Submitted on June 24, 2008
Revised on May 26, 2009
Accepted on May 29, 2009
Prolonged Effects of B-Type Natriuretic Peptide Infusion on Cardiac Remodeling After Sustained Myocardial Injury
Isaac George, Brad Morrow1, Kai Xu1, Geng-Hua Yi, Jeffrey W. Holmes2, Ed X. Wu3, Zhihe Li4, Andrew A Protter5, Mehmet C Oz1, and Jie Wang6*
1 Columbia University
2 University of Virginia
3 The University of Hong Kong
4 Scios Inc
5 Scios, Inc.
6 College of P&S Columbia University
* To whom correspondence should be addressed. E-mail: jw147{at}columbia.edu.
Brain 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 following ischemic injury in an awake canine model. Dogs were chronically instrumented for hemodynamics. Ischemia was created by daily coronary embolization (Embo) (3.1 x 104 beads/day) for 3 wks; 60 minutes after the first embolization, BNP (100 ng/kg/min) (n=6) or saline (Control) (n=6) was continuously infused via a left atrial catheter for 3 wks. Hemodynamics and echocardiography were performed in an awake state at baseline, 3 wks after Embo plus BNP infusion, and 4 wks after stopping Embo plus BNP infusion. End-systolic elastance (Ees) and LV dP/dt were preserved throughout Embo plus BNP therapy versus Control therapy (Ees: 3.76 ± 1.01 vs. 1.41 ± 0.16 mmHg/ml; LV dP/dt: 2417 ± 96 vs. 2068 ± 95 mmHg/s, respectively, both p<0.05 vs. Control). LV end-diastolic dimension was significantly smaller in BNP-treated dogs compared to Control dogs (4.29 ± 0.10 vs. 4.77 ± 0.17 cm, respectively), and ejection fraction was maintained in treated dogs versus Control dogs (53 ± 1 vs. 46 ± 2%, respectively) (both p<0.05 vs. Control). COX-2 expression in terminal LV tissue was significantly reduced after BNP therapy. Treatment with continuous infusion BNP preserved LV geometry, improved systolic function, and prevented the progression of systolic HF after persistent ischemic injury.
