Serial Cardiac Function in Aging and Obese Mice
In response to new research initiatives, we have developed the expertise to serially monitor cardiovascular function in aging and obese mice which require more post-operative and peri-procedural care to allow serial survival monitoring.
Functional studies serially assess cardiac function (Medrano et al, 2016) in aged mice treated either with various agents or with vehicle (control) for extended time (one to three months, but longer is possible if needed). At time zero, non-invasive measurements of “baseline” cardiac function and structure using echo and Doppler are performed under 1% isofluorane anesthesia. Then mice are randomly allocated to treatment and control groups. Animals undergo by 2D echocardiography (Vevo 770 RMV-707B 30-MHz probe, VisualSonics) and Doppler (DSPW, 10-MHz) measurements (Cieslik et al, 2011; Haudek et al, 2010) every month to identify potential changes in cardiac function. Quantitation of LV function and structure are done with two-dimensionally guided M-mode images from parasternal short-axis views at the midpapillary level. We use left atrial volume as a structural indicator of elevated LV end diastolic pressures. Left atrial dimensions are collected to obtain the chamber volume using prolate ellipse: LA Volume = (4π x D1 x D2 x L)/(3x2x2x2). Cardiac aging is characterized by measuring systolic parameters (LVID, LVPW thickness, LV Volume, Cardiac Output, Peak Aortic Velocity) and diastolic parameters (E-Peak Velocity, E/A Peak Velocity ratio, Isovolumic Relaxation Time and LA Volume) correcting these for heart rate. The Doppler mitral flow velocity envelope is analyzed using a parametric model that allows discrimination of stiffness from viscoelastic elements. This approach allowed us to quantitate the fibrosis contribution in the aged mouse heart. It is essential to note that each mouse will serve as its own control.
First, we assessed cardiac function in the aging mouse heart (Cieslik et al, 2011; Trial et al, 2017), then we started to examine heart function in response to various treatments where each animal serves as its own control (Cieslik et al, 2013; Cieslik et al, 2018).