Quantitative Ultrasound Study, The Dogs Of Pacing In Heart Failure And Cardiac Hypertrophy In Rat Left Ventricular Early Diastolic Function

Part One Early detection of diastolic dysfunction using QTVI and STI in dogs with congestive heart failure due to rapid ventricular pacingObjectives:To observe the changes of left ventricular early diastolic dysfunction (LV-EDD) with rapid pacing induced congestive heart failiure(CHF) canine model by quantitative tissue velocity imaging(QTVI) and speckle tracking imaging(STI) techniques.Through observing the changes of each index during CHF,we are trying to find out some indices which are suitable for clinical diagnosis for early diastlic heart failiure.Methods:14 dogs were selcted with rapid right ventricular pacing(RVP) at 240 beats per minute for two weeks to serve as heart failure model.Echocardiography,cardiac catheterization,and endomyocardial biopsies were performed at baseline,during pacing,and at two weeks.Regular echocardiography,QTVI,STI,left ventricular(LV) pressures and myocardial pathology were observed and analyzed during the progressive development of diastolic dysfunction produced by RVP.The indices measured as follow:①Aortic blood pressure(ABP),mean blood pressure(MBP),LV end-diastolic pressure(LVEDP),the peak rates of LV pressure rise(LV +dp/dt_max) and decline(LV -dp/dt_max) by cardiac catheterization.②All dogs underwent standard 2D, M-mode and Doppler echocardiographic examinations with detailed evaluation of the left heart function,such as The left and right atrial diameters(LAD),interventricular septum and left ventricular post wall thickness,left ventricular stroke volume(SV) and ejection fractions (EF),isovolumetric relaxation time(IVRT),Tei index,peak early(E) and peak late(A) velocities of mitral inflow and the E/A ratio,etc.③The peak myocardial systolic(S'),early diastolic(E'),late diastolic(A'),isovolumetric relaxation(R),isovolumetric contraction(C) velocities and diastolic times indices were acquired from six mitral annular sites with QTVI. The times from the aortic valve closure(AVC) to R wave(Time-R) of ECG and to peak E' (Time-E') of mitral annulus were also measured by QTVI.④Longitudinal strain(LS), mean strain(MS),rotation,rotational rate(RR) and torsion were measured using STI.⑤The correlations were analyzed between echocardiographic parameters and LVEDP, -dP/dtmax and the receiver operating characteristic curve(ROC) analysis were analysed for sensitivity,specificity and cutoff value.Results:After about 2 weeks of rapid pacing,the heart function of all dogs was impaired.Postmortem examination showed heart chamber delatation,papillary muscle edema,mitral valve injure and mild pericardial effusion.Light and transmission electron micrographs demonstrate myocardial damages in the left ventricle due to RVP. LV-EDD was detected by a significant increase in LV end-diastolic pressure(LVEDP, 5.80±4.6 vs.35.00±8.1 mmHg),a significant decrease in the peak rates of LV pressure decline(LV-dp/dtmax,3.04±0.5 vs.1.80±0.3 kmmHg/s).LV-EDD was identified using QTVI in this model within 24 hours.The commonly used mitral annular QTVI parameters,such as Sm,Em,Am,as well as new parameters,such as Time-R,Time-E',S'/R and E'/R,were significantly changed during RVP and they were correlated with LVEDP and LV -dp/dt_max.The new parameters of Time-R and Time-E' were delayed with RVP and S'/R and E'/R decreased with RVP.In addition,using ROC analysis,Time-R was shown to be the most powerful predictor of LV-EDD changes.The studies about speckle tracking imaging(STI) include five parts.①Longitudinal strain(LS) and mean strain(MS) parameters steadily decreased with RVP expecially MS.②Longitudinal strain rate(LSR) changed significantly with RVP,expecially peak early diastolic longitudinal strain rate(LSR-E).③During the progressive development of diastolic dysfunction induced by RVP,the trend of rotation degree at three short axis views was different.Rotation at mitral short axis view decreased and the rotation at apex failed significantly after 12 hours of RVP,but demonstrated a small increase after the second week of pacing.④The difference on time to peak rotation and rotation rate among the three short axis views were not significant and there was a sequential shortening from basal loop to apical loop. However,the time to peak rotation and rotation rate were delayed in heart failure dog with RVP.⑤There were close relations among LVEDP,-dp/dt_max and the indices of LPS,MS,LSR-E and rotation rate,etc.Conclusions:QTVI is a sensitive and specific quantitative method that can be used for the early detection of LV-EDD changes.The novel indices,including Time-R, Time-E',S'/R,and E'/R,can serve as effective,noninvasive LV-EDD markers.STI is a novel technique to assess LV diastolic function;MS,LSR,Rotation and Rotation rate are potential parameters to become clinical tool for quantifying LV diastolic function.Part Two Left ventricular diastolic dysfunction assessment by tissue Doppler imaging in a myocardial hypertrophy model of rat[Objective]To evaluate the left ventricular function of different myocardial hypertrophy rat models by Tissue Doppler Imaging(TDI) and to observe its feasibility and characteristics.[Methods]1.Thirty-five 14～16 weeks male rats were assigned to three group:spontaneously hypertensive rats(SHR)(n=15),Suprarenal abdominal aortic coarctation(SAAC) (n=10) and Wistar Kyoto rats(WKY)(n=10) as control.Tail-cuff blood pressure, heart rate and body weight were measured in all three groups.All rats underwent echocardiographic exam with TDI for left ventricular function evaluation.2.Thirty male Lewis rats(217±21.58g) at age of 8 weeks were used.Myocardial hypertrophy model was obtained by suprarenal abdominal aorta banding with ligation. Mitral annular velocity measurement by TDI and regular two-dimensional echocardiography with M-mode were examined at baseline and at 10-days,20-days, 30-days and 40-days post banding.[Results]1.Compared with WKY group,the left ventricular wall thickness of both SHR and SAAC were increased significantly(WKY:1.59±0.15 mm;SHR:2.11±0.25 mm; SAAC:2.32±0.25 mm;P＜0.01).The left ventricular end diastolic and systolic dimensions of SHR were the smallest in three groups.There were no significant changes of Eject Fraction and Fraction Shortening among the three groups(P＞0.05).2.The early diastolic filling wave(E) and late filling wave(A) of transmitral flow were increased while the E/A ratio was decreased in SHR group,but the fusion of E and A wave of transmitral flow occurred in some rats due to rapid heart rate.But it was not commonly fused with mitral annular tissue Doppler imaging of Ea and Aa at rapid heart rate(29%of TDI vs.63%of mitral inflow).3.The early and late diastolic peak velocity of mitral annulus(Ea and Aa) in myocardial hypertrophy rats were increased but their ratios(Ea/Aa) was decreased at the same time(WKY:1.18; SHR:0.85;SAAC:0.85;P＜0.01),and the ratio difference still existed even after the affection of heart rate was ruled out(P＜0.05).There were no significant difference of echocardiographic and TDI parameters between SHR and SAAC groups(P＞0.05).4.After suprarenal abdominal aorta banding in Lewis rat,compared with baseline,the left ventricular end diastolic and end systolic wall thickness and ventricular dimension were progressively increased,while eject fraction(EF) and fraction shortening(FS) were decreased(P＜0.01).The left ventricle demonstrated centrifugal myocardial hypertrophy.5.After suprarenal abdominal aorta banding in Lewis rat,the peak myocardial systolic velocity at the mitral annulus(Sa) did not change significantly throughout this study. There was no significant correlation with EF(r=0.216,P=0.071).The peak myocardial early diastolic velocity(Ea),late diastolic velocity(Aa) at the mitral annulus and Ea/Aa indices were also not stable after aortic banding and there were no significant difference in repeated measurements at with followup(P＞0.05).But the E/Ea was increased and the index had a statistically significant difference(P＜0.001). [Conclusions] 1.The left ventricle showed centricity myocardial hypertrophy in SHR and SAAC; and centrifugal myocardial hypertrophy in Lewis rats with abdominal aortic banding. 2.Mitral annular tissue Doppler imaging showed less fusion of Ea and Aa wave even at rapid heart rate compaired with mitral inflow of E and A waves. 3.The index of Ea/Aa of mitral annulus could demonstrate the early change of left ventricular diastolic dysfunction in hypertrophy rats;E/Ea radio was a sensitive and stable index to evaluate left ventricular diastolic dysfunction.