Interleukin-1β blockade improves left ventricular systolic/diastolic function and restores contractility reserve in severe ischemic cardiomyopathy in the mouse
S Toldo, E Mezzaroma, E Bressi… - Journal of …, 2014 - journals.lww.com
Journal of cardiovascular pharmacology, 2014•journals.lww.com
Background: Interleukin-1β (IL-1β) modulates the inflammatory response during acute
myocardial infarction (AMI) and progression to ischemic cardiomyopathy. We investigated
whether blockade of IL-1β after the onset of the cardiac dysfunction prevented left ventricular
(LV) adverse remodeling in a mouse model of anterior nonreperfused AMI. Methods: Infarct
size and LV systolic function were assessed by echocardiography 7 days after coronary
artery ligation. Mice with large infarct size and LV ejection fraction (LVEF)< 40% were …
myocardial infarction (AMI) and progression to ischemic cardiomyopathy. We investigated
whether blockade of IL-1β after the onset of the cardiac dysfunction prevented left ventricular
(LV) adverse remodeling in a mouse model of anterior nonreperfused AMI. Methods: Infarct
size and LV systolic function were assessed by echocardiography 7 days after coronary
artery ligation. Mice with large infarct size and LV ejection fraction (LVEF)< 40% were …
Abstract
Background:
Interleukin-1β (IL-1β) modulates the inflammatory response during acute myocardial infarction (AMI) and progression to ischemic cardiomyopathy. We investigated whether blockade of IL-1β after the onset of the cardiac dysfunction prevented left ventricular (LV) adverse remodeling in a mouse model of anterior nonreperfused AMI.
Methods:
Infarct size and LV systolic function were assessed by echocardiography 7 days after coronary artery ligation. Mice with large infarct size and LV ejection fraction (LVEF)< 40% were randomly assigned to treatment with a monoclonal antibody directed toward IL-1β antibody (10 mg/kg IL-1β-AB) or with a cyclosporine directed antibody (10 mg/kg control-AB). Echocardiogram was repeated after 10 weeks, followed by assessment of contractile reserve using isoproterenol challenge and LV catheterization.
Results:
After 10 weeks, control-AB–treated mice showed significantly increased LV end-diastolic diameter (+ 15%, P< 0.001) and decreased LVEF (− 18%, P= 0.050). IL-1β-AB had no significant effect on LV end-diastolic diameter (+ 10%, P= 0.25 vs. control-AB) but significantly prevented LVEF reduction (+ 7%, P= 0.031 vs. control-AB), enlargement of the right ventricle (P= 0.024), impairment in myocardial performance index (P= 0.028) and contractile reserve (P= 0.008), and increased LV end-diastolic pressure (P= 0.030).
Conclusions:
IL-1β blockade using a monoclonal antibody in mice with severe LV dysfunction after AMI prevents further deterioration in LV systolic and diastolic function and restores contractile reserve.
Lippincott Williams & Wilkins