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HOUSTON, TX, United States

Grimes K.M.,University of Texas Health Science Center at San Antonio | Reddy A.K.,Baylor College of Medicine | Reddy A.K.,Indus Instruments | Lindsey M.L.,University of Mississippi Medical Center | Buffenstein R.,University of Texas Health Science Center at San Antonio
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2014

The naked mole-rat (NMR) is the longest-lived rodent known, with a maximum lifespan potential (MLSP) of >31 years. Despite such extreme longevity, these animals display attenuation of many age-associated diseases and functional changes until the last quartile of their MLSP. We questioned if such abilities would extend to cardiovascular function and structure in this species. To test this, we assessed cardiac functional reserve, ventricular morphology, and arterial stiffening in NMRs ranging from 2 to 24 years of age. Dobutamine echocardiography (3 μg/g ip) revealed no age-associated changes in left ventricular (LV) function either at baseline or with exercise-like stress. Baseline and dobutamine-induced LV pressure parameters also did not change. Thus the NMR, unlike other mammals, maintains cardiac reserve with age. NMRs showed no cardiac hypertrophy, evidenced by no increase in cardiomyocyte cross-sectional area or LV dimensions with age. Age-associated arterial stiffening does not occur since there are no changes in aortic blood pressures or pulse-wave velocity. Only LV interstitial collagen deposition increased 2.5-fold from young to old NMRs (P < 0.01). However, its effect on LV diastolic function is likely minor since NMRs experience attenuated age-related increases in diastolic dysfunction in comparison with other species. Overall, these findings conform to the negligible senescence phenotype, as NMRs largely stave off cardiovascular changes for at least 75% of their MLSP. This suggests that using a comparative strategy to find factors that change with age in other mammals but not NMRs could provide novel targets to slow or prevent cardiovascular aging in humans. © 2014 the American Physiological Society.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 100.00K | Year: 2004

DESCRIPTION (provided by applicant): Mice are now the primary model for determining the function of proteins expressed by specific genes many of which have cardiac and vascular implications. While the mouse cardiovascular system is similar to that of man in many respects, the limitations as a model of the human cardiovascular system are largely unknown because there are few suitable devices and techniques for making serial vascular measurements in mice. Our overall goal is to develop an ultrasound-based Mouse Vascular Research System (MVRS) that can be used to characterize vascular physiology in mice. Measurement capabilities will include blood velocities and vessel wall displacements from which we can determine and calculate diameter, volume, pressure, impedance spectra, segmental pulse wave velocity, characteristic impedance, forward and backward waves, and reflection coefficients. The MVRS will thus facilitate sophisticated analysis of vascular mechanics and will also allow simple and rapid screening for arterial abnormalities. We will use our commercially successful Doppler Signal Processing Workstation for mice (developed with prior SBIR funding) as a starting point to address the following specific aims during phase I: 1) Develop a 20 MHz ultrasound Doppler tissue displacement detector for vascular wall motion detection with 1/2 micron resolution; 2) Develop a dual gate, single probe 20 MHz ultrasound pulsed Doppler displacement detector for simultaneous acquisition of near and far arterial wall displacement signals; 3) Develop a dual channel pulsed Doppler velocimeter for simultaneous velocity monitoring at two adjacent locations to compute pulse wave velocity and arterial volume waves; and 4) Show feasibility of non-invasively measuring multiple Doppler signals simultaneously from peripheral vessels in mice with high spatial and temporal resolution. During Phase II we will refine the dual channel, dual gate pulsed Doppler system; develop comprehensive software for data acquisition, real time analysis, report generation, and user interface; and perform extensive in vivo validation in mice. Though our primary focus is on cardiovascular physiology, we will also add M-Mode imaging to assist in probe positioning and Doppler gate setting. The result will be a cost-effective commercial product that will act as an enabling technology for advancing the use of mice as models of human cardiovascular diseases and conditions.

Hartley C.J.,Baylor College of Medicine | Reddy A.K.,Baylor College of Medicine | Madala S.,Indus Instruments | Entman M.L.,Baylor College of Medicine | And 2 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2011

With the growth of genetic engineering, mice have become increasingly common as models of human diseases, and this has stimulated the development of techniques to assess the murine cardiovascular system. Our group has developed nonimaging and dedicated Doppler techniques for measuring blood velocity in the large and small peripheral arteries of anesthetized mice. We translated technology originally designed for human vessels for use in smaller mouse vessels at higher heart rates by using higher ultrasonic frequencies, smaller transducers, and higher-speed signal processing. With these methods one can measure cardiac filling and ejection velocities, velocity pulse arrival times for determining pulse wave velocity, peripheral blood velocity and vessel wall motion waveforms, jet velocities for the calculation of the pressure drop across stenoses, and left main coronary velocity for the estimation of coronary flow reserve. These noninvasive methods are convenient and easy to apply, but care must be taken in interpreting measurements due to Doppler sample volume size and angle of incidence. Doppler methods have been used to characterize and evaluate numerous cardiovascular phenotypes in mice and have been particularly useful in evaluating the cardiac and vascular remodeling that occur following transverse aortic constriction. Although duplex ultrasonic echo-Doppler instruments are being applied to mice, dedicated Doppler systems are more suitable for some applications. The magnitudes and waveforms of blood velocities from both cardiac and peripheral sites are similar in mice and humans, such that much of what is learned using Doppler technology in mice may be translated back to humans. © 2011 by the American Physiological Society.

Pollonini L.,University of Houston | Pollonini L.,Future Health | Rajan N.O.,Future Health | Rajan N.O.,Methodist Research Institute | And 6 more authors.
Journal of Medical Systems | Year: 2012

Remote patient monitoring (RPM) holds great promise for reducing the burden of congestive heart failure (CHF). Improved sensor technology and effective predictive algorithms can anticipate sudden decompensation events. Enhanced telemonitoring systems would promote patient independence and facilitate communication between patients and their physicians. We report the development of a novel hand-held device, called Blue Box, capable of collecting and wirelessly transmitting key cardiac parameters derived from three integrated biosensors: 2 lead electrocardiogram (ECG), photoplethysmography and bioelectrical impedance (bioimpedance). Blue Box measurements include time intervals between consecutive ECG R-waves (RR interval), time duration of the ECG complex formed by the Q, R and S waves (QRS duration), bioimpedance, heart rate and systolic time intervals. In this study, we recruited 24 healthy subjects to collect several parameters measured by Blue Box and assess their value in correlating with cardiac output measured with Echo-Doppler. Linear correlation between the heart rate measured with Blue Box and cardiac output from Echo- Doppler had a group average correlation coefficient of 0.80. We found that systolic time intervals did not improve the model significantly. However, STIs did inversely correlate with increasing workloads. © Springer Science+Business Media, LLC 2010.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2010

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