Echocardiographic integrated backscatter for assessing reduction of aortic valve calcifications by R-568 in a rat model of chronic kidney disease.

Chronic kidney disease (CKD) and secondary hyper-parathyroidism are associated with calcific aortic valve disease (CAVD). Innovative modalities for imaging CAVD are warranted. Our aim was to use echocardiographic calibrated integrated backscatter (cIB) to quantitatively determine the preventive effect of the calcimimetic R-568 on CAVD in a CKD rat model, and to compare the results with those of micro-computed tomography and histology. Thirty-six male Wistar rats were followed for 7 wk. Rats were divided into four groups with respect to treatment: (1) adenine 0.5% to induce CKD + vehicle; (2) adenine + R-568 (30 mg/kg/d); (3) control, normal diet + vehicle; (4) controls, normal diet + R-568. At week 7, cIB values of the aortic valve were significantly lower in R-568-treated group 2 than in vehicle-treated group 1. This was confirmed by the significantly lower calcified volume observed on micro-computed tomography and the calcified area observed on histology. There were no significant differences in fractional area change and aortic valve area between groups. In conclusion, echocardiographic cIB was able to quantitatively assess a reduction in CAVD by R-568 in a rat model of CKD.

Echocardiographic integrated backscatter for detecting progression and regression of aortic valve calcifications in rats.

BACKGROUND: Calcification is an independent predictor of mortality in calcific aortic valve disease (CAVD). The aim of this study was to evaluate the use of non-invasive, non-ionizing echocardiographic calibrated integrated backscatter (cIB) for monitoring progression and subsequent regression of aortic valvular calcifications in a rat model of reversible renal failure with CAVD, compared to histology. METHODS: 28 male Wistar rats were prospectively followed during 21 weeks. Group 1 (N=14) was fed with a 0.5% adenine diet for 9 weeks to induce renal failure and CAVD. Group 2 (N=14) received a standard diet. At week 9, six animals of each group were killed. The remaining animals of group 1 (N=8) and group 2 (N=8) were kept on a standard diet for an additional 12 weeks. cIB of the aortic valve was calculated at baseline, 9 and 21 weeks, followed by measurement of the calcified area (Ca Area) on histology. RESULTS: At week 9, cIB values and Ca Area of the aortic valve were significantly increased in the adenine-fed rats compared to baseline and controls. After 12 weeks of adenine diet cessation, cIB values and Ca Area of group 1 decreased compared to week 9, while there was no longer a significant difference compared to age-matched controls of group 2. CONCLUSIONS: cIB is a non-invasive tool allowing quantitative monitoring of CAVD progression and regression in a rat model of reversible renal failure, as validated by comparison with histology. This technique might become useful for assessing CAVD during targeted therapy.

Occurrence of cardiovascular calcifications in normal, aging rats.

BACKGROUND: Cardiovascular calcification is an independent predictor of morbidity and mortality and increases with age. Animal models are frequently used to investigate the underlying pathophysiology. Only scarce data regarding the effect of aging on calcifications in these animal models are available. The aim of this study is to investigate the occurrence of cardiovascular calcifications in normal, aging rats. METHODS: A mixed inbred/outbred population of 44 male Lewis/Wistar rats was studied. Group 1 of three-month-old rats, group 2 twelve-month-old, group 3 twenty-four-month-old and group 4 thirty-month-old rats. Calibrated integrated backscatter (cIB) values and blood parameters (creatinine, parathyroid hormone (PTH)) were measured, followed by ex-vivo micro-CT and histology as reference methods. RESULTS: Cardiovascular calcifications developed with age, as demonstrated by significantly increasing cIB values of the aortic valve and myocardium. This was confirmed by a significant increase in the calcified volume on ex-vivo micro-CT and in the histological calcium score. There was also a significantly higher level of creatinine and PTH with age. CONCLUSIONS: As in humans, cardiovascular calcifications progressively increase with age in the normal rat. Therefore the aging rat model could be used for studying calcifying cardiovascular disease. cIB might have a value in future studies for the early detection of subclinical calcifications in humans.

Integrated backscatter for the in vivo quantification of supraphysiological vitamin D(3)-induced cardiovascular calcifications in rats.

Cardiovascular calcifications are frequently found in the aging population and are independent predictors of future cardiovascular events. Integrated backscatter (IB) of ultrasound reflectivity can easily quantify calcifications. For this purpose, 30 male Wistar rats received 25,000 IU/kg/day of vitamin D(3) (group 1, n = 8), 18,800 IU/kg/day (group 2, n = 8), or injections with the vehicle only (group 3, n = 14), for 10 weeks. Echocardiographic calibrated IB (cIB) was measured and calculated at baseline and after 10 weeks, followed by ex vivo micro-CT and histopathology of the aortic valve, ascending aorta, and myocardium. After 10 weeks, the mean cIB value of the aortic valve was significantly higher for vitamin D(3)-dosed animals compared to controls. The mean cIB value of the ascending aorta and the myocardium was also significantly higher in group 1 compared to group 3. In vivo IB results were confirmed by ex vivo micro-CT and histopathology. In conclusion, IB is a non-ionizing, feasible, and reproducible tool to quantify cardiovascular calcifications in an in vivo rat model. The integration of IB in the standard echocardiographic examination for the quantification of cardiovascular calcifications could be useful for serial evaluation of treatment efficacy and for prognosis assessment.