Strikingly, FFFF I/R mice showed a progressive deterioration of cardiac function from 2 to 4 weeks post-surgery, while this functional impairment was ameliorated in DKO mice after 4 weeks (Fig 5B).
Cellular electrophysiological remodeling of the infarcted heart may lead to the deterioration of cardiac function and/or to arrhythmias.
We have also shown that injection of the biopolymer fibrin glue preserves left ventricular geometry and prevents a deterioration of cardiac function following myocardial infarction.
Sustained sympathetic activation leads to further deterioration of cardiac function through a variety of mechanisms including stimulation of cardiomyocyte apoptosis [12], direct toxicity to cardiomyocytes [13], and induction of ventricular dysrhythmias [14].
After prolonged HFD (16 20 weeks), these phenotypes are much more pronounced and accompanied by other severe metabolic dysregulation including dyslipidemia & ectopic triglyceride storage, hypo-adiponectinemia, adipose tissue hypoxia, cell death and remodeling, beta-cell decompensation, mild hyperglycemia, and deterioration of cardiac function [7], [8], [11].
After 16 20 weeks of HFD, these phenotypes are much more pronounced and additional severe metabolic dysregulations are present including dyslipidemia & ectopic triglyceride storage, hypo-adiponectinemia, adipose tissue hypoxia, cell death and remodeling, beta-cell decompensation, mild hyperglycemia, and deterioration of cardiac function [4] [6].
Let-7 inhibition prevented deterioration of cardiac functions compared to control treatment which was especially due to improvements in the infarcted, apical cardiac segments.
Concurrently, mutants experience impairment of cardiac function.
A 10%% decline of the left ventricular ejection fraction (LVEF) below the lower limit of normal or an absolute decline of 45%% or decline of 20%% at any level is indicative of cardiac function deterioration.
Cardiac death occurs after irreversible cessation of cardiac function.
Second, "irreversible cessation" of cardiac function meant that at least five minutes had to pass without a heartbeat.
