Inflammatory processes in load-induced right ventricular failure

Background: Transient increase in pulmonary arterial (PA) pressure has been shown to induce a persistent right ventricular (RV) failure characterized by a RV-arterial decoupling, associated to activation of apoptotic pathways and local overexpression of TNF-alpha (Dewachter et al . Crit Care Med 2010; 38: 1405-13). Objectives: We hypothesized therefore that inflammatory cytokines might contribute to the development of persistent RV failure in this “pulmonary hypertension crisis” model. Methods: Sixteen dogs were randomized to a 90-min PA constriction- or to a SHAM-operation, followed 30 minutes later by hemodynamic measurements including effective pulmonary arterial elastance (Ea) to estimate RV afterload and RV end-systolic elastance (Ees) to estimate RV contractility determined by the single beat method (Brimioulle et al . Am J Physiol 2003; 284: H1625-30), but also blood sampling. After sacrifice of the animals, RV free wall was sampled to assess, by RTQPCR and ELISA, respectively gene and protein expressions of interleukin (IL)-1 beta, -6 and -10. Results: The transient increase in PA pressure persistently increased Ea, and decreased Ees, Ees/Ea and cardiac output, indicating RV failure with altered RV-arterial coupling. As compared to the SHAM group, 90-min PA constriction increased RV relative gene and protein expressions of IL-1 beta and IL-6, and decreased RV relative gene and protein expressions of IL-10, an anti-inflammatory cytokine. The pro-inflammatory IL-6/IL-10 ratio was increased in the RV and in the serum in the PA constriction- compared to the SHAM- group. Conclusions: Acute afterload-induced persistent RV failure appears to be related to local and systemic activation of inflammation.