Overpacing-induced heart failure in dogs caused profound right ventriculo-arterial uncoupling (Ees/Ea 0.8 vs 1.5 in controls; P<0.01) due to failure of RV systolic function to adapt.
Does overpacing-induced heart failure cause right ventriculo-arterial uncoupling in a dog model?
In an experimental dog model, overpacing-induced heart failure leads to profound right ventriculo-arterial uncoupling despite only borderline pulmonary hypertension, driven by increased pulmonary arterial resistance and elastance without adequate RV systolic adaptation.
Absolute Event Rate: 0.8% vs 1.5%
p-value: p=<0.01
Pulmonary hypertension on heart failure (HF) limits exercise capacity and survival probably because of associated right ventricular (RV) failure. This study investigated the mechanisms of RV function adaptation to early pulmonary hypertension in experimental HF. Seven weeks of rapid ventricular pacing in six dogs induced a HF characterized by cardiomegaly and decreased left ventricular ejection fraction. Compared with eight control dogs, pulmonary hypertension was borderline, with a mean pulmonary artery pressure increased to only 23 ± 2 (means ± SE) mmHg. However, the pulmonary vascular impedance spectrum was globally shifted to higher pressures, with an increase in 0 Hz impedance (resistance) to 662 ± 69 vs. 455 ± 41 dynes·cm(-5)·m(2) in controls (P < 0.01) and in characteristic impedance to 183 ± 20 vs. 104 ± 7 dynes·cm(-5)·m(2) in controls (P < 0.01). There was no change in RV end-systolic elastance (Ees), but arterial elastance (Ea) was increased to 1.8 ± 0.3 vs. 0.9 ± 0.1 mmHg/ml in controls so that RV-arterial coupling defined by the Ees-to-Ea ratio (Ees/Ea) was decreased to 0.8 ± 0.1 vs. 1.5 ± 0.1 in controls (P < 0.01). Inhaled nitric oxide, 40 ppm or 5 μg·kg(-1)·min(-1) nitroprusside i.v., did not affect Ees/Ea. Fifty milligrams (i.v.) of milrinone increased Ees/Ea to 1.6 ± 0.2 by an isolated increase in Ees. We conclude that overpacing-induced HF is accompanied by a borderline pulmonary hypertension but profound RV-arterial uncoupling explained by the failure of RV systolic function to adapt combined effects of increased pulmonary arterial resistance and elastance.
Pagnamenta et al. (2010) studied Heart failure with borderline pulmonary hypertension (n=14). Rapid ventricular pacing vs. Control dogs was evaluated on Right ventriculo-arterial coupling (Ees/Ea ratio) (p=<0.01). Overpacing-induced heart failure in dogs caused profound right ventriculo-arterial uncoupling (Ees/Ea 0.8 vs 1.5 in controls; P<0.01) due to failure of RV systolic function to adapt.