Circadian variation in human peripheral blood flow levels and exercise responses.
Circadian variation in heart rate, oral temperature, and in peripheral blood flow levels of humans at rest and during exercise
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Circadian variation in heart rate, oral temperature, and in peripheral blood flow levels of humans at rest and during exercise
Telemetry of arterial flow in various conditions in man with Doppler ultrasonic flowmeter
It has been found in connection with American and Soviet manned space missions that a reduction in the circulating red blood cell mass (RCM) is a result of the effect of space flight on the human hematological system. An experiment conducted during the 10-day Spacelab 1 mission in November 1983 was designed to measure factors involved in the control of erythrokinetics which might be altered after exposure to microgravity. In this experiment a decrement in RCM approximately equal to that observed in crewmen returning from Apollo flights of similar duration (7) was measured. Erythropoietin decreased in flight in all crew members. The lack of significant change in erythropoietin with a significant decrease in reticulocyte number and a decrease of about 1 percent per day in mean RCM suggests that inhibition of erythropoiesis ms not the primary or only cause of the inflight RCM reduction.
The frequency response characteristics of human cardiovascular regulation during hypotensive stress have not been determined. We therefore exposed 10 male volunteers to seven frequencies (0.004-0.1 Hz) of oscillatory lower body negative pressure (OLBNP; 0-50 mmHg). Fourier spectra of arterial pressure (AP), central venous pressure (CVP), stroke volume (SV), cardiac output (CO), heart rate (HR), and total peripheral resistance (TPR) were determined and first harmonic mean, amplitude, and phase angles with respect to OLBNP are presented. AP was relatively well regulated as demonstrated by small oscillations in half amplitude (3.5 mmHg) that were independent of OLBNP frequency and similar to unstressed control spectra. Due to the biomechanics of the system, the magnitudes of oscillations in calf circumference (CC) and CVP decreased with increasing frequency; therefore, we normalized responses by these indexes of the fluid volume shifted. The ratios of oscillations in AP to oscillations in CC increased by an order of magnitude, whereas oscillations in CVP to oscillations in CC and oscillations in AP to oscillations in CVP both tripled between 0.004 and 0.1 Hz. Therefore, even though the amount of fluid shifted by OLBNP decreased with increasing frequency, the magnitude of both CVP and AP oscillations per volume of fluid shifted increased (peaking at 0.08 Hz). The phase relationships between variables, particularly the increasing lags in SV and TPR, but not CVP, indicated that efferent responses with lags of 5-6 s could account for the observed responses. We conclude that, at frequencies below 0.02 Hz, the neural system of humans functioned optimally in regulating AP; OLBNP-induced decreases in SV (by as much as 50%) were counteracted by appropriate oscillations in HR and TPR responses. As OLBNP frequency increased, SV, TPR, and HR oscillations increasingly lagged the input and became less optimally timed for AP regulation.
No abstract available
Red blood cell formation or erythropoiesis in the bone marrow and exit into circulation are known to be affected by mechanical loading. Specifically, space anemia is a condition observed during prolonged microgravity unloading in which the red blood cell (RBC) mass in circulation is reduced. However, the mechanisms causing space anemia are yet to be clearly established, but may include increased hemolysis of RBC in circulation, decreased RBC production or a combination of both factors. The presentation of space anemia is comparable to chronic anemia conditions associated with aging, disuse, and poor health. Molecular dysregulation in the RBC's life cycle is poorly defined and is a significant concern in the context of disuse anemia as mechanotransduction significantly alters of gene expression, protein synthesis and cell signaling pathways. Our study analyzes mouse single cell RNA sequencing libraries from the bone marrow, circulating blood, and spleen and integrates the RBC lineage populations from the tissues into a RBC life cycle atlas. This study also probes how age at time of spaceflight contributes to the molecular signature of space anemia. The overarching objective of the study is to develop a mechanistic understanding of space anemia and translate the findings to a better understanding of aging, disuse, and poor health-related anemia to defining the role of mechanical loading in health and devise potential therapeutic interventions. Important findings of our study are: 1) that mechanical unloading in microgravity alters the proportion of developmental RBC lineage cells, skewing toward progenitor, indicating that fewer RBCs may be present in blood; 2) that late reticulocyte number is elevated in the bone marrow of older animals, suggesting a failure to enter circulation; and 3) that the molecular signature of the circulating RBCs is not significantly altered in microgravity. However, expression markers for eryptosis and erythrophagocytosis are elevated in circulating and spleen RBCs, suggesting spaceflight may shorten the lifetime of RBCs after exit from the marrow. In conclusion our results suggest early stages of erythropoiesis proliferation and differentiation in the marrow are key factors in space anemia and mechanical loading may be a necessary step of RBC entry in circulation.
Isotonic training effects on circulation for limb muscular strength characteristics, using peak blood flow and venous compliance measurements
Blood supplying the brain in vertebrates is carried primarily by the carotid vasculature. In most mammals, cerebral blood flow is supplemented by the vertebral arteries, which anastomose with the carotids at the base of the brain. In other tetrapods, cerebral blood is generally believed to be supplied exclusively by the carotid vasculature, and the vertebral arteries are usually described as disappearing into the dorsal musculature between the heart and head. There have been several reports of a vertebral artery connection with the cephalic vasculature in snakes. We measured regional blood flows using fluorescently labeled microspheres and demonstrated that the vertebral artery contributes a small but significant fraction of cerebral blood flow (approximately 13% of total) in the rat snake Elaphe obsoleta. Vascular casts of the anterior vessels revealed that the vertebral artery connection is indirect, through multiple anastomoses with the inferior spinal artery, which connects with the carotid vasculature near the base of the skull. Using digital subtraction angiography, fluoroscopy, and direct observations of flow in isolated vessels, we confirmed that blood in the inferior spinal artery flows craniad from a point anterior to the vertebral artery connections. Such collateral blood supply could potentially contribute to the maintenance of cerebral circulation during circumstances when craniad blood flow is compromised, e.g., during the gravitational stress of climbing.
Snakes have provided useful vertebrate models for understanding circulatory adaptation to gravity, attributable to their elongate body shape and evolutionary diversificaton in terms of ecology and behavior. Recently we have studied cardiovascular responses of snakes to hypergravic acceleration forces produced acutely in the head-to-tail direction (+Gz) on a short-arm centrifuge. Snakes were held in a nearly straight position within a horizontal plastic tube and subjected to a linear force gradient during acceleration. Carotid blood flow provided an integrated measure of cardiovascular performance. Thus, cardiovascular tolerance of snakes to stepwise increments of Gz was measured as the caudal Gz force at which carotid blood flow ceased. Tolerance to increasing Gz varies according to adaptive evolutionary history inferred from the ecology and behavior of species. With respect to data for six species we investigated, multiple regression analysis demonstrates that Gz tolerance correlates with gravitational habitat, independently of body length. Relative to aquatic and non-climbing species, carotid blood flow is better maintained in arboreal or scansorial species, which tolerate hypergravic forces of +2 to +3.5 Gz. Additionally, semi-arboreal rat snakes (Elaphe obsoleta) exhibit plasticity of responses to long-term, intermittent +1.5 Gz stress. Compared to non-acclimated controls, acclimated snakes show greater increases of heart rate during head-up tilt or acceleration, greater sensitivity of arterial pressure to circulating catecholamines, higher blood levels of prostaglandin ratios favorable to maintenance of arterial blood pressure, and medial hypertrophy in major arteries and veins. As in other vertebrates, Gz tolerance of snakes is enhanced by acclimation, high arterial pressure, comparatively large blood volume, and body movements. Vascular studies of snakes suggest the importance to acclimation of local responses involving vascular tissue, in addition to centrally mediated responses to fluid shifts.
Exposure to high altitudes can result in the evolved-gas condition referred to as decompression sickness (DCS). Ultrasonic monitoring techniques have clearly demonstrated the presence of venous gas emboli (VGE) during decompression. Although important to DCS research and our understanding of the physiological mechanisms of this condition, Venus gas emboli have not been considered clinically hazardous, unless in extreme numbers. Arterial gas emboli (AGE), on the other hand, are generally viewed with great concern. Arterial gas emboli can enter the cerebral arterial circulation and arrest blood flow resulting in potentially serious injury. Left ventricular gas emboli were observed with echo imaging in five volunteer subjects during exposure to simulated altitude. These serendipitous findings occurred during altitude exposure under 3 separate research protocols involving 79 subject exposures. The voluntary, fully informed consent of the subjects used in this research was obtained as required by AFR 169-3. A Hewlett-Packard SONOS 1000 Echo Imaging System was used to monitor for precordial gas emboli. The improved resolution of the SONOS 1000 appears to account for these new findings. Four subjects had high incidence DCS and VGE during previous research flights. One subject only had one flight. The altitudes and AGE onset times for the five cases were: (1) 25,500 ft/2:23, (2) 29,000 ft/0:27, (3) 19,500 ft/3:49, (4) 29,500 ft/3:15, and (5) 29,500 ft/1:31. In all five cases, at the time of AGE onset, the VGE scores were high from all monitored locations. Four of the cases were symptomatic at the time of AGE onset (pain and skin mottling). No cerebral manifestations were observed. All subjects were immediately recompressed to ground level and successfully treated with 2 hours of post-breathing or with hyperbaric oxygen therapy. In conclusion, previously undetected AGE were demonstrated--with and without DCS symptoms--during exposure to altitude. It appears that this gas transferred from the venous side to the arterial side via either intracardiac defects or the pulmonary circulation. The clinical and operational implications of this finding are yet to be determined.
Cardiovascular functions were studied in semi-arboreal rat snakes (Elaphe obsoleta) following long-term, intermittent exposure to +1.5 Gz (head-to-tail acceleration) on a centrifuge. Snakes were held in a nearly straight position within horizontal plastic tubes during periods of centrifugation. Centrifugal acceleration, therefore, subjected snakes to a linear force gradient with the maximal force being experienced at the tail. Compared to non-centrifuged controls, Gz-acclimated snakes showed greater increases of heart rate during head-up tilt or acceleration, greater sensitivity of arterial pressure to circulating catecholamines, higher blood levels of corticosterone, and higher blood ratios of prostaglandin F 2 alpha/prostaglandin E2. Cardiovascular tolerance to increased gravity during graded Gz acceleration was measured as the maximum (caudal) acceleration force at which carotid arterial blood flow became null. When such tolerances were adjusted for effects of body size and other continuous variables incorporated into an analysis of covariance, the difference between the adjusted mean values of control and acclimated snakes (2.37 and 2.84 Gz, respectively) corresponded closely to the 0.5 G difference between the acclimation G (1.5) and Earth gravity (1.0). As in other vertebrates, cardiovascular tolerance to Gz stress tended to be increased by acclimation, short body length, high arterial pressure, and comparatively large blood volume. Voluntary body movements were important for promoting carotid blood flow at the higher levels of Gz stress.
This slide presentation reviews the effects of enhanced exposure to CO2 on Earth and in space. The effects of enhanced exposure to CO2 are experienced in almost all bodily systems. In space some of the effects are heightened due to the fluid shifts to the thorax and head. This fluid shift results in increased intracranial pressure, congested cerebral circulation, increased Cerebral Blood Flow (CBF) and Intravenous dilatation. The mechanism of the effect of CO2 on CBF is diagrammed, as is the Cerebrospinal Fluid (CSF) production. A listing of Neuroendocrine targets is included.
Exposure to microgravity during space flight results in profound physiologic changes. Numerous studies have shown changes in circulating populations of peripheral blood immune cells immediately after space flight. It is currently unknown if these changes result from exposure to microgravity or are caused by the stress of reentry and readaptation to gravity. We have developed the whole blood staining device as a system for the staining of whole blood collected during space flight for subsequent flow cytometric analysis, This device contains all liquids to address safety issues concerned with space flight and also moves the cells through the staining, lyse/fixation and dilution steps.
Although severe hypovolemia can lead to hypotension and neurological decline, many patients with neurosurgical disorders experience a significant hypovolemia while autonomic compensatory mechanisms maintain a normal blood pressure. To assess the effects of normotensive hypovolemia upon cerebral hemodynamics, transcranial Doppler ultrasound monitoring of 13 healthy volunteers was performed during graded lower-body negative pressure of up to -50 mm Hg, an accepted laboratory model for reproducing the physiological effects of hypovolemia. Middle cerebral artery flow velocity declined by 16% +/- 4% (mean +/- standard error of the mean) and the ratio between transcranial Doppler ultrasound pulsatility and systemic pulsatility rose 22% +/- 8%, suggesting cerebral small-vessel vasoconstriction in response to the sympathetic activation unmasked by lower-body negative pressure. This vasoconstriction may interfere with the autoregulatory response to a sudden fall in blood pressure, and may explain the common observation of neurological deficit during hypovolemia even with a normal blood pressure.
To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.
It has been reported that hypokinesia and bed rest induce cardiovascular changes similar to those observed in space flights. Using an animal model that was developed in our laboratory and that was extensively studied and characterized in our laboratory and other laboratories in this country and abroad, we have studied circulatory mechanisms that occur during exposure to hypokinesia (with or without negative tilt) as well as during readaptation to control conditions (free activity). We believe that this study contributes to better understanding of mammalian circulatory mechanisms that operate under 1-g force and will serve to provide control data to be compared with cardiovascular data obtained in conditions of a Space lab. Because survey and anesthesia drastically decrease cardiac output and other circulatory parameters in rats, only unanesthetized rats were used in experiments. Aorta and right atrium of the animals were permanently cannulated fifteen to twenty days before experiments. Arterial and right ventricular blood pressures, cardiac output, cerebral and other regional blood flow, ECG, other cardiovascular parameters, and oxygen consumption were measured with techniques routinely used in our laboratory. Specifically, we undertook the following investigations during the period of three years: (1) A study of circulatory changes (right ventricular pressure, arterial blood pressure, heart rate, cardiac output) during exposure of rats to hypokinetic conditions. Used the head down tilted Holton-Musacchia system in order to compare the results with the results already obtained on unrestrained rats, (2) Humoral changes were investigated in animals exposed to hypokinesia; also, lymphocyte and neutrophil levels in hypokinetic animals (with or without tilt) were determined to ascertain the level of induced stress and possible changes observed in weightless animals, and (3) circulating blood volume was determined during and after hypokinesia.
Cardiopulmonary responses to acute hypoxia (HY), fluid loading by saline infusion (FL), and head-down tilt (HD) of mechanically ventilated anesthetized dogs were investigated by measuring thermodynamics and pulmonary gas exchange. It was found that HD decreased the total respiratory compliance both during HY and normoxia (NO) and that the reduction in compliance by FL was twice as large as by HD. Superimposing HD on HY doubled the increase in vascular resistance due to HY alone. In the systemic circulation, HD lowered the resistance to below NO levels. There was a significant positive correlation between the changes in blood volume and in pulmonary artery pressure for experimental transitions, suggesting that a shift in blood volume from systemic to pulmonary circulations and changes in the total blood volume may contribute substantially to these apparent changes in resistance.
Theoretical considerations on flow of blood through capillary