Abstract 311: Single-Dose Isoproterenol does not Depress Cardiac Function in Mice
Rationale: Myocardial injury after repeated or continuous administration of isoproterenol (ISO) in preclinical models has been widely described in the literature by our lab and others. Recent controversial reports using a one-time dose of ISO, to mimic a Takotsubo-like cardiomyopathy, demonstrated pronounced and reversible depression of cardiac function at one-week post injection with widespread myocyte death followed by robust myocardial regeneration and recovery of cardiac function.
Hypothesis: Single-dose ISO does not produce depression of cardiac function
Methods and Results: C57Bl/6 mice were given a single subcutaneous injection of vehicle (saline) or 5, 200, or 300 mg/kg of ISO. Cardiac function was measured using transthoracic echocardiography with cardiac strain analysis at baseline prior to ISO injection and after 1, 7, 14, and 28 days post-injection. Animals were sacrificed after 1, 7, and 28 days post-injection for evaluation of gross heart weight (HW), HW/body weight (BW) and HW/tibia length (TL). Left ventricular (LV) functional measurements revealed no significant differences in global systolic function (ejection fraction and fractional shortening) between vehicle- or ISO-treated animals at any concentration. Additionally, no significant differences were detected between vehicle- or ISO-treated animals in any cardiac dimensions measured by echocardiography (LV cross-sectional area, internal diameter, end-diastolic or end-systolic volumes) or in gross HW, HW/BW or HW/TL. LV global cardiac strain was also not significantly different between vehicle and ISO-treated animals at any time point. When apical regions of the LV endocardium (the area most predominantly affected by Takotsubo cardiomyopathy) were specifically examined using strain analysis, no significant differences could be detected between vehicle and ISO-treated animals at any time point.
Conclusion: Single-dose ISO injury in a mouse model does not produce any depression of cardiac function at 1 week post injection.
Author Disclosures: M. Wallner: None. J.M. Duran: None. S. Koller: None. S. Mohsin: None. S. Lis: None. T.E. Sharp: None. R.M. Berretta: None. S.R. Houser: None.
- © 2015 by American Heart Association, Inc.