An Investigation Of The Relationship Between Left Ventricular Myocardial Collagen And Systolic Deformation In Spontaneously Hypertensive Rats

Backgrounds and ObjectivesMyocardial fibrosis is known to be related to the development of cardiacdysfunction in hypertension. Our previous studies found an age-related trend in leftventricular geometry, myocardial contractile properties and its interstitial collagenaccumulation in spontaneously hypertensive rats (SHR), where myocytes hypertrophyand collagen deposition appear after28weeks of age and might be correlated to thefollowing impaired contractile properties and diastolic function. In this part, we observedthe distribution of myocardial collagen in different area (subendocardial andsubepicardial myocardium) and its relationship with the myocardial multi-dimensionaldeformation and global left ventricular function in SHR from12to84weeks of age, toexplore the importance of myocardial collagen accumulation in the development ofcardiac dysfunction in hypertension.MethodsSHR and WKY rats were randomly divided into several groups,8-10for each group,experiments were performed at different weeks (from12to84wk).①Echocardiographicmeasurements included LV and LA diameter, relative wall thickness(RWT) and leftventricular mass index(LVMI), LVEF and FS, transmitral diastolic inflowvelocities(E,A).②2-dimensional strain echocardiography (2DSE) measurementsincluded end-systolic LV longitudinal strain (SL),radial strain (SR) and circumferentialstrain (SC).③histological measurement included myocardial collagen volume fraction(CVF) in subendocardial and subepicardial myocardium, Perivascular collagen area(PVCA).④Invasive parameters included left ventricular end-diastolic pressure (LVEDP)and LV±dp/dtmax.⑤Linear correlation of the cardiac function, myocardial collagen andsystolic deformation. Results1. left ventricular index: SHR kept in high blood pressure, diastolic pressurecontinuely increased from45wk of age (p<0.05); RWT and LVMI increased with age,significantly higher at28and36wk respectively and then reached the highest at75-84wks (p<0.05), both of which were different from WKY group after75wk (p<0.05);LVEF decreased at75wk (p<0.05); LAD increased at45wk (p<0.05).2.2DSE index: SL, SC and SR of SHR progressively increased from12to28wks,reaching the highest at28wk(p <0.05), SL declined at45wk (p <0.05), while SC、SRdecreased at75wk (p <0.05), all reached the minimum at84wk (p <0.05); Comparedwith WKY group, SL, SC and SR of SHR were significantly lower during75-84wks (p<0.05), at the same time, LVEF decreased (p <0.05).3.Histologic index: CVF、PVCA in SHR increased with age, CVF in subendocardialmyocardium significantly higher than in subepicardial myocardium from66wk and thedifference became much bigger in75wk (p<0.05), CVF in in subendocardial andsubepicardial myocardium significantly increased at the age of66and75-84wksrespectively（p<0.05）, PVCA also increased at66wk（p<0.05）;Compared with controlgroup, CVF and PVCA only had the trend of increasement at36wk （p>0.05）,significantly increasement appeared at75-84wks in SHR(p <0.05).4. Cardiac catheterization index: In SHR, LV±dp/dtmaxprominently increased at28wk (p<0.05), and significantly decreased at75wk (p<0.05), whereas LVEDP increaseduntil45wk and prominently higher than the WKY rats(p<0.05).5. Linear correlation analysis: SL and CVF in subendocardial myocardium showed anegatively correlation(r=-0.47,p=0.002), however SL showed no obvious correlation withCVF in subepicardial myocardium; SR、 SC and CVF in subendocardial myocardiumshowed a negatively correlation (value-0.37~-0.41, p<0.05), LVEDP was alsoassociated with CVF (r=0.57, p <0.01). Conclusions1. Collagen accumulation in myocardium appears from28week of age in both SHRand WKY rats, which may be an age-related changes；Pathological myocardial fibrosisconcerned with hypertension begins at66week in SHR, with the accumulation ofperivascular collagen and interstitial collagen developing from endocardium toepicardium.2. The development of pathological myocardial fibrosis in SHR correlates with theprogression of damaged multi-dimensional systolic strian and the later destroyed cardiacfunction, where longitudinal strain decreases firstly and LVEF declines when alldirections of myocardial strain reduced, which could provide a myocardial mechanicaland pathological basis for the investigation of the development of hypertensive cardiacdysfunction.