Abstract 260: Time Course Observation of Left Ventricular Hypertrophy and Regression Induced by an Improved Technique

Abstract

In order to study the left ventricular hypertrophy (LVH) and its regression, we improved the surgical technique for producing LV pressure overload and its reversing mouse model using the titanium clip placement for transverse aortic banding (AB) and removal for debanding (DB). A time course study on heart function and histology proved the importance of the regression time. Materials and methods: The technique was applying titanium clip for AB and removing for DB with minimal invasion. A total of 95 male C57BL6 mice weighing 20-30 g were used in this study. Experimental groups included: control (n=11), AB 3 (11), 4 (12), and 6 (12) wks, DB at 3 (12), 4 (11), and 6 (12) wks of AB for 1 wk. Carotid arteries velocity were measured to evaluate the constrictive level. Heart/body weight ratio, cardiac wall thickness from echocardiography, LV pressure from catheterization and heart histology studies were used to evaluate the pressure overload and hypertrophy. Results: The echocardiographic and histology results indicated that AB induce significent LVH which was a concentric hypertrophy at AB 3 wks and then progressively become a dilated hypertrophy at AB 6 wks. The cardiac function also indicated a stable ejection fraction before 3 wks of AB and then gradually declined at AB 6 wks. After 6 wks AB, the enlargement in LV dimensions becomes significant. When deband at 3 and 4 wks for one week, there were significant regression of hypertrophy but the regression is limited after AB 6 wks and the evidences of lung congestion were apparent. In catheterizaiton, the LV systolic pressure were markedly elevated in AB mice but these pressure elevations became less at AB 6 wks and the LV end-diastolic pressure (LVEDP) at AB 6 wks was elevated significantly. After DB at AB 3 and 4 wks, the pressure parameters retriced close to normal but LVEPD elevation retreat is limited in the DB 6 wks group. Conclusion: With applying and removing titanium clip to induce pressure overload and reversing can provide a relatively simple, effecive, consistent and minimal invasive methods to establish the mouse model for studying LVH and its regression. Our data indicate that AB induced mouse LVH could be retriced close to normal when remove the constriction at the concentric LVH phase but the regression is limited in dilated LVH.