Abstract 18010: Temporal Kinetics of Remote Ischemic Preconditioning: Transfer of Protection With Plasma Dialysate From Healthy Volunteers to an Isolated Mouse Heart

Abstract

Objective: We aimed to analyze the temporal kinetics of cardioprotection by humoral factor(s) in healthy volunteers undergoing remote ischemic preconditioning (RIPC), a maneuver known to protect against myocardial injury, using infarct size in an isolated mouse heart as read-out. Methods: Ten healthy volunteers underwent RIPC by 3 cycles of 5 min upper-limb blood pressure cuff inflation and 5 min deflation. Venous blood samples were obtained at baseline before RIPC and after 5 and 30 min, 1, 6 and 24 h and daily up to 7 days. Plasma was dialyzed against the 20-fold volume of Krebs-Henseleit buffer for 24 h (cut-off: 12-14 kDa). Isolated mouse hearts were mounted on a Langendorff apparatus and perfused with Krebs-Henseleit buffer at a pressure of 100 mmHg. Before undergoing 20 min global ischemia and 120 min reperfusion, hearts were perfused with dialysate for 15 min. Infarct size was assessed by TTC-staining. The cardioprotective potential of the plasma dialysate obtained 5 min after RIPC was further evaluated by decreasing its dilution (1:10) in those samples, which did not induce cardioprotection in a dilution of 1:20. Results: The cardioprotective effect of RIPC was present in all cases 30 min after RIPC, lasted for at least 6 days and vanished thereafter (see Figure). Plasma taken 5 min after RIPC induced cardioprotection in only 50 % of cases, when using a dialysate with a 1:20 dilution. Decreasing the dilution to 1:10 induced cardioprotection in all cases (Figure insert). Conclusion: A single RIPC-maneuver induces the release of (a) dialyzable, humoral factor(s), which reduce(s) infarct size no later than 5 min after RIPC and remain(s) operative for up to 6 days. These results imply that cardioprotection is at least in part effected by (a) factor(s) which is/are quickly released/activated, long-lasting and/or continuously produced for quite a while after RIPC.