Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor

Michelsen, Marie Mide; Støttrup, Nicolaj Brejnholt; Schmidt, Michael; Løfgren, Bo; Jensen, Rebekka Vibjerg; Tropak, Michael B.; St-Michel, E. Jean; Redington, Andrew N.; Bøtker, Hans Erik

doi:10.1007/s00395-012-0260-x

Cited by 93 publications

(99 citation statements)

References 49 publications

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“…16 Preconditioning effects of an exercise bout has also been shown previously on cardiac function in patients with coronary artery disease. 17 Early reports have raised concerns about the application of repeated IPC, suggesting repeated protocols may negate vascular protection.…”

Section: Discussionmentioning

confidence: 67%

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Jones

Nyakayiru

Bailey

et al. 2014

Eur J Prev Cardiolog

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Section: Discussionmentioning

confidence: 67%

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Jones

Nyakayiru

Bailey

et al. 2014

Eur J Prev Cardiolog

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“…This demonstrates the ability of IPC to reduce damage upon ischaemic injury in remote areas, possibly through a blood-borne pathway. Furthermore, evidence is present for between-species protection of RIPC, because rabbit hearts demonstrated protection against prolonged ischaemia when perfused with human preconditioned serum (Shimizu et al 2009;Michelsen et al 2012). This suggests a similarity in the factor(s) conferring protection across species, and that such agent(s) remains conserved during such procedures, allowing binding to the recipient receptors.…”

Section: Application Of Ipc In (Pre)clinical Workmentioning

confidence: 99%

“…Interestingly, recent work in animals (Michelsen et al 2012) and humans (Seeger et al 2015) has demonstrated the ability of exercise to protect against cardiac and endothelial ischaemia-reperfusion injury. Moreover, we demonstrated the ability of IPC to enhance exercise performance (de Groot et al 2010), whilst others found effects of IPC in various types of exercise.…”

Section: Summary Future Directions and The Potential Clinical Relevamentioning

confidence: 99%

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms

Thijssen

Maxwell

Green

et al. 2016

Experimental Physiology

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Professor Dick H. J. Thijssen's work is focused on the (primary and secondary) prevention of cardiovascular disease. His work focuses on exploring and understanding the benefits of exercise training and (repeated) ischaemic preconditioning, but also examines the link between the preconditioning effects of exercise and ischaemic preconditioning. The benefits of these interventions are linked to improvement in micro-and macrovessel function and structure, and he explores factors that moderate these effects (e.g. older age, cardiovascular disease). The benefits on the arterial wall, but also activation of the preconditioning pathways, may contribute to the reduction in cardiovascular risk associated with both interventions. His work also aims to understand (haemodynamic) stimuli, such as shear stress and arterial pressure, that mediate improvement in vascular function and structure. Ultimately, this work contributes to identification of (non-)pharmacological strategies in the management of patients with cardiovascular risk and/or disease. New Findings r What is the topic of this review?This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. r What advances does it highlight?We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences.Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size).

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“…The same plasma can be dialyzed, and the dialysate applied to a virgin heart achieves cardioprotection equal in strength to cardioprotection in the RIPC-treated animal. 15,16 The exact nature of the circulating cardioprotective factors released by RIPC remains unknown. RIPC by transient limb ischemia is dependent on intact neural pathways 17 and nitric oxide-sensitive nerve stimulation to release bloodborne, hydrophobic, and small (molecular mass <15 kDa) circulating factor(s), [18][19][20] modify the prosurvival kinase phosphatidylinositol 3-kinase (PI3K)-Akt and the mitogen-activated protein kinase p44/p42 extracellular signal-regulated kinase (ERK)1/2, glycogen-synthase kinase GSK-3β, 21 and STAT5 signaling 22 and finally converge at the mitochondrial level to prevent mitochondrial permeability transition pore opening in early reperfusion (Figure).…”

Section: Schmidt Et Al Remote Ischemic Preconditioning 1279mentioning

confidence: 99%

Remote Ischemic Preconditioning

Schmidt

Kristiansen

Bøtker

2013

Circulation Research

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During the past 3 decades, several experimental studies have shown that ischemic conditioning reduces myocardial damage by modifying ischemia-reperfusion injury. A recent study in the Lancet indicates that remote ischemic preconditioning translates into clinical benefit in patients undergoing coronary artery bypass surgery. The implications of the study extend to patients undergoing elective and acute coronary angioplasty and beyond.Adjunctive therapies to reduce myocardial ischemiareperfusion injury related to cardiac surgery and percutaneous coronary interventions have yet to find their way into clinical practice, mainly because no pharmacological or mechanical cardioprotective strategy has convincingly shown clinically relevant benefit to the patient.1 That may be about to change. In a recent study by Thielmann et al, 2 329 low-risk patients undergoing elective isolated on-pump first-time coronary artery bypass grafting (CABG) were randomized to either standard CABG or CABG preceded by remote ischemic preconditioning (RIPC), achieved by 3 cycles of 5-minute upper limb ischemia through inflation of a blood pressure cuff followed by 5-minute deflation. The results indicate that RIPC confers a prognostic benefit to the patient.The study was conducted as a single-center, double-blind, randomized, controlled trial. The primary end point was perioperative myocardial injury assessed by troponin I release measured at 6, 12, 24, 48, and 72 hours after surgery. The secondary end points comprised all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and repeat revascularization at 30 days, 1 year, and at completion of follow-up, ranging from 1 to >4 years with a mean of 1.54 years. The group demographics were well-matched, and there were no significant differences in baseline risk factors.The authors demonstrated acutely reduced myocardial injury (assessed by troponin I release), as also shown previously by others 3 but, in addition, they also found a reduction in allcause and cardiac mortality, as well as MACCE in the intervention group during the follow-up period. During the follow-up period, MACCE occurred 23 times in the control group versus 8 times in the RIPC group (P=0.011). The authors observed 11 deaths in the control group and only 3 deaths in the RIPC group (P=0.046). The combined end point (death, MACCE, and repeat revascularization) exhibited a hazard ratio of 0.38 (0.21-0.70) in favor of RIPC. There was no difference between groups regarding the need for revascularization.The present study is noteworthy because it is the first to show that the reduction in surrogate end points in patients treated with RIPC before CABG translates into clinical benefit. Although several trials have investigated the effect of RIPC in the context of CABG 3-5 and a recent meta-analysis of these trials indicates that RIPC reduces troponin release in these patients, 6 there is continued skepticism regarding the clinical efficacy of RIPC. In contrast to earlier studies, Thielmann et al 2 conducted a detail...

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Exercise-induced cardioprotection is mediated by a bloodborne, transferable factor

Cited by 93 publications

References 49 publications

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Impact of eight weeks of repeated ischaemic preconditioning on brachial artery and cutaneous microcirculatory function in healthy males

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms

Remote Ischemic Preconditioning

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