taking into account for the first time both bone and muscle systems of both humans and animals; and 2) to investigate the efficacy and limitations of exercise countermeasures on the musculoskeletal system under microgravity in humans.The Framework for Scoping Studies (Arksey and O'Malley 2005) and the Cochrane Handbook for Systematic Reviews of Interventions (Higgins JPT 2011) were used to guide this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was utilized in obtaining the combined results (Moher, Liberati et al. 2009). Data sources, PubMed, Embase, Scopus, and Web of Science were searched for published articles through October 2019 using the Mesh terms of microgravity, musculoskeletal system, and exercise countermeasures. A total of 84 references were selected, including 40 animal studies and 44 studies with human participants. The heterogeneity in the study designs, methodologies, and outcomes deemed this review unsuitable for a meta-analysis. Thus, we present a narrative synthesis of the results for the key domains under five categories: 1) Skeletal muscle responses to microgravity in humans 2) Skeletal muscle responses to microgravity in animals 3) Adaptation of the skeletal system to microgravity in humans 4) Adaptation of the skeletal system to microgravity in animals 5) Effectiveness of exercise countermeasures on the human musculoskeletal system in microgravity. Existing studies have produced only limited data on the combined effects on bone and muscle of human spaceflight, despite the likelihood that the effects on these two systems are complicated due to the components of the musculoskeletal system being anatomically and functionally interconnected. Bone is directly affected by muscle atrophy as well as by changes in muscle strength, notably at muscle attachments. Given this interplay, the most effective exercise countermeasure is likely to be robust, individualized, resistive exercise, primarily targeting muscle mass and strength.

An assessment of pulmonary function testing and ventilatory kinematics by optoelectronic plethysmography.

New advances in computer processing and imaging have allowed the development of innovative techniques to assess lung function. A promising methodology is optoelectronic plethysmography (OEP). OEP evaluates ventilatory kinematics through the use of infrared imaging. Markers are placed, and images read on the chest, back and abdomen of subjects. Currently, this system is used mainly in research settings, but in the future may have broad applicability to patient populations such as very young children, patients with neuromuscular disease and patients who cannot be tested with classical spirometry testing. This paper presents the history and development of OEP, along with a summary of the OEP methodology, a discussion of research findings and results to date, as well as application and limitations.

Effects of a community-based intervention on physical activity: the Pawtucket Heart Health Program.

OBJECTIVES: The effect of a community-based physical activity program in Pawtucket, RI, was evaluated relative to one in a comparison community. METHODS: Cross-sectional surveys of 7529 residents of Pawtucket, RI, and 7732 residents of the comparison city were conducted at 2-year intervals during 7 years of intervention. RESULTS: There were no differences in self-reported knowledge of the benefits of physical activity, attempts to increase exercise, or prevalence of physical inactivity between Pawtucket and the comparison community. CONCLUSIONS: Future community-based physical activity interventions should attempt to involve a wider range of individuals.

A comparison of exercise performance on bicycle and rowing ergometers in female master recreational rowers.

Limited information exists on the response to maximal exercise testing in female masters level recreational rowers. This study examined cardiorespiratory and physiologic responses to progressive, incremental exercise using a variable resistance rowing ergometer and a cycle ergometer in six experienced female masters level rowers. Maximal oxygen uptake (VO2 max:33.8 +/- 7.3, 33.5 +/- 6.6 ml.kg-1.min-1) and minute ventilation (VEmax: 86.1 +/- 9.6 l.min-1, 88.7 +/- 13.8 l.min-1) were similar during both tests (rower vs cycle). Maximal heart rates were significantly higher on the cycle ergometer (177 +/- 9 beats/min-1) compared to the rowing ergometer (173 +/- 11 beats/min-1), while peak power on the rowing ergometer (175 +/- 22 watts) was lower than the cycle ergometer (187 +/- 41 watts). Blood lactate levels taken 1 minute following exercise were similar on the rowing ergometer (10.5 +/- 1.7 mM/l) and cycle ergometer (11.8 +/- 1.5 mM/l) and indicated maximal effort was achieved in all subjects. Ventilatory threshold levels were significantly different on the rower (2.0 +/- 0.16) versus the cycle ergometer (1.9 +/- 0.18) (p = 0.38). These data suggest that the cycle and rowing ergometers yield relatively similar results when testing maximal exercise performance in this population.

Cross-sectional relationship between diet and physical activity in two southeastern New England communities.

The hypothesis that health promotive diets associated with higher levels of habitual physical activity confound the relationship between regular physical activity and health has not been well explored in epidemiologic studies. We evaluated self-reported physical activity, Willett Food Frequency dietary data, sociodemographic and physiologic factors cross-sectionally for 2,004 household survey participants in two southeastern New England communities. We compared the dietary habits of sedentary participants (n = 964) to those of moderately active (n = 600) and very active (n = 440) participants after adjusting for age, gender, education, smoking status, year of survey, and total calories. Our results showed that moderately active and very active participants consumed more fiber, less total fat, and less saturated fat than sedentary participants (P < .01). They also consumed more vitamins (A, C, D, E), beta carotene, and calcium, (P < .01), and ate more fruits and vegetables (P < .001) than sedentary participants. We found these relationships in both New England communities studied. This association between regular physical activity and diet suggests that the relationship of habitual physical activity and chronic disease may be confounded by diet.

Physical activity, physical fitness, and coronary heart disease risk factors.

The relationships between physical activity, physical fitness, and coronary heart disease risk factors measured in a large community sample were evaluated. Self-reported physical activity using a single question, maximal oxygen consumption estimates derived from the Pawtucket Heart Health Step Test, blood pressure, nonfasting lipids, and body mass index were cross-sectionally evaluated in 381 men and 556 women. The correlation of estimated maximal oxygen consumption and self-reported physical activity was modest but statistically significant (r = 0.13 in men and r = 0.19 in women). Blood pressure, body mass index, and HDL cholesterol were correlated with physical fitness (r = 0.24-0.65) and correlated to self-reported physical activity (r = 0.09-0.14). Evaluation of coronary heart disease risk factors using both physical activity and physical fitness revealed a complex relationship that generally showed a stronger relationship with measures of physical fitness than with physical activity. This study suggests that simultaneous measurement of physical activity and physical fitness may be useful in epidemiologic studies of habitual physical activity and chronic disease.

Developing a competency-based preventive medicine curriculum for medical schools.

Trends in patient morbidity and mortality, cost-effectiveness, and national recommendations mandate that we practice more preventive medicine. To address this need, we set out to develop a comprehensive curriculum in preventive medicine for medical schools. We constructed a competency-based (i.e., performance-based) curriculum with specific educational objectives defined by outcomes. Subject areas were subdivided by life stages, and learning objectives were created separately for epidemiology, assessment, and intervention. We hope that adoption of such an educational blueprint by medical schools will measurably enhance the attitudes, knowledge, and skills necessary for the incorporation of preventive principles into all aspects of clinical medicine.

Coronary care unit requirements of patients with acute myocardial infarction treated with or without thrombolytic therapy: a pilot study.

OBJECTIVE: To determine if patients with acute myocardial infarction who receive thrombolytic therapy require more nursing care hours and a longer length of stay in the coronary care unit than those patients with acute myocardial infarction who do not receive thrombolytic therapy. DESIGN: Retrospective cohort study using the coronary care unit data base and patient classification records. SETTING: Northeastern university-affiliated, community-based, cardiovascular tertiary care center. PATIENTS: All patients admitted to the coronary care unit with a diagnosis of acute myocardial infarction were screened. Of these, 20 patients who also had a patient classification form completed were included in the study. Ten of these patients had received thrombolytic therapy and 10 had not. The patients were grouped according to treatment with a thrombolytic agent or conventional treatment. There was no significant difference in age between the groups (64 +/- 19 years and 67 +/- 15 years). OUTCOME MEASURES: Nursing care hours per patient per day and length of stay per patient in the coronary care unit. RESULTS: On days 1 and 2 of hospitalization, there were no significant differences in total nursing care hours provided per patient per day. On days 3 and 4, those patients who received thrombolytic therapy received fewer nursing care hours compared with those who did not (11.1 and 9.2 vs 13.8 and 12.7 hours per patient day, respectively; p < or = 0.05). Patients who were treated with thrombolytic therapy also had a significantly shorter coronary care unit stay (3.1 vs 4.0 days; p < or = 0.05). CONCLUSION: In this retrospective, observational pilot study, patients who received thrombolytic therapy for treatment of acute myocardial infarction had a significantly shorter coronary care unit stay and required significantly less nursing care on days 3 and 4.

Prevalence of right ventricular perfusion defects after inferior myocardial infarction assessed by low-level exercise with technetium 99m sestamibi tomographic myocardial imaging.

To assess the prevalence of right ventricular perfusion defects after a recent inferior wall myocardial infarction, 33 patients were studied 6 to 14 days after infarction with low-level exercise testing and technetium 99m (99mTc) sestamibi (SPECT) imaging. Twenty-two control subjects with a < 5% likelihood of coronary artery disease undergoing exercise 99mTc sestamibi imaging were also studied. For each image the right ventricle was computer isolated from reconstructed transverse cardiac slices, followed by reorientation into oblique slices. Both right and left ventricular images were visually assessed for defects. A quantitative method of defect detection was also applied to the right ventricle. For the right ventricle, 100% of the stress images and 96% of the rest images were adequate for interpretation. Right ventricular stress perfusion defects were identified in 10 (30%) of 33 patients with recent inferior infarction, with 50% completely or partially normalizing on rest images, consistent with ischemia. Of 14 patients with left ventricular inferoseptal defects, eight (57%) had right ventricular defects compared with 2 (11%) of 19 without inferoseptal defects (p < 0.005). We concluded that the right ventricle can be adequately assessed for perfusion defects by means of exercise with 99mTc sestamibi SPECT imaging. Defects of the right ventricle after inferior myocardial infarction occur frequently, and many have evidence of ischemia. Right ventricular perfusion defects are closely associated with left ventricular inferoseptal defects.

Echocardiographic assessment of the cardiac anatomy in patients with multifocal atrial tachycardia: a comparison with atrial fibrillation.

Although multifocal atrial tachycardia (MAT) has been recognized since 1968, few data exist on its associated anatomic correlates. Using echocardiography, the authors describe the cardiac anatomy observed in hospitalized patients with MAT. Because MAT closely resembles atrial fibrillation (AF), these echocardiographic data are compared with those from an age- and sex-matched population with AF. There were 25 patients in each of the MAT and AF groups. Biatrial enlargement was present in both groups. However, the atrial enlargement was mild and significantly less in the MAT group. The MAT group had normal ventricular and aortic dimensions. Right ventricular dysfunction was rare in both groups. Moderate to severe global left ventricular dysfunction was present in 7 of 25 in the MAT group and in 9 of 25 in the AF group. Systolic wall-motion abnormalities were significantly less in the MAT group. Severe Doppler and structural abnormalities were not common in the MAT group. Based on these parameters, physiologic and not anatomic factors are probably more important in the genesis of MAT as compared with AF.

Comparison of dobutamine and exercise using technetium-99m sestamibi imaging for the evaluation of coronary artery disease.

Studies using dobutamine thallium-201 myocardial perfusion imaging have suggested a high sensitivity and specificity for the detection of coronary artery disease. However, few data are available comparing dobutamine with exercise stress for the detection and localization of perfusion defects. This study compared the effects of dobutamine and exercise stress using technetium-99m sestamibi single-photon emission computed tomographic imaging in the same patients in a prospective crossover trial. Twenty-four patients with a high likelihood of coronary artery disease underwent tomographic myocardial imaging at rest, after symptom-limited treadmill exercise, and after intravenous dobutamine (maximum 30 micrograms/kg/min). Tomograms of the left ventricle were divided into 20 segments and were interpreted without knowledge of patient identity or stress protocol. Dobutamine was well tolerated by all patients. Segment-by-segment concordance between exercise and dobutamine images was highly significant (kappa = 0.56, p < 0.0001). Global first-order agreement (normal vs abnormal) between exercise and dobutamine studies was 96% (kappa = 0.65, p = 0.02); global second-order agreement (normal vs fixed vs ischemic defect) was 88% (kappa = 0.45, p = 0.02). Regional first- and second-order agreement were 96 and 93%, respectively (p < 0.001 for both). Twenty patients underwent coronary angiography. Comparisons between exercise and angiography and between dobutamine and angiography were similar for both global agreement (95 vs 100%, p = NS) and regional agreement (77 vs 72%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of exercise, dipyridamole, and adenosine by use of technetium 99m sestamibi tomographic imaging.

BACKGROUND: Pharmacologic stress has been shown in animal studies to induce high degrees of myocardial hyperemia. At these levels of myocardial blood flow, the myocardial uptake of technetium 99m sestamibi may plateau and may affect the diagnostic accuracy. This study compared the effects of myocardial hyperemia induced by exercise, dipyridamole, and adenosine on 99mTc sestamibi tomographic imaging in normal subjects and patients with ischemic coronary artery disease. METHODS AND RESULTS: Twenty subjects (group I, 10 normal subjects; group II, 10 patients with known coronary artery disease) underwent 99mTc sestamibi tomographic imaging after rest, exercise, dipyridamole infusion, and adenosine infusions on separate occasions. Total and background-corrected myocardial counts of the resulting images were calculated. Visual and computer-generated quantitative myocardial perfusion defect analysis was performed in subjects in group II. For subjects in both groups I and II, there were no significant differences in the background-corrected myocardial counts obtained with exercise, dipyridamole, and adenosine stress. There were no significant differences in the myocardial perfusion defects obtained after the three different modes of stress, including percentage defect size, stress deficit percentage, percentage of ischemia, count deficit index, and defect nadir. CONCLUSIONS: The myocardial uptake of 99mTc sestamibi in normal subjects and patients with coronary artery disease is comparable after exercise, dipyridamole, and adenosine stress. In addition, the defect sizes and intensities with 99mTc sestamibi after all forms of stress were equivalent. Thus 99mTc sestamibi, in combination with either adenosine or dipyridamole infusions, provides imaging data equivalent to those with exercise and may be considered an alternative in patients unable to undergo adequate exercise.

Pretreatment with theophylline does not affect adenosine-induced thallium-201 myocardial imaging.

This study was designed to evaluate the effects of intravenous theophylline given before intravenous adenosine for thallium-201 imaging. Sixteen patients with known reversible thallium-201 defects were randomized to a double-blind crossover study of a 45-minute infusion of placebo or theophylline (given as the ethylenediamine salt, aminophylline, mean concentration 16.1 mg/L) before adenosine thallium-201 imaging. Adenosine was infused for 6 minutes at a rate of 140 micrograms/kg/min. Thallium-201 (2.5 to 3.0 mCi) was administered after 3 minutes of infusion. Blood pressure, heart rate, symptoms, and the electrocardiogram were monitored continuously. Planar thallium-201 imaging was obtained in three standard views and was interpreted using blinded segmental analysis and computerized quantitation. Systolic and diastolic blood pressure at baseline and during adenosine administration were similar following treatment with theophylline and placebo. The increase in heart rate observed during adenosine infusion was significantly reduced by theophylline pretreatment. Adenosine-induced symptoms (both cardiac and noncardiac) as well as ischemic electrocardiographic changes were significantly reduced after theophylline infusion (p < 0.05). In one patient, Mobitz type II heart block seen during adenosine infusion following placebo was absent with theophylline pretreatment. The size of adenosine-induced thallium-201 defects was unchanged by theophylline infusion using either segmental analysis (8 +/- 4 vs 9 +/- 5) or a computerized score (47 +/- 27 vs 45 +/- 21). Despite reduction in both symptoms and ischemic electrocardiographic changes, theophylline does not alter thallium-201 imaging following intravenous adenosine infusion.

Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon.

OBJECTIVES: The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease. BACKGROUND: Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent. METHODS: In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 +/- 1.0 mg/liter (low), 8.2 +/- 1.8 mg/liter (medium) and 13.2 +/- 2.3 mg/liter (high). RESULTS: Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations. CONCLUSIONS: It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease.

Effects of intravenous theophylline on exercise-induced myocardial ischemia. I. Impact on the ischemic threshold.

OBJECTIVES: Theophylline has been shown to delay the onset of myocardial ischemia and to prolong exercise duration. The present study was done to evaluate the mechanisms and actions of intravenous theophylline on the onset of ischemia and exercise duration. BACKGROUND: The ischemic threshold may be altered by the differential coronary vasodilation induced by endogenous adenosine. Theophylline is a competitive receptor antagonist of adenosine and may have a potential as an anti-ischemic medication. METHODS: A double-blind, placebo-controlled crossover trial using an infusion of intravenous theophylline (8.0 +/- 2.0 mg/liter) or placebo before exercise in 12 patients was done. Oxygen uptake, heart rate, blood pressure and heart rate-blood pressure product were determined at the onset of > or = 0.1-mV ST segment depression and angina pectoris, as well as at peak exercise. The extent of myocardial ischemia was evaluated by electrocardiographic criteria and quantitation of thallium-201 images at peak exercise. RESULTS: When compared with placebo, theophylline significantly delayed time to the onset of exercise-induced ischemia. Ischemia occurred at a higher heart rate-blood pressure product and oxygen uptake. Exercise duration was prolonged but was not associated with greater ischemia, as determined by oxygen uptake, ST segment depression, angina pectoris and size of thallium-201 defect. CONCLUSIONS: It is concluded that theophylline favorably alters myocardial ischemia not only by delaying its onset but also by enabling it to occur at a higher threshold without causing deleterious effects during exercise. The mechanism for the increased ischemic threshold may be through the inhibition of adenosine and the coronary steal phenomenon.