Intermittent cycles of remote ischemic preconditioning for diabetic foot ulcer healing

NewsBot · Jun 18, 2015

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Intermittent cycles of remote ischemic preconditioning augment diabetic foot ulcer healing.
Shaked G, Czeiger D, Abu Arar A, Katz T, Harman-Boehm I, Sebbag G
Wound Repair Regen. 2015 Mar;23(2):191-196. doi: 10.1111/wrr.12269

The morbidity and mortality caused by diabetic foot ulcer (DFU) are still significant. Conservative treatment of DFU is often ineffective. Treatment modalities using stem cells directly into the DFU or systematically have been introduced recently. Ischemic preconditioning (IPC) has been proved to be a cheap, simple, and safe method which can augment stem cells number in the peripheral blood circulation. This study's purpose was to test whether IPC can improve DFU healing. Forty diabetic patients were enrolled and divided into study and control groups. All patients received their regular treatment. The study group patients received in addition brief, transient cycles of IPC while the control group patients received a sham procedure only. The procedure was repeated every 2 weeks to complete a follow-up period of 6 weeks. The ulcers were photographed to measure wound area, and the degree of granulation tissue was assessed. No serious adverse events were noted. Twenty-two patients from the study group and 12 from the control group completed the entire follow-up. The ratio of patients who reached complete healing of their ulcer was 9/22 (41%) in the study group compared with 0/12 (0%) in the control group, p = 0.01. Furthermore, the mean remaining ulcer area at the end of the follow-up was significantly smaller in the study group, 25 ± 6% of the initial area vs. 61 ± 10% in the control group, p = 0.007. The degree of granulation increased after one cycle of treatment in 8/24 (33%) study patients compared to 3/16 (19%) in the control group, p = 0.47. Remote, repeated IPC significantly improves the healing of DFU. This simple, safe, inexpensive treatment method should be considered to be routinely applied to diabetic patients with DFU in addition to other regular treatment modalities.
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NewsBot · Jan 29, 2016

2012 review:
Remote Ischemic Conditioning: From Bench to Bedside
Shiang Yong Lim and Derek John Hausenloy
Front Physiol. 2012; 3: 27.

Remote ischemic conditioning (RIC) is a therapeutic strategy for protecting organs or tissue against the detrimental effects of acute ischemia-reperfusion injury (IRI). It describes an endogenous phenomenon in which the application of one or more brief cycles of non-lethal ischemia and reperfusion to an organ or tissue protects a remote organ or tissue from a sustained episode of lethal IRI. Although RIC protection was first demonstrated to protect the heart against acute myocardial infarction, its beneficial effects are also seen in other organs (lung, liver, kidney, intestine, brain) and tissues (skeletal muscle) subjected to acute IRI. The recent discovery that RIC can be induced non-invasively by simply inflating and deflating a standard blood pressure cuff placed on the upper arm or leg, has facilitated its translation into the clinical setting, where it has been reported to be beneficial in a variety of cardiac scenarios. In this review article we provide an overview of RIC, the potential underlying mechanisms, and its potential as a novel therapeutic strategy for protecting the heart and other organs from acute IRI.
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NewsBot · Sep 8, 2017

Remote Ischemic Conditioning
Promising Potential in Wound Repair in Diabetes?
Jano A. Boghossian, Bellal Joseph, Marvin J. Slepian, and David G. Armstrong
Journal of the American Podiatric Medical Association: July 2017, Vol. 107, No. 4, pp. 313-317.

Remote ischemic conditioning involves the use of a blood pressure cuff or similar device to induce brief (3–5 min) episodes of limb ischemia. This, in turn, seems to activate a group of distress signals that has shown the potential ability to improve healing of the heart muscle and other organ systems. Until recently, this has not been tested in people with diabetic foot ulcers. The purpose of this review was to provide background on remote ischemic conditioning and recent data to potentially support its use as an adjunct to healing diabetic foot ulcers and other types of tissue loss. We believe that this inexpensive therapy has the potential to be deployed and incorporated into a variety of other therapies to prime patients for healing and to reduce morbidity in patients with this common, complex, and costly complication.
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NewsBot · Dec 5, 2019

Effects of ischemic conditioning on maximal voluntary plantar flexion contractions.
Cruz RSO et al
J Electromyogr Kinesiol. 2019 Oct;48

Intermittent blood flow restriction to local or remote vascular beds induces endogenous protection against ischemia-reperfusion injury in several tissues and organs. When applied non-invasively by placing occlusion cuffs on the limbs, this ischemic conditioning has been shown to elicit an acute ergogenic response. However, the underlying mechanisms behind this phenomenon remain unknown. Prior research suggest that ischemic conditioning may operate via improved motor discharges from the central nervous system, thus enhancing the electrochemical activation and force generation of agonist muscles. Here we show that, for healthy individuals performing maximal voluntary contractions of the plantar flexors, the acute benefit elicited by ischemic conditioning on maximal isometric ankle torque production is largely explained by parallel gains in the surface myoelectrical activity of the triceps surae. However, the magnitude of this response appears to vary between individuals. These findings indicate that enhanced levels of agonist activity contribute to the ergogenic effect of ischemic conditioning during maximal efforts, thereby enabling more direct assessments of neural output following the procedure.
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NewsBot · Sep 28, 2020

This clinical trial was just registered:
Remote Ischemic Conditioning and Diabetic Foot Ulcers

Study type: Randomized, double blinded, interventional, single-site study. Two groups: Active receiving RIC therapy from the LifeCuff device and standard of care treatment without RIC.

Study population: Adults (18 to 90) with diabetes myelitis presenting with diabetic foot ulcers.

Randomization and sample size: Subjects will be allocated on a 1:1 ratio, yielding a minimum per protocol population (PP Population) of 15 patients in the Active group and 15 in the control group.

Study timeline: Total amount of time from the Screening Visit to the Final Visit is approximately 16 weeks. For patients who meet inclusion criteria, they are randomized into Active or Control treatment groups. In addition they are stratified into groups based on wound etiology: neuropathic (defined as insensate at 2 or more of 5 sites verified by insensitivity to the 5.07 Semmes-Weinstein 10 g monofilament), ischemic (defined as ABI of 0.7 neuro-ischemic (meeting both of above criteria) Subjects will present at DMU Foot and Ankle Clinic on weeks 0, 3, 6, 9, and 12 for the following measurements: 40mL venous blood draw (VEGF, SDF1a) 2mm punch biopsy (CD34+) Local wound perfusion (Laser Speckle[FK2] ) Ulcer size measured by digital planimetry (TissueAnalytics)
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NewsBot · Jul 15, 2021

Impact of repeated remote ischemic conditioning on diabetic foot ulcers: A proof-of-concept study
Matthew Regulski et al
Wound Repair Regen. 2021 Jul 8. doi: 10.1111/wrr.12956.

Patients with a diabetic foot ulcer (DFU) suffer disabilities and are at increased risk for lower extremity amputation. Current standard of care includes debridement, topical antibiotics, and weight off-loading-still resulting in low rates of healing. Previous small-scale research has indicated that repeated remote ischemic conditioning (rRIC) is a novel modality that delivers significantly higher DFU healing rates. This proof-of-concept study was performed to expand the research on the utility of rRIC as an adjunctive treatment in the healing of chronic DFUs. Forty subjects (41 wounds) received rRIC treatment three times weekly in addition to standard of care for 12 weeks. Subjects that did not heal in this time frame but had a significant reduction in wound size were eligible to continue for an 8-week extension period. By the end of the extension period, 31 of the 41 DFU wounds (75.6%) in this study were determined to be healed. This compares favourably to the 25-30% standard of care average healing rate. For additional comparison, another group of patients receiving standard of care alone, by the same investigator, was selected and matched by wound size at baseline and wound location. For this matching cohort, after 20 weeks of treatment, only 15 of the 41 DFU comparison wounds (36.6%) were determined to be healed, in line with other standard of care results. In the rRIC treatment group, the 10 wounds that did not heal, experienced an average reduction in wound area of 54.3%. The results of this proof-of-concept study reinforce earlier evidence that the addition of rRIC to local wound care significantly improves the healing of chronic diabetic foot ulcers.
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