The evolving concept of physiological ischemia training vs. ischemia preconditioning

Abstract

Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning.

Randomized clinical trial of physiological ischemic training for patients with coronary heart disease complicated with heart failure: Safety of training, VEGF of peripheral blood and quality of life

“…The intervention study was a 12-week programme of progressive and individually PIT as described in our previous study ( 3 ). Training was isometric handgrip exercise-induced physical ischemia training.…”

“…A new physiological ischemic training (PIT) programme for older adults has been described by Ni and co-workers ( 3 ). It refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for approximately 4 weeks to trigger molecular and cellular mechanisms to promote angiogenesis and the formation of collateral vessels and protect remote ischemia areas.…”

“…The programme can cause vascular endothelial growth factor (VEGF) and endothelial progenitor cells (EPCs) to increase in peripheral blood, and retrohoming to heart and promote collateral circulation ( 4 ). Our previous study indicated that isometric handgrip exercise-induced physical ischemia training may promote remote collateral growth in CAD patients through EPCs and VEGF release ( 3 ), and the segment score of ischemia area of single-photon emission computed tomography (SPECT) reduced significantly.…”

Isometric Exercise Training for Managing Vascular Risk Factors in Mild Cognitive Impairment and Alzheimer’s Disease

“…The concept that remote ischemic conditioning (RIC) of a limb can support and improve the healthy functioning of distant organs such as the kidneys, heart and the brain has been successfully demonstrated through techniques such as RIC (Hess et al, 2015) and physiological ischemic training (PIT; Ni et al, 2015). …”

“…Inspired by RIC, recently the feasibility of PIT to stimulate remote ischemia has also been investigated. PIT is a technique whereby skeletal muscle is subjected to intense contraction via isometric contraction or tourniquet in order to stimulate physiological ischemia (Ni et al, 2015 ). In animal models, PIT applied eight times daily for 4 weeks to a normal healthy limb has been shown to upregulate vascular endothelial growth factor (VEGF) and facilitate angiogenesis improving blood flow and capillary supply in a remote pathological ischemeic limb (Shen et al, 2009 ; Zhao et al, 2011 ).…”