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Small-scale rheographic devices for use on a space ship were developed and used during flights for the study of blood flow in vascular regions. The processes that occur during space flight and the adaptation of the human body to weightlessness are understood. The future condition of the cosmonauts' health is predicted.
We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.
Acceleration effects on regional distribution of pulmonary blood flow and associated disturbances in ventilation/perfusion ratios in humans and dogs
Vertical distribution of pulmonary blood flow (VDPBF) was studied, using radioactive microsphere emboli, in dogs without thoracotomy in the right decubitus position during exposure to lateral accelerations of 1, 2, 4, and 6 G. At all levels of force environment studied, an inverse linear relationship was observed between vertical height in the thorax and pulmonary blood flow (ml/min/ml lung tissue) with a decrease in flow to the most dependent region of the lung despite large increases in intravascular pressures at this site. Changes in blood flow were smallest at the mid-lung level, the hydrostatic 'balance point' for vascular and pleural pressures. These force environment-dependent changes in VDPBF are not readily explainable by the Starling resistor analog. Gravity-dependent regional differences in pleural and associated interstitial pressures, plus possible changes in vascular tone resulting from inadequate aeration of blood in the most dependent regions of the lung, probably also affect VDPBF.
Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.
Gravity is a physical force, much like shear stress or mechanical stretch, and should affect organ and cellular function. Researchers have shown that gravity plays a role in ventilation and blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Short exposure to microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function resulting in reduced ventilation at the base and no ventilation of the upper half of the lung. Microgravity also decreased metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. Rats, in the tail-suspended head-down tilt model, experienced transient loss of lung water, contrary to an expected increase due to pooling of blood in the pulmonary vasculature. Hypergravity has also been found to increase the proliferation of several different cell lines (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. These studies show that changes in the gravity environment will affect several aspects of organ and cellular function and produce major change in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. We conducted studies that addressed the following question: Does the susceptibility of lung fibroblasts, vascular smooth muscle, and endothelial cells to anoxia/reoxygenation injury change following exposure to hypergravity conditions?
To test the hypothesis that head-down-tilt bed rest (HDBR) for 14 days alters vascular reactivity to vasodilatory and vasoconstrictor stimuli, the reactive hyperemic forearm blood flow (RHBF, measured by venous occlusion plethysmography) and mean arterial pressure (MAP, measured by Finapres) responses after 10 min of circulatory arrest were measured in a control trial (n = 20) and when sympathetic discharge was increased by a cold pressor test (RHBF + cold pressor test; n = 10). Vascular conductance (VC) was calculated (VC = RHBF/MAP). In the control trial, peak RHBF at 5 s after circulatory arrest (34.1 +/- 2.5 vs. 48.9 +/- 4.3 ml . 100 ml-1 . min-1) and VC (0.34 +/- 0.02 vs. 0.53 +/- 0.05 ml . 100 ml-1 . min-1 . mmHg-1) were reduced in the post- compared with the pre-HDBR tests (P < 0. 05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). The ability of the cold pressor test to lower forearm blood flow was less in the post- than in the pre-HDBR test (P < 0.05), despite similar increases in MAP. These data suggest that regulation of vascular dilation and the interaction between dilatory and constrictor influences were altered with bed rest.
Changes in blood flow and blood redistribution were measured by impedance plethysmography in the pelvic and leg regions of six male and four female subjects during three 5-min exposures to -20, -40, and -60 mm Hg lower body negative pressure (LBNP). Female subjects demonstrated significantly higher mean heart rate and lower leg blood flow indices than the male subjects during the recumbent control periods. Men had slightly higher mean resting systolic and diastolic blood pressures and higher mean control pelvic blood indices. Women demonstrated significantly less blood pooling in the legs and slightly less in the pelvic region than the men. All of the 18 tests with male subjects at -60 mm Hg were completed without initial signs of syncope, while only two of the tests with women were completed successfully without the subject exhibiting presyncopal conditions. Results indicate that impedance plethysmography can be used to measure segmental cardiovascular responses during LBNP and that females may be less tolerant to -60 mm Hg LBNP than males.
In a recent study by Tsukimoto et al. (J. Appl. Physiol. 68: 2488-2493, 1990), CO2 inhalation appeared to reduce the size of the high ventilation-perfusion ratio (VA/Q) mode commonly observed in anesthetized mechanically air-ventilated dogs. In that study, large tidal volumes (VT) were used during CO2 inhalation to preserve normocapnia. To separate the influences of CO2 and high VT on the VA/Q distribution in the present study, we examined the effect of inspired CO2 on the high VA/Q mode using eight mechanically ventilated dogs (4 given CO2, 4 controls). The VA/Q distribution was measured first with normal VT and then with increased VT. In the CO2 group at high VT, data were collected before, during, and after CO2 inhalation. With normal VT, there was no difference in the size of the high VA/Q mode between groups [10.5 +/- 3.5% (SE) of ventilation in the CO2 group, 11.8 +/- 5.2% in the control group]. Unexpectedly, the size of the high VA/Q mode decreased similarly in both groups over time, independently of the inspired PCO2, at a rate similar to the fall in cardiac output over time. The reduction in the high VA/Q mode together with a simultaneous increase in alveolar dead space (estimated by the difference between inert gas dead space and Fowler dead space) suggests that poorly perfused high VA/Q areas became unperfused over time. A possible mechanism is that elevated alveolar pressure and decreased cardiac output eliminate blood flow from corner vessels in nondependent high VA/Q regions.
PURPOSE: Patients with idiopathic orthostatic intolerance often have debilitating symptoms on standing that are suggestive of cerebral hypoperfusion despite the absence of orthostatic hypotension. SUBJECTS AND METHODS: We evaluated the effects of graded head-up tilt on cerebral blood flow as determined by transcranial Doppler measurements in 10 patients with idiopathic orthostatic intolerance (nine women, one man, 22 to 47 years) and nine age- and sex-matched control subjects. RESULTS: In patients, mean (+/- SD) arterial pressure at 0 degrees head-up tilt was 90 +/- 11 mm Hg and was well maintained at all tilt angles (90 +/- 11 mm Hg at 75 degrees). In controls, mean arterial pressure was 85 +/- 7 mm Hg at 0 degrees and 82 +/- 11 mm Hg at 75 degrees head-up tilt. There was a substantial decrease in peak velocity with increasing tilt angle in patients (28% +/- 10%) but not in controls (10% +/- 10% at 75 degrees, P <0.001). Similarly, mean velocity decreased 26% +/- 13% in patients and 12% +/- 11% in controls (P = 0.01). With increasing head-up tilt, patients had a significantly greater increase in regional cerebrovascular resistance than controls. CONCLUSIONS: In patients with idiopathic orthostatic intolerance, peak and mean middle cerebral artery blood flow velocity decreased in response to head-up tilt despite well sustained arterial blood pressure. These observations indicate that in this group of patients, regulation of cerebrovascular tone may be impaired and might therefore be a target for therapeutic interventions.
The objective of this study is to investigate the effects of cold only, commercially available gloves only, and the combination of gloves and cold on the blood flow and surface (skin) temperature of the medial and proximal phalanxes of digit 3, the metacarpal region of the hand, and the forearm.
Personal thermoregulatory systems which provide chest cooling are used in the industrial and aerospace environments to alleviate thermal stress. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objectives of this study were to compare the effectiveness of two passive cooling vests, and to measure the body temperature and circulatory changes produced by each cooling vest configuration. A Life Enhancement Technologies, (LET) ice vest garment and a Steele, Inc. vest were used to cool the chest region of 11 male subjects (25 to 55 yr) in this study. Calf, forearm and finger blood flows were measured using a tetrapolar impedance rheograph. The subjects, seated in an upright position at normal room temperature (approximately 21 C) were tested for 60 min. with the cooling system operating at its maximum cooling capacity. Blood flows were recorded continuously using a computer data acquisition system with a sampling frequency of 250 Hz. Oral, right and left ear temperatures and cooling system parameters were logged manually every 5 min. Arm, leg, chest and rectal temperatures; heart rate; respiration; and an activity index were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. No significant differences were found in either the oral or ear temperature responses to the two vests. However, the rectal and mean skin temperatures at the end of the cooling period were both significantly lower (P less than 0.05), approximately 0.2 and 1.9 C, respectively for the LET vest than for the Steele garment. These data show that different vest configurations may produce different thermal responses in healthy male subjects which should be considered in the use of these cooling garments.
The Visual Impairment and Intracranial Pressure (VIIP) syndrome affects 60% of astronauts returning from long-duration missions and is characterized by structural and functional changes of the eye (3). Upon entry into weightlessness, approximately two liters of fluid translocates from the lower body to the thorax and cephalad regions, potentially contributing to elevated intracranial and intraocular pressures. The choroid is the vasculature that supplies blood flow to the posterior part of the retina and has limited autoregulation. As a consequence these vessels may engorge during a cephalad fluid shift, contributing to structural changes in the retina. The purpose of this experiment was to quantify changes in choroid thickness during a fluid shift. In order to fulfill this objective, it was also necessary to improve the measurement technique for assessing choroid thickness.
For exercise to be sustained, it is essential that adequate blood flow be provided to skeletal muscle. The local vascular control mechanisms involved in regulating muscle perfusion during exercise include metabolic control, endothelium-mediated control, propagated responses, myogenic control, and the muscle pump. The primary determinant of muscle perfusion during sustained exercise is the metabolic rate of the muscle. Metabolites from contracting muscle diffuse to resistance arterioles and act directly to induce vasodilation, or indirectly to inhibit noradrenaline release from sympathetic nerve endings and oppose alpha-adrenoreceptor-mediated vasoconstriction. The vascular endothelium also releases vasodilator substances (e.g., prostacyclin and nitric oxide) that are prominent in establishing basal vascular tone, but these substances do not appear to contribute to the exercise hyperemia in muscle. Endothelial and smooth muscle cells may also be involved in propagating vasodilator signals along arterioles to parent and daughter vessels. Myogenic autoregulation does not appear to be involved in the exercise hyperemia in muscle, but the rhythmic propulsion of blood from skeletal muscle veins facilitates venous return to the heart and muscle perfusion. It appears that the primary determinants of sustained exercise hyperemia in skeletal muscle are metabolic vasodilation and increased vascular conductance via the muscle pump. Additionally, sympathetic neural control is important in regulating muscle blood flow during exercise.
Work during the initial six months of this program has proceeded along three lines: (1) technical development of blood flowmeter instrumentation: (2) surgical considerations related to special problems of chronic implantation of flowmeter probes: (3) study of the relationship between levels of blood flow and organ activity. Principal engineering effort has been focused on the fundamental phenomena operative in the flowmeter probe and on probe design. Two probes have been constructed and a third is nearing completion. A previously unrecognized source of zero drift has been discovered and corrected. has been designed, assembled, tested and successfully employed in work on the several probes. A significant innovation which has been introduced is the use of a transformer coupled input for suppression of unwanted common mode signals. New low noise transistor amplifiers with characteristics suitable for space vehicle packaging are being developed. Linearity of the present apparatus has been found to extend at least into the near turbulent flow region. Attention has been directed to the two vascular beds of physiologic interest that present particular problems with regard to chronic implantation of flowmeter probes, the myocardium and the liver. Surgical techniques have been perfected that will permit myocardial and liver blood flow measurement. Two groups of animals have successfully undergone surgery and await the implantation of probes. Studies of the relationship between organ blood flow and levels of physiologic activity have been initiated. The first organ system studied was the heart, For the first time autoregulatory mechanisms have been demonstrated within the myocardial vascular bed which rapidly and precisely maintain coronary blood flow at a level i n keeping with the magnitude of cardiac work, Following a summary statement of the status of the program, the work performed is described, A financial review of expenditures incurred and a proposal for future funding are appended,
Personal thermoregulatory systems which are used by astronauts to alleviate thermal stress during extravehicular activity have been applied to the therapeutic management of multiple sclerosis. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objectives of this study were to compare the effectiveness of two passive and two active cooling vests and to measure the body temperature and circulatory changes produced by each cooling vest configuration. The MicroClimate Systems and the Life Enhancement Tech(LET) lightweight liquid cooling vests, the Steele Vest and LET's Zipper Front Garment were used to cool the chest region of 10 male and female subjects (25 to 55 yr.) in this study. Calf, forearm and finger blood flows were measured using a tetrapolar impedance rheograph. The subjects, seated in an upright position at normal room temperature (approx.22C), were tested for 60 min. with the cooling system operated at its maximum cooling capacity. Blood flows were recorded continuously using a computer data acquisition system with a sampling frequency of 250 Hz. Oral, right and left ear temperatures and cooling system parameters were logged manually every 5 min. Arm, leg, chest and rectal temperatures; heart rate; respiration; and an activity index were recorded continuously on a U.F.I., Inc. Biolog ambulatory monitor. In general, the male and female subjects' oral and ear temperature responses to cooling were similar for all vest configurations tested. Oral temperatures during the recovery period were significantly (P<0.05) lower than during the control period, approx. 0.2 - 0.5C, for both men and women wearing any of the four different garments. The corresponding ear temperatures were significantly (P<0.05) decreased approx.0.2 - 0.4C by the end of the recovery period. Compared to the control period, no significant differences were found in rectal temperatures during cooling and recovery periods.
A major focus of our program has been to develop a sensitive noninvasive procedure to quantify early weightlessness-induced changes in cardiovascular function or potential dysfunction. Forty studies of healthy young volunteers (10 men and 10 women, each studied twice) were conducted to determine changes in the sympatho-vagal balance of autonomic control of cardiovascular regulation during graded headward and footward blood volume shifts. Changes in sympatho-vagal balance were classified by changes in the mean levels and spectral content of cardiovascular variables and verified by changes in circulating levels of catecholamines and pancreatic polypeptide. Possible shifts in intra/extravascular fluid were assessed from changes in hematocrit and plasma mass density while changes in the stimulus to regulate plasma volume were determined from Plasma Renin Activity (PRA). Autonomic blockade was used to unmask the relative contribution of sympathetic and parasympathetic efferent influences in response to 10 min each of 0, 20 and 40 mmHg Lower Body Negative Pressure (LBNP) and 15 and 30 mmHg Positive Pressure (LBPP). The combination of muscarinic blockade with graded LBNP and LBPP was used to evoke graded increases and decreases in sympathetic activity without parasympathetic contributions. The combination of beta blockade with graded LBNP and LBPP was used to produce graded increases and decreases in parasympathetic activity without beta sympathetic contributions. Finally, a combination of both beta and muscarinic blockades with LBNP and LBPP was used to determine the contribution from other, primarily alpha adrenergic, sources. Mean values, spectral analyses and time frequency analysis of R-R interval (HR), Arterial Pressure (AP), peripheral blood flow (RF), Stroke Volume (SV) and peripheral resistance (TPR) were performed for all phases of the study. Skin blood Flow (SF) was also measured in other studies and similarly analyzed. Spectra were examined for changes in three frequency regions (low 0.006 - 0.005 Hz (LF), mid 0.05 - 0.15 Hz (W), and high 0.15 - 0.45 Hz (EF)). The primary objective of the study was to indicate which changes in the mean values and/or spectra of cardiovascular variables consistently correlated with changes in sympatho-vagal balance in response to headward and footward fluid shifts. A secondaey objective was to quantify the vascular and extravascular fluid shifts evoked by LBNP and LBPP. The principal hypothesis being tested was that headward fluid shifts would evoke an increase in parasympathetic activity and footward fluid shifts would evoke an increase in sympathetic activity both of which would be detected by spectral analysis and verified by circulating hormones. Hematocrit (HCT), plasma mass density and plasma renin activity increased with muscarinic blockade and with LBNP, a response indicative of a plasma shift to extravascular spaces. Beta blockade alone or after muscarinic blockade had no effect on HCT or plasma mass density. With respect to intravascular fluid volume distribution, LBNP and LBPP produced sufficient upper body vascular fluid shifts to evoke appropriate autonomic regulatory responses.
Personal thermoregulatory systems which provide chest cooling are used in the industrial and aerospace environments to alleviate thermal stress. However, little information is available regarding the physiologic and circulatory changes produced by routine operation of these systems. The objectives of this study were to compare the effectiveness of two passive and two active cooling vests, and to measure the body temperature and circulatory changes produced by each cooling vest configuration. The MicroClimate Systems and the Life Enhancement Tech(LET) lightweight liquid cooling vests, the Steele Vest and LET's Zipper Front Garment were used to cool the chest region of 11 male and 10 female subjects (25 to 55 yr.) in this study. Calf, forearm and finger blood flows were measured using a tetrapolar impedance rheograph. The subjects, seated in an upright position at normal room temperature (approx.21 C), were tested for 60 min. with the cooling system operated at its maximum cooling capacity. Blood flows were recorded continuously using a computer data acquisition system with a sampling frequency of 250 Hz. Oral, right and left ear temperatures and cooling system parameters were logged manually every 5 min. Arm, leg, chest and rectal temperatures; heart rate; respiration; and an activity index were recorded continuously on a URI Inc. Biolog ambulatory monitor. In general, the male and female subjects' rectal and ear temperature responses to cooling were similar for all vest configurations tested. Oral temperatures during the recovery period were significantly (P<0.05) lower than during the control period, approx.0.2 - 0.5 C, for both men and women wearing any of the four different garments. The corresponding car temperatures were significantly (P<0.05) decreased approx.0.2 - 0.3 C by the end of the recovery period. Compared to the control period, no significant differences were found in rectal temperatures during cooling and recovery periods. These results show that all vest configurations elicit a similar thermal response in both male and female subject groups. However, subject population variance was rather large and may have masked differences between the vests. One vest may prove more effective than another for a given individual, and experience is the only means of determining this.