This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mankad, S. Articles by Kramer, C. M. Search for Related Content PubMed PubMed Citation Articles by Mankad, S. Articles by Kramer, C. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Attack Hazardous Substances DB LOSARTAN POTASSIUM Related Collections Remodeling Imaging CT and MRI Acute myocardial infarction

(Circulation. 2001;103:2845.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Combined Angiotensin II Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Further Attenuates Postinfarction Left Ventricular Remodeling

Sunil Mankad, MD; Thomas A. d’Amato, MD, PhD; Nathaniel Reichek, MD; Walter E. McGregor, MD; Jeff Lin, MD; Deepak Singh, MD; Walter J. Rogers, MS; Christopher M. Kramer, MD

From the Division of Cardiology, Department of Medicine (S.M., N.R., W.J.R.), and the Division of Cardiothoracic Surgery (T.A.D., W.E.M., J.L., D.S.), Allegheny General Hospital, Pittsburgh, Pa, and the Departments of Medicine and Radiology, University of Virginia Health System, Charlottesville (C.M.K.).

Correspondence to Sunil Mankad, MD, Director, Coronary Care Unit, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212. E-mail smankad{at}wpahs.org

Background—ACE inhibition (ACEI) attenuates post–myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT₁) antagonism alone or in combination with ACEI are unclear. Accordingly, we investigated the effects of AT₁ antagonism, ACEI, and their combination in a well-characterized ovine postinfarction model.

Methods and 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), AT₁ blockade (losartan 50 mg/d, n=13), and combination therapy with sACEI+AT₁ 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 (EDVI, ESVI) and ejection fraction (EF). Change in regional percent intramyocardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj %S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: ESVI (+1.0±0.4, +0.7±0.4, +0.6±0.3, +0.9±0.5, and +0.4±0.2* mL/kg); EDVI (+0.9±0.4, +0.7±0.5, +0.6±0.5, +0.9±0.5, and +0.4±0.3 mL/kg); EF (-24±7, -18±6, -14±7, -18±10, and -11±9* %); and Adj %S (-8±4, -7±3, -5±3, -5±3, and -2±3* %) for Control, sACEI, hACEI, AT₁ blockade, and CT, respectively (*P<0.04 versus sACEI, AT₁ blockade, and control; P<0.05 versus control; P<0.002 versus AT₁ 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+AT₁ blockade shows promise in attenuating postinfarction LV remodeling but was not clearly superior to hACEI in the present study.

Key Words: remodeling • myocardial infarction • magnetic resonance imaging • angiotensin

This article has been cited by other articles:

				P. H. Pun, R. W. Lehrich, S. R. Smith, and J. P. Middleton Predictors of Survival after Cardiac Arrest in Outpatient Hemodialysis Clinics Clin. J. Am. Soc. Nephrol., May 1, 2007; 2(3): 491 - 500. [Abstract] [Full Text] [PDF]

				S. Voros, Z. Yang, C. M. Bove, W. D. Gilson, F. H. Epstein, B. A. French, S. S. Berr, S. P. Bishop, M. R. Conaway, H. Matsubara, et al. Interaction between AT1 and AT2 receptors during postinfarction left ventricular remodeling Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1004 - H1010. [Abstract] [Full Text] [PDF]

				D. M. McNamara, R. Holubkov, L. Postava, K. Janosko, G. A. MacGowan, M. Mathier, S. Murali, A. M. Feldman, and B. London Pharmacogenetic interactions between angiotensin-converting enzyme inhibitor therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure J. Am. Coll. Cardiol., November 16, 2004; 44(10): 2019 - 2026. [Abstract] [Full Text] [PDF]

				T. Unger and Jun Li The role of the renin-angiotensin-aldosterone system in heart failure Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1_suppl): S7 - S10. [Abstract] [PDF]

				J. Yoshida, K. Yamamoto, T. Mano, Y. Sakata, N. Nishikawa, M. Nishio, T. Ohtani, T. Miwa, M. Hori, and T. Masuyama AT1 Receptor Blocker Added to ACE Inhibitor Provides Benefits at Advanced Stage of Hypertensive Diastolic Heart Failure Hypertension, March 1, 2004; 43(3): 686 - 691. [Abstract] [Full Text] [PDF]

				A.K. Hasnat, E. T. van der Velde, J. K.F. Hon, and M. H. Yacoub Reproducible model of post-infarction left ventricular dysfunction: haemodynamic characterization by conductance catheter Eur. J. Cardiothorac. Surg., July 1, 2003; 24(1): 98 - 104. [Abstract] [Full Text] [PDF]

				T. Sugie, Y. Kagaya, M. Takeda, H. Yahagi, C. Takahashi, J. Takahashi, M. Ninomiya, J. Watanabe, R. Ichinohasama, F. Tezuka, et al. Should increasing the dose or adding an AT1 receptor blocker follow a relatively low dose of ACE inhibitor initiated in acute myocardial infarction? Cardiovasc Res, June 1, 2003; 58(3): 611 - 620. [Abstract] [Full Text] [PDF]

				Y. Nakamura, M. Yoshiyama, T. Omura, K. Yoshida, Y. Izumi, K. Takeuchi, S. Kim, H. Iwao, and J. Yoshikawa Beneficial effects of combination of ACE inhibitor and angiotensin II type 1 receptor blocker on cardiac remodeling in rat myocardial infarction Cardiovasc Res, January 1, 2003; 57(1): 48 - 54. [Abstract] [Full Text] [PDF]

				M. Saeed, N. Watzinger, G. A. Krombach, G. K. Lund, M. F. Wendland, M. Chujo, and C. B. Higgins Left Ventricular Remodeling after Infarction: Sequential MR Imaging with Oral Nicorandil Therapy in Rat Model Radiology, September 1, 2002; 224(3): 830 - 837. [Abstract] [Full Text] [PDF]

				Z. Yang, C. M. Bove, B. A. French, F. H. Epstein, S. S. Berr, J. M. DiMaria, J. J. Gibson, R. M. Carey, and C. M. Kramer Angiotensin II Type 2 Receptor Overexpression Preserves Left Ventricular Function After Myocardial Infarction Circulation, July 2, 2002; 106(1): 106 - 111. [Abstract] [Full Text] [PDF]

				J. L. Zhuo, F. A.O. Mendelsohn, and M. Ohishi Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT1 Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease Hypertension, February 1, 2002; 39(2): 634 - 638. [Abstract] [Full Text] [PDF]