Remote Ischemic Conditioning Group Research Articles

Survival benefits of remote ischemic conditioning in sepsis

BackgroundSepsis remains the leading cause of death in the surgical intensive care unit. Prior studies have demonstrated a survival benefit of remote ischemic conditioning (RIC) in many disease states. The aim of this study was to determine the effects of RIC on survival in sepsis in an animal model and to assess alterations in inflammatory biochemical profiles. We hypothesized that RIC alters inflammatory biochemical profiles resulting in decreased mortality in a septic mouse model. Materials and methodsEight to 12 week C57BL/6 mice received intra-peritoneal injection of 12.5-mg/kg lipopolysaccharide (LPS). Septic animals in the experimental group underwent RIC at 0, 2, and 6 h after LPS by surgical exploration and alternate clamping of the femoral artery. Six 4-min cycles of ischemia-reperfusion were performed. Primary outcome was survival at 5-d after LPS injection. Secondary outcome was to assess the following serum cytokine levels: interferon-γ (IFN-γ), interleukin (IL)-10, IL-1β, and tumor necrosis factoralpha (TNFα) at the baseline before LPS injection, 0 hour after LPS injection, and at 2, 4, 24 hours after induction of sepsis (RIC was performed at 2 h after LPS injection). Kaplan–Meier survival analysis and log-rank test were used. ANOVA test was used to compare cytokine measurements. ResultsWe performed experiments on 44 mice: 14 sham and 30 RIC mice (10 at each time point). Overall survival was higher in the experimental group compared to the sham group (57% versus 21%; P = 0.02), with the highest survival rate observed in the 2-hour post-RIC group (70%). On Kaplan–Meier analysis, 2-h post-RIC group had increased survival at 5 days after LPS (P = 0.04) with hazard ratio of 0.3 (95% confidence interval = 0.09-0.98). In the RIC group, serum concentrations of IFN-γ, IL-10, IL-1β, and TNFα peaked at 2 h after LPS and then decreased significantly over 24 hours (P < 0.0001) compared to the baseline. ConclusionsRIC improves survival in sepsis and has the potential for implementation in the clinical practice. Early implementation of RIC may play an immune-modulatory role in sepsis. Further studies are necessary to refine understanding of the observed survival benefits and its implications in sepsis management.

Cost-effectiveness of remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction.

Remote ischaemic conditioning seems to improve long-term clinical outcomes in patients undergoing primary percutaneous coronary intervention. Remote ischaemic conditioning can be applied with cycles of alternating inflation and deflation of a blood-pressure cuff. We evaluated the cost-effectiveness of remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction from the perspective of the Danish healthcare system. Between February 2007 and November 2008, 251 patients with ST-elevation myocardial infarction were randomly assigned to remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention (n=126) or to primary percutaneous coronary intervention alone (n=125). During a 4-year follow-up period, we used data from Danish medical registries and medical records to estimate within-trial cardiovascular medical care costs and major adverse cardiac and cerebrovascular event-free survival. After 4 years of follow-up, mean cumulative cardiovascular medical care costs were €2763 (95% confidence interval 207-5318, P=0.034) lower in the remote ischaemic conditioning group than in the control group (€12,065 vs. €14,828), while mean major adverse cardiac and cerebrovascular event-free survival time was 0.30 years (95% confidence interval 0.03-0.57, P=0.032) higher in the remote ischaemic conditioning group than in the control group (3.51 vs. 3.21 years). In the cost-effectiveness plane, remote ischaemic conditioning therapy was economically dominant (less costly and more effective) in 97.26% of 10,000 bootstrap replications. Remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention appears to be a cost-effective treatment strategy in patients with ST-elevation myocardial infarction.

Remote Ischemic Conditioning for Preventing Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions/Coronary Angiography: A Meta-Analysis of Randomized Controlled Trials.

It is uncertain whether remote ischemic conditioning (RIC) has a protective effect on contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI)/coronary artery angiography (CAG). We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of RIC on CI-AKI in such patients. PubMed, MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases were searched for RCTs that assessed the effect of RIC on CI-AKI in patients undergoing PCI/CAG. Ten RCTs with 1389 patients (RIC group, 757 and control, 632) were included. The RIC group significantly exerted a lower risk of CI-AKI compared to the controls (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.34-0.77, P = .001), and they had the similar effect on major adverse cardiovascular events within 1 year (OR = 0.36, 95% CI = 0.20-0.66, P < .001). The RIC reduced the rates of death within 30 days, but this was not significant (OR = 0.16, 95% CI = 0.02-1.34, P = .091). The RIC was associated with a significantly lower incidence of CI-AKI in patients following elective PCI/CAG (OR = 0.54, 95% CI = 0.33-0.87, P = .011). The RIC before not after the intervention was effective in reducing the occurrence of CI-AKI (OR: 0.37 vs 1.05, P = .022). The RIC of the upper arm has statistically significant effect on protecting CI-AKI but not that of the lower limb (OR: 0.41 vs 1.41, P = .004). The effect of RIC on CI-AKI was similar between patients with a mean estimated glomerular filtration rate <60 mL/min/1.73 m(2) and those with mean rates ≥60 (OR: 0.23 vs 0.41, P = .333). The RIC reduced the incidence of CI-AKI in those receiving PCI/CAG. And RIC of the upper arm significantly reduced the risk of CI-AKI but not RIC of the lower limb in patients undergoing PCI/CAG.

Secondary brain injury in trauma patients: the effects of remote ischemic conditioning.

Management of traumatic brain injury (TBI) is focused on preventing secondary brain injury. Remote ischemic conditioning (RIC) is an established treatment modality that has been shown to improve patient outcomes secondary to inflammatory insults. The aim of our study was to assess whether RIC in trauma patients with severe TBI could reduce secondary brain injury. This prospective consented interventional trial included all TBI patients admitted to our Level 1 trauma center with an intracranial hemorrhage and a Glasgow Coma Scale (GCS) score of 8 or lower on admission. In each patient, four cycles of RIC were performed within 1 hour of admission. Each cycle consisted of 5 minutes of controlled upper limb (arm) ischemia followed by 5 minutes of reperfusion using a blood pressure cuff. Serum biomarkers of acute brain injury, S-100B, and neuron-specific enolase (NSE) were measured at 0, 6, and 24 hours. Outcome measure was reduction in the level of serum biomarkers after RIC. A total of 40 patients (RIC, 20; control, 20) were enrolled. The mean (SD) age was 46.15 (18.64) years, the median GCS score was 8 (interquartile range, 3-8), and the median head Abbreviated Injury Scale (AIS) score was 3 (interquartile range, 3-5), and there was no difference between the RIC and control groups in any of the baseline demographics or injury characteristics including the type and size of intracranial bleed or skull fracture patterns. There was no difference in the 0-hour S-100B (p = 0.9) and NSE (p = 0.72) level between the RIC and the control group. There was a significant reduction in the mean levels of S-100B (p = 0.01) and NSE (p = 0.04) at 6 hours and 24 hours in comparison with the 0-hour level in the RIC group. This study showed that RIC significantly decreased the standard biomarkers of acute brain injury in patients with severe TBI. Our study highlights the novel therapeutic role of RIC for preventing secondary brain insults in TBI patients. Therapeutic study, level III.

Remote ischemic conditioning and cardioprotection: a systematic review and meta-analysis of randomized clinical trials.

Remote ischemic conditioning (RIC) represents an innovative cardioprotective method that has been investigated in numerous clinical studies providing miscellaneous results. This systematic review and meta-analysis sought to assess RIC-induced effects on myocardial injury biomarkers and clinical outcomes in clinical situations at risk of myocardial ischemia/reperfusion damage. PubMed and Cochrane databases were searched for randomized clinical trials testing any RIC protocol versus a control in a situation or procedure at risk of cardiac ischemia/reperfusion damage, including coronary angioplasty and cardiac or major vascular surgery. Data were collected from publications reporting biological markers of myocardial injury or clinical events, including major adverse cardiovascular and cerebral events (MACCE), all-cause mortality, myocardial infarction incidence, and repeat revascularization. Standardized mean difference (SMD) (continuous outcomes) and odds ratios (OR) (dichotomous outcomes) were compared between groups. Heterogeneity was investigated by means of meta-analysis regression. A total of 53 articles (44 studies) were identified by the search, with 5,317 patients included in the systematic meta-analysis. RIC significantly reduced troponin area under curve (AUC) (SMD -0.27, 95% confidence interval (CI): [-0.36, -0.18]; p < 0.01) and troponin peak (SMD: -0.22, 95% CI: [-0.30, -0.15]; p < 0.01). The same reduction was observed with creatine kinase MB (CK-MB) AUC and peak. Long-term MACCE and all-cause mortality were significantly lower in the RIC group (OR: 0.42, 95% CI [0.28, 0.64]; p < 0.01 vs. OR: 0.27, 95% CI [0.13, 0.58]; p < 0.01, respectively), as was myocardial infarction incidence (OR: 0.54, 95% CI [0.40, 0.73]; p < 0.01). We observed no difference regarding repeat revascularization. RIC appears to be an effective method for reducing ischemia/reperfusion myocardial injury, and our findings suggest that it may reduce long-term clinical events.

224 Stromal Derived Factor 1 Alpha is a Mediator of Conditioning in Human and Rat Myocardium

BackgroundWe have recently demonstrated that stromal cell-derived factor 1α (SDF-1α) limits myocardial infarct size (IS) in a murine model of ischaemia-reperfusion injury (IRI) via its receptor CXCR4. This study aimed...

The Angiogenic Effects of Ischemic Conditioning in Experimental Critical Limb Ischemia

Ischemic conditioning (IC) is a method of angiogenic stimulus for limb ischemia. Here, we aimed to investigate the effects of short-term repeated ischemic stimulus on critical lower limb ischemic injury. Rats were divided into four groups consisting of 40 animals in each group: sham, ischemia, local IC, and remote IC groups. Right-leg critical limb ischemia was achieved through ligation of the iliac artery and vein in male Sprague-Dawley rats except the sham group. Repeated transient ischemia using the tourniquet method was used for IC of lower extremities in the local and remote groups. IC was performed on the right leg for the local group and on the left leg for the remote group. Ten rats in each group were sacrificed for evaluation on days 1, 7, 14, and 30. Endothelial progenitor cell (EPC) counts were measured. Gastrocnemius muscles were evaluated for the degree of ischemia. Laser Doppler blood flow measurements were performed in order to make comparison between the blood flows of the limbs of the groups. The blood flow in the right limb of rats in the sham (1.65 perfusion units [PU]) and local IC (1.67 PU) groups was significantly higher than the ischemic group (1.17 PU) (p = .001 and p = .022 respectively). The levels of EPCs in the ischemia (1.09 ± 0.5) and remote IC groups (1.36 ± 0.8) were significantly higher than the sham (0.38 ± 0.2) group on day 7 (p = .026 and p = .002 respectively). Remote IC and local IC groups exhibited increased histopathological ischemia on day 7 when compared with sham group (p = .001, p = .01 respectively). The angiogenic scores on the 7th, 14th and 30th days for local IC and remote IC groups were significantly higher than sham and ischemia groups. IC seems to be the potent activator of angiogenesis in ischemic tissue. This study provides preliminary data showing that repeated short ischemic stimuli may reduce critical ischemic injury by promoting angiogenesis.

Remote ischemic conditioning enhanced the early recovery of renal function in recipients after kidney transplantation: a randomized controlled trial

BackgroundTo investigate whether remote ischemic conditioning (RIC) can attenuate ischemic reperfusion injury (IRI) in recipients after kidney transplantation using donation after cardiac death. MethodsForty-eight recipients referred for kidney transplantation were recruited. The paired recipients who received the kidneys from the same donor were randomly assigned (one received RIC and the other did not). RIC was induced by three 5-min cycles of brief repetitive ischemia and reperfusion by clamping the exposed external iliac artery. Blood samples were withdrawn at hour 2, hour 12, days 1–7, day 14, and day 30 to measure serum creatinine level and estimated glomerular filtration rate after transplantation. Urine samples were collected at hours 2, 12, 24, and 48 to measure urine neutrophil gelatinase–associated lipocalin after transplantation. Renal tissues were obtained at 30 min for histologic changes after transplantation. ResultsThere were no significant differences in clinical characteristics of the recipients and donors between RIC and control groups. The serum creatinine level was lower in the RIC group compared with that of the control group (12 h, days 1–14, P < 0.05; other P > 0.05); the estimated glomerular filtration rate was higher in the RIC group compared with that of the control group (12 h, days 1–14, P < 0.05; other P > 0.05); urine neutrophil gelatinase–associated lipocalin, an early marker of IRI, was lower in the RIC group at hours 2, 12, 24, and 48 (2 h, 48 h, P > 0.05; 12 h, 24 h, P < 0.05) compared with that of the control group. The graft pathology showed no differences between RIC and control groups. ConclusionsRIC enhanced the early recovery of renal function in recipients after kidney transplantation. Our results provide a novel potential approach to attenuate transplantation-associated IRI.