Remote ischemic preconditioning protects the spinal cord against ischemic insult: An experimental study in a porcine model Henri Haapanen, MD, Johanna.

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Remote ischemic preconditioning protects the spinal cord against ischemic insult: An experimental study in a porcine model Henri Haapanen, MD, Johanna Herajärvi, MB, Oiva Arvola, MD, Tuomas Anttila, MB, Tuomo Starck, PhD, Mika Kallio, MD, PhD, Vesa Anttila, MD, PhD, Hannu Tuominen, MD, PhD, Kai Kiviluoma, MD, PhD, Tatu Juvonen, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 151, Issue 3, Pages 777-785 (March 2016) DOI: 10.1016/j.jtcvs.2015.07.036 Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Motor-evoked potential response. The figure is modeled from 1 pig. The definitions of the onset latency, peak latency, and peak-to-peak amplitude are shown as lines with arrows. MEP, Motor-evoked potential. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 777-785DOI: (10.1016/j.jtcvs.2015.07.036) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 A simplified overview of the protocol. Baseline included anesthesia induction, invasive hemodynamic monitoring, thoracotomy, configuration of baseline MEP, and measurements. Before the start of spinal cord ischemia there was a 15-minute interval (FLUSH) for the data collection after RIPC and surgical preparation. Blood samples were taken at several timepoints, indicated by upward arrows. CTRL, Control; RIPC, remote ischemic preconditioning; SA, segmental artery. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 777-785DOI: (10.1016/j.jtcvs.2015.07.036) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Peak-to-peak amplitude of right hind limb. Measurements are compared to the baseline value of 0. A clinically significant 50% decrease in the amplitude is marked with a dotted line. The amplitude change starts to diminish steadily after ligation of the left subclavian artery in the control group, whereas the amplitude is higher in the RIPC group after remote ischemic preconditioning. Values represent medians; error bars represent the interquartile range. RIPC, Remote ischemic preconditioning; CTRL, control; Subclavian l.sin, ligation of left subclavian artery; 5 SA, ligation of 5th segmental artery; 9 SA, ligation of 9th segmental artery; post op, postoperatively. *P < .05; **P < .01; ***P < .001 at a single timepoint. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 777-785DOI: (10.1016/j.jtcvs.2015.07.036) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Peak-to-peak amplitude in the left hind limb. Measurements are compared to a baseline value of 0. A clinically significant 50% decrease in the amplitude is marked with a dotted line. The difference is statistically significant after RIPC. Overall, the trend shows a slightly better preservation of the spinal cord in the RIPC group after ischemia. Values represent medians; error bars represent the interquartile range. RIPC, Remote ischemic preconditioning; CTRL, control; Subclavian l.sin, ligation of left subclavian artery; 5 SA, ligation of 5th segmental artery; 9 SA, ligation of 9th segmental artery; post op, postoperatively. *P < .05; ∇P < .06 at a single timepoint. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 777-785DOI: (10.1016/j.jtcvs.2015.07.036) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Onset latency in the right hind limb. Measurements are compared to a baseline value of 0. The onset latency is significantly reduced in the RIPC group after intervention until the last segmental artery occlusion. Values represent medians; error bars represent the interquartile range. RIPC, Remote ischemic preconditioning; CTRL, control; PR, post–remote ischemic preconditioning; Subclavian l.sin, ligation of left subclavian artery; 5 SA, ligation of 5th segmental artery; 9 SA, ligation of 9th segmental artery; post op, postoperatively. *P < .05 at a single timepoint. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 777-785DOI: (10.1016/j.jtcvs.2015.07.036) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 Histologic findings from spinal cord. The presented photomicrographs are from ventral horns of the (A) control group porcine and (B) RIPC group porcine. Although the infarction score difference was not significant, the evident ischemia can be seen in the control group porcine. Spinal cord anterior horn shows ischemic, eosinophilic motor neurons (arrowheads), and vacuolar rarefaction of the background (asterisk), whereas in the RIPC group (B), stromal elements and motor neurons (arrow) are viable. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 777-785DOI: (10.1016/j.jtcvs.2015.07.036) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions

Motor-evoked potential amplitude is higher after remote ischemic preconditioning. The Journal of Thoracic and Cardiovascular Surgery 2016 151, 777-785DOI: (10.1016/j.jtcvs.2015.07.036) Copyright © 2016 The American Association for Thoracic Surgery Terms and Conditions