Myocardial Infarction in a Murine Model of Cardiac Sympathetic Hyperactivity

Background: Dysautonomia is one of the main pathophysiological mechanisms that define the prognosis of ischemic heart disease and heart failure.The search for new treatment opportunities requires a deeper understanding of the cardiac effects of chronic sympathetic activation.Objective: The aim of this study was to analyze left ventricular infarct size and ventricular function in a transgenic mouse model with overexpression of the cardiac Gs- protein, in the context of myocardial ischemia/reperfusion and chronic infarction.Methods: Transgenic mice (TG) overexpressing cardiac Gs- and wild-type (WT) mice were subjected to 30-minute regional myocardial ischemia followed by 2-hour reperfusion (IR), or non-reperfusion (I) with a 28-day follow-up period.Infarct size (IS) was quantified using 2,3,5-triphenyltetrazolium chloride, and left ventricular function was evaluated by echocardiography and hemodynamic study.Each experimental group was accompanied by a control group (WT/TG Sham-2hrs and WT/TG Sham-28d).Results: There were no significant differences in IS after IR between TG and WT mice (57.3 3.5% vs. 59.2 2.5%, respectively, p = NS).A significant increase in heart rate was evident in TG mice throughout the protocol.A decrease in ejection fraction (WT: Sham-28d: 82 2.4% vs. I-28d: 44 4% and TG: Sham-28d 89 2% vs. I-28d 42 3%; p < 0.05) was observed together with a decrease in shortening fraction and left ventricular fractional area changes compared with baseline values and their respective control (Sham) groups.However, no differences were observed between the WT and TG groups.Conclusions: Cardiac G s - protein overexpression does not increase infarct size or modify left ventricular function in acute ischemia/ reperfusion and chronic infarction compared with their respective controls.