Abstract
BackgroundRodent models are increasingly used to study the development and progression of arterial stiffness. Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. Thus, we sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive rats (SHR) are detectable by PWV and EaI measurements when made under isoflurane anesthesia, and 2) if these two uniquely acquired assessments of arterial elasticity correlate.MethodsWe obtained PWV and EaI measurements in isoflurane anesthetized young and old SHRs, which are known to have significant differences in arterial stiffness. Doppler pulse waves were recorded from carotid and iliac arteries and the distance (D) between probe applantation sites was recorded. Simultaneously, an EKG was obtained, and the time intervals between the R-wave of the EKG to the foot of the Doppler waveforms were measured and averaged over three cardiac cycles. Pulse-transit time (T) of the carotid to iliac artery was determined, and PWV was calculated as Distance (D)/Time (T), where D = the distance from the carotid to the iliac notch and T = (R to iliac foot) - (R to carotid foot). EaI was subsequently determined from pressure volumes loops obtained via left ventricle catheterization.ResultsPWV and EaI were found to be significantly faster in the older rats (13.2 ± 2.0 vs. 8.0 ± 0.8 m/sec, p < 0.001; 120 ± 20 vs. 97 ± 16 mmHg/μl/g, p <0.05). Bland-Altman analyses of intra- and inter-observer measures demonstrate a statistically significant relationship between readings (p < 0.0001). PWV and EaI measurements were found to be significantly and positively correlated with a correlation coefficient of 0.53 (p < 0.05).ConclusionOur study suggests that isoflurane administration does not limit Doppler PWV or EaI measures in their ability to provide accurate, in vivo assessments of relative arterial stiffness in isoflurane anesthetised SHR rats. Furthermore, PWV data obtained in these rats correlate well with invasively determined EaI.
Highlights
Decreased arterial elasticity, which results in increased stiffness of the central elastic arteries such as the aorta, is the primary cause of increased systolic pressure with advancing age and is a powerful independent predictor of cardiovascular disease, mortality and morbidity [1,2,3]
The goals of this study were 1) to determine if known differences in arterial stiffness could be detected by pulse wave velocity (PWV) using conventional ultrasound equipment and by elastance index (EaI) measurements made in Spontaneously Hypertensive Rat (SHR) isoflurane anesthetized rats, and 2) to determine if the non-invasively obtained Doppler PWV assessment of arterial elasticity correlates with the invasively determined EaI obtained under isoflurane anesthesia
We conclude that color-flow Doppler is very helpful in acquiring high quality pulse waves that allow for reproducible calculation of PWV, and that measurement of Doppler derived PWV provides an effective assessment of relative arterial stiffness in isoflurane anesthetized SHR rats
Summary
Decreased arterial elasticity, which results in increased stiffness of the central elastic arteries such as the aorta, is the primary cause of increased systolic pressure with advancing age and is a powerful independent predictor of cardiovascular disease, mortality and morbidity [1,2,3]. Rodent models are increasingly being utilized to study the development and progression of arterial stiffening, and both the non-invasive Doppler derived pulse wave velocity (PWV) and the invasively determined effective arterial elastance index (EaI) have been used to assess arterial stiffness in mice and rats [4,5,6,7,8,9,10,11,12,13]. Rodent models are increasingly used to study the development and progression of arterial stiffness Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. We sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive rats (SHR) are detectable by PWV and EaI measurements when made under isoflurane anesthesia, and 2) if these two uniquely acquired assessments of arterial elasticity correlate
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