Abstract 14878: Baroreflex Failure Induces Striking Volume Intolerance In A Rat Model With Normal Left Ventricular Function
Background: In patients with heart failure with preserved ejection fraction (HFpEF), minor (intravascular) volume reduction often rapidly resolves pulmonary edema. Major risk factors of HFpEF such as aging and hypertension are known to promote arteriosclerosis (SCLEROSIS). Since SCLEROSIS impairs baroreceptor transduction and baroreflex is a powerful regulator of intravascular stressed blood volume, we hypothesized that SCLEROSIS-induced baroreflex failure plays a critical role in the pathogenesis of HFpEF. The purpose of this investigation is to examine if baroreflex failure causes striking volume intolerance and predisposes to pulmonary edema in an animal model with normal left ventricular function.
Method and results: In 5 anesthetized Sprague-Dawley rats with normal left ventricular function, we vascularily isolated the bilateral carotid sinuses and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We mimicked the normal baroreflex (NORMAL) by matching the CSP to arterial pressure (AP) and the baroreflex failure (FAILURE) by keeping CSP at a constant value regardless of AP. We infused dextran stepwise (infused volume: ΔV) until left atrial pressure (LAP) reaches 15 mmHg. To examine volume sensitivity, we obtained the LAP-ΔV relationship (LAPΔVR) under NORMAL and FAILURE. We fitted a monoexponential curve to the LAPΔVR and estimated critical ΔV at which LAP reaches 20 mmHg. FAILURE markedly decreased critical ΔV (17.22±1.91 vs. 11.16±1.58 ml/kg, p<0.01), while increased AP at the critical ΔV (151.4±18.8 vs. 178.8±17.8 mmHg, p<0.05). Since the difference of critical ΔV (∼6.0 ml/kg) reaches 1/3 of physiological stressed volume, baroreflex failure had major impact on the volume tolerance.
Conclusion: Baroreflex failure induces striking volume intolerance in the absence of left ventricular dysfunction and would play an important role in the pathogenesis of HFpEF.
- © 2011 by American Heart Association, Inc.