D008: Progressive ventricular pacing in the rabbit characterized by differential atrial and ventricular activation of BNP gene-expression

We have newly established a small animal model of rapid ventricular pacing-induced progressive heart failure in the rabbit, which evolves from asymptomatic left ventricular (LV) dysfunction (ALVD) to overt congestive heart failure (CHF) through a well defined pacing protocol. It was our objective to characterize for the first time cardiac function and geometry as well as atrial and ventricular BNP gene-expression, a sensitive molecular marker of hypertrophic myocardial remodeling. After implantation of a pacemaker system, six in rabbits (3–4 kg) underwent chronic progressive pacing, starting at 330 beats per minute (bpm), then 360 bpm, and then 380 bpm for ten days each (CHF). Five rabbits underwent pacing at 330 bpm for ten days only (ALVD). Before the onset of pacing (CTRL) and at the end of each pacing interval, mean arterial pressure (MAP) was assessed invasively and an echocardiogram was obtained. LV enddiastolic (LVEDd) and endsystolic diameter (LVESd) were determined and fractional shortening (FS) was calculated. BNP gene-expression (BNP) was assessed in atrial, right ventricular (RV), and LV tissue by Northern analysis with a rabbit-specific full length cDNA. (See Table) CTRL (n = 5) ALVD (n = 5) CHF (n = 6) MAP (mmHg) 74 ± 2 65 ± 2a 57 ± 3a, b FS (%) 48 ± 3 33 ± 5a 26 ± 3a LVEDd (mm) 11,0 ± 0,1 13,2 ± 0,1a 14,5 ± 0,1a BNP-atria-(AU) 0,13 ± 0,05 1,89 ± 0,44a 1,73 ± 0,43a BNP-LV (AU) 0,12 ± 0,04 0,77 ± 0,37 1,59 ± 0,25a, b BNP-RV (AU) 0.36 ± 0.10 0.97 ± 0.15a 1.86 ± 0.25a, b ap < 0,05 vs. CTRL, bp < 0,05 vs. ALVD Rapid pacing in the rabbit is associated with progressive LV dysfunction and dilatation. Full early activation of atrial and progressive biventricular activation of BNP gene-expression provide new insight into the temporal regulation of cardiac BNP during the progression to CHF. Furthermore, BNP gene expression may be utilized as a sensitive marker to study the effects of therapeutic interventions upon ventricular remodeling in experimental heart failure.