title: Remote ischemic preconditioning triggers changes in autonomic nervous system activity: implications for cardioprotection.
abstract: Cardioprotective efficacy of remote ischemic preconditioning (RIPC) remains controversial. Experimental studies investigating RIPC have largely monitored cardiovascular changes during index ischemia and reperfusion with little work investigating changes during RIPC application. This work aims to identify cardiovascular changes associated with autonomic nervous system (ANS) activity during RIPC and prior to index ischemia. RIPC was induced in anesthetized male C57/Bl6 mice by four cycles of 5 min of hindlimb ischemia using inflated cuff (200 mmHg) followed by 5 min reperfusion. Electrocardiography (ECG) and microcirculatory blood flow in both hindlimbs were recorded throughout RIPC protocol. Heart rate variability (HRV) analysis was performed using ECG data. Hearts extracted at the end of RIPC protocol were used either for measurement of myocardial metabolites using high-performance liquid chromatography or for Langendorff perfusion to monitor function and injury during 30 min index ischemia and 2 h reperfusion. Isolated-perfused hearts from RIPC animals had significantly less infarct size after index ischemia and reperfusion (34 ± 5% vs. 59 ± 7%; mean ± SEP< 0.05). RIPC protocol was associated with increased heart rate measured both in ex vivo and in vivo. Frequency ratio of HRV spectra was altered in RIPC compared to control. RIPC was associated with a standard hyperemic response in the cuffed-limb but there was a sustained reduction in blood flow in the uncuffed contralateral limb. RIPC hearts (prior to index ischemia) had significantly lower phosphorylation potential and energy charge compared to the control group. In conclusion, RIPC is associated with changes in ANS activity (heart rate, blood flow, HRV) and mild myocardial ischemic stress that would contribute to cardioprotection.
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, Faculty of Medicine & Dentistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Safa
authors.initials: S
authors.lastname: Abdul-Ghani
authors.affiliation: Research Institute for Complex Problems of Hygiene and Occupational Diseases, Novokuznetsk Kemerovo Oblast, Russia.
authors.forename: Arnold N
authors.initials: AN
authors.lastname: Fleishman
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, Faculty of Medicine & Dentistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Igor
authors.initials: I
authors.lastname: Khaliulin
authors.affiliation: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Marco
authors.initials: M
authors.lastname: Meloni
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, Faculty of Medicine & Dentistry, University of Bristol, Bristol, United Kingdom.
authors.forename: Gianni D
authors.initials: GD
authors.lastname: Angelini
authors.affiliation: Bristol Heart Institute, School of Clinical Sciences, Faculty of Medicine & Dentistry, University of Bristol, Bristol, United Kingdom m.s.suleiman@bristol.ac.uk.
authors.forename: M-Saadeh
authors.initials: MS
authors.lastname: Suleiman
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology*; D006339:Heart Rate; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism
keywords: Autonomic nervous system; blood flow; cardiac; ischemia; remote ischemic preconditioning