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Activation of apoptotic pathways in experimental acute afterload-induced right ventricular failure

Introduction

The pathobiology of persistent right ventricular (RV) failure observed after an acute increase in pulmonary artery pressure (Ppa) remains incompletely understood. We hypothesized that these severe complications might be related to an activation of apoptotic pathways.

Methods

Fourteen anesthetized dogs were randomised to a transient 90 minutes pulmonary artery constriction or to a SHAM operation, followed 30 minutes later by hemodynamic measurements including effective arterial elastance (Ea) to estimate RV afterload and end-systolic elastance (Ees) to estimate RV contractility, and sampling of cardiac tissue to assess apoptosis by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry.

Results

Transient increase in Ppa persistently increased Ea from 0.75 ± 0.08 to 1.37 ± 0.18 mmHg/ml, and decreased Ees from 1.06 ± 0.09 to 0.49 ± 0.09 mmHg/ml, Ees/Ea from 1.44 ± 0.06 to 0.34 ± 0.03 and cardiac output from 3.78 ± 0.16 to 1.46 ± 0.10 l/minute, indicating RV failure. As compared with the SHAM-operated group, and with left ventricular tissue in animals with persistent RV failure, there were decreased gene expressions of RV and septal Bcl-2, with no changes in the gene expressions of Bax and Bak, and an increase in the Bax/Bcl-2 ratio. RV and septal Bcl-XL, and RV Bcl-w gene expressions were decreased as compared with the SHAM-operated group. There were activations of RV caspases 8 and 9, and of RV and septal caspase 3. Diffuse RV and septal apoptosis was confirmed by TUNEL staining. There were also increased RV and septal protein expressions of TNFα.

Conclusions

Acute afterload-induced persistent RV failure appears to be related to an early activation of apoptotic pathways, and to a myocardial increase of TNFα.

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Correspondence to C Dewachter.

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Dewachter, C., Dewachter, L., Rondelet, B. et al. Activation of apoptotic pathways in experimental acute afterload-induced right ventricular failure. Crit Care 14, P133 (2010). https://doi.org/10.1186/cc8365

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Keywords

  • Pulmonary Artery
  • Right Ventricular
  • Apoptotic Pathway
  • Pulmonary Artery Pressure
  • Quantitative Polymerase Chain Reaction