Sham Remote Ischemic Preconditioning Research Articles

Protective effect of remote ischemic preconditioning on blood pressure control in magnetic resonance-guided focused ultrasound operations

Backrgound. Magnetic resonance-guided focused ultrasound (MR-FUS) is a new non-invasive technology for the surgical treatment of extrapyramidal movement disorders for such pathologies as essential tremor, Parkinson’s disease, etc. In these cases, the brain is injured and a zone of ischemia is formed. Arterial hypertension (AH) is one of the most common pathologies, which is often accompanied by neurological diseases. Objective. To investigate the effect of the remote ischemic preconditioning (RIPC) on blood pressure (BP) during MR-FUS surgery. Design – blinded, randomized, controlled, 2-group study with sham preconditioning. Materials and Methods. Patients were randomized into the RIPC group (cuff systolic BP (SBP) >50 mmHg, n=42) and the group with sham RIPC (cuff diastolic BP (DBP), n=39) before surgery in regime 3 cycles each 5 min with 5 min rest between cycles. Results. While there was a decrease in SBP and DBP before and after the operation in the RIPC group, there was an increase (p<0.001) in the sham RIPC group. Using the Difference-in-Difference equation for SBP, SBP was 8.9 (5.9–11.9) mm Hg higher in the sham RIPC group than in the RIPC group (p<0.01). Conclusion. As a result, MR-FUS operations showed a significant decrease in BP during RIPC compared to the imitation, which confirms the angioprotective effect of preconditioning.

Effect of remote ischemic preconditioning on postoperative gastrointestinal function in patients undergoing laparoscopic colorectal cancer resection.

Patients undergoing laparoscopic colorectal cancer resection have a high incidence of postoperative gastrointestinal dysfunction (POGD). Remote ischemic preconditioning (RIPC) is an organ protection measure. The study investigated the effect of RIPC on postoperative gastrointestinal function. In this single-center, prospective, double-blinded, randomized, parallel-controlled trial, 100 patients undergoing elective laparoscopic colorectal cancer resection were randomly assigned in a 1:1 ratio to receive RIPC or sham RIPC (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the right upper arm served as RIPC stimulus. Patients were followed up continuously for 7 days after surgery. The I-FEED score was used to evaluate the patient's gastrointestinal function after the surgery. The primary outcome of the study was the I-FEED score on POD3. Secondary outcomes include the daily I-FEED scores, the highest I-FEED score, the incidence of POGD, the changes in I-FABP and the inflammatory markers (IL-6 and TNF-α), and the time to first postoperative flatus. A total of 100 patients were enrolled in the study, of which 13 patients were excluded. Finally, 87 patients were included in the analysis, 44 patients in the RIPC group and 43 patients in the sham-RIPC group. Patients assigned to the RIPC group had a lower I-FEED score on POD3 compared with the sham-RIPC group (mean difference 0.86; 95% CI: 0.06 to 1.65; P = 0.035). And patients in the RIPC group were also associated with a lower I-FEED score on POD4 vs the sham-RIPC group (mean difference 0.81; 95% CI: 0.03 to 1.60; P = 0.043). Compared with the sham-RIPC group, the incidence of POGD within 7days after surgery was lower in the RIPC group (P = 0.040). At T1, T2, and T3 time points, inflammatory factors and I-FABP were considerably less in the RIPC group compared to the sham-RIPC group. The time to the first flatus and the first feces was similar in both groups. RIPC reduced I-FEED scores, decreased the incidence of postoperative gastrointestinal dysfunction, and lowered concentrations of I-FABP and inflammatory factors.

Remote ischemic preconditioning enhances aerobic performance by accelerating regional oxygenation and improving cardiac function during acute hypobaric hypoxia exposure.

Remote ischemic preconditioning (RIPC) may improve exercise performance. However, the influence of RIPC on aerobic performance and underlying physiological mechanisms during hypobaric hypoxia (HH) exposure remains relatively uncertain. Here, we systematically evaluated the potential performance benefits and underlying mechanisms of RIPC during HH exposure. Seventy-nine healthy participants were randomly assigned to receive sham intervention or RIPC (4 × 5 min occlusion 180 mm Hg/reperfusion 0 mm Hg, bilaterally on the upper arms) for 8 consecutive days in phases 1 (24 participants) and phase 2 (55 participants). In the phases 1, we measured the change in maximal oxygen uptake capacity (VO2max) and muscle oxygenation (SmO2) on the leg during a graded exercise test. We also measured regional cerebral oxygenation (rSO2) on the forehead. These measures and physiological variables, such as cardiovascular hemodynamic parameters and heart rate variability index, were used to evaluate the intervention effect of RIPC on the changes in bodily functions caused by HH exposure. In the phase 2, plasma protein mass spectrometry was then performed after RIPC intervention, and the results were further evaluated using ELISA tests to assess possible mechanisms. The results suggested that RIPC intervention improved VO2max (11.29%) and accelerated both the maximum (18.13%) and minimum (53%) values of SmO2 and rSO2 (6.88%) compared to sham intervention in hypobaric hypoxia exposure. Cardiovascular hemodynamic parameters (SV, SVRI, PPV% and SpMet%) and the heart rate variability index (Mean RR, Mean HR, RMSSD, pNN50, Lfnu, Hfnu, SD1, SD2/SD1, ApEn, SampEn, DFA1and DFA2) were evaluated. Protein sequence analysis showed 42 unregulated and six downregulated proteins in the plasma of the RIPC group compared to the sham group after HH exposure. Three proteins, thymosin β4 (Tβ4), heat shock protein-70 (HSP70), and heat shock protein-90 (HSP90), were significantly altered in the plasma of the RIPC group before and after HH exposure. Our data demonstrated that in acute HH exposure, RIPC mitigates the decline in VO2max and regional oxygenation, as well as physiological variables, such as cardiovascular hemodynamic parameters and the heart rate variability index, by influencing plasma Tβ4, HSP70, and HSP90. These data suggest that RIPC may be beneficial for acute HH exposure.

Effect of remote ischemic preconditioning on cerebral oxygen saturation in aneurysmal subarachnoid hemorrhage: Secondary analysis of a randomized controlled trial

Remote ischemic preconditioning (RIPC) can ameliorate cerebral vasospasm and delayed cerebral ischemia and improve neurological outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Monitoring of regional cerebral oxygen saturation (rScO2) during the critical phase after aSAH can help detect ischemia and assess the effect of RIPC intervention. We investigated the effect of RIPC on rScO2 in patients with aSAH. Our study was a single-center, prospective, parallel-group, randomized pilot trial. After approval by institutional ethics committee, consenting patients (n = 25) with aSAH presenting within 72 h of ictus and scheduled for surgical clipping of cerebral aneurysm were randomized 1:1 to true RIPC (inflation of upper extremity blood pressure cuff thrice to 30 mmHg above systolic blood pressure for 5 min) or sham RIPC (inflation of blood pressure cuff thrice to 30 mmHg for 5 min). In this secondary analysis, our outcome measures assessed by a blinded observer were incidence of cerebral oxygen desaturation (COD) during 7–10 days after ictus and Glasgow outcome scale extended (GOSE) at discharge. The incidence of COD (decrease in rScO2 > 20% from baseline) was lower in the RIPC group (15.4% versus 33.3%); p = 0.378. The absence of ipsilateral COD resulted in a higher mean GOSE (estimate 1.15, p = 0.015). The RIPC group had a higher mean GOSE compared to sham group (estimate 0.8, p = 0.027). This pilot trial demonstrated that RIPC has the potential to prevent COD in patients with aSAH. Larger trials with cerebral oxygenation as the primary outcome are needed to confirm our findings.

Effect of remote ischemic preconditioning on cerebral vasospasm, biomarkers of cerebral ischemia, and functional outcomes in aneurysmal subarachnoid hemorrhage (ERVAS): A randomized controlled pilot trial.

BACKGROUND:Cerebral vasospasm can complicate aneurysmal subarachnoid hemorrhage (aSAH), contributing to cerebral ischemia. We explored the role of remote ischemic preconditioning (RIPC) in reducing cerebral vasospasm and ischemia and improving outcomes after aSAH.MATERIALS AND METHODS:Patients with ruptured cerebral aneurysm undergoing surgical clipping and meeting the trial criteria were randomized to true RIPC (n = 13) (inflating upper extremity blood pressure cuff thrice to 30 mmHg above systolic pressure for 5 min) or sham RIPC (n = 12) (inflating blood pressure cuff thrice to 30 mmHg for 5 min) after ethical approval. A blinded observer assessed outcome measures-cerebral vasospasm and biomarkers of cerebral ischemia. We also evaluated the feasibility and safety of RIPC in aSAH and Glasgow Outcome Scale-Extended (GOSE).RESULTS:Angiographic vasospasm was seen in 9/13 (69%) patients; 1/4 patients (25%) in true RIPC group, and 8/9 patients (89%) in sham RIPC group (P = 0.05). Vasospasm on transcranial Doppler study was diagnosed in 5/25 (20%) patients and 1/13 patients (7.7%) in true RIPC and 4/12 patients (33.3%) in sham RIPC group, (P = 0.16). There was no difference in S100B and neuron-specific enolase (NSE) levels over various time-points within groups (P = 0.32 and 0.49 for S100B, P = 0.66 and 0.17 for NSE in true and sham groups, respectively) and between groups (P = 0.56 for S100B and P = 0.31 for NSE). Higher GOSE scores were observed with true RIPC (P = 0.009) unlike sham RIPC (P = 0.847) over 6-month follow-up with significant between group difference (P = 0.003). No side effects were seen with RIPC.CONCLUSIONS:RIPC is feasible and safe in patients with aSAH and results in a lower incidence of vasospasm and better functional outcome.

Effects of Different Doses of Remote Ischemic Preconditioning on Kidney Damage Among Patients Undergoing Cardiac Surgery: A Single-Center Mechanistic Randomized Controlled Trial.

We have previously shown that remote ischemic preconditioning reduces acute kidney injury (acute kidney injury) in high-risk patients undergoing cardiopulmonary bypass and that the protective effect is confined to patients who exhibit an increased urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 in response to remote ischemic preconditioning. The purpose of this study was to determine the optimal intensity of remote ischemic preconditioning to induce required [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] changes and further explore mechanisms of remote ischemic preconditioning. Observational and randomized controlled, double-blind clinical trial. University Hospital of Muenster, Germany. High-risk patients undergoing cardiac surgery as defined by the Cleveland Clinic Foundation Score. In the interventional part, patients were randomized to receive either one of four different remote ischemic preconditioning doses (3 × 5 min, 3 × 7 min, 3 × 10 min remote ischemic preconditioning, or 3 × 5 min remote ischemic preconditioning + 2 × 10 min remote ischemic preconditioning in nonresponders) or sham-remote ischemic preconditioning (control). The primary endpoint of the interventional part was change in urinary [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] between pre- and postintervention. To examine secondary objectives including acute kidney injury incidence, we included an observational cohort. A total of 180 patients were included in the trial (n = 80 observational and n = 100 randomized controlled part [20 patients/group]). The mean age was 69.3 years (10.5 yr), 119 were men (66.1%). Absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] were significantly higher in all remote ischemic preconditioning groups when compared with controls (p < 0.01). Although we did not observe a dose-response relationship on absolute changes in [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] across the four different remote ischemic preconditioning groups, in the 15 patients failing to respond to the lowest dose, nine (60%) responded to a subsequent treatment at a higher intensity. Compared with controls, fewer patients receiving remote ischemic preconditioning developed acute kidney injury within 72 hours after surgery as defined by both Kidney Disease: Improving Global Outcomes criteria (30/80 [37.5%] vs 61/100 [61.0%]; p = 0.003). All doses of remote ischemic preconditioning significantly increased [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] and significantly decreased acute kidney injury compared with controls. High-dose remote ischemic preconditioning could stimulate [tissue inhibitor of metalloproteinases-2]*[insulin-like growth factor-binding protein 7] increases in patients refractory to low-dose remote ischemic preconditioning.

The clinical utility of remote ischemic preconditioning in protecting against cardiac surgery-associated acute kidney injury: A pilot randomized clinical trial.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-known, serious complication and a well-recognized independent risk factor for higher morbidity and mortality among patients undergoing cardiac surgery. The aim of the study was to assess the efficacy of remote ischemic preconditioning (RIPC) in reducing the incidence of CSA-AKI, measured with the standard creatinine technique and using neutrophil gelatinase-associated lipocalin (NGAL) serum concentrations as a potential new biomarker of kidney damage. The ethics committee of the Medical University of Lodz prospectively approved the protocol (approval No. RNN/286/13/KE). The study was retrospectively registered with the U.S. National Institutes of Health - NIH (29 June 2017; ClinicalTrials.gov identifier: NCT03205410). We conducted a prospective single-center double-blind randomized and controlled tudy. Data was collected from patients admitted to the Cardiosurgery Clinic at the Medical University of Lodz (Poland) between January and December 2014, scheduled for elective cardiac surgery (an off-pump coronary artery bypass). A total of 28 patients were randomized to receive either RIPC (n = 14) or sham RIPC (n = 14). After the induction of anesthesia, the patients assigned to the RIPC group underwent 3 cycles of five-minute inflation to 200 mm Hg and five-minute deflation of the upper-arm cuff. The control group had a deflated cuff placed on the upper arm for 30 min. The authors measured the patients' serum creatinine concentration to check for the occurrence of a CSA-AKI within 48 h after cardiac surgery, and NGAL serum concentration to check its level within 3 h after the operation. Fewer patients in RIPC group developed CSA-AKI within 48 h after cardiac surgery than in the control group (29% vs 93%; p = 0.003). Fewer patients in the RIPC group presented an increase in NGAL 3 h after surgery (medians: 124 vs 176.7; p = 0.0003). In patients undergoing an off-pump coronary artery bypass, RIPC significantly reduces the occurrence of CSA-AKI and protects against increased postoperative NGAL levels.

Effect of Remote Ischemic Preconditioning in Patients Undergoing Hepatectomy With Portal Triad Clamping: A Randomized Controlled Trial.

Remote ischemic preconditioning (RIPC) is reported to reduce liver injury in patients undergoing hepatectomy for colorectal liver metastasis, but its role is unclear in hepatocellular carcinoma patients with portal triad clamping during hepatectomy. In this prospective, randomized trial, 140 patients with hepatocellular carcinoma undergoing liver resection requiring portal triad clamping were randomized to a RIPC group or a control group. Patients in the RIPC group received RIPC (3 cycles of 5-minute ischemia and 5-minute reperfusion in right upper limb with cuff pressure at 30 kPa [225 mm Hg]) approximately 10 minutes after induction of anesthesia. In the control group, patients received sham RIPC (the cuff was not inflated). The primary outcome was the postoperative peak level of total bilirubin (TBIL) and was analyzed with the independent t test. Secondary outcomes were liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. Data from 136 patients (69 in the RIPC group and 67 in the control group) were analyzed. The RIPC group had on average a 5.9 μmol lower peak level of TBIL than the control group; the mean difference is -5.9, and the 95% confidence interval (CI) reverses to -17.9 to 6.1. There were no significant differences between the 2 groups in liver function test at postoperative days 1, 3, and 5; postoperative morbidity and mortality during the first month; and the length of postoperative hospital stay. We found no evidence that RIPC can reduce postoperative liver injury after hepatectomy.

Early Renal-Protective Effects of Remote Ischemic Preconditioning in Elderly Patients with Non-ST-Elevation Myocardial Infarction (NSTEMI).

BackgroundWith the wide clinical application of angiography, contrast-enhanced nephropathy (CIN) has become the third-leading cause of acute kidney injury (AKI). Remote ischemic preconditioning (RIPC) is a non-fatal ischemia-reperfusion injury that can provide protection against lethal ischemia-reperfusion. This study aimed to assess the effect of RIPC on CIN in elderly patients with non-ST-elevation myocardial infarction (NSTEMI).Material/MethodsPatients were randomly divided into 2 groups with 119 patients in each group treated with interventional therapy. Patients in the RIPC group received distal ischemic preconditioning 2 h before contrast exposure, while patients in the control group received a sham RIPC procedure. Incidence of CIN was the primary outcome. Changes in creatinine, NGAL, and KIM-1 after contrast administration were secondary outcomes.ResultsCIN occurred in a total of 27 (12.3%) patients, including 12 (10.1%) in the RIPC group and 15 (15.1%) in the control group (P=0.329). RIPC treatment significantly reduced the levels of NGAL (P=0.024) and KIM-1 (P=0.007) at 12 h after contrast administration, suggesting RIPC treatment reduces sub-clinical renal damage. Subgroup analysis revealed that significant reduction of KIM-1 and NGAL by RIPC, mainly occurring in patients with a Mehran risk score of 6–10.ConclusionsAlthough RIPC did not significantly reduce CIN incidence in elderly patients with NSTEMI, the application of more sensitive biomarkers – NGAL and KIM-1 – indicated a reduction of sub-clinical renal damage by RIPC, especially in the early stage of injury. As a simple and well-tolerated method, RIPC may be a potentially feasible option to prevent CIN.

Effect of remote ischemic preconditioning on cerebral vasospasm and biomarkers of cerebral ischemia in aneurysmal subarachnoid hemorrhage (ERVAS): A protocol for a randomized, controlled pilot trial.

INTRODUCTION:Cerebral vasospasm is a dreaded complication of aneurysmal subarachnoid hemorrhage (aSAH) predisposing to delayed cerebral ischemia. We intend to study the cerebroprotective effects of remote ischemic preconditioning (RIPC) in patients with aSAH.MATERIALS AND METHODS:This is a single-center, prospective, parallel group, randomized, pilot trial, approved by the Institutional Ethics Committee. Patients with aSAH admitted to our hospital for surgical clipping; fulfilling the trial inclusion criteria will be randomized to true RIPC (n = 12) (inflating upper extremity blood pressure cuff thrice for 5 min to 30 mmHg above systolic blood pressure) or sham RIPC (n = 12) (inflating blood pressure cuff thrice for 5 min to 30 mmHg) in 1:1 allocation ratio using a computerized random allocation sequence and block randomization.RESULTS:Our primary outcome measure is vasospasm on cerebral angiography and transcranial Doppler study, and concentration of serum S100B and neuron-specific enolase at 24 h after RIPC and on day 7 of ictus. Our secondary outcomes are safety of RIPC, cerebral oxygen saturation, and Glasgow coma score, and extended Glasgow outcome scale scores at discharge and at 1, 3, and 6 months following discharge. Outcome measures will be assessed by an observer blinded to the study intervention.CONCLUSION:If our preliminary results demonstrate a beneficial effect of RIPC, this would serve as a clinically applicable and safe preemptive method of protection against cerebral ischemia.

Safety and Efficacy of Remote Ischemic Preconditioning in Patients With Severe Carotid Artery Stenosis Before Carotid Artery Stenting

Background: Remote ischemic preconditioning (RIPC) can inhibit recurrent ischemic events effectively in patients with acute or chronic cerebral ischemia. However, it is still unclear whether RIPC can impede ischemic injury after carotid artery stenting (CAS) in patients with severe carotid artery stenosis. Methods: Subjects with severe carotid artery stenosis were recruited in this randomized controlled study, and assigned to RIPC, sham, and no intervention (control) groups. All subjects received standard medical therapy. Subjects in the RIPC and sham groups underwent RIPC and sham RIPC twice daily, respectively, for 2 weeks before CAS. Plasma neuron-specific enolase and S-100B were used to evaluate safety, hypersensitive C-reactive protein, and new ischemic diffusion-weighted imaging lesions were used to determine treatment efficacy. The primary outcomes were the presence of ≥1 newly ischemic brain lesions on diffusion-weighted imaging within 48 hours after stenting and clinical events within 6 months after stenting. Results: We randomly assigned 189 subjects in this study (63 subjects in each group). Both RIPC and sham RIPC procedures were well tolerated and completed with high compliance (98.41% and 95.24%, respectively). Neither plasma neuron-specific enolase levels nor S-100B levels changed significantly before and after treatment. No severe adverse event was attributed to RIPC and sham RIPC procedures. The incidence of new diffusion-weighted imaging lesions in the RIPC group (15.87%) was significantly lower than in the sham group (36.51%; relative risk, 0.44; 96% confidence interval, 0.20–0.91; P &lt;0.01) and the control group (41.27%; relative risk, 0.39; 96% confidence interval, 0.21–0.82; P &lt;0.01). The volumes of lesions were smaller in the RIPC group than in the control and sham groups ( P &lt;0.01 each). Ischemic events that occurred after CAS were 1 transient ischemic attack in the RIPC group, 2 strokes in the control group, and 2 strokes and 1 transient ischemic attack in the sham group, but these results were not significantly different among the 3 groups ( P =0.597). Conclusions: RIPC is safe in patients undergoing CAS, which may be able to decrease ischemic brain injury secondary to CAS. However, the mechanisms and effects of RIPC on clinical outcomes in this cohort of patients need further investigation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01654666

Nephroprotective effects of remote ischemic preconditioning in coronary angiography.

Contrast-induced nephropathy (CIN) is a formidable side effect of iodinated contrast medium use in subjects undergoing coronary angiogram (CAG). Remote ischemic preconditioning (RIPC) may reduce the risk of CIN. The aim of the study was to investigate the nephroprotective effects of RIPC in coronary heart disease (CHD) in patients, undergoing CAG, with mild to moderate lowered estimated glomerular filtration rate (eGFR). In the randomized, blinded, sham RIPC (sRIPC) controlled study 51 patients with CHD and GFR less than 80 mL/min/m2, undergoing CAG, were investigated. The patients were randomized for RIPC (n = 26, 60.5±2.0 years) or sRIPC (n = 25, 62.96±1.7). RIPC was performed before the CAG by means of 3-5-minute cycle cuff pumped on the upper arm + 50 mm Hg above the systolic blood pressure (BP), while in sRIPC it corresponded to diastolic BP. The primary endpoint was the development of CIN and secondary - change of biomarkers (creatinine, urea, neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C). In RIPC group, CIN occurred in 28% of cases, while in sRIPC - 3.8%. All investigated markers increased in sRIPC and declined in RIPC; the difference was significant in markers between the groups before and after CAG. RIPC proved nephroprotective effect in prevention of contrast-induced nephropathy in CHD subjects with mild to moderate lowered eGFR.

Pilot randomized controlled trial on early and late remote ischemic preconditioning prior to complex cardiac surgery in young infants.

Remote ischemic preconditioning involves providing a brief ischemia-reperfusion event to a tissue to create subsequent protection from a more severe ischemia-reperfusion event to a different tissue/organ. The few pediatric remote ischemic preconditioning studies in the literature show conflicting results. We conducted a pilot randomized controlled trial to determine the feasibility of conducting a larger trial and to gather provisional data on the effect of early and late remote ischemic preconditioning on outcomes of infants after surgery for congenital heart disease. This single-center, double-blind randomized controlled trial of remote ischemic preconditioning vs control (sham-remote ischemic preconditioning) in young infants going for surgery for congenital heart disease at the Stollery Children's Hospital. Remote ischemic preconditioning was performed at 24-48h preoperatively and immediately prior to cardiopulmonary bypass. Remote ischemic preconditioning stimulus was performed with blood pressure cuffs around the thighs. Primary outcomes were feasibility and peak blood lactate level on day 1 postoperatively. Fifty-two patients were randomized but seven patients became ineligible after randomization leaving 45 patients included in the study. In theincluded patients, 7 (15%) had protocol deviations (five infants did not have the preoperative intervention and two did not receive the intervention in the operating room). From a comfort point of view, only one subject in the control group and two in the Remote ischemic preconditioning group received sedation during the preoperative intervention. There were no study-related adverse events and no complications to the limbs subjected to preconditioning. There were no significant differences between the Remote ischemic preconditioning group and the control group in the highest blood lactate level on day 1 postoperatively (mean difference, 1.28; 95%CI, -0.22, 2.78; P-value=0.093). In infants who underwent surgery for congenital heart disease, our pilot randomized controlled trial on early and late remote ischemic preconditioning proved to be feasible but did not find any significant difference in acute outcomes. A larger trial may be necessary.

The Impact of Remote Ischemic Preconditioning on Arterial Stiffness and Heart Rate Variability in Patients with Angina Pectoris.

Remote ischemic preconditioning (RIPC) is the set of ischemia episodes that protects against subsequent periods of prolonged ischemia through the cascade of adaptive responses; however, the mechanisms of RIPC are not entirely clear. Here, we aimed to study the impact of RIPC in patients with stable angina pectoris and compare it with healthy individuals with respect to arterial stiffness and heart rate variability. In the randomized, sham-controlled, crossover blind design study, a group of 30 coronary heart disease (CHD) patients (63.9 ± 1.6 years) with stable angina pectoris NYHA II-III and a control group of 20 healthy individuals (58.2 ± 2.49) were both randomly allocated for remote RIPC or sham RIPC. Arterial stiffness, pulse wave velocity (Spygmacor, Australia), and heart rate variability (HRV) were recorded before and after the procedure followed by the crossover examination. In the group of healthy individuals, RIPC showed virtually no impact on the cardiovascular parameters, while, in the CHD group, the systolic and central systolic blood pressure, central pulse pressure, and augmentation decreased, and total power of HRV improved. We conclude that ischemic preconditioning reduces not only systolic blood pressure, but also reduces central systolic blood pressure and improves arterial compliance and heart rate modulation reserve, which may be associated with the antianginal effect of preconditioning.

Remote ischaemic pre-conditioning does not affect clinical outcomes following coronary Artery bypass grafting. A systematic review and meta-analysis

BackgroundTrials of remote ischemic pre-conditioning (RIPC) have suggested this intervention reduces complications of angioplasty and coronary artery by-pass grafting (CABG). The aim of this work was to conduct a systematic review and meta-analysis of the effects of RIPC on mortality and myocardial damage in patients undertaking coronary artery bypass grafting with/without valve surgery. MethodsA systematic review and subsequent meta-analysis of randomized controlled trials of RIPC versus usual care or sham RIPC was performed. ResultsEighteen studies, totalling 4551 participants were analysed. RIPC reduced post troponin release as indicated by area under the curve at 72h (μg·L−1) Mean Difference (MD) −3.72 (95% CI −3.92 to −3.53, p<0.00001). However there was no significant difference between RIPC and control when mortality odds ratio (OR) 1.27 (95% CI 0.87 to 1.86, p=0.22); the incidence of new onset atrial fibrillation OR 0.82 (95% CI 0.67 to 1.01, p=0.06); inotropic support OR 1.27 (95% CI 0.84 to 1.91, p=0.25); intensive care unit stay in days MD −0.02 (95% CI −0.12 to 0.07, p=0.61); Hospital stay in days MD 0.18 (95% CI −0.30 to 0.66, p=0.47) and serum creatinine MD −0.00 (95% CI −0.07 to 0.07, p=0.97) were compared. ConclusionsRIPC reduces does not confer any clinical benefit in patients undertaking CABG with/without valve surgery.

Abstract 17: Remote Ischemic Preconditioning Reduces New Vascular Brain Injury early after Carotid Artery Stenting: A Randomized Controlled Trial

Introduction: Cerebral embolization is a major complication of carotid artery stenting (CAS). Remote ischemic preconditioning (RIPC) have been shown to reduce distal embolization in coronary stenting, but it is unclear whether RIPC can reduce embolization after CAS. Objective: To evaluate the effect of RIPC on cerebral embolization after CAS Hypothesis: We assessed the hypothesis that RIPC can reduce new vascular brain injury early after CAS. Methods: 189 symptomatic carotid artery stenosis patients treated with CAS, were allocated randomly to RIPC group, control group, and sham RIPC group. All patients received standard background medical therapy. Patients in the RIPC and sham RIPC group underwent RIPC and sham RIPC twice daily respectively. The primary outcome was incidence of new brain parenchymal lesions on MRI at 48hr after CAS. The secondary outcomes were lesion size and occurrence of clinical events within 6 months after CAS. One-way ANOVA, Chi-Square test and Wilcoxon signed-rank test were used accordingly. Results: 162 patients, who completely finished CAS and MRI, were included in the primary analysis. Incidence of new lesions on post-treatment MRI was 19.23% in the RIPC group, 46.43% in the control group (RR, 0.41; 95% CI 0.22-0.77; p=0.003) and 42.59% in the sham RIPC group (RR, 0.45; 95% CI 0.24-0.85; p=0.009). Median volumes of new lesions and median total lesion volume were both smaller in RIPC group than other 2 groups (p&lt;0.01 each). However, no statistical difference was observed between the groups regarding clinical events. Conclusions: RIPC was associated with a significant reduction in the occurrence of new brain parenchymal lesions within 2 days of CAS. These results need to be replicated and future larger studies should be sufficiently powered to examine the effect of RIPC on clinical events after CAS.

Effect of Remote Ischemic Preconditioning on Platelet Activation Induced by Coronary Procedures

In this study, we aim to assess whether remote ischemic preconditioning (RIPC) reduces platelet activation during coronary angiography (CA) and/or percutaneous coronary interventions. We studied 30 patients who underwent CA because of a suspect of stable angina. Patients were randomized to RIPC (3 short episodes of forearm ischemia) or sham RIPC (controls) before the procedure. Blood samples were collected at baseline, at the end of the procedure, and 24 hours later. Monocyte-platelet aggregate (MPA) formation and platelet CD41 in the MPA gate and CD41 and CD62 expression in the platelet gate were assessed by flow cytometry, in the absence and in the presence of adenosine diphosphate (ADP) stimulation. A significant increase in platelet activation occurred during the invasive procedure in controls, which persisted at 24 hours. However, compared with controls, RIPC group showed no or a lower increase in platelet variables, including MPA formation (p <0.0001) and CD41 (p = 0.002) in the MPA gate and CD41 (p <0.0001) and CD62 (p = 0.002) in the platelet gate. ADP increased platelet activation at baseline, but did not further increase platelet reactivity during the invasive procedure in either groups. Percutaneous coronary interventions, performed in 10 patients (6 in the RIPC group and 4 in controls), did not have any further significant effect on platelet activation and reactivity compared with CA alone. In conclusion, RIPC reduces platelet activation occurring during CA. In contrast, no effects were observed on platelet response to ADP stimulation, probably related to the administration of an ADP antagonist in all patients.

Effect of Remote Ischemic Preconditioning on Kidney Injury Among High-Risk Patients Undergoing Cardiac Surgery

No interventions have yet been identified to reduce the risk of acute kidney injury in the setting of cardiac surgery. To determine whether remote ischemic preconditioning reduces the rate and severity of acute kidney injury in patients undergoing cardiac surgery. In this multicenter trial, we enrolled 240 patients at high risk for acute kidney injury, as identified by a Cleveland Clinic Foundation score of 6 or higher, between August 2013 and June 2014 at 4 hospitals in Germany. We randomized them to receive remote ischemic preconditioning or sham remote ischemic preconditioning (control). All patients completed follow-up 30 days after surgery and were analyzed according to the intention-to-treat principle. Patients received either remote ischemic preconditioning (3 cycles of 5-minute ischemia and 5-minute reperfusion in one upper arm after induction of anesthesia) or sham remote ischemic preconditioning (control), both via blood pressure cuff inflation. The primary end point was the rate of acute kidney injury defined by Kidney Disease: Improving Global Outcomes criteria within the first 72 hours after cardiac surgery. Secondary end points included use of renal replacement therapy, duration of intensive care unit stay, occurrence of myocardial infarction and stroke, in-hospital and 30-day mortality, and change in acute kidney injury biomarkers. Acute kidney injury was significantly reduced with remote ischemic preconditioning (45 of 120 patients [37.5%]) compared with control (63 of 120 patients [52.5%]; absolute risk reduction, 15%; 95% CI, 2.56%-27.44%; P = .02). Fewer patients receiving remote ischemic preconditioning received renal replacement therapy (7 [5.8%] vs 19 [15.8%]; absolute risk reduction, 10%; 95% CI, 2.25%-17.75%; P = .01), and remote ischemic preconditioning reduced intensive care unit stay (3 days [interquartile range, 2-5]) vs 4 days (interquartile range, 2-7) (P = .04). There was no significant effect of remote ischemic preconditioning on myocardial infarction, stroke, or mortality. Remote ischemic preconditioning significantly attenuated the release of urinary insulinlike growth factor-binding protein 7 and tissue inhibitor of metalloproteinases 2 after surgery (remote ischemic preconditioning, 0.36 vs control, 0.97 ng/mL2/1000; difference, 0.61; 95% CI, 0.27-0.86; P < .001). No adverse events were reported with remote ischemic preconditioning. Among high-risk patients undergoing cardiac surgery, remote ischemic preconditioning compared with no ischemic preconditioning significantly reduced the rate of acute kidney injury and use of renal replacement therapy. The observed reduction in the rate of acute kidney injury and the need for renal replacement warrants further investigation. German Clinical Trials Register Identifier: DRKS00005333.

Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double-blinded controlled clinical trial

Novel cardioprotective strategies are required to improve clinical outcomes in high risk patients undergoing coronary artery bypass graft (CABG)±valve surgery. Remote ischemic preconditioning (RIC), in which brief episodes of non-lethal ischemia and reperfusion are applied to the arm or leg, has been demonstrated to reduce perioperative myocardial injury following CABG±valve surgery. Whether RIC can improve clinical outcomes in this setting is unknown and is investigated in the effect of remote ischemic preconditioning on clinical outcomes (ERICCA) trial in patients undergoing CABG surgery. (ClinicalTrials.gov Identifier: NCT01247545). The ERICCA trial is a multicentre randomized double-blinded controlled clinical trial which will recruit 1,610 high-risk patients (Additive Euroscore ≥5) undergoing CABG±valve surgery using blood cardioplegia via 27 tertiary centres over 2years. The primary combined endpoint will be cardiovascular death, non-fatal myocardial infarction, coronary revascularization and stroke at 1year. Secondary endpoints will include peri-operative myocardial and acute kidney injury, intensive care unit and hospital stay, inotrope score, left ventricular ejection fraction, changes of quality of life and exercise tolerance. Patients will be randomized to receive after induction of anesthesia either RIC (4 cycles of 5min inflation to 200mmHg and 5min deflation of a blood pressure cuff placed on the upper arm) or sham RIC (4 cycles of simulated inflations and deflations of the blood pressure cuff). The findings from the ERICCA trial have the potential to demonstrate that RIC, a simple, non-invasive and virtually cost-free intervention, can improve clinical outcomes in higher-risk patients undergoing CABG±valve surgery.

Limb Remote Ischemic Preconditioning Protects the Spinal Cord from Ischemia–Reperfusion Injury

It remains to be established whether spinal cord ischemic tolerance can be induced by limb remote ischemic preconditioning (RIPC), and the mechanisms underlying the neuroprotective effects of RIPC on the spinal cord need to be clarified. Spinal cord ischemia was studied in New Zealand White rabbits. In experiment 1, all rabbits were subjected to 20-min spinal cord ischemia by aortic occlusion. Thirty minutes before ischemia, rabbits were subjected to sham intervention or RIPC achieved by bilateral femoral artery occlusion (10 min ischemia/10 min reperfusion, two cycles). Dimethylthiourea (500 mg/kg, intravenously), a hydroxyl radical scavenger, or vehicle was given 1 h before RIPC. Antioxidant enzyme activity was measured along with spinal cord histology and neurologic function. In experiment 2, rabbits were subjected to spinal cord ischemia, with or without RIPC. In addition, rabbits were pretreated with various doses of hexamethonium. RIPC improved neurologic function and reduced histologic damage. This was associated with increased endogenous antioxidant activity. Dimethylthiourea inhibited the protective effects of RIPC. In contrast, there was no effect of hexamethonium on the protective effect of RIPC. An initial oxidative stress acts as a trigger to upregulate antioxidant enzyme activity, rather than the neural pathway, and plays an important role in the formation of the tolerance against spinal cord ischemia by limb RIPC.