Study On Echocardiographic Methodology In Wistar Rat

Objectives: The aim of this study was to evaluate the feasibility andaccuracy of echocardiographic examination of both cardiac structure and function inthe rat. The study also measured normal reference value for both cardiac structureand function on various age rats, and revealed the pattern of age-associated changesin cardiac structure and function in the rat.Methods: Specific pathogen-free Wistar rats were obtained from Tianjinexperimental animal center, at 4(n=12), 8(n=12), 20(n=12), 48(n=12), 72(n=12)weeks of ages. Rats weight were measured. All parameters of both cardiac structureand function were determined by color Doppler echocardiography with synchronousrecord of leadⅡelectrocardiogram. Each parameter was assessed from 3 to 5cardiac cycle to calculate average value. Rats also underwent hemodynamicsanalysis to determine left ventricular maximal rate of pressure rise and decline(+dP/dtmax and-dP/dtmin), LVEDP, and LVESP. At the end of study, rats wereanesthetized and sacrificed, the hearts were removed, and left ventricular mass wasmeasured, and then histopathologic study was performed with routine HE stained.Results:1. All images of 2-DE, M mode, color Doppler spectrum, and blood flow couldbe easily obtained by echocardiography, and Doppler frequency color spectrum ofmitral inner annulus pattern could be clearly obtained by tissue Doppler imaging inmore than 90％rats.2. The rat weight increased with age, the body weight increased from fourth toeighth weeks of age is the most rapid growing phase, weight increased 3.24-fold. 20to 48 weeks of age was persistent growth and 48 to 72 weeks of age, body weighttends to increase, however no statistics significant. Compared with 4 weeks group,LV mass index declined with age. Left ventricular myocardial weight in ratsnecropsy was increased following by age, the most rapid weight increased was in 4to 8 weeks of age, increased 3.6 fold, and the heaviest was in 72 weeks of age (1.27±0.06g). In addition, using 2D area-length and M mode method, leftventricular myocardial weight was increased following by age, however no statisticssignificance between 48 weeks and 72 weeks group. Positive correlation between2D area-length examination with the rats necropsy weight results (r=0.909) wasbetter than between M mode method with the rats necropsy weight results (r=0.780).3. Left atrial and right atrial dimensions were increased with age, and thelargest was in 72th week of age. In present study, there is a highly significantincrease between 4 and 8 weeks of age in aortic root diameter and pulmonary arterydiameter, no significant difference between 8 and 20 weeks of age, and slowlysignificant increased between 20 and 48 weeks of age, however no statisticssignificant difference between 48 and 72 weeks of age. LVEDD, IVS, and LVPWthickness were increased with age, however no statistics significant between 20, 48,and 72 weeks groups.4. The comparison of left ventricular systolic and diastolic function between 5groups; no differences were found in HR, EF％, and FS％in all groups afteranesthetic. SV and CO were significantly greater in the 8 weeks group compared to4 weeks group, and the greatest was in 72 weeks of age, however no statisticssignificant between 20, 48, and 72 weeks group. V_E increased from 4 weeks(0.67±0.13 m/s) to 8 weeks (0.89±0.17 m/s) of age and no significance differencesbetween 8 and 20 weeks group. Mitral inner annulus tissue Doppler imaging, Eapeak value initially increased after 8 weeks of age and then slowly decreased withage, however Aa peak value was tendency increased following by age. Ee/Aaratio＞1 at 4, 8, and 20 weeks group, conversely Ee/Aa ratio＜1 at 48 and 72 weeksgroup.5. Left ventricular end systolic pressure was no significant differences between8, 20, 48 and 72 weeks group; left ventricular end diastolic pressure wassignificantly increased from 20 to 72 weeks of age, however no statistics significantbetween 4, 8, and 20 weeks group.6. There is a highly positive correlation between EF％and FS％examined byechocardiography with+dP/dtmax and LVSP examined by hemodynamics analysis;and also between VE, IVRT, and Ea with -dP/dtmin.7. There is a negative coeeelation between left atrial dimension (LAD) with Ea and Ea/Aa ratio (r=-0.543, r=-0.473), and a positive correlation between LAD andAa (r=0.356).8. Histopathologic analysis demonstrated focal fibrosis in the endocardium leftventricular of 72 weeks group and there was no clearly fibrotic process at 4 weeks to48 weeks of age.Conclusions:1. High frequency transthoracic echocardiographic approach has a greatfeasibility to obtain the high quality of cardiac imaging and measure manyparameters of both cardiac structure and function in experimental rats.2. The result of non-invasive high frequency transthoracic echocardiographyexamination was associated with invasive hemodynamics method result. It showedthat non-invasive rat echocardiographic has a great accuracy, therefore can replaceinvasive method to evaluate cardiac function of rats.3. Cardiovascular system of normal rats was changed following by age andweight increasing, and there was a series of changing in cardiac structure, 4 to 8weeks of age was a relative rapid growth phase, 8 to 48 weeks of age was apersistent growth phase, and 48 to 72 weeks of age was a relative slow growthphase.4. We did not find age-related changes in left ventricular systolic function,nevertheless there was a significant decreased in left ventricular diastolic function at48 and 72 weeks of age rats that was examined by tissue Doppler imaging.5. Focal fibrosis and reduce in cardiomyocytes were found at 72 weeks of agein normal rats. It showed that for that moment, rats have coincided tosenescence-period.