Abstract 3161: Dietary Copper Restrition is Associated With Accelerated Failure of the Pressure-overloaded Right Ventricle
RATIONALE: The pathological hallmark of severe pulmonary artery hypertension (PAH) is the vaso-obstructive angioproliferative lesion. In contrast, the right ventricle (RV) in PAH-associated heart failure exhibits a decreased capillary density. It is unknown whether capillary rarefaction contributes to the transition from compensated RV hypertrophy to dilatation and failure. Although dietary copper restriction (DCR) as an anti-angiogenic strategy may treat the pulmonary vascular disease in PAH, it may also worsen RV function.
METHODS: 6 week old male Sprague Dawley rats underwent surgical banding of the pulmonary artery (PAB). One group received a normal diet, whereas a second group received a diet severely restricted in copper content. 6 weeks after surgery, RV function was determined using echocardiography and hemodynamic measurements.
RESULTS: Isolated pressure overload was not associated with RV dysfunction or capillary rarefaction, but the combination of PAB and DCR resulted in severe RV dilatation (see figure⇓), loss of RV capillaries and extensive cardiac fibrosis.
CONCLUSIONS: DCR in combination with pressure overload leads to severe RV failure. Capillary rarefaction may play a role in the transition from compensated hypertrophy to RV failure in PAH. Careful cardiac monitoring is recommended in clinical trials evaluating the benefit of anti-angiogenic drugs in PAH.