Genetically modified mice have created the need for accurate noninvasive left ventricular mass (LVM) measurements. Recent technical advances provide two-dimensional images adequate for LVM calculation using the area-length method, which in humans is more accurate than M-mode methods. We compared the standard M-mode and area-length methods in mice over a wide range of LV sizes and weights (62-210 mg). Ninety-one CD-1 mice (38 normal, 44 aortic banded, and 9 inherited dilated cardiomyopathy) were imaged transthoracically (15 MHz linear transducer, 120 Hz). Compared with necropsy weights, area-length measurements showed higher correlation than the M-mode method (r = 0.92 vs. 0.81), increased accuracy (bias +/- SD: 1.4 +/- 27.1% vs. 36.7 +/- 51.6%), and improved reproducibility. There was no significant difference between end-systolic and end-diastolic estimates. The truncated ellipsoid estimation produced results similar in accuracy to the area-length method. Whereas current echocardiographic technology can accurately and reproducibly estimate LVM with the two-dimensional, area-length formula in a variety of mouse models, additional technological improvements, rather than refinement of geometric models, will likely improve the accuracy of this methodology.

The application of left ventricular pressure-volume analysis to transgenic mice to characterize the cardiac phenotype has been problematic due to the small size of the mouse heart and the rapid heartbeat. Conductance technology has been miniaturized for the mouse and can solve this problem. However, there has been no validation of this technique. Accordingly, we performed echocardiography followed by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD-1 mice. Raw conductance volumes were corrected for an inhomogenous electrical field (alpha) and parallel conductance (G(pi)) yielding a stroke volume of 14.1 +/- 3.7 microliter/beat, end-diastolic volume of 20.8 +/- 6.5 microliter, and end-systolic volume of 9.0 +/- 5.8 microliter. The mean conductance volumes were no different from those derived by flow probe and echocardiography but did differ from ultrasonic crystals. G(pi) was determined to be 14.9 +/- 8.7 microliter. However, hypertonic saline altered dimension and pressure in the mouse left ventricle. Although G(pi) can be determined by the hypertonic saline method, saline altered hemodynamics, questioning its validity in the mouse. Although mean measures of absolute volume may be similar among different techniques, individual values did not correlate.

Research shows that certain antihypertensives taken during midlife confer Alzheimer’s disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including CSF amyloid β levels (Aβ) and ACE activity, arterial function and cognition in participants with a parental history of AD. This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier (BBB) crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E ε4 (APOE ε4) status and randomized to receive 5mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Aβ1–42 and ACE activity, arterial function and cognition. Participants were middle-aged (mean 54yrs) highly educated (mean 15.4yrs), and included 50% men and 50% APOEε4 carriers. While results did not show a treatment effect on CSF Aβ1–42 (p=0.836), data revealed that ramipril can inhibit CSF ACE activity (p=0.009) and improve blood pressure (BP), however there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved BP, but did not influence CSF Aβ1–42. While larger trials are needed to confirm our CSF Aβ results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of Angiotensin II-mediated inhibition of acetylcholine.

In middle-aged adults free of known cardiovascular disease, TPA but not grayscale plaque features was associated with CVD risk factors and predicted incident CHD events. For CHD, prediction indices for TPA were similar to carotid plaque score but less than for CAC.

These findings support the potential use of the ultrasound texture contrast for evaluating arterial injury and CVD risk. Advances in knowledge: This paper contributes to the literature in that it describes how the greyscale texture feature "contrast" is related to CVD risk factors.

Background We hypothesized that measures of common carotid artery echolucency and grayscale texture features were associated with cardiovascular disease ( CVD ) risk factors and could predict CVD events. Methods and Results Using a case‐cohort design, we measured common carotid artery ultrasound images from 1788 participants in Exam 1 of the MESA study (Multi‐Ethnic Study of Atherosclerosis) to derive 4 grayscale features: grayscale median, entropy, gray level difference statistic‐contrast, and spatial gray level dependence matrices‐angular second moment. CVD risk factor associations were determined by linear regression. Cox proportional hazard models with inverse selection probability weighting and adjustments for age, sex, race/ethnicity, CVD risk factors, and C‐reactive protein were used to determine if standardized values for grayscale median, entropy, gray level difference statistic‐contrast, and spatial gray level dependence matrices‐angular second moment could predict incident coronary heart disease, stroke, and total CVD events over a median 13 years follow‐up. Participants were mean ( SD ) 63.1 (10.3) years of age, 52.6% female, 32.1% white, 27.8% black, 23.3% Hispanic, and 16.8% Chinese. There were 283 coronary heart disease, 120 stroke, and 416 CVD events. Several associations of grayscale features with CVD risk factors were identified. In fully adjusted models, higher gray level difference statistic‐contrast was associated with a lower risk of incident coronary heart disease (hazard ratio 0.82, 95% CI 0.71–0.94, p adj =0.005) and CVD events (hazard ratio 0.87, 95% CI 0.77–0.98, p adj =0.018); higher spatial gray level dependence matrices‐angular second moment was associated with a higher risk of CVD events (hazard ratio 1.09, 95% CI 1.00–1.19, p adj =0.044). Conclusions Gray level difference statistic‐contrast and spatial gray level dependence matrices‐angular second moment predicted CVD events independent of risk factors, indicating their potential use as biomarkers to assess future CVD risk.

Echocardiographic diagnosis of myocardial ischemia is based on visualizing hypokinesis, which occurs late in the ischemic cascade. We hypothesized that temporal changes in endocardial motion may constitute sensitive early markers of ischemia. Two protocols were performed in 19 anesthetized pigs. Protocol 1 included 54 intracoronary balloon occlusions. Transthoracic images were acquired at baseline and every 15 s during 5 min of occlusion and reperfusion. In protocol 2, ischemia was induced in 12 animals by use of graded dobutamine infusion, after creating significant partial occlusions without a resting wall motion abnormality. Systolic and diastolic endocardial motion was color encoded using color kinesis and analyzed using custom software. All ischemic episodes caused detectable and reversible changes. The earliest sign of ischemia was tardokinesis in 31/54 occlusions, whereas hypokinesis appeared first in 23/54 cases. Dobutamine-induced ischemia caused tardokinesis first in 9/12 and hypokinesis in 3/12 animals. Reversible ischemic changes in regional left ventricular performance can be objectively detected using analysis of echocardiographic images and will likely improve the early noninvasive diagnosis of acute ischemia.

The effects of septic shock (endotoxin; EDTX) on arterial mechanical properties were studied in anesthetized rabbits, both in the absence (EDTX alone) and presence (EDTX + fluids) of fluid resuscitation. Aortic pressure-flow (n = 20) and pressure-diameter (n = 10) measurements were used to calculate systemic arterial and regional aortic mechanical properties. At 3 h of EDTX shock, EDTX-alone rabbits had elevated total peripheral resistance (TPR, + 30%, P < 0.05), reduced cardiac output (CO, -40%, P < 0.05), and increased aortic characteristic impedance (Zc, +78%, P < 0.05). In contrast, the EDTX + fluids group responded with decreased TPR (-30%, P < 0.05), a tendency to increase CO (+23%), and elevated Zc (+46%, P < 0.05). A reduction in aortic diameter (-20%, P < 0.05) and an increase in elastic modulus (+50%, P < 0.05) and water content (+23%, P < 0.02) of the aortic wall were observed following endotoxemia. Thus following EDTX 1) "hyperdynamic" septic shock profile (i.e., low TPR, high CO) was observed only when concomitant fluid replacement was provided, 2) aortic wall stiffening was present due to both increased smooth muscle tone and vessel wall edema, and 3) fluid resuscitation resulted in discordant changes in TPR and Zc, suggesting differential flow-induced vasodilation between arteriolar and aortic smooth muscle.