Abstract 3028: Muscle Microdialysis to Confirm Subischemic Injury in a Clinical Trial of Remote Ischemic Preconditioning

Abstract

Introduction: Transient exposure to sublethal ischemia-reperfusion injury of one tissue confers a protective effect to remote organs, referred to as remote ischemic preconditioning (RIPC). Confirmation that the desired effect of sublethal ischemia is occurring in the tissues used to induce RIPC requires an objective measure before this technique can be used consistently in the clinical practice. Methods: Three to four RIPC sessions were conducted during non-consecutive days in patients with aneurysmal SAH aged 18-80, within days 4-12 of aneurysm rupture. Sessions consisted of 4 cycles of 5-minutes of lower extremity blood pressure cuff inflation to 30 mmHg above the systolic blood pressure, followed by 5 minutes of reperfusion. The absence of dorsalis pedis pulse was confirmed by Doppler evaluation and, if pulse signals were detected, the cuff was inflated until they disappeared. During periods of reperfusion, distal pulse recovery was confirmed. To evaluate limb sublethal ischemic injury, patients were monitored with a microdialysis probe inserted into the mass of the gastrocnemius muscle on the preconditioning limb. Glucose, lactate, pyruvate, lactate/pyruvate ratio, and glycerol levels were compared before and immediately after the RIPC sessions. Results: Twenty-one RIPC sessions were performed in 6 patients (50% male, mean age 48.5, Fisher 4, H&H 2-4). The procedure was well tolerated and there were no systemic changes in HR, BP or CVP. An average follow up of 25 days of daily examination after the last RIPC session demonstrated no complications associated with the RIPC procedure or the microdialysis probe implantation. Muscle microdialysis during the RIPC sessions showed a significant increase in L/P ratio (21.2 to 26.8, p=0.001) and lactate (3.0 to 3.9mmol/L, p=0.002), indicating muscle ischemia. There was no significant variation in glycerol (234 to 204μ g/L, p=0.43), indicating no permanent cell damage. Conclusion: The RIPC protocol used in this study is safe, well tolerated, and induces transient metabolic changes in skeletal muscles comparable with sublethal ischemia. Muscle microdialysis can be used safely as a confirmatory tool in the induction of RIPC.