008 * RNASE1 AS A POTENTIAL MEDIATOR OF REMOTE ISCHAEMIC PRECONDITIONING FOR CARDIOPROTECTION

Abstract

Abstract Objectives: Remote ischaemic preconditioning (RIPC) is a non-invasive strategy for protecting the heart against ischaemia-repeRfusion injury (IRI). We have recently shown that the inhibition of extracellular RNA (eRNA) using RNAse1 protected the heart against acute IRI in rodent animal models. Based on this previous work in animals, the role of the eRNA/RNase1 system in cardiac RIPC in humans should be defined. Method(s): Fourteen patients underwent cardiac surgery with a previous RIPC (4 x 5degreemin arm ischaemia) or a sham procedure. Circulating eRNA was quantified from arterial or coronary sinus blood using the Master Pure RNA purification kit (Epicentre Biotechnologies). Total RNA concentration was quantified with NanoDrop ND-2000 (peqLab Biotechnologie GmbH). RNase activity was quantified at indicated time points by an enzymatic assay. Result(s): Before surgery, eRNA levels were similar in both groups (14.12 +/- 6degreeng/ml). In patients without RIPC, arterial eRNA levels rose during (87 +/- 12degreeng/ml) and peaked after (127 +/- 11degreeng/ml) surgery; while eRNA levels in coronary sinus blood were significantly higher (206 +/- 32degreeng/ml). Interestingly, applying an RIPC protocol significantly increased levels of plasma endogenous vascular RNase1 (>7-fold) and the arterial (22 +/- 6degreeng/ml) and coronary sinus (27degreeng/ml) circulating eRNA were significantly hydrolysed. Conclusion(s): After RIPC, the beneficial RNAse1 increased while the damaging eRNA decreased. The present findings imply a significant contribution of the RIPC-dependent endothelial RNAse1-release for improving the outcome of cardiac surgery, while the exact mechanism of RNase1-induced cardioprotection still remains unclear.