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

Abstract

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).

Effects of Exercise on Vascular Function, Structure, and Health in Humans

“…Likewise, studies on endothelin and angiotensin-mediated vasoconstriction and exercise training are scant and the impacts of training are not particularly well described (Maeda et al 2001;Adams et al 2005;Thijssen et al 2007;Van Guilder et al 2007;Nyberg et al 2014). Also, recent evidence relating to the impacts of ischemic preconditioning raise the intriguing prospect that biologically active agents derived from working skeletal muscle may have effects on the remote vascular territories (Thijssen et al 2016).…”

Remote ischaemic conditioning in the context of type 2 diabetes and neuropathy: the case for repeat application as a novel therapy for lower extremity ulceration

“…RRIC improves skin perfusion in addition to endothelial function, even 8 days beyond RRIC intervention cessation, as demonstrated by Jones et al [45]. It is also suspected that the effects from repeated ischaemia may be due in part to shear stress [57], leading to the mobilisation of EPCs recorded by Kimura et al and thus neovascularisation and improved vascular function [197]. …”

“…Early studies focused upon cardiac [reviewed in 36] and renal [reviewed in 49, 50] endpoints. More recently, the use of RIC has been studied in subarachnoid haemorrhage management, thromboembolic stroke, cardiovascular complications following major vascular surgery, cutaneous blood flow, transplantation surgery [51, 52], skin and lung applications [51], skeletal muscle [53], endothelial function [54, 55] (particularly in RRIC) [reviewed in 56, 57], hypertension [58], and exercise performance [46], some showing more promise than others.…”

“…The mechanisms of RRIC are less well studied than in RIC [57]. Although it would seem logical that they may be similar to RIC, gene expression studies by Depre et al and Shen et al demonstrated this is not correct [194, 195].…”

Ischemic preconditioning: Potential impact on exercise performance and underlying mechanisms

“…As this method is relatively easy to conduct and noninvasive, IPC may have various advantages in athletic and clinical settings. Regarding clinical relevance, the effects of repeated tissue exposure to ischemic preconditioning on cardiovascular function and potential mechanisms have been extensively reviewed 3) . However, the mechanisms on how IPC may influence exercise performance are largely unknown; either vascular function or metabolic efficiency may relate to exercise performance in response to IPC.…”