727-5 Differential Role of Circulating and Ventricular ANP as a Marker for Cardiac Filling Pressures and Ventricular Remodeling in a Model of Pacing Induced Heart Failure and Cardiac Hypertrophy

Abstract

Previous studies have suggested that circulating atrial natriuretic peptide (ANP) is a marker for cardiac filling pressures and ventricular myocardial production of ANP a marker for ventricular hypertrophy and/or dilatation. To address the role of circulating ANP as a marker for ventricular hypertrophy and dilatation as compared to cardiac filling pressures, we developed a new canine model of pacing induced heart failure that in contrast to previous pacing models produces sustained ventricular hypertrophy. This involves gradually increasing the pacing rate from 180 to 240 bpm over 30 days (PROG PACE, n = 5) followed by 4 weeks of recovery (REC, n = 6). Four NORMAL dogs served as controls. Diastolic dimension (LVEDd) and EF were assessed by echo. LV mass was assessed by echo prior to rapid ventricular pacing (pre-RVP) in the PROG PACE (4.2 ± 0.2 g/kg) and REC (4.7 ± 0.2 g/kg) dogs. LV mass was assessed at autopsy after PROG PACE and REC and in NORMAL dogs. Ventricular ANP was assessed by sensitive and specific immunohistochemical staining for ANP 1–28. NORMAL PROG PACE REC LVEDd (mm) 39 ± 2 50 ± l *† 49 ± l *† EF(%) 49 ± 5 21 ± 3 *† 37 ± 2 *† PCWP(mmHg) 2.3 ± 0.6 21.5 ± 3.8 * 7.5 ± 0.9 *# CO (Llmin) 3.13 ± 0.18 1.47 ± 0.23 * 3.58 ± 0.34 # LV mass (g/kg) 4.6 ± 0.3 5.4 ± 0.3 † 55 ± 0.2 † ANP(pg/mL) 46 ± 8 181 ± 59 * 68 ± 15 * = p < 0.05 vs NORMAL. † = p < 0.05 vs pre-RVP. # = P < 0.05 vs PROG PACE. Immunohistochemistry was markedly positive for ANP in ventricular myocardium in both PROG PACE and REC dogs. Immunostaining of NORMAL ventricular myocardium was negative. These studies confirm that circulating ANP more closely parallels changes in cardiac filling pressures as compared to cardiac dilatation and/or ventricular hypertrophy. In contrast local ventricular ANP emerges as a sensitive local tissue marker for ventricular hypertrophy and dilatation in this novel model of heart failure and ventricular remodeling.