Muscle Microdialysis to Confirm Sublethal Ischemia in the Induction of Remote Ischemic Preconditioning Arzu Bilgin-Freiert & Joshua R. Dusick & Nathan R. Stein & Maria Etchepare & Paul Vespa & Nestor R. Gonzalez Received: 28 December 2011 / Revised: 9 March 2012 / Accepted: 13 March 2012 / Published online: 10 April 2012 # Springer Science+Business Media, LLC 2012 Abstract Exposure of one tissue to ischemia–reperfusion confers a systemic protective effect, referred to as remote ischemic preconditioning (RIPC). Confirmation that the de- sired effect of ischemia is occurring in tissues used to induce RIPC requires an objective demonstration before this tech- nique can be used consistently in the clinical practice. En- rolled patients underwent three to four RIPC sessions on non-consecutive days. Sessions consisted of 4 cycles of 5 min of leg cuff inflation to 30 mmHg above the systolic blood pressure followed by reperfusion. Absence of leg pulse was confirmed by Doppler evaluation. To evaluate limb transient ischemia, patients were monitored with mus- cle microdialysis. Glucose, lactate, lactate/pyruvate ratio, and glycerol levels were measured. Fourteen microdialysis sessions were performed in seven patients undergoing RIPC (42.8 % male; mean age, 51.8; Fisher grade 4 in all seven patients, Hunt and Hess grade 5 in five patients, four in one patient and one in one patient). An average follow-up of 29 days demonstrated no complications associated with the procedure. Muscle microdialysis during RIPC sessions showed a significant increase in lactate/pyruvate ratio (21.2 to 26.8, p 0 0.001) and lactate (3.0 to 3.9 mmol/L, p 0 0.002), indicating muscle ischemia. There was no significant variation in glycerol (234 to 204 μg/L, p 0 0.43), indicating no perma- nent cell damage. The RIPC protocol used in this study is safe, well tolerated, and induces transient metabolic changes con- sistent with sublethal ischemia. Muscle microdialysis can be used safely as a confirmatory tool in the induction of RIPC. Keywords Metabolic changes . Muscle microdialysis . Remote ischemic preconditioning . Ischemia Introduction Ischemic preconditioning has been shown to endogenously increase tolerance against critical ischemia in multiple tis- sues [1–5]. Transient exposure to ischemia and reperfusion in one organ or tissue also confers a systemic protective effect to remote organs, referred to as remote ischemic preconditioning (RIPC) [6–8]. The clinical application of RIPC has been reported in the cardiology and vascular surgery literature, particularly in patients undergoing cardiac transplantation or vascular sur- gery who may be prone to ischemia intraoperatively [9–11]. The use of ischemic preconditioning for neuroprotection in humans has been limited, with only two studies that have been published. Chan et al. [12] demonstrated a significantly slower decline in oxygen tension and pH among individuals under- going temporary parent vessel occlusion for aneurysm clip- ping when the patients were preconditioned with a short 2-min direct occlusion of the parent vessel compared with individu- als without preconditioning. A second human study of the feasibility and safety of RIPC in patients with aneurysmal subarachnoid hemorrhage (SAH) has been published recently [13], which demonstrated that induction of RIPC by limb ischemia using a blood pressure cuff is safe. Other experiences applying RIPC in humans are limited to investigations in A. Bilgin-Freiert : J. R. Dusick : N. R. Stein : M. Etchepare : P. Vespa : N. R. Gonzalez (*) Departments of Neurosurgery and Radiology, UCLA David Geffen School of Medicine, 10833 LeConte Ave., Room 18-251 Semel, Los Angeles, CA 90095-7039, USA e-mail: ngonzalez@mednet.ucla.edu Transl. Stroke Res. (2012) 3:266–272 DOI 10.1007/s12975-012-0153-1