Aortic acceleration as a noninvasive index of left ventricular contractility in the mouse.

The maximum value of the first derivative of the invasively measured left ventricular (LV) pressure (+ dP/dt or P') is often used to quantify LV contractility, which in mice is limited to a single terminal study. Thus, determination of P' in mouse longitudinal/serial studies requires a group of mice at each desired time point resulting in "pseudo" serial measurements. Alternatively, a noninvasive surrogate for P' will allow for repeated measurements on the same group of mice, thereby minimizing physiological variability and requiring fewer animals.

16-Channel Flexible System to Measure Electrophysiological Properties of Bioengineered Hearts.

As tissue engineering continues to mature, it is necessary to develop new technologies that bring insight into current paradigms and guide improvements for future experiments. To this end, we have developed a system to characterize our bioartificial heart model and compare them to functional native structures. In the present study, the hearts of adult Sprague-Dawley were decellularized resulting in a natural three-dimensional cardiac scaffold.

Conditioning of Cardiovascular Tissue Using a Noncontact Magnetic Stretch Bioreactor with Embedded Magnetic Nanoparticles.

Bioreactor systems, an integral component of tissue engineering, are designed to simulate complex in vivo conditions to impart functionality to artificial tissue. All standard forms of stretch bioreactors require physical contact with artificial heart muscle (AHM). However, we believe that noncontact stretch bioreactors have the potential to lead to higher functional benefit of AHM.

32-Channel System to Measure the Electrophysiological Properties of Bioengineered Cardiac Muscle.

The purpose of this study was to develop, assess, and validate a custom 32-channel system to analyze the electrical properties of 3-D artificial heart muscle (3D-AHM). In this study, neonatal rat cardiac cells were cultured in a fibrin gel to drive the formation of 3D-AHM. Once the tissues were fully formed, the customized electrocardiogram (EKG) sensing system was used to obtain the different electrophysiological characteristics of the muscle constructs.

Doppler velocity measurements from large and small arteries of mice.

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.

A novel handheld device for use in remote patient monitoring of heart failure patients--design and preliminary validation on healthy subjects.

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.

Feasibility of dual Doppler velocity measurements to estimate volume pulsations of an arterial segment.

If volume flow was measured at each end of an arterial segment with no branches, any instantaneous differences would indicate that volume was increasing or decreasing transiently within the segment. This concept could provide an alternative method to assess the mechanical properties or distensibility of an artery noninvasively using ultrasound. The goal of this study was to determine the feasibility of using Doppler measurements of pulsatile velocity (opposed to flow) at two sites to estimate the volume pulsations of the intervening arterial segment.

Multichannel pulsed Doppler signal processing for vascular measurements in mice.

The small size, high heart rate and small tissue displacement of a mouse require small sensors that are capable of high spatial and temporal tissue displacement resolutions and multichannel data acquisition systems with high sampling rates for simultaneous measurement of high fidelity signals. We developed and evaluated an ultrasound-based mouse vascular research system (MVRS) that can be used to characterize vascular physiology in normal, transgenic, surgically altered and disease models of mice. The system consists of multiple 10/20MHz ultrasound transducers, analog electronics for Doppler displacement and velocity measurement, signal acquisition and processing electronics and personal computer based software for real-time and off-line analysis.

Doppler estimation of reduced coronary flow reserve in mice with pressure overload cardiac hypertrophy.

Aortic banding produces pressure overload cardiac hypertrophy in mice, leading to decompensated heart failure in four to eight weeks, but the effects on coronary blood flow velocity and reserve are unknown. To determine whether coronary flow reserve (CFR) was reduced, we used noninvasive 20-MHz Doppler ultrasound to measure left main coronary flow velocity at baseline (B) and at hyperemia (H) induced by low (1%) and high (2.5%) concentrations of isoflurane gas anesthesia.

Effects of isoflurane on coronary blood flow velocity in young, old and ApoE(-/-) mice measured by Doppler ultrasound.

The commonly used anesthetic agent isoflurane (ISO) is a potent coronary vasodilator that could potentially be used in the assessment of coronary reserve, but its effects on coronary blood flow in mice are unknown. Coronary reserve is reduced by age, coronary artery disease and other cardiac pathologies in man, and some of these conditions can now be modeled in mice. Accordingly, we used Doppler ultrasound to measure coronary flow velocity in mice anesthetized with low (1%) and high (2.

Characterization of arterial wave propagation and reflection in mice.

Wave propagation through the arterial system changes with age and disease state, and mutant mice are often used to study these conditions. We have developed several noninvasive ultrasonic techniques to measure blood velocity and vessel wall motion from which we can calculate aortic pulse wave velocity (PWV), local compliance, impedance spectra, characteristic impedance (Zc), augmentation index (AI), and forward and backward waves in intact anesthetized mice. We found altered vascular mechanics in many mutant strains of mice.

Noninvasive ultrasonic measurement of arterial wall motion in mice.

To facilitate assessment of arterial function, we developed a noninvasive Doppler method for measuring vessel motion in genetically altered mice. A 20 MHz probe was held by an alligator clip and positioned over the carotid arteries of 16 mice including six 3 to 5-month old wild-type (WT), four 30-month old senescent (Old), two apolipoprotein-E (ApoE), and four alpha smooth muscle actin (alphaSMA) mice. Doppler signals were obtained simultaneously from both vessel walls and from blood flow using one or two probes.

Pulsed Doppler signal processing for use in mice: design and evaluation.

We have developed and evaluated a high-frequency, real-time pulsed Doppler and physiological signal acquisition and analysis system specifically for use in mice. The system was designed to provide sampling rates up to 125 kilosamples/s (ksps) with software controlled data acquisition and analysis in real-time. Complex fast Fourier transforms are performed every 0.

Noninvasive ultrasonic measurement of arterial wall motion in mice.

Despite the extensive use of genetically altered mice to study cardiovascular physiology and pathology, it remains difficult to quantify arterial function noninvasively in vivo. We have developed a noninvasive Doppler method for quantifying vessel wall motion in anesthetized mice. A 20-MHz probe was held by an alligator clip and positioned over the carotid arteries of 16 mice, including six 3- to 5-mo-old wild-type (WT), four 30-mo-old senescent (old), two apolipoprotein E null (ApoE), and four alpha-smooth muscle actin null (alpha-SMA) mice.

Noninvasive blood pressure measurement in mice using pulsed Doppler ultrasound.

Existing tail-cuff pressure devices for mice use tail flow sensors that measure only systolic and mean pressure. We developed a method to obtain systolic and diastolic pressure in mice using a pulsed Doppler flow velocity sensor and a tail-cuff and validated the method against pressure signals obtained simultaneously from a fluid-filled catheter. The tail-cuff was pressurized to suprasystolic levels to completely occlude the tail artery and then released gradually.