Biomedical subjects

Craig J Hartley

Publications and source records attributed to Craig J Hartley.

13 recordsLinked to original sources

PubMed2006

Blood flow in compliant arteries: an effective viscoelastic reduced model, numerics, and experimental validation.

The focus of this work is on modeling blood flow in medium-to-large systemic arteries assuming cylindrical geometry, axially symmetric flow, and viscoelasticity of arterial walls. The aim was to develop a reduced model that would capture certain physical phenomena that have been neglected in the derivation of the standard axially symmetric one-dimensional models, while at the same time keeping the numerical simulations fast and simple, utilizing one-dimensional algorithms. The viscous Navier-Stokes equations were used to describe the flow and the linearly viscoelastic membrane equations to model the mechanical properties of arterial walls. Using asymptotic and homogenization theory, a novel closed, "one-and-a-half dimensional" model was obtained. In contrast with the standard one-dimensional model, the new model captures: (1) the viscous dissipation of the fluid, (2) the viscoelastic nature of the blood flow - vessel wall interaction, (3) the hysteresis loop in the viscoelastic arterial walls dynamics, and (4) two-dimensional flow effects to the leading-order accuracy. A numerical solver based on the 1D-Finite Element Method was developed and the numerical simulations were compared with the ultrasound imaging and Doppler flow loop measurements. Less than 3% of difference in the velocity and less than 1% of difference in the maximum diameter was detected, showing excellent agreement between the model and the experiment.

Algorithms↗

PubMed2006

Resolving the hemodynamic inverse problem.

The "hemodynamic inverse problem" is the determination of arterial system properties from pressures and flows measured at the entrance of an arterial system. Conventionally, investigators fit reduced arterial system models to data, and the resulting model parameters represent putative arterial properties. However, no unique solution to the inverse problem exists-an infinite number of arterial system topologies result in the same input impedance (Zin) and, therefore, the same pressure and flow. Nevertheless, there are exceptions to this theoretical limitation; total peripheral resistance (Rtot), total arterial compliance (Ctot), and characteristic impedance (ZO) can be uniquely determined from input pressure and flow. Zin is determined completely by Ctot and Rtot at low frequencies, Zo at high frequencies, and arterial topology and reflection effects at intermediate frequencies. We present a novel method to determine the relative contribution of Zo, Ctot, Rtot and arterial topology/reflection to Zin without assuming a particular reduced model. This method is tested with a large-scale distributed model of the arterial system, and is applied to illustrative cases of measured pressure and flow. This work, thus, lays the theoretical foundation for determining the arterial properties responsible for increased pulse pressure with age and various arterial system pathologies.

Animals↗

PubMed2005

Vasa vasorum imaging: a new window to the clinical detection of vulnerable atherosclerotic plaques.

Complications of vulnerable atherosclerotic plaques (rupture, luminal and mural thrombosis, intraplaque hemorrhage, rapid progression to stenosis, spasm, and so forth) lead to heart attacks and strokes. It remains difficult to identify what plaques are vulnerable to these complications. Despite recent developments such as thermography, spectroscopy, and magnetic resonance imaging, none of them is approved for clinical use. Intravascular ultrasound (IVUS), a relatively old yet widely available clinical tool for guiding intracoronary procedures, is increasingly used for characterization of atherosclerotic plaques. However, inability of IVUS in measuring plaque activity limits its value in detection of vulnerable plaques. In this review, we present new information suggesting that microbubble contrast-enhanced IVUS can measure activity and inflammation within atherosclerotic plaques by imaging vasa vasorum density. An increasing body of evidence indicates that vasa vasorum density may be a strong marker for plaque vulnerability. We suggest that a combination of structural assessment (cap thickness, lipid core, calcification, etc) and vasa vasorum density imaging by IVUS can serve as the most powerful clinically available tool for characterization of vulnerable plaques. Due to space limitations, all IVUS images and movies are posted on the website of the Ultimate IVUS Collaborative Project: http://www.ultimateivus.com.

Albumins↗

PubMed2005

Pulsed Doppler signal processing for use in mice: applications.

We have developed a high-frequency, high-resolution Doppler spectrum analyzer (DSPW) and compared its performance against an adapted clinical Medasonics spectrum analyzer (MSA) and a zero-crossing interval histogram (ZCIH) used previously by us to evaluate cardiovascular physiology in mice. The aortic velocity (means +/- SE: 92.7 +/- 2.5 versus 82.2 +/- 1.8 cm/s) and aortic acceleration (8194 +/- 319 versus 5178 +/- 191 cm/s2) determined by the DSPW were significantly higher compared to those by the MSA. Aortic ejection time was shorter (48.3 +/- 0.9 versus 64.6 +/- 1.8 ms) and the isovolumic relaxation was longer (17.6 +/- 0.6 versus 13.5 +/- 0.6 ms) when determined by the DSPW because it generates shorter temporal widths in the velocity spectra when compared to the MSA. These data indicate that the performance of the DSPW in evaluating cardiovascular physiology was better than that of the MSA. There were no significant differences between the aortic pulse wave velocity determined by using the ZCIH (391 +/- 16 cm/s) and the DSPW (394 +/- 20 cm/s). Besides monitoring cardiac function, we have used the DSPW for studying peripheral vascular physiology in normal, transgenic, and surgical models of mice. Several applications such as the detection of high stenotic jet velocities (> 4 m/s), vortex shedding frequencies (250 Hz), and subtle changes in wave shapes in peripheral vessels which could not obtained with clinical Doppler systems are now made possible with the DSPW.

Algorithms↗

PubMed2005

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 0.1 ms (or longer up to 10 ms) to provide 0.1-ms time resolution and using 64-1024 sample segments of the Doppler audio signals resulting in frequency resolution ranging from 122-1953 Hz. The system was evaluated by its response to frequency swept signals with slopes (accelerations) and magnitudes (velocities) comparable to actual blood velocity signals in mice. Signals up to a maximum frequency of 125 kHz and a maximum acceleration of 20 MHz/s were processed and displayed. This corresponds to a maximum velocity of 480 (960) cm/s and a maximum acceleration of 750 (1500) m/s2 when Doppler shifts are measured with a 20- (10-) MHz probe, thereby allowing us to measure high stenotic jet velocities. The directional transitions of the spectrogram across zero frequency and across Nyquist frequency (sampling rate/2) were smooth with no discernible artifacts. Signals with period as low as 2 ms were processed and displayed at sweep speed that is ten times that in clinical Doppler systems, so that measurements of small temporal events can be made with precision. Thus, the new system can measure higher blood velocities with higher spatial and temporal resolution than is possible using clinical Doppler systems adapted for use in mice.

Algorithms↗

PubMed2004

Determinants of cardiac electrophysiological properties in mice.

INTRODUCTION: The transgenic mouse is a popular model for human inherited cardiac disease. Electrophysiology (EP) studies have recently been performed in transgenic mice to characterize the electrical phenotype of the heart. However, little is known regarding the impact of experimental conditions or model selection on the outcome of EP studies in mice. METHODS AND RESULTS: We investigated the effects of experimental conditions on mouse cardiac EP by (1) comparing the findings of transesophageal pacing with those of invasive intracardiac pacing, (2) elucidating the effects of commonly used anesthetic agents, and (3) determining the impact of changes in body temperature. We also investigated the effects of model selection by (1) studying the dependence on mouse strain, and (2) exploring the effects of age. We found that EP parameters derived by both transesophageal and intracardiac pacing/recordings methods were similar. On the other hand, the anesthetic mixture of ketamine, xylazine, and acepromazine had profound effects on cardiac EP compared to sodium pentobarbital or isoflurane. Meanwhile, compared to normal body temperature (97-99 F), low body temperature (92-94 F) prolonged most cardiac EP parameters, while high body temperature (102-104 F) had little effect. Heart rate was a sensitive indicator of changes in body temperature. Significant differences were observed in specialized conduction system properties among the mouse strains studied (FVB, C57, and DBA). Furthermore, atrial electrical remodeling was evidently associated with age, while ventricular electrical properties were virtually unaltered. In comparison with corresponding invasive EP parameters, we found that the QT interval was not a reliable EP index in the mouse. CONCLUSIONS: Cardiac EP variability may result from differences in experimental techniques including anesthesia and body temperature and from differences in mouse selection including strain and age. The influence of these factors should be considered when characterizing the electrical phenotype of transgenic mice in cardiovascular research.

Age Factors↗

PubMed2004

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. Doppler signals were obtained simultaneously from both vessel walls and from blood flow. The calculated displacement signals from the near and far walls were subtracted to generate a diameter signal from which the excursion and an augmentation index were calculated. The excursion ranged between 13 microm (in ApoE) and 95 microm (in alpha-SMA). The augmentation index was lowest in the WT mice (0.06) and highest in the old mice (0.29). We conclude that Doppler signal processing may be used to measure vessel wall motion in mice with high spatial and temporal resolution and that diameter signals can replace pressure signals for calculating the augmentation index. This noninvasive method is able to identify and confirm characteristic changes in arterial properties previously associated with age, atherosclerosis, and the absence of vascular tone.

Actins↗

PubMed2003

Measurement of aortic input impedance in mice: effects of age on aortic stiffness.

Mice are used with increasing frequency as models of human cardiovascular diseases, but significant gaps exist in our knowledge of vascular function in the aging mouse. We determined aortic input impedance spectra, pulse wave velocity, and augmentation index in adult (8-mo-old) and old (29-mo-old) mice to determine whether arterial stiffening occurred with age in mice as it does in humans. Pressure and blood velocity signals measured simultaneously from the same location in the ascending aorta were used to determine input impedance spectra (0-10 harmonics). The first minimum of the impedance modulus occurred at the second harmonic in adult mice but shifted to the fourth harmonic in old mice. Characteristic impedance (average of 2nd-10th harmonic) was 57% higher in old mice: 471 +/- 62 vs. 299 +/- 10 (SE) dyn.s.cm-3 (P < 0.05). Pulse pressure and augmentation index, determined from the aortic pressure signals, were also higher in old mice: 42 +/- 2.2 vs. 29 +/- 4.9 mmHg (P < 0.05) and 37 +/- 5 vs. 14 +/- 2% (P < 0.005). Aortic pulse wave velocity measured from the timing of upstrokes of the Doppler velocity signals was 45% higher in old mice: 416 +/- 22 vs. 286 +/- 14 cm/s (n = 3, P < 0.01). These results reproduce age-related findings reported in humans and confirm that mice may be used as models of age-related vascular stiffening.

Aging↗

PubMed2003

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. The pressure at which the tail flow reappeared was recorded as systolic and the pressure at which the tail flow became continuous was recorded as diastolic. Regression analysis of tail-cuff pressures over catheter pressures obtained from healthy mice (n = 16) showed a high degree of association (r(sys) = 0.95, r(dia) = 0.94, both at p < 0.001). Bland-Altman analysis showed good agreement between the two methods, with a mean difference of -13 ( +/- 12 SD) mmHg and 3 ( +/- 10 SD) mmHg in the systolic (58 to 250 mmHg) and diastolic (48 to 178 mmHg) pressure measurements, respectively. Bland-Altman plots of tail-cuff blood pressures of a second group of mice (n = 20) showed good agreement between repeated measurements obtained on the same day, but had higher variability between measurements made on different days.

Animals↗

PubMed2003

Doppler evaluation of peripheral vascular adaptations to transverse aortic banding in mice.

Transverse aortic banding in mice is commonly used to produce pressure overload, but the resulting cardiac hypertrophy is variable and the actual load produced is unknown. The purposes of the study were to characterize peripheral blood flow in banded mice using noninvasive Doppler methods, investigate whether changes in flow could predict the amount of cardiac hypertrophy induced and validate the simplified Bernoulli equation for estimating the pressure drop across the stenosis in very small vessels. Wild-type mice underwent aortic banding (n=15) or sham operation (n=6). Doppler velocity was measured in the right and left carotid arteries (RCA and LCA) 1 day later, and the heart weight/body weight ratio was measured at 7 days. The RCA/LCA peak velocity ratio at 1 day was significantly correlated with the heart weight/body weight ratio at 7 days after banding (r=0.62, p<0.005). In another 12 banded mice, serial Doppler velocity signals were obtained from the aortic banding site, the abdominal aorta (ABD) and the RCA and LCA before, 1 day after and 7 days after banding. Peak RCA velocity increased significantly after banding and both peak LCA velocity and peak ABD velocity decreased significantly. Mean velocities of RCA, LCA and ABD were unchanged before and after banding, suggesting that mice utilize peripheral arterial adaptations to maintain normal cerebral and peripheral perfusion. There was a significant positive correlation (r=0.83, p<0.001) between the RCA/LCA peak velocity ratio and peak jet velocity across the aortic banding site. Our data indicate that changes in carotid velocity after aortic banding can be used to estimate the pressure drop across the aortic band and to predict loading and resulting cardiac hypertrophy in mice. Additionally, we validated that the simplified Bernoulli equation (DeltaP=4V2) can be used to estimate the pressure drop across the aortic band in mice noninvasively.

Animals↗

PubMed2003

Effect of age on peripheral vascular response to transverse aortic banding in mice.

The placement of a ligature to constrict the transverse aorta has become a standard procedure to induce cardiac hypertrophy in mice. Apart from cardiac response, there are adaptive changes in the proximal and distal arterial system that function to maintain adequate peripheral perfusion. The purpose of this study was to characterize the peripheral vascular response by measuring the carotid blood flow using noninvasive Doppler methods, and to investigate the effect of aging on the adequacy and timing of the response after aortic banding in mice. Five 16-month-old and 9 4-month-old male B6D2F1 mice underwent transverse aortic banding. Blood flow velocity was measured with Doppler in the right and left carotid arteries (RCA and LCA) before, 1 day after, and 7 days after, banding. Pulsatility index defined as (peak - minimum)/mean velocity was used to estimate local compliance and distal arterial resistance. The RCA/LCA mean velocity ratio was lower and pulsatility index ratio was higher at 1 day after banding in older mice. However, at 7 days, the RCA/LCA mean velocity ratio and pulsatility index ratio were similar between the 2 age groups. Our data indicate that there is an age-related delay in the development of vascular adaptations in carotid arteries after aortic banding. Older mice take a longer time for adaptation to establish adequate and equal mean flow velocity in the carotid arteries.

Aging↗

PubMed2002

Noninvasive cardiovascular phenotyping in mice.

With the growth of genetic engineering, mice have become common as models of human diseases, which in turn has stimulated the development of techniques to monitor and image the murine cardiovascular system. Invasive methods are often more quantitative, but noninvasive methods are preferred when measurements must be repeated serially on living animals during development or in response to pharmacological or surgical interventions. Because of the small size and high heart rates in mice, high spatial and temporal resolutions are required to preserve signal fidelity. Monitoring of body temperature and the electrocardiogram is essential when animals must be anesthetized for a measurement or other procedure. Several other groups have developed cardiovascular imaging modalities suitable for murine applications, and ultrasound is the most widely used. Our group has developed and applied high-resolution Doppler probes and signal processing for measuring blood velocity in the heart and peripheral vessels of anesthetized mice noninvasively. We can measure cardiac filling and ejection velocities as indices of systolic and diastolic ventricular function and for timing of cardiac events; velocity pulse arrival times for determining pulse-wave velocity and arterial stiffness; peripheral velocity waveforms as indices of arterial resistance, compliance, and wave reflections; stenotic velocities for estimation of pressure drop and detection of vorticity; and tail artery velocity for determining systolic and diastolic blood pressure using a pressure cuff. These noninvasive methods are convenient and easy to apply and have been used to detect and evaluate numerous cardiovascular phenotypes in mutant mice.

Anesthesia↗

PubMed2002

Heart failure and greater infarct expansion in middle-aged mice: a relevant model for postinfarction failure.

Young mice tolerate myocardial loss after coronary artery ligation (CAL) without congestive heart failure (CHF) signs or mortality. We predicted a CHF phenotype after CAL in aged mice. Left coronary artery ligation produced permanent myocardial infarcts (MI). Mortality was higher in male 14-mo-old C57BL/6N mice (Older mice) than in 2-mo-old mice (Young mice) (16 of 25 Older mice died vs. 0 of 10 Young mice, P < 0.02). After 8 wk, rales, weight loss, and lethargy preceded deaths. Captopril (50 mg x kg(-1) x day(-1)) increased Older mouse survival (6 of 22 died, P < 0.02). Captopril improved systolic function (peak aortic blood velocity) from 76 +/- 6% of baseline in untreated Older mice to 93 +/- 8% (P < 0.036). At 24 h, MI comprised 28 +/- 4% of the left ventricle in Young mice, surprisingly larger than that in Older mice (18 +/- 2%, P < 0.011). Endocardial area underlying the infarct scar was significantly larger in Older mice than in Young mice. Captopril did not reduce expansion but markedly reduced septal hypertrophy. Aging reduces compensatory ability in mice despite smaller acute infarcts. Less effective myocardial repair, greater infarct expansion, and septal hypertrophy are seen with aging. Aging is a more relevant murine model of post-MI heart failure in patients.

Age Factors↗