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Acta Physiologica 2010; Volume 200, Supplement 678 Part II
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Autumn Meeting 2010
10/16/2010-10/16/2010
Université Libre de Bruxelles, Brussels, Belgium
ACTIVATION OF APOPTOTIC PATHWAYS IN EXPERIMENTAL ACUTE AFTERLOAD-INDUCED RIGHT VENTRICULAR FAILURE
Abstract number: P-04
Dewachter1 C., Dewachter1 L., Rondelet1 B., Fesler1 P., Brimioulle1 S., Kerbaul1 F., Naeije1 R.
1Laboratory of Physiology, Faculty of Medecine, Free University of Brussels, Belgium.
The pathobiology of persistent right ventricular (RV) failure observed after an acute increase in pulmonary artery pressure (Ppa) remains incompletely understood. We here tested the hypothesis that persistent RV dysfunction might be related to an activation of apoptotic pathways. 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 endsystolic elastance (Ees) to estimate RV contractility, and sampling of myocardial tissue to assess apoptosis by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry. 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/min, indicating RV failure. As compared to the SHAM-operated group, and to 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 to 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 tumor necrosis factor-alpha. Acute afterload-induced persistent RV failure appears to be related to an early activation of apoptotic pathways.
To cite this abstract, please use the following information:
Acta Physiologica 2010; Volume 200, Supplement 678 Part II :P-04