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563 records · Page 32

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NASA NTRS1995

Simultaneous cerebrovascular and cardiovascular responses during presyncope

BACKGROUND AND PURPOSE: Presyncope, characterized by symptoms and signs indicative of imminent syncope, can be aborted in many situations before loss of consciousness occurs. The plasticity of cerebral autoregulation in healthy humans and its behavior during this syncopal prodrome are unclear, although systemic hemodynamic instability has been suggested as a key factor in the precipitation of syncope. Using lower body negative pressure (LBNP) to simulate central hypovolemia, we previously observed falling mean flow velocities (MFVs) with maintained mean arterial blood pressure (MABP). These findings, and recent reports suggesting increased vascular tone within the cerebral vasculature at presyncope, cannot be explained by the classic static cerebral autoregulation curve; neither can they be totally explained by a recent suggestion of a rightward shift in this curve. METHODS: Four male and five female healthy volunteers were exposed to presyncopal LBNP to evaluate their cerebrovascular and cardiovascular responses by use of continuous acquisition of MFV from the right middle cerebral artery with transcranial Doppler sonography, MABP (Finapres), and heart rate (ECG). RESULTS: At presyncope, MFV dropped on average by 27.3 +/- 14% of its baseline value (P < .05), while MABP remained at 2.0 +/- 27% above its baseline level. Estimated cerebrovascular resistance increased during LBNP. The percentage change from baseline to presyncope in MFV and MABP revealed consistent decreases in MFV before MABP. CONCLUSIONS: Increased estimated cerebrovascular resistance, falling MFV, and constant MABP are evidence of an increase in cerebral vascular tone with falling flow, suggesting a downward shift in the cerebral autoregulation curve. Cerebral vessels may have a differential sensitivity to sympathetic drive or more than one type of sympathetic innervation. Future work to induce dynamic changes in MABP during LBNP may help in assessing the plasticity of the cerebral autoregulation mechanism.

Non-NASA Center↗

NASA NTRS1994

Extracellular matrix controls tubulin monomer levels in hepatocytes by regulating protein turnover

Cells have evolved an autoregulatory mechanism to dampen variations in the concentration of tubulin monomer that is available to polymerize into microtubules (MTs), a process that is known as tubulin autoregulation. However, thermodynamic analysis of MT polymerization predicts that the concentration of free tubulin monomer must vary if MTs are to remain stable under different mechanical loads that result from changes in cell adhesion to the extracellular matrix (ECM). To determine how these seemingly contradictory regulatory mechanisms coexist in cells, we measured changes in the masses of tubulin monomer and polymer that resulted from altering cell-ECM contacts. Primary rat hepatocytes were cultured in chemically defined medium on bacteriological petri dishes that were precoated with different densities of laminin (LM). Increasing the LM density from low to high (1-1000 ng/cm2), promoted cell spreading (average projected cell area increased from 1200 to 6000 microns2) and resulted in formation of a greatly extended MT network. Nevertheless, the steady-state mass of tubulin polymer was similar at 48 h, regardless of cell shape or ECM density. In contrast, round hepatocytes on low LM contained a threefold higher mass of tubulin monomer when compared with spread cells on high LM. Furthermore, similar results were obtained whether LM, fibronectin, or type I collagen were used for cell attachment. Tubulin autoregulation appeared to function normally in these cells because tubulin mRNA levels and protein synthetic rates were greatly depressed in round cells that contained the highest level of free tubulin monomer. However, the rate of tubulin protein degradation slowed, causing the tubulin half-life to increase from approximately 24 to 55 h as the LM density was lowered from high to low and cell rounding was promoted. These results indicate that the set-point for the tubulin monomer mass in hepatocytes can be regulated by altering the density of ECM contacts and changing cell shape. This finding is consistent with a mechanism of MT regulation in which the ECM stabilizes MTs by both accepting transfer of mechanical loads and altering tubulin degradation in cells that continue to autoregulate tubulin synthesis.

Non-NASA Center↗

NASA NTRS1992

Mathematical modeling of human cardiovascular system for simulation of orthostatic response

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

NASA Discipline Cardiopulmonary↗

NASA NTRS2004

Calcium balance in mature male rats with unloaded hindlimbs

BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p < 0.05). This difference was not due to urinary Ca excretion since it was lower in HU than C rats (1.27 +/- 0.51 mg x d(-1) vs. 2.35 +/- 0.82 mg x d(-1), p < 0.05). Fecal Ca in HU rats exceeded dietary Ca by 4-7%, Restricting dietary Ca to 0.1% was followed by an increase in serum 1,25-dihydroxyvitamin D (1,25-D) and greater intestinal Ca absorption than in rats fed 0.5% Ca. Ca balances in rats fed 0.1% Ca were also more negative in HU than C rats (-2.4 vs. -0.03 mg x d(-1), p < 0.05). Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.

Hindlimb Suspension/physiology↗

NASA NTRS2021

Circadian Rhythms and Homeostatic Mechanisms for Sleep Regulation

This chapter examines circadian rhythms and homeostatic mechanisms for sleep regulation. It reviews the current evidence describing the two-process model of sleep regulation and how to assess disruption to either of these sleep drives. This chapter also reviews the role of the photic and non-photic resetting of the circadian rhythm and describes how some aspects of modern society can cause sleep and circadian disruption. Furthermore, this chapter describes how misalignment between the circadian rhythm and sleep homeostat, such as occurs during jet lag and shiftwork, can lead to sleep disruption. The short and long-term consequences of circadian misalignment are also reviewed.

Sleep↗