Remote Limb Ischemic Conditioning and Motor Learning: Evaluation of Factors Influencing Response in Older Adults
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Remote limb ischemic conditioning (RLIC) is a clinically feasible method of promoting tissue protection against subsequent ischemic insult. Recent findings from our lab demonstrated that RLIC robustly enhances motor learning in young, healthy humans. The next step is to determine which individuals would receive maximum benefit from RLIC before applying these findings to clinical rehabilitation populations such as stroke. Numerous factors, such as age, sex, body mass index (BMI), and cardiovascular comorbidities may influence the response. Sixty-nine participants aged 40–80 were randomized to receive either RLIC (n = 33) or sham (n = 36) conditioning. Participants underwent seven consecutive sessions consisting of RLIC or sham conditioning with a blood pressure cuff on the upper extremity and motor training on a stability platform balance task, with two follow-up sessions. Balance change (post-test–pre-test) was compared across participants, groups, and the factors of age, sex, BMI, and comorbidities. Participants in both groups improved their performance on the balance task from pre- to post-test. Overall balance change was independently associated with age and BMI. There was no difference in balance change between RLIC and Sham groups. However, RLIC significantly enhanced balance performance in participants with no comorbidities. Compared with our previous study in young adults, middle-aged and older adults demonstrated smaller improvements on the balance task. RLIC enhanced learning in middle-aged and older adults only in the absence of pre-defined comorbidities. RLIC may be a promising tool for enhancing motor recovery, but the accumulation of comorbidity with age may decrease its effectiveness.
KeywordsIschemic preconditioning Psychomotor performance Comorbidity Cardiovascular disease
The authors thank Adrianna Samatmanivong for assistance with data collection, and the study participants for generously giving their time. This study was funded by the National Institute of Health R01 HD085930.
This study was funded by NIH R01HD085930.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 1.Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74(5):1124–36.Google Scholar
- 4.Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: underlying mechanisms and clinical application. Atherosclerosis. 2009;204(2):334–41. https://doi.org/10.1016/j.atherosclerosis.2008.10.029.Google Scholar
- 10.Ferdinandy P, Hausenloy DJ, Heusch G, Baxter GF, Schulz R. Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev. 2014;66(4):1142–74. https://doi.org/10.1124/pr.113.008300.Google Scholar
- 15.He Z, Crook JE, Meschia JF, Brott TG, Dickson DW, McKinney M. Aging blunts ischemic-preconditioning-induced neuroprotection following transient global ischemia in rats. Curr Neurovasc Res. 2005;2(5):365–74.Google Scholar
- 18.Moro L, Pedone C, Mondi A, Nunziata E, Antonelli IR. Effect of local and remote ischemic preconditioning on endothelial function in young people and healthy or hypertensive elderly people. Atherosclerosis. 2011;219(2):750–2. https://doi.org/10.1016/j.atherosclerosis.2011.08.046.Google Scholar
- 22.Yetgin T, Magro M, Manintveld OC, Nauta ST, Cheng JM, den Uil CA, et al. Impact of multiple balloon inflations during primary percutaneous coronary intervention on infarct size and long-term clinical outcomes in ST-segment elevation myocardial infarction: real-world postconditioning. Basic Res Cardiol. 2014;109(2):403. https://doi.org/10.1007/s00395-014-0403-3.Google Scholar
- 25.Abete P, Cacciatore F, Ferrara N, Calabrese C, de Santis D, Testa G, et al. Body mass index and preinfarction angina in elderly patients with acute myocardial infarction. Am J Clin Nutr. 2003;78(4):796–801.Google Scholar
- 29.Abete P, Ferrara N, Cacciatore F, Sagnelli E, Manzi M, Carnovale V, et al. High level of physical activity preserves the cardioprotective effect of preinfarction angina in elderly patients. J Am Coll Cardiol. 2001;38(5):1357–65.Google Scholar
- 30.Moolman JA, Genade S, Tromp E, Opie LH, Lochner A. Ischaemic preconditioning does not protect hypertrophied myocardium against ischaemia. S Afr Med J. 1997;87(Suppl 3):C151–6.Google Scholar
- 31.Niccoli G, Scalone G, Cosentino N, Fabretti A, Mirizzi AM, Gramegna M, et al. Protective effect of pre-infarction angina on microvascular obstruction after primary percutaneous coronary intervention is blunted in humans by cardiovascular risk factors. Circ J. 2014;78(8):1935–41.Google Scholar
- 32.Takeuchi T, Ishii Y, Kikuchi K, Hasebe N. Ischemic preconditioning effect of prodromal angina is attenuated in acute myocardial infarction patients with hypertensive left ventricular hypertrophy. Circ J. 2011;75(5):1192–9.Google Scholar
- 33.Randall MD, Gardiner SM, Bennett T. Enhanced cardiac preconditioning in the isolated heart of the transgenic ((mREN-2) 27) hypertensive rat. Cardiovasc Res. 1997;33(2):400–9.Google Scholar
- 35.Sloth AD, Schmidt MR, Munk K, Schmidt M, Pedersen L, Sorensen HT, et al. Impact of cardiovascular risk factors and medication use on the efficacy of remote ischaemic conditioning: post hoc subgroup analysis of a randomised controlled trial. BMJ Open. 2015;5(4):e006923. https://doi.org/10.1136/bmjopen-2014-006923.Google Scholar
- 36.Jung O, Jung W, Malinski T, Wiemer G, Schoelkens BA, Linz W. Ischemic preconditioning and infarct mass: the effect of hypercholesterolemia and endothelial dysfunction. Clin Exp Hypertens. 2000;22(2):165–79.Google Scholar
- 37.Kocic I, Konstanski Z, Kaminski M, Dworakowska D, Dworakowski R. Experimental hyperlipidemia prevents the protective effect of ischemic preconditioning on the contractility and responsiveness to phenylephrine of rat-isolated stunned papillary muscle. Gen Pharmacol. 1999;33(3):213–9.Google Scholar
- 40.Kyriakides ZS, Psychari S, Iliodromitis EK, Kolettis TM, Sbarouni E, Kremastinos DT. Hyperlipidemia prevents the expected reduction of myocardial ischemia on repeated balloon inflations during angioplasty. Chest. 2002;121(4):1211–5.Google Scholar
- 43.Kocsis GF, Pipis J, Fekete V, Kovacs-Simon A, Odendaal L, Molnar E, et al. Lovastatin interferes with the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts. Am J Physiol Heart Circ Physiol. 2008;294(5):H2406–9. https://doi.org/10.1152/ajpheart.00862.2007.Google Scholar
- 44.Kelle I, Akkoc H, Uyar E, Erdinc M, Evliyaoglu O, Saribas S, et al. The combined effect of rosuvastatin and ischemic pre- or post-conditioning on myocardial ischemia-reperfusion injury in rat heart. Eur Rev Med Pharmacol Sci. 2015;19(13):2468–76.Google Scholar
- 50.Wider J, Przyklenk K. Ischemic conditioning: the challenge of protecting the diabetic heart. Cardiovasc Diagn Ther. 2014;4(5):383–96. https://doi.org/10.3978/j.issn.2223-3652.2014.10.05.Google Scholar
- 52.Zhuo C, Wang Y, Wang X, Wang Y, Chen Y. Cardioprotection by ischemic postconditioning is abolished in depressed rats: role of Akt and signal transducer and activator of transcription-3. Mol Cell Biochem. 2011;346(1–2):39–47.Google Scholar
- 53.Lee SM, Hutchinson M, Staikopoulos V, Saint DA. Amitriptyline pharmacologically preconditions rat hearts against cardiac ischemic-reperfusion injury. Int J Cardiol. 2015;190:353–9.Google Scholar
- 56.Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010;375(9716):727–34. https://doi.org/10.1016/S0140-6736(09)62001-8.Google Scholar
- 60.Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81. https://doi.org/10.1016/j.jbi.2008.08.010.Google Scholar
- 66.Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol. 2006;26(5):968–76. https://doi.org/10.1161/01.ATV.0000216787.85457.f3.Google Scholar
- 67.Zhou C, Liu Y, Yao Y, Zhou S, Fang N, Wang W, et al. Beta-blockers and volatile anesthetics may attenuate cardioprotection by remote preconditioning in adult cardiac surgery: a meta-analysis of 15 randomized trials. J Cardiothorac Vasc Anesth. 2013;27(2):305–11. https://doi.org/10.1053/j.jvca.2012.09.028.Google Scholar