Canine Model of Early Left Ventricular Dysfunction

Background. Recent studies have reported that asymptomatic left ventricular dysfunction (ALVD) in humans is characterized by early neurohumoral activation. Specifically, atrial natriuretic factor (ANF) and norepinephrine are activated without activation of the renin-angiotensin-aldosterone system (RAAS). The current study describes hemodynamic and renal function associated with this neurohumoral profile in a canine model of early and presumably "asymptomatic" ventricular dysfunction. We hypothesized that the neurohumoral profile observed in ALVD is associated with preservation of renal function despite significant hemodynamic compromise. Methods and Results. ALVD was produced by ventricular pacing at 180 beats per minute for 10 days. Intravascular volume expansion was performed before and after producing ALVD in eight conscious dogs. The model ofALVD was characterized by decreases in ejection fraction (48+2 to 29±4%), cardiac output (4.64±0.29 to 2.89±0.17 L/min), and mean arterial pressure (119±4 to 108±4 mm Hg). Atrial pressures and systemic vascular resistance were increased. ANF (60±19 to 165±27 pg/mL) and norepinephrine (382±+127 to 690±211 pg/mL) were activated, whereas the RAAS was not. Creatinine clearance and sodium excretion (UNa V) were unchanged after producing ALVD. The natriuretic response to volume expansion in ALVD was completely intact, with increases in UNa V similar to that observed with volume expansion before producing ALVD. Conclusions. The current study demonstrates that significant ventricular dysfunction with peripheral vasoconstriction can be associated with normal renal function and thus suggests an important functional role for the neurohumoral profile ofALVD in preserving sodium balance. (Circulation 1993;87:2016-2022)