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At least 253 records · Page 14

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Non-NASA Center↗

Pharmacologic or genetic interference with atrogene signaling protects against glucocorticoid-induced musculoskeletal and cardiac disease

Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of vitamin D receptor (VDR) signaling with the VDR ligands calcitriol or eldecalcitol prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of the 3 tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ΔRING mice afforded temporary or sustained protection from GC excess in bone or skeletal and heart muscle. We concluded that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the 3 tissues.

Research & Experimental Medicine↗

The autonomic laboratory

The autonomic nervous system can now be studied quantitatively, noninvasively, and reproducibly in a clinical autonomic laboratory. The approach at the Mayo Clinic is to study the postganglionic sympathetic nerve fibers of peripheral nerve (using the quantitative sudomotor axon reflex test [QSART]), the parasympathetic nerves to the heart (cardiovagal tests), and the regulation of blood pressure by the baroreflexes (adrenergic tests). Patient preparation is extremely important, since the state of the patient influences the results of autonomic function tests. The autonomic technologist in this evolving field needs to have a solid core of knowledge of autonomic physiology and autonomic function tests, followed by training in the performance of these tests in a standardized fashion. The range and utilization of tests of autonomic function will likely continue to evolve.

NASA Discipline Cardiopulmonary↗

Cardiovascular orthostatic function of Space Shuttle astronauts during and after return from orbit

Routine entry, landing, and seat egress after Space Shuttle flights is observed to be associated with drops in blood pressure and increases in heart rate that indicate that the cardiovascular system is performing at its maximum capacity in a large fraction (30 percent) of the study population. It is not apparent that adequate cardiovascular reserve capacity remains to accommodate unaided emergency egress after either current or extended space flights.

Charles, John B.↗

Space research on organs and tissues

Studies in space on various physiological systems have and will continue to provide valuable information on how they adapt to reduced gravitational conditions, and how living in a 1 g (gravity) environment has guided their development. Muscle and bone are the most notable tissues that respond to unweighting caused by lack of gravity. The function of specific muscles and bones relates directly to mechanical loading, so that removal of 'normal forces' in space, or in bedridden patients, causes dramatic loss of tissue mass. The cardiovascular system is also markedly affected by reduced gravity. Adaptation includes decreased blood flow to the lower extremities, thus decreasing the heart output requirement. Return to 1 g is associated with a period of reconditioning due to the deconditioning that occurs in space. Changes in the cardiovascular system are also related to responses of the kidney and certain endocrine (hormone-producing) organs. Changes in respiratory function may also occur, suggesting an effect on the lungs, though this adaptation is poorly understood. The neurovestibular system, including the brain and organs of the inner ear, must adapt to the disorientation caused by lack of gravity. Preliminary findings have been reported for liver. Additionally, endocrine organs responsible for release of hormones such as insulin, growth hormone, glucocorticoids, and thyroid hormone may respond to spaceflight.

Tischler, Marc E.↗

Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.

Investigation in 19 conscious dogs of the importance of the sympathetic nervous system in the coronary and cardiac response to altitude (hypoxic) hypoxia. Beta-adrenergic blockade was used to minimize the cardiac effect associated with sympathetic receptors. It is shown that the autonomic nervous system, and particularly the sympathetic nervous system, is responsible for the increase in ventricular function and myocardial oxygen consumption that occurs during hypoxia. Minimizing this response through appropriate conditioning and training may improve the operating efficiency of the heart and reduce the hazard of hypoxia and other environmental stresses, such as acceleration, which are encountered in advanced aircraft systems.

Erickson, H. H.↗

NASA Accelerates SpaceCube Technology into Orbit

On May 11, 2009, STS-125 Space Shuttle Atlantis blasted off from Kennedy Space Center on a historic mission to service the Hubble Space Telescope (HST). In addition to sending up the hardware and tools required to repair the observatory, the servicing team at NASA's Goddard Space Flight Center also sent along a complex experimental payload called Relative Navigation Sensors (RNS). The main objective of the RNS payload was to provide real-time image tracking of HST during rendezvous and docking operations. RNS was a complete success, and was brought to life by four Xilinx FPGAs (Field Programmable Gate Arrays) tightly packed into one integrated computer called SpaceCube. SpaceCube is a compact, reconfigurable, multiprocessor computing platform for space applications demanding extreme processing capabilities based on Xilinx Virtex 4 FX60 FPGAs. In a matter of months, the concept quickly went from the white board to a fully funded flight project. The 4-inch by 4-inch SpaceCube processor card was prototyped by a group of Goddard engineers using internal research funding. Once engineers were able to demonstrate the processing power of SpaceCube to NASA, HST management stood behind the product and invested in a flight qualified version, inserting it into the heart of the RNS system. With the determination of putting Xilinx into space, the team strengthened to a small army and delivered a fully functional, space qualified system to the mission.

Petrick, David↗

Differential baroreflex control of heart rate in sedentary and aerobically fit individuals

PURPOSE: We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy young adults. METHODS: Arterial and aortic (ABR) baroreflex functions were assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively. Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of both pressure and suction delivered to the carotid sinus via a neck chamber collar, independent of drug administration. RESULTS: During vasoactive drug injection, mean arterial pressure (MAP) was similarly altered in average fit (AF) and high fit (HF) groups. However, the heart rate (HR) response range of the arterial baroreflex was significantly attenuated (P < 0.05) in HF (31+/-4 beats x min(-1)) compared with AF individuals (46+/-4 beats x min(-1)). When sustained neck suction and pressure were applied to counteract altered carotid sinus pressure during SN and PE administration, isolating the ABR response, the response range remained diminished (P < 0.05) in the HF population (24+/-3 beats x min(-1)) compared with the AF group (41+/-4 beats x min(-1)). During CBR perturbation, the HF (14+/-1 beats-min(-1)) and AF (16+/-1 beats-min(-1)) response ranges were similar. The arterial baroreflex response range was significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS: These data confirm that reductions in arterial-cardiac reflex sensitivity are mediated by diminished ABR function. More importantly, these data suggest that the integrative relationship between the ABR and CBR contributing to arterial baroreflex control of HR is inhibitory in nature and not altered by exercise training.

NASA Discipline Cardiopulmonary↗

Evaluation of heart rate changes: electrocardiographic versus photoplethysmographic methods

The heart rate (HR) variation to forced deep breathing (HRDB) and to the Valsalva maneuver (Valsalva ratio; VR) are the two most widely used tests of cardiovagal function in human subjects. The HR is derived from a continuously running electrocardiographic (ECG) recording. Recently, HR derived from the arterial waveform became available on the Finapres device (FinapHR), but its ability to detect rapid changes in HR remains uncertain. We therefore evaluated HRDB and VR derived from FinapHR using ECG-derived HR (ECGHR) recordings as the standard. We also compared the averaged HR on Finapres (Finapav) with beat-to-beat Finapres (FinapBB) values. Studies were undertaken in 12 subjects with large HR variations: age, 34.5 +/- 9.3 (SD) years; six males and six females. FinapBB values were superimposable upon ECGHR for both HRDB and VR. In contrast, Finapav failed to follow ECGHR for HRDB and followed HRECG with a lag for the VR. To evaluate statistically how closely FinapHR approximated ECGHR, we undertook regression analysis, using mean values for each subject. To compare the two methods, we evaluated the significance of the difference between test and standard values. For HRDB, FinapBB reproducibly recorded HR (R2 = 0.998), and was significantly (p = 0.001) better than Finapav (R2 = 0.616; p < 0.001). For VR, HRBB generated a VR that was not significantly different from the correct values, while HRav generated a value that was slightly but consistently lower than the correct values (p < 0.001). We conclude that FinapHR reliably records HR variations in the beat-to-beat mode for cardiovascular HR tests.

Non-NASA Center↗

Ultrasound Techniques for Space Applications

Ultrasound has proven to be a safe non-invasive technique for imaging organs and measuring cardiovascular function. It has unique advantages for application to problems with man in space including evaluation of cardiovascular function both in serial studies and during critical operations. In addition, specialized instrumentation may be capable of detecting the onset of decompression sickness during EVA activities. A spatial location and three-dimensional reconstruction system is being developed to improve the accuracy and reproducibility for serial comparative ultrasound studies of cardiovascular function. The three-dimensional method permits the acquisition of ultrasonic images from many views that can be recombined into a single reconstruction of the heart or vasculature. In addition to conventional imaging and monitoring systems, it is sometimes necessary or desirable to develop instrumentation for special purposes. One example of this type of development is the design of a pulsed-Doppler system to monitor cerebral blood flow during critical operations such as re-entry. A second example is the design of a swept-frequency ultrasound system for the detection of bubbles in the circulatory system and/or soft tissues as an early indication of the onset of decompression sickness during EVA activities. This system exploits the resonant properties of bubbles and can detect both fundamental and second harmonic emissions from the insonified region.

Rooney, James A.↗

Preliminary Results from the Joint Russian and US Field Test: Measurement of Sensorimotor and Cardiovascular Responses Immediately Following Landing of the Soyuz Spacecraft

Ongoing collaborative research efforts between NASA's Neuroscience and Cardiovascular Laboratories, and the Institute of Biomedical Problems' (IBMP) Sensory-Motor and Countermeasures Laboratories have been measuring functional sensorimotor, cardiovascular and strength responses following bed rest, dry immersion, short duration (Space Shuttle) and long duration (Mir and International Space Station) space flights. While the unloading paradigms associated with dry immersion and bed rest have do serve as acceptable flight analogs, testing of crew responses following the long duration flights does not begin until a minimum of 24 hours after landing. As a result it is not possible to estimate the nonlinear trend of the early (<24 hr) recovery process nor is it possible to accurately assess the full impact of the decrements associated with long duration flight. To overcome these limitations both the Russian and U.S. sides have implemented testing at the time of landing and before the flight crews have left the landing site. By joint agreement this research effort has been identified as the functional Field Test (FT). For practical reasons the FT has been divided into two phases: the full FT and a preliminary pilot version (PFT) of the FT that is reduced in both length and scope. The primary goal of this research is to determine functional abilities in long duration space flight crews beginning as soon after landing as possible (< 2 hr) with one to three immediate follow-up measurements on the day of landing. This goal has both sensorimotor and cardiovascular elements including an evaluation of NASA's new anti-orthostatic compression garment as compared with the Russian Kentavr garment. Functional sensorimotor measurements will include, but are not limited to, assessment of hand/eye coordination, ability to egress from a seated position, walk normally without falling, measurement of dynamic visual acuity, ability to discriminate different forces generated with both the hands and legs, recovery from a fall, a coordinated walk involving tandem heel-to-toe placement and determination of postural ataxia while standing. The cardiovascular portion of the investigation includes blood pressure and heart rate measurements during a timed stand test in conjunction with postural ataxia testing. In addition to the immediate post-landing collection of data for the full FT, postflight data will be acquired at a minimum of one to three more other times within the 24 hr following landing and continue until functional sensorimotor and cardiovascular responses have returned to preflight normative values. The PFT represents a single trial run comprised of jointly agreed tests from the full FT and relies heavily on IBMP's Sensory-Motor and Countermeasures Laboratories for content, and implementation. The PFT is currently scheduled for the September 2013 landing of the Soyuz spacecraft (34S). Testing will include: (1) a sit-to-stand test, (2) recovery from a fall where the crewmember begins in the prone position on the ground and then stands for 3 min while cardiovascular stability is determined and postural ataxia data are acquired, and (3) a tandem heel-to-toe walk to determine changes in the central locomotor program. Video, cardiovascular parameters (heart rate and blood pressure), data from body-worn inertial sensors and severity of postflight motion sickness will be available for analysis. It is our intent to present, at this celebratory symposium, a summary of these data obtained from two crewmembers. In summary, the level of functional deficit is expected to be most profound during the acquisition of gravity loads immediately after landing when the demands for crew intervention in response to emergency operations will be greatest. Clearly measureable performance parameters such as ability to perform a seat egress, recover from a fall or the ability to see clearly when walking, and related physiological data (orthostatic responses) are required to provide an evidence base for characterizing programmatic risks and the degree of variability among crewmembers. Overall, these early functional and related physiological measurements will allow estimation of nonlinear sensorimotor and cardiovascular recovery trends to an accuracy that has not been previously captured in over 50 years of space flight.

Reschke, M. F.↗

Consequences of cardiovascular adaptation to spaceflight: implications for the use of pharmacological countermeasures

There is little evidence obtained from space flight to support the notion that occurrence of cardiac dysrhythmias, impaired cardiac and vascular function, and manifestation of asymptomatic cardiovascular disease represent serious risks during space flight. Therefore, the development of orthostatic hypotension and instability immediately after return from spaceflight probably reflect the most significant operational risks associated with the cardiovascular system of astronauts. Significant reductions in stroke volume and lower reserve for increasing peripheral vascular resistance contribute to ineffective maintenance of systemic arterial blood pressure during standing after spaceflight despite compensatory elevations in heart rate. The primary mechanism underlying reduced stroke volume appears to be a reduction in preload associated with less circulating blood volume while inadequate peripheral vasoconstriction may be caused partly by hyporeactivity of receptors that control arterial smooth muscle function. A focus for development of future countermeasures for hemodynamic responses to central hypovolemia includes the potential application of pharmacological agents that specifically target and restore blood volume (e.g., fludrocortisone, electrolyte-containing beverages) and reserve for vasoconstriction (e.g., midodrine, vasopressin). Based on systematic evaluations, acute physical exercise designed to elicit maximal effort or inspiratory resistance have shown promise as successful countermeasures that provide protection against development of orthostatic hypotension and intolerance without potential risks and side effects associated with specific pharmacological interventions.

Non-NASA Center↗

Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 C-acclimated hamsters

The relationship of norepinephrine (NE) concentration and endogenous turnover rates in both myocardial and spleen tissues in the golden hamster is examined as a function of chronic exposure to either high or low ambient temperatures. Changes in myocardial and spleen NE turnover values are discussed in terms of functional alterations in sympathetic nerve activity and the importance of such changes in temperature acclimation. It is found that acclimation of hamsters to 7 C for 7-10 weeks results in decreased myocardial NE concentration and an apparent increase in myocardial NE turnover. In contrast, exposure to 34 C for 6-8 weeks results in increased myocardial NE concentration and an apparent decrease in NE turnover in both myocardial and spleen tissues. The implication of altered NE synthesis is that sympathetic nerve activity is reduced with heat acclimation and is enhanced with cold acclimation.

Jones, S. B.↗

LabHEART: an interactive computer model of rabbit ventricular myocyte ion channels and Ca transport

An interactive computer program, LabHEART, was developed to simulate the action potential (AP), ionic currents, and Ca handling mechanisms in a rabbit ventricular myocyte. User-oriented, its design allows switching between voltage and current clamp and easy on-line manipulation of key parameters to change the original formulation. The model reproduces normal rabbit ventricular myocyte currents, Ca transients, and APs. We also changed parameters to simulate data from heart failure (HF) myocytes, including reduced transient outward (I(to)) and inward rectifying K currents (I(K1)), enhanced Na/Ca exchange expression, and reduced sarcoplasmic reticulum Ca-ATPase function, but unaltered Ca current density. These changes caused reduced Ca transient amplitude and increased AP duration (especially at lower frequency) as observed experimentally. The model shows that the increased Na/Ca exchange current (I(NaCa)) in HF lowers the intracellular [Ca] threshold for a triggered AP from 800 to 540 nM. Similarly, the decrease in I(K1) reduces the threshold to 600 nM. Changes in I(to) have no effect. Combining enhanced Na/Ca exchange with reduced I(K1) (as in HF) lowers the threshold to trigger an AP to 380 nM. These changes reproduce experimental results in HF, where the contributions of different factors are not readily distinguishable. We conclude that the triggered APs that contribute to nonreentrant ventricular tachycardia in HF are due approximately equally (and nearly additively) to alterations in I(NaCa) and I(K1). A free copy of this software can be obtained at http://www.meddean.luc.edu/lumen/DeptWebs/physio/bers.html.

NASA Discipline Cardiopulmonary↗

Cardiovascular effects of weightlessness and ground-based simulation

A large number of animal and human flight and ground-based studies were conducted to uncover the cardiovascular effects of weightlessness. Findings indicate changes in cardiovascular function during simulations and with spaceflight that lead to compromised function on reambulation and/or return to earth. This altered state termed cardiovascular deconditioning is most clearly manifest when in an erect body state. Hemodynamic parameters inidicate the presence of excessive tachnycardia, hypotension (leading to presyncope in one-third of the subjects), decreased heart volume, decreased plasma and circulating blood volumes and loss of skeletal muscle mass, particularly in the lower limbs. No clinically harmful effects were observed to date, but in-depth follow-ups were limited, as was available physiologic information. Available data concerning the causes for the observed changes indicate significant roles for mechanisms involved with body fluid-volume regulation, altered cardiac function, and the neurohumoral control of the control of the peripheral circulation. Satisfactory measures are not found. Return to preflight state was variable and only slightly dependent on flight duration. Future progress awaits availability of flight durations longer than several weeks.

Sandler, Harold↗

Neural blockade during exercise augments central command's contribution to carotid baroreflex resetting

This investigation was designed to determine central command's role on carotid baroreflex (CBR) resetting during exercise. Nine volunteer subjects performed static and rhythmic handgrip exercise at 30 and 40% maximal voluntary contraction (MVC), respectively, before and after partial axillary neural blockade. Stimulus-response curves were developed using the neck pressure-neck suction technique and a rapid pulse train protocol (+40 to -80 Torr). Regional anesthesia resulted in a significant reduction in MVC. Heart rate (HR) and ratings of perceived exertion (RPE) were used as indexes of central command and were elevated during exercise at control force intensity after induced muscle weakness. The CBR function curves were reset vertically with a minimal lateral shift during control exercise and exhibited a further parallel resetting during exercise with neural blockade. The operating point was progressively reset to coincide with the centering point of the CBR curve. These data suggest that central command was a primary mechanism in the resetting of the CBR during exercise. However, it appeared that central command modulated the carotid-cardiac reflex proportionately more than the carotid-vasomotor reflex.

NASA Discipline Cardiopulmonary↗

A framework for challenges and solutions in biodesign research

The bioeconomy represents an advanced economic paradigm that builds upon previous agricultural, industrial, and digital economic models. It seeks to tackle critical global challenges such as resource scarcity, escalating healthcare demands, and environmental degradation. At the heart of the bioeconomy is biomanufacturing, which uses natural or engineered enzymes or cell factories built from ​biological components like promoters, terminators, regulatory sequences, reporters, and functional genes into various chassis hosts (including animal, microbial, plant, and de novo systems) to create products such as food, energy, medicine, materials, chemicals, and engineered tissue/organs. An enabler of biomanufacturing is biodesign – also known as biosystems design and closely related to synthetic biology or engineering biology. This interdisciplinary field aims to understand and predictably modify existing life forms or create entirely new biological entities/systems using rational engineering strategies and automated design tools. Through these capabilities, biodesign supports the discovery, optimization, and creation of efficient platforms for biomanufacturing.

59 BASIC BIOLOGICAL SCIENCES↗

Automated assessment of noninvasive filling pressure using color Doppler M-mode echocardiography

Assessment of left ventricular filling pressure usually requires invasive hemodynamic monitoring to follow the progression of disease or the response to therapy. Previous investigations have shown accurate estimation of wedge pressure using noninvasive Doppler information obtained from the ratio of the wave propagation slope from color M-mode (CMM) images and the peak early diastolic filling velocity from transmitral Doppler images. This study reports an automated algorithm that derives an estimate of wedge pressure based on the spatiotemporal velocity distribution available from digital CMM Doppler images of LV filling.

Non-NASA Center↗