title: Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling.
abstract: BACKGROUND
  ACE inhibition (ACEI) attenuates post-myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT(1)) antagonism alone or in combination with ACEI are unclear. Accordingly, we investigated the effects of AT(1) antagonism, ACEI, and their combination in a well-characterized ovine postinfarction model.
  
  
  RESULTS
  Beginning 2 days after transmural anteroapical MI, 62 sheep were treated with 1 of 5 treatment regimens: no therapy (control, n=12), standard-dose ACEI (sACEI; ramipril 10 mg/d, n=14), high-dose ACEI (hACEI; ramipril 20 mg/d, n=8), AT(1) blockade (losartan 50 mg/d, n=13), and combination therapy with sACEI+AT(1) blockade (CT; ramipril 10 mg/d+losartan 50 mg/d, n=15). MRI was performed before and 8 weeks after MI to quantify changes in LV end-diastolic and end-systolic volume indices (DeltaEDVI, DeltaESVI) and ejection fraction (DeltaEF). Change in regional percent intramyocardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj Delta%S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: DeltaESVI (+1.0+/-0.4, +0.7+/-0.4, +0.6+/-0.3, +0.9+/-0.5, and +0.4+/-0.2* mL/kg); DeltaEDVI (+0.9+/-0.4, +0.7+/-0.5, +0.6+/-0.5, +0.9+/-0.5, and +0.4+/-0.3 mL/kg); DeltaEF (-24+/-7, -18+/-6, -14+/-7, -18+/-10, and -11+/-9* %); and Adj Delta%S (-8+/-4, -7+/-3, -5+/-3, -5+/-3, and -2+/-3* %) for Control, sACEI, hACEI, AT(1) blockade, and CT, respectively (*P<0.04 versus sACEI, AT(1) blockade, and control; P<0.05 versus control; P<0.002 versus AT(1) blockade and control). EDVI and ESVI at 8 weeks after MI were smallest with CT (P<0.02 versus all).
  
  
  CONCLUSIONS
  Combination therapy with sACEI+AT(1) blockade shows promise in attenuating postinfarction LV remodeling but was not clearly superior to hACEI in the present study.
authors.affiliation: Division of Cardiology, Department of Medicine, Allegheny General Hospital, Pittsburgh, PA 15212, USA. smankad@wpahs.org
authors.forename: S
authors.initials: S
authors.lastname: Mankad
authors.forename: T A
authors.initials: TA
authors.lastname: d'Amato
authors.forename: N
authors.initials: N
authors.lastname: Reichek
authors.forename: W E
authors.initials: WE
authors.lastname: McGregor
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: D
authors.initials: D
authors.lastname: Singh
authors.forename: W J
authors.initials: WJ
authors.lastname: Rogers
authors.forename: C M
authors.initials: CM
authors.lastname: Kramer
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D007091:Image Processing, Computer-Assisted; D019808:Losartan / Q000494:pharmacology; D019028:Magnetic Resonance Imaging, Cine; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017257:Ramipril / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019808:Losartan; D017257:Ramipril