Prolonged effects of B-type natriuretic peptide infusion on cardiac remodeling after sustained myocardial injury

1 Division of Cardiothoracic Surgery, Department of Surgery and 2 Division of Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University and 3 Department of Biomedical Engineering, Columbia University, New York, New York; 4 Faculty of Engineering, University of Hong Kong, Hong Kong, People's Republic of China; 5 Scios Incorporated, Fremont, California; and 6 Institute of Molecular and Experimental Therapeutics, East China Normal University, Shanghai, People's Republic of China Submitted 24 June 2008 ; accepted in final form 29 May 2009 B-type natriuretic peptide (BNP) is an established first-line therapy for acute decompensated heart failure (HF), but its efficacy in preventing left ventricular (LV) remodeling after myocardial injury is unknown. The goal of this study was to evaluate the effects of BNP therapy on remodeling after ischemic injury in an awake canine model. Dogs were chronically instrumented for hemodynamics. Ischemia was created by daily coronary embolization (Embo; 3.1 x 10 4 beads/day) for 3 wk; 60 min after the first embolization, BNP (100 ng·kg –1 ·min –1 ; n = 6) or saline (control; n = 6) was continuously infused via a left atrial catheter for 3 wk. Hemodynamics and echocardiography were performed in an awake state at baseline, 3 wk after Embo + BNP infusion, and 4 wk after stopping Embo + BNP infusion. End-systolic elastance (E es ) and LV change in pressure over time (dP/d t ) were preserved throughout Embo + BNP therapy versus control therapy (E es : 3.76 ± 1.01 vs. 1.41 ± 0.16 mmHg/ml; LV dP/d t : 2,417 ± 96 vs. 2,068 ± 95 mmHg/s; both P < 0.05 vs. control). LV end-diastolic dimension was significantly smaller in BNP-treated dogs compared with control dogs (4.29 ± 0.10 vs. 4.77 ± 0.17 cm), and ejection fraction was maintained in treated dogs vs. control dogs (53 ± 1% vs. 46 ± 2%) (both P < 0.05 vs. control). Cyclooxygenase (COX)-2 expression in terminal LV tissue was significantly reduced after BNP therapy. Treatment with continuous infusion of BNP preserved LV geometry, improved systolic function, and prevented the progression of systolic HF after persistent ischemic injury. heart failure; myocardial function Address for reprint requests and other correspondence: J. Wang, Inst. of Molecular and Experimental Therapeutics, East China Normal Univ., Shanghai, China (e-mail: jw147{at}columbia.edu )