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At least 847 records · Page 47

Design of functional materials based on new principles of disorder. Final Report

Disorder is present to some extent in every material. The disorder can be sparse and localized – individual defects – or globally such as in a glass. Normally disorder is considered to be detrimental to function. However, this is not necessarily always the case. This project addressed the question: How does disorder provide new potentialities for the behavior of a material that would be absent in a crystalline material of the same composition? We have discovered a new principle for disordered matter: Independence of bond-level response. This work has introduced the possibility of creating new classes of mechanical meta-materials with applications everywhere from microscopic biological molecules (allostery) to large scale architectural disordered networks. During the course of this grant, we have subsequently elaborated on these novel ideas about bond-level independence of properties in disordered materials. In particular, this study has required that we understand the limits of disorder. That is, if crystals are perfect order, is there another diametrically opposed pole which is the most disordered state? We have shown that, in a well-defined way, jamming is one extreme disordered pole of rigid matter. Jamming is a far-from-equilibrium way of creating a rigid solid by rapidly quenching a random distribution of particles to a mechanically stable system at zero temperature. To understand the jammed state of matter, we have elucidated the low-frequency excitation of these systems. This has allowed a new way of understanding materials that cannot be easily classified as crystals or glasses. These ideas can be extended to address the mechanical properties of polycrystalline matter. Memory formation in matter can take inspiration from memory that occurs in a biological context. The issue of memory formation raises another set of questions at the heart of how the energy landscape is organized and how it can be manipulated to store information in a solid. This project has explored how to understand the degree to which multiple memories can be stored in a single system and has created a holistic understanding of how inputs can be used to create a desired response.

36 MATERIALS SCIENCE↗

Effects of graded LBNP on MSNA and interstitial norepinephrine

Exposure to lower body negative pressure (LBNP) leads to an increased activation of the sympathetic nervous system (SNS) and an increase in muscle sympathetic nerve activity (MSNA). In this study, we examined the relationship between MSNA and interstitial norepinephrine (NE(i)) concentrations during LBNP. Twelve healthy volunteers were studied (26 +/- 6 yr). Simultaneous MSNA and microdialysis data were collected in six of these subjects. Measurements of MSNA (microneurography) and NE(i) (microdialysis, vastus lateralis) were performed at rest and then during an incremental LBNP paradigm (-10, -30, and -50 mmHg). MSNA rose as a function of LBNP (P < 0.001, n = 12). The plasma norepinephrine (NE(p)) concentration was 0.9 +/- 0.1 nmol/l at rest (n = 12). NE(i) measured in six subjects rose from 5.2 +/- 0.8 nmol/l at rest to 17.0 +/- 1.7 nmol/l at -50 mmHg (P < 0.001). Of note, the rise in NE(p) with LBNP was considerably less compared with the changes in NE(i) (Delta21 +/- 6% vs. Delta197 +/- 52%, n = 6, P < 0.015). MSNA and NE(i) showed a significant linear relationship (r = 0.721, P < 0.004). Activation of the SNS increased MSNA and NE(i) levels. The magnitude of the NE(i) increase was far greater than that seen for NE(p) suggesting that NE movement into the circulation decreases with baroreceptor unloading.

NASA Discipline Cardiopulmonary↗

The Radio Frequency Health Node Wireless Sensor System

The Radio Frequency Health Node (RFHN) wireless sensor system differs from other wireless sensor systems in ways originally intended to enhance utility as an instrumentation system for a spacecraft. The RFHN can also be adapted to use in terrestrial applications in which there are requirements for operational flexibility and integrability into higher-level instrumentation and data acquisition systems. As shown in the figure, the heart of the system is the RFHN, which is a unit that passes commands and data between (1) one or more commercially available wireless sensor units (optionally, also including wired sensor units) and (2) command and data interfaces with a local control computer that may be part of the spacecraft or other engineering system in which the wireless sensor system is installed. In turn, the local control computer can be in radio or wire communication with a remote control computer that may be part of a higher-level system. The remote control computer, acting via the local control computer and the RFHN, cannot only monitor readout data from the sensor units but can also remotely configure (program or reprogram) the RFHN and the sensor units during operation. In a spacecraft application, the RFHN and the sensor units can also be configured more nearly directly, prior to launch, via a serial interface that includes an umbilical cable between the spacecraft and ground support equipment. In either case, the RFHN wireless sensor system has the flexibility to be configured, as required, with different numbers and types of sensors for different applications. The RFHN can be used to effect realtime transfer of data from, and commands to, the wireless sensor units. It can also store data for later retrieval by an external computer. The RFHN communicates with the wireless sensor units via a radio transceiver module. The modular design of the RFHN makes it possible to add radio transceiver modules as needed to accommodate additional sets of wireless sensor units. The RFHN includes a core module that performs generic computer functions, including management of power and input, output, processing, and storage of data. In a typical application, the processing capabilities in the RFHN are utilized to perform preprocessing, trending, and fusion of sensor data. The core module also serves as the unit through which the remote control computer configures the sensor units and the rest of the RFHN.

Valencia, J. Emilio↗

Application of color Doppler flow mapping to calculate orifice area of St Jude mitral valve

BACKGROUND: The effective orifice area (EOA) of a prosthetic valve is superior to transvalvular gradients as a measure of valve function, but measurement of mitral prosthesis EOA has not been reliable. METHODS AND RESULTS: In vitro flow across St Jude valves was calculated by hemispheric proximal isovelocity surface area (PISA) and segment-of-spheroid (SOS) methods. For steady and pulsatile conditions, PISA and SOS flows correlated with true flow, but SOS and not PISA underestimated flow. These principles were then used intraoperatively to calculate cardiac output and EOA of newly implanted St Jude mitral valves in 36 patients. Cardiac output by PISA agreed closely with thermodilution (r=0.91, Delta=-0.05+/-0.55 L/min), but SOS underestimated it (r=0.82, Delta=-1.33+/-0.73 L/min). Doppler EOAs correlated with Gorlin equation estimates (r=0.75 for PISA and r=0.68 for SOS, P<0.001) but were smaller than corresponding in vitro EOA estimates. CONCLUSIONS: Proximal flow convergence methods can calculate forward flow and estimate EOA of St Jude mitral valves, which may improve noninvasive assessment of prosthetic mitral valve obstruction.

NASA Discipline Cardiopulmonary↗

Thermally induced magnetic relaxation in square artificial spin ice

The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here in this paper, we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system $-$ square artificial spin ice $-$ we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Using time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Fiber-Optic Sensor Would Monitor Growth of Polymer Film

A proposed optoelectronic sensor system would measure the increase in thickness of a film of parylene (a thermoplastic polymer made from para-xylene) during growth of the film in a vapor deposition process. By enabling real-time monitoring of film thickness, the system would make it possible to identify process conditions favorable for growth and to tailor the final thickness of the film with greater precision than is now possible. The heart of the sensor would be a pair of fiber-optic Fabry-Perot interferometers, depicted schematically in the figure. (In principle, a single such interferometer would suffice. The proposal calls for the use of two interferometers for protective redundancy and increased accuracy.) Each interferometer would include a light source, a fiber-optic coupler, and photodetectors in a control box outside the deposition chamber. A single-mode optical fiber for each interferometer would run from inside the control box to a fused-silica faceplate in a sensor head. The sensory tips of the optical fibers would be polished flush with the free surface of the faceplate. In preparation for use, the sensor head would be mounted with a hermetic seal in a feed-through port in the deposition chamber, such that free face of the faceplate and the sensory tips of the optical fibers would be exposed to the deposition environment. During operation, light would travel along each optical fiber from the control box to the sensor head. A small portion of the light would be reflected toward the control box from the end face of each fiber. Once growth of the parylene film started, a small portion of the light would also be reflected toward the control box from the outer surface of the film. In the control box, the two reflected portions of the light beam would interfere in one of the photodetectors. The difference between the phases of the interfering reflected portions of the light beam would vary in proportion to the increasing thickness of the film and the known index of refraction of the film, causing the photodetector reading to vary in proportion to a known sinusoidal function of film thickness. Electronic means of monitoring this variation and the corresponding variation in phase and thickness are well established in the art of interferometry. Hence, by tracking the cumulative change in phase difference from the beginning of deposition, one could track the growing thickness of the film to within a small fraction of a wavelength of light.

Beamesderfer, Michael↗

Reduced Order Modeling for Prediction and Control of Large-Scale Systems.

This report describes work performed from June 2012 through May 2014 as a part of a Sandia Early Career Laboratory Directed Research and Development (LDRD) project led by the first author. The objective of the project is to investigate methods for building stable and efficient proper orthogonal decomposition (POD)/Galerkin reduced order models (ROMs): models derived from a sequence of high-fidelity simulations but having a much lower computational cost. Since they are, by construction, small and fast, ROMs can enable real-time simulations of complex systems for onthe- spot analysis, control and decision-making in the presence of uncertainty. Of particular interest to Sandia is the use of ROMs for the quantification of the compressible captive-carry environment, simulated for the design and qualification of nuclear weapons systems. It is an unfortunate reality that many ROM techniques are computationally intractable or lack an a priori stability guarantee for compressible flows. For this reason, this LDRD project focuses on the development of techniques for building provably stable projection-based ROMs. Model reduction approaches based on continuous as well as discrete projection are considered. In the first part of this report, an approach for building energy-stable Galerkin ROMs for linear hyperbolic or incompletely parabolic systems of partial differential equations (PDEs) using continuous projection is developed. The key idea is to apply a transformation induced by the Lyapunov function for the system, and to build the ROM in the transformed variables. It is shown that, for many PDE systems including the linearized compressible Euler and linearized compressible Navier-Stokes equations, the desired transformation is induced by a special inner product, termed the “symmetry inner product”. Attention is then turned to nonlinear conservation laws. A new transformation and corresponding energy-based inner product for the full nonlinear compressible Navier-Stokes equations is derived, and it is demonstrated that if a Galerkin ROM is constructed in this inner product, the ROM system energy will be bounded in a way that is consistent with the behavior of the exact solution to these PDEs, i.e., the ROM will be energy-stable. The viability of the linear as well as nonlinear continuous projection model reduction approaches developed as a part of this project is evaluated on several test cases, including the cavity configuration of interest in the targeted application area. In the second part of this report, some POD/Galerkin approaches for building stable ROMs using discrete projection are explored. It is shown that, for generic linear time-invariant (LTI) systems, a discrete counterpart of the continuous symmetry inner product is a weighted L2 inner product obtained by solving a Lyapunov equation. This inner product was first proposed by Rowley et al., and is termed herein the “Lyapunov inner product“. Comparisons between the symmetry inner product and the Lyapunov inner product are made, and the performance of ROMs constructed using these inner products is evaluated on several benchmark test cases. Also in the second part of this report, a new ROM stabilization approach, termed “ROM stabilization via optimization-based eigenvalue reassignment“, is developed for generic LTI systems. At the heart of this method is a constrained nonlinear least-squares optimization problem that is formulated and solved numerically to ensure accuracy of the stabilized ROM. Numerical studies reveal that the optimization problem is computationally inexpensive to solve, and that the new stabilization approach delivers ROMs that are stable as well as accurate. Summaries of “lessons learned“ and perspectives for future work motivated by this LDRD project are provided at the end of each of the two main chapters.

97 MATHEMATICS AND COMPUTING↗

Respiratory modulation of human autonomic rhythms

We studied the influence of three types of breathing [spontaneous, frequency controlled (0.25 Hz), and hyperventilation with 100% oxygen] and apnea on R-R interval, photoplethysmographic arterial pressure, and muscle sympathetic rhythms in nine healthy young adults. We integrated fast Fourier transform power spectra over low (0.05-0.15 Hz) and respiratory (0.15-0.3 Hz) frequencies; estimated vagal baroreceptor-cardiac reflex gain at low frequencies with cross-spectral techniques; and used partial coherence analysis to remove the influence of breathing from the R-R interval, systolic pressure, and muscle sympathetic nerve spectra. Coherence among signals varied as functions of both frequency and time. Partialization abolished the coherence among these signals at respiratory but not at low frequencies. The mode of breathing did not influence low-frequency oscillations, and they persisted during apnea. Our study documents the independence of low-frequency rhythms from respiratory activity and suggests that the close correlations that may exist among arterial pressures, R-R intervals, and muscle sympathetic nerve activity at respiratory frequencies result from the influence of respiration on these measures rather than from arterial baroreflex physiology. Most importantly, our results indicate that correlations among autonomic and hemodynamic rhythms vary over time and frequency, and, thus, are facultative rather than fixed.

Non-NASA Center↗

Signal averaging technique for noninvasive recording of late potentials in patients with coronary artery disease

An advanced non invasive signal averaging technique was used to detect late potentials in two groups of patients: Group A (24 patients) with coronary artery disease (CAD) and without sustained ventricular tachycardia (VT) and Group B (8 patients) with CAD and sustained VT. Recorded analog data were digitized and aligned using a cross correlation function with fast Fourier transform schema, averaged and band pass filtered between 60 and 200 Hz with a non-recursive digital filter. Averaged filtered waveforms were analyzed by computer program for 3 parameters: (1) filtered QRS (fQRS) duration (2) interval between the peak of the R wave peak and the end of fQRS (R-LP) (3) RMS value of last 40 msec of fQRS (RMS). Significant change was found between Groups A and B in fQRS (101 -/+ 13 msec vs 123 -/+ 15 msec; p < .0005) and in R-LP vs 52 -/+ 11 msec vs 71-/+18 msec, p <.002). We conclude that (1) the use of a cross correlation triggering method and non-recursive digital filter enables a reliable recording of late potentials from the body surface; (2) fQRS and R-LP durations are sensitive indicators of CAD patients susceptible to VT.

NASA Discipline Cardiopulmonary↗

Large scale crystallization of protein pharmaceuticals in microgravity via temperature change

The major objective of this research effort is the temperature driven growth of protein crystals in large batches in the microgravity environment of space. Pharmaceutical houses are developing protein products for patient care, for example, human insulin, human growth hormone, interferons, and tissue plasminogen activator or TPA, the clot buster for heart attack victims. Except for insulin, these are very high value products; they are extremely potent in small quantities and have a great value per gram of material. It is feasible that microgravity crystallization can be a cost recoverable, economically sound final processing step in their manufacture. Large scale protein crystal growth in microgravity has significant advantages from the basic science and the applied science standpoints. Crystal growth can proceed unhindered due to lack of surface effects. Dynamic control is possible and relatively easy. The method has the potential to yield large quantities of pure crystalline product. Crystallization is a time honored procedure for purifying organic materials and microgravity crystallization could be the final step to remove trace impurities from high value protein pharmaceuticals. In addition, microgravity grown crystals could be the final formulation for those medicines that need to be administered in a timed release fashion. Long lasting insulin, insulin lente, is such a product. Also crystalline protein pharmaceuticals are more stable for long-term storage. Temperature, as the initiation step, has certain advantages. Again, dynamic control of the crystallization process is possible and easy. A temperature step is non-invasive and is the most subtle way to control protein solubility and therefore crystallization. Seeding is not necessary. Changes in protein and precipitant concentrations and pH are not necessary. Finally, this method represents a new way to crystallize proteins in space that takes advantage of the unique microgravity environment. The results from two flights showed that the hardware performed perfectly, many crystals were produced, and they were much larger than their ground grown controls. Morphometric analysis was done on over 4,000 crystals to establish crystal size, size distribution, and relative size. Space grown crystals were remarkably larger than their earth grown counterparts and crystal size was a function of PCF volume. That size distribution for the space grown crystals was a function of PCF volume may indicate that ultimate size was a function of temperature gradient. Since the insulin protein concentration was very low, 0.4 mg/ml, the size distribution could also be following the total amount of protein in each of the PCF's. X-ray analysis showed that the bigger space grown insulin crystals diffracted to higher resolution than their ground grown controls. When the data were normalized for size, they still indicated that the space crystals were better than the ground crystals.

Long, Marianna M.↗

Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy

Backgorund: Quantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy. Aim: We compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm. Methods: {sup 13}N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares. Results: All HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). Conclusions: Anatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Fundamentals of Microbial Community Resistance and Resilience

Microbial communities are at the heart of all ecosystems, and yet microbial community behavior in disturbed environments remains difficult to measure and predict. Understanding the drivers of microbial community stability, including resistance (insensitivity to disturbance) and resilience (the rate of recovery after disturbance) is important for predicting community response to disturbance. Here, we provide an overview of the concepts of stability that are relevant for microbial communities. First, we highlight insights from ecology that are useful for defining and measuring stability. To determine whether general disturbance responses exist for microbial communities, we next examine representative studies from the literature that investigated community responses to press (long-term) and pulse (short-term) disturbances in a variety of habitats. Then we discuss the biological features of individual microorganisms, of microbial populations, and of microbial communities that may govern overall community stability. We conclude with thoughts about the unique insights that systems perspectives – informed by meta-omics data – may provide about microbial community stability.

59 BASIC BIOLOGICAL SCIENCES↗

SU-E-T-617: Plan Quality Estimation of Intensity-Modulated Radiotherapy Cases for Lung Cancer

Purpose: To estimate the planning quality of intensity-modulated radiotherapy in lung cancer cases and to provide preliminary data for the development of a planning quality assurance algorithm. Methods: 42 IMRT plans previously used in cases of solitary lung cancers were collected. Organs in or near the thoracic cavity, such as lung (ipsilateral, contralateral), heart, liver, esophagus, cord and bronchus were considered as organs at risk (OARs) in this study. The coverage index (CVI), conformity index (CI), homogeneity index (HI), volume, irregularity (standard deviation of center-surface distance) were used to compare PTV dose characteristics. The effective uniform dose (EUD), V10Gy, and V20Gy of the OARs were used to compare OAR dose characteristics. Results: Average CVI, CI, HI values were 0.9, 0.8, 0.1, respectively. CVI and CI had narrow Gaussian distribution curves without a singular value, but one case had a relatively high (0.25) HI because of location and irregular shape (Irregularity of 18.5 when average was 12.5) of PTV. EUDs tended to decrease as OAR-PTV distance increased and OAR-PTV overlap volume decreased. Conclusion: This work indicates the potential for significant plan quality deviation of similar lung cancer cases. Considering that this study were from a single department, differences in the treatment results for a given patient would be much more pronounced if multiple departments (and therefore more planners) were involved. Therefore, further examination of QA protocols is needed to reduce deviations in radiation treatment planning.

61 RADIATION PROTECTION AND DOSIMETRY↗

Arterial baroreflex control of sympathetic nerve activity during acute hypotension: effect of fitness

We examined arterial baroreflex control of muscle sympathetic nerve activity (MSNA) during abrupt decreases in mean arterial pressure (MAP) and evaluated whether endurance training alters baroreflex function. Acute hypotension was induced nonpharmacologically in 14 healthy subjects, of which 7 were of high fitness (HF) and 7 were of average fitness (AF), by releasing a unilateral arterial thigh cuff after 9 min of resting ischemia under two conditions: control, which used aortic and carotid baroreflex (ABR and CBR, respectively) deactivation; and suction, which used ABR deactivation alone. The application of neck suction to counteract changes in carotid sinus transmural pressure during cuff release significantly attenuated the MSNA response (which increased 134 +/- 32 U/14 s) compared with control (which increased 195 +/- 43 U/14 s) and caused a greater decrease in MAP (19 +/- 2 vs. 15 +/- 2 mmHg; P < 0.05). Furthermore, during both trials, the HF subjects exhibited a greater decrease in MAP compared with AF subjects despite an augmented baroreflex control of MSNA. These data indicate that the CBR contributes importantly to the MSNA response during acute systemic hypotension. Additionally, we suggest that an impaired control of vascular reactivity hinders blood pressure regulation in HF subjects.

Non-NASA Center↗

Role of microtubules in the contractile dysfunction of hypertrophied myocardium

OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

NASA Discipline Cardiopulmonary↗

Effects of gene deletion of the tissue inhibitor of the matrix metalloproteinase-type 1 (TIMP-1) on left ventricular geometry and function in mice

Alterations in the expression and activity of the matrix metalloproteinases (MMPs) and the tissue inhibitors of the MMPs (TIMPs) have been implicated in tissue remodeling in a number of disease states. One of the better characterized TIMPs, TIMP-1, has been shown to bind to active MMPs and to regulate the MMP activational process. The goal of this study was to determine whether deletion of the TIMP-1 gene in mice, which in turn would remove TIMP-1 expression in LV myocardium, would produce time-dependent effects on LV geometry and function. Age-matched sibling mice (129Sv) deficient in the TIMP-1 gene (TIMP-1 knock-out (TIMP-1 KO), n=10) and wild-type mice (n=10) underwent comparative echocardiographic studies at 1 and 4 months of age. LV catheterization studies were performed at 4 months and the LV harvested for histomorphometric studies. LV end-diastolic volume and mass increased (18+/-4 and 38+/-3%, respectively, P<0.05) at 4 months in the TIMP-1 KO group; a significant increase compared to wild-type controls (P<0.05). At 4 months, LV and end-diastolic wall stress was increased by over two-fold in the TIMP-1 KO compared to wild type (P<0.05). However, LV systolic pressure and ejection performance were unchanged in the two groups of mice. LV myocyte cross-sectional area was unchanged in the TIMP-1 KO mice compared to controls, but myocardial fibrillar collagen content was reduced. Changes in LV geometry occurred in TIMP-1 deficient mice and these results suggest that constitutive TIMP-1 expression participates in the maintenance of normal LV myocardial structure. Copyright 2000 Academic Press.

Non-NASA Center↗

Effect of upright tilt on ventricular/vascular coupling in chronically instrumented primates

Studies of the hydraulic loading conditions on the heart in humans, especially pulsatile load, have primarily been limited to the supine state. Therefore, we have chosen a nonhuman primate model, the baboon, to assess left ventricular/vascular coupling in both supine and upright positions. Primate subjects were studied by catheterization under sedation and then after surgical implantation of transducers. This allowed the evaluation of postural stress in the chronically instrumented conscious baboon and then after light dissociative doses of ketamine. Basic hemodynamic variables were evaluated for baboons in supine and upright positions. Fourier analysis was applied to aortic pressure and flow to obtain input and characteristic impedance and the ratio of pulsatile (Wp) to total (Wt) left ventricular power (Wp/Wt). The aortic reflected, or backward, pressure was also calculated. Peripheral resistance increased (P = 0.01) and reflected pressure decreased (17.74 +/- 1.50 vs. 15.21 +/- 2 mmHg; P < 0.01) in upright subjects. Characteristic impedance and Wp/Wt were unchanged. Postoperatively, peripheral resistance increased (2,651 +/- 311 vs. 3,667 +/- 276; P < 0.05) and mean power and Wt decreased (P < 0.01) without changes in reflected pressure. All variables were unchanged after light dissociative doses of ketamine. Thus there is no significant change in efficiency of left ventricular/vascular coupling formulated in terms of Wp/Wt or input impedance with postural stress.

NASA Program Space Physiology and Countermeasures↗

Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans

It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within +/-90 degrees of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within +/-45 degrees of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.

NASA Discipline Neuroscience↗