Establishment And Study Of Rat Left Ventricular Hypertrophy Regression Model Through Small Incision On The Suprasternal Fossa

Background and objectivesMyocardial hypertrophy induced by pressure overload is one of the important causesof heart failure and sudden cardiac death. As the clinical common causes of pressureoverload, aortic stenosis and hypertension can induce persistent pathological changes ofcardiac hypertrophy, which may not be effectively reversed by drug intervention onhypertension and aortic valve replacement, and eventually result in heart failure. Previousstudies indicate us that it is not enough to focus on relieving the pressure load, so a series ofinnovative researches directing against molecular pathogenesis are carried out in full swing.But few studies are conducted to explore changes of left ventricular hypertrophy and leftventricular function effects when removing the pressure load completely.Therefore, it is essential to establish an ideal model about left ventricular hypertrophyand its reversed condition, which well mimics the typical changes during the left ventricularpressure overload-unloaded process, to study the possible molecular pathogenesis. Previousresearches tend to complete pressure overload inducing left ventricular hypertrophy byligating abdominal aorta. Also it is generally supposed that the closer to heart ligation sitegets, the better of effects. Ascending aorta and aortic arch coarctation model whichappeared in recent years is relatively rare and always needs artificial ventilation support.The aortic arch’s ligation would induce unwanted pressure rises of right brain and rightlimbs, which will change the collateral circle and reduce afterload as a consequence, and ofcourse, trachea intubation would induce serious complications, not to mention thecomplicated protocol of accomplishing small animals’ tracheal intubation.The present studies are designed to explore a steady animal model of left ventricularhypertrophy with simple, less-invasive and reproducible features via ligating supravalvularaortic without artificial ventilation. And as it should be, the structure-function patterns arecautiously observed by means of various methods at different time-point in differentgroups. Methods1. The experimental animals were randomized3times in turn and assigned to5groups:sham-operated group (sham group),3weeks of aortic banding(AB)group (AB8W group),9weeks of AB group (AB9W group),15weeks of AB group (AB15W group), earlydebanding (DB) group (3weeks of AB followed by6weeks of DB), late DB group (9weeks of AB followed by6weeks of DB).2. After intraperitoneal injection anesthesia induction, the animals underwent aorticbanding marked by the isolated thymocytes through small incision on the suprasternal fossawithout artificial ventilation. Which leads to an approximate50%reduction in ascendingaorta. Sham-operated rat underwent similar surgery without AB. The animals allocated toLVH reversal groups were subjected to the second operation to cut the silk suturesurrounding the aortic arch3weeks or9weeks after the initial banding surgery.3. Transthoracic echocardiography was performed before surgery and3,6,9,12,15weeks after surgery for animals subjected to AB and3,6weeks for animals subjected toDB.4. Hemodynamic assessment was examined for each group at the last time point.5. At the time of death, body weights and left ventricle (LV) weights were obtainedafter rats were sacrificed. Then the LV was saved in-80℃refrigerator. Elisa technologywas used to test the collagen I and collagen III of the LV for each group at the last timepoint.6. The samples of left ventricular myocardium were obtained for HE staining andSirius red picric acid staining to observe the cell morphology and collagen content.Result1. The model of promoting LVH regression in rat was successfully developed withoutartificial ventilation. The overall mortality rate was11.8%.2. Echocardiography examination informed us:(1)3weeks after surgery, the leftventricle in banding group, which was different from sham-operation group, exhibitedobvious concentric hypertrophy. Significant difference of the data on LVPW and IVS wereobserved. And the above indicators showed a slight upward trend on6,9weeks aftersurgery.(2)15weeks later, the symptom of decompensated heart failure appeared inbanding group rats. The left ventricular ejection fractions decreased dramatically.(3) After band removal, most parameters changed into the direction of baseline during the following6weeks period. There were significant differences in every echocardiograp-hic parameterbetween early DB and late DB group.(4)The LVPW、IVS descend to the baseline after3weeks of DB, but the LVEDd and LVESd descend to the baseline after6weeks of DB inearly DB group. The above parameters also improved in late DB group, but still differencecompared to sham-operated.3. Compared to sham-operated, LVSP、LVDP were increase in all AB group, There wassignificant difference in LVDP with AB15W and sham-operated, which Prompted a leftventricular failure. Release of pressure overload for6weeks resulted in a completenormalization of LVSP,+dp/dt max, and-dp/dt max in early DB group, but not late DBgroup.4. Elisa test informed us: LV collagen content was markedly elevated in AB group, thelonger AB the higher collagen content. There was no difference in collagen content betweenearly DB group and sham group, but not in late BD group.5. Histological examination by optical microscope in each AB groups showed myocyteand myofibrillar disarray, hypertrophy, and extensive interstitial fibrosis. After DB surgery,the LVH regressed significantly, and degree of reversal was more conspicuous in early DBthan late DB.Conclusions(1) These facts confirm that we can effectively establish rat LVH regression modelthrough this modified method with simple, less-invasive features.(2)LVH soon appeared inAB group; LVH regression appeared after DB, and is associated with duration of pressureoverload, the length of DB time and collagen content.(3)The advantage of this model issimple, less-invasive and reproducible. Ultimately, this study will facilitate the study ofmolecular mechanisms about left ventricular hypertrophy regression.