TY - JOUR
T1 - Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction
AU - Borgdorff, Marinus A.J.
AU - Koop, Anne Marie C.
AU - Bloks, Vincent W.
AU - Dickinson, Michael G.
AU - Steendijk, Paul
AU - Sillje, Herman H.W.
AU - Van Wiechen, Maarten P.H.
AU - Berger, Rolf M.F.
AU - Bartelds, Beatrijs
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2015/2
Y1 - 2015/2
N2 - 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. ±. 5. days, 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.
AB - 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. ±. 5. days, 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.
UR - https://www.scopus.com/pages/publications/84917710853
U2 - 10.1016/j.yjmcc.2014.11.024
DO - 10.1016/j.yjmcc.2014.11.024
M3 - Article
C2 - 25486580
AN - SCOPUS:84917710853
SN - 0022-2828
VL - 79
SP - 244
EP - 253
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -