Abstract 19203: LCZ696 Reduces Myocardial Infarct Size in a Rodent Model of Acute Myocardial Injury in the Setting of Hypertension
Introduction: LCZ696, equimolar valsartan and sacubitril, is the first angiotensin receptor neprilysin inhibitor (ARNi) treatment for heart failure (HF). LCZ696 blocks the renin-angiotensin-aldosterone system (RAAS) at the level of the type 1 angiotensin 2 receptor (AT1R) and augments the natriuretic peptide system (NPS) by inhibiting neprilysin (NEP). These pathways are affected during the neurohormonal progression of HF as well as acute myocardial injury (AMI). However, the effect of LCZ696 on AMI has not been evaluated.
Purpose: To evaluate the effects of acute LCZ696 administration at the time of reperfusion on myocardial infarct size and myocardial damage during AMI in the setting of hypertension.
Methods: Male spontaneously hypertensive rats (SHR) at 16-20 weeks old were subjected to 30 minutes of left coronary artery ligation followed by 24 hours of reperfusion. Five minutes prior to reperfusion, LCZ696 (n=7) or vehicle saline (n=7) was administered via intracardiac injection into the left ventricular (LV) cavity. Plasma was collected 4 hours post-reperfusion for cardiac troponin (cTn-I) measurement and at 24 hr post-reperfusion LV area-at-risk (AAR) and infarct analysis was performed.
Results: LCZ696 significantly reduced circulating troponin levels and myocardial infarct per AAR. Infarct size within the AAR was significantly reduced in the LCZ696 group compared to vehicle (32% ± 4 vs. 57% ± 5, p<0.05). This change was accompanied by a reduction in circulating plasma cTn-I levels at 4 hours post-reperfusion in the LCZ696 group compared to the vehicle group (49 ng/mL ± 8 vs 103 ng/mL ± 10, p<0.01).
Conclusions: LCZ696 reduces the size of myocardial infarction when given immediately prior to reperfusion in a rodent model of AMI in the setting of hypertension. LCZ696 may have utility as a therapy for acute myocardial injury.
Author Disclosures: R.K. Trivedi: None. D.J. Polhemus: None. A.L. Scarborough: None. T.T. Goodchild: None. D.J. Lefer: None.
- © 2016 by American Heart Association, Inc.