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Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction.

Abstract：

BACKGROUND:Right ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are unknown. We used an experimental approach based upon clinical signs of RVF to delineate functional and biological processes associated with RVF. METHODS AND RESULTS:Wistar rats were subjected to a pulmonary artery banding (PAB n=12) or sham surgery (CON, n=7). After 52±5days, 5/12 PAB rats developed clinical symptoms of RVF (inactivity, ruffled fur, dyspnea, ascites) necessitating termination (PAB+CF). We compared these to PAB rats with RVF without clinical symptoms (PAB-). PAB resulted in reduced cardiac output, RV stroke volume, TAPSE, and increased end diastolic pressure (all p<0.05 vs. CON) in all rats, but PAB+CF rats were significantly more affected than PAB-, despite similar pressure load (p=ns). Pressure-volume analysis showed enhanced contractility (end systolic elastance) in PAB- and PAB+CF, but diastolic function (end diastolic elastance, end diastolic pressure) deteriorated especially in PAB+CF. In PAB+CF capillary density was lower than in PAB-. Gene-array analysis revealed downregulation of both fatty acid oxidation and carbohydrate metabolism in PAB+CF. CONCLUSION:Chronic PAB led to different degrees of RVF, with half of the rats developing severe clinical symptoms of RVF, associated with progressive deterioration of diastolic function, hypoxia-prone myocardium, increased response to oxidative stress and suppressed myocardial metabolism. This model represents clinical RVF and allows for unraveling of mechanisms involved in the progression from RV adaptation to RV failure and the effect of intervention on these mechanisms.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Borgdorff MA,Koop AM,Bloks VW,Dickinson MG,Steendijk P,Sillje HH,van Wiechen MP,Berger RM,Bartelds B

doi

10.1016/j.yjmcc.2014.11.024

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

244-53

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(14)00384-8

journal_volume

pub_type

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Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction.