Remote Ischemic Preconditioning In Patients Research Articles

Association between Ranolazine, Ischemic Preconditioning, and Cardioprotection in Patients Undergoing Scheduled Percutaneous Coronary Intervention.

Background and Objectives: Remote ischemic preconditioning (RIPC) has demonstrated efficacy in protecting against myocardial ischemia-reperfusion injury when applied before percutaneous coronary revascularization. Ranolazine, an anti-ischemic drug, has been utilized to minimize ischemic events in chronic angina patients. However, there is a lack of trials exploring the combined effects of ranolazine pretreatment and RIPC in patients undergoing percutaneous coronary interventions (PCIs). Materials and Methods: The present study is a prospective study which enrolled 150 patients scheduled for nonemergent percutaneous coronary revascularization. Three groups were formed: a control group undergoing only PCIs, an RIPC group with RIPC applied to either upper limb before the PCI (preconditioning group), and a group with RIPC before the PCI along with prior ranolazine treatment for stable angina (ranolazine group). Statistical analyses, including ANOVAs and Kruskal-Wallis tests, were conducted, with the Bonferroni correction for type I errors. A repeated-measures ANOVA assessed the changes in serum enzyme levels (SGOT, LDH, CRP, CPK, CK-MB, troponin I) over the follow-up. Statistical significance was set at p < 0.05. Results: The ranolazine group showed (A) significantly lower troponin I level increases compared to the control group for up to 24 h, (B) significantly lower CPK levels after 4, 10, and 24 h compared to the preconditioning group (p = 0.020, p = 0.020, and p = 0.019, respectively) and significantly lower CPK levels compared to the control group after 10 h (p = 0.050), and (C) significantly lower CK-MB levels after 10 h compared to the control group (p = 0.050). Conclusions: This study suggests that combining RIPC before scheduled coronary procedures with ranolazine pretreatment may be linked to reduced ischemia induction, as evidenced by lower myocardial enzyme levels.

Effect of remote ischemic preconditioning in patients undergoing laparoscopic colorectal cancer surgery: a randomized controlled trial

Background Remote ischemic preconditioning (RIPC) is reported to reduce ischemia-reperfusion injury (IRI) in many vital organs by inhibiting a systemic inflammatory response. Inflammation also plays an essential role in the pathophysiology of prolonged post-operative ileus (PPOI) in patients undergoing colorectal cancer (CRC) surgery. However, the role of RIPC is unclear in reducing the incidence of PPOI in patients undergoing CRC surgery. Methods This was a prospective, randomized trial of RIPC vs. placebo-controlled in patients undergoing elective laparoscopic CRC surgery. Eighty patients were randomized to either a RIPC group or a control group (40 per arm), with computer-generated randomization. The aim was to determine whether RIPC improved the recovery of gut function. The primary outcomes assessed were time to gastrointestinal tolerance and incidence of PPOI. Results Median time to stool of the RIPC group was significantly lower than that of the control group [RIPC vs. control, 4.0 (3.0, 6.0) vs. 5.0 (4.0, 7.8) days, p = 0.027]. Median time to gastrointestinal tolerance and incidence of PPOI in the RIPC group were lower than the control group; however, there were no statistical differences between the two groups [RIPC vs. control: 5.0 (3.0, 7.0) vs. 6.0 (4.0, 8.8) days, p = 0.178; 15 vs. 30%, p = 0.108]. Conclusion RIPC could shorten the median time to stool in patients undergoing laparoscopic CRC surgery, but did not improve the overall recovery time of gut function or reduce the incidence of PPOI. Registration number ChiCTR2100043313 (http://www.chictr.org.cn). Key points Question: In patients undergoing laparoscopic CRC surgery, does RIPC improve time to the overall recovery of gut function and reduce the incidence of PPOI? Findings: In this randomized clinical trial that included 80 patients undergoing elective laparoscopic CRC surgery, no significant difference was found between the RIPC group and the control group concerning median time to gastrointestinal tolerance and incidence of PPOI. Meaning: RIPC did not improve the time for overall recovery of gut function or reduce the incidence of PPOI in patients undergoing laparoscopic CRC surgery.

Attenuated inflammatory profile following single and repeated handgrip exercise and remote ischemic preconditioning in patients with cerebral small vessel disease.

Background: Similar to remote ischemic preconditioning bouts of exercise may possess immediate protective effects against ischemia-reperfusion injury. However, underlying mechanisms are largely unknown. This study compared the impact of single and repeated handgrip exercise versus remote ischemic preconditioning on inflammatory biomarkers in patients with cerebral small vessel disease (cSVD). Methods: In this crossover study, 14 patients with cSVD were included. All participants performed 4-day of handgrip exercise (4x5-minutes at 30% of maximal handgrip strength) and remote ischemic preconditioning (rIPC; 4x5-minutes cuff occlusion around the upper arm) twice daily. Patients were randomized to start with either handgrip exercise or rIPC and the two interventions were separated by > 9days. Venous blood was drawn before and after one intervention, and after 4-day of repeated exposure. We performed a targeted proteomics on inflammation markers in all blood samples. Results: Targeted proteomics revealed significant changes in 9 out of 92 inflammatory proteins, with four proteins demonstrating comparable time-dependent effects between handgrip and rIPC. After adjustment for multiple testing we found significant decreases in FMS-related tyrosine kinase-3 ligand (Flt3L; 16.2% reduction; adjusted p-value: 0.029) and fibroblast growth factor-21 (FGF-21; 32.8% reduction adjusted p-value: 0.029) after single exposure. This effect did not differ between handgrip and rIPC. The decline in Flt3L after repeated handgrip and rIPC remained significant (adjusted p-value = 0.029), with no difference between rIPC and handgrip (adjusted p-value = 0.98). Conclusion: Single handgrip exercise and rIPC immediately attenuated plasma Flt3L and FGF-21, with the reduction of Flt3L remaining present after 4-day of repeated intervention, in people with cSVD. This suggests that single and repeated handgrip exercise and rIPC decrease comparable inflammatory biomarkers, which suggests activation of shared (anti-)inflammatory pathways following both stimuli. Additional studies will be needed to exclude the possibility that this activation is merely a time effect.

Neuroprotective effect of remote ischemic preconditioning in patients undergoing cardiac surgery: A randomized controlled trial.

BackgroundThe neuroprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing elective cardiopulmonary bypass (CPB)-assisted coronary artery bypass graft (CABG) or valvular cardiac surgery remains unclear.MethodsA randomized, double-blind, placebo-controlled superior clinical trial was conducted in patients undergoing elective on-pump coronary artery bypass surgery or valve surgery. Before anesthesia induction, patients were randomly assigned to RIPC (three 5-min cycles of inflation and deflation of blood pressure cuff on the upper limb) or the control group. The primary endpoint was the changes in S-100 calcium-binding protein β (S100-β) levels at 6 h postoperatively. Secondary endpoints included changes in Neuron-specific enolase (NSE), Mini-mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA) levels.ResultsA total of 120 patients [mean age, 48.7 years; 36 women (34.3%)] were randomized at three cardiac surgery centers in China. One hundred and five patients were included in the modified intent-to-treat analysis (52 in the RIPC group and 53 in the control group). The primary result demonstrated that at 6 h after surgery, S100-β levels were lower in the RIPC group than in the control group (50.75; 95% confidence interval, 67.08 to 64.40 pg/ml vs. 70.48; 95% CI, 56.84 to 84.10 pg/ml, P = 0.036). Compared to the control group, the concentrations of S100-β at 24 h and 72 h and the concentration of NSE at 6 h, 24 h, and 72 h postoperatively were significantly lower in the RIPC group. However, neither the MMSE nor the MoCA revealed significant between-group differences in postoperative cognitive performance at 7 days, 3 months, and 6 months after surgery.ConclusionIn patients undergoing CPB-assisted cardiac surgery, RIPC attenuated brain damage as indicated with the decreased release of brain damage biomarker S100-β and NSE.Clinical trial registration[ClinicalTrials.gov], identifier [NCT01231789].

Safety and efficacy of remote ischemic preconditioning in patients with severe carotid artery stenosis before carotid artery stenting: A proof-of-concept, randomized controlled trial

Background: Remote ischemic preconditioning (RIPC) has been proposed as a possible potential treatment for ischemic stroke. This study aimed to investigate the frequency of micro-embolic brain infarcts after RIPC in patients with stroke who underwent elective carotid artery stenting (CAS) treatment.&#x0D; Methods: This study was managed at Shiraz University of Medical Sciences in southwest Iran. Patients undergoing CAS were randomly allocated into RIPC and control groups. Patients in the RIPC group received three intermittent cycles of 5-minute arm ischemia followed by reperfusion using manual blood cuff inflation/deflation less than 30 minutes before CAS treatment. Afterward, stenting surgery was conducted. Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), was acquired within the first 24 hours after CAS.&#x0D; Results: Seventy-four patients were recruited (79.7% men, age: 72.30 ± 8.57). Both groups of RIPC and control had no significant difference in baseline parameters (P &gt; 0.05). Fifteen patients (40.5%) in the RIPC group and 19 (54.1%) patients in the control group developed restricted lesions in DWI MRI. In DWI+ patients, there were no significant differences according to the number of lesions, lesion surface area, largest lesion diameter, cortical infarcts percent, and ipsilateral and bilateral infarcts between the two groups.&#x0D; Conclusion: Although RIPC is a safe and non-invasive modality before CAS to decrease infarcts, this study did not show the advantage of RIPC in the prevention of infarcts following CAS. It may be because of the small sample size.

Remote ischemic preconditioning in patients undergoing cardiac surgery with six ischemic cycles.

We have previously shown that remote ischemic preconditioning (RIP), which utilizes in part the extracellular RNA (eRNA)/RNase1 pathway, can induce ischemic tolerance in humans. Because RIP has thus far been tested only with four cycles of extremity ischemia/reperfusion, we investigated the influence of six cycles of ischemia on the eRNA/RNase1 pathway in cardiac patients. Six cycles of RIP were carried out in 14 patients undergoing cardiac surgery. Blood samples were taken at 13 timepoints during surgery and at three timepoints after surgery for determining serum levels of RNase1, eRNA, and TNF-α. Trans-cardiac gradients between the myocardial blood inflow and outflow were calculated. Between the fourth and the sixth RIP cycles, a noticeable increase in the levels of eRNA (fourth: 151.6 (SD: 44.2) ng/ml vs sixth: 181.8 (SD: 87.5) ng/ml, p = .071), and a significant increase in RNase1 (fourth: 151.1 (SD: 42.6) U/ml vs sixth: 175.3 (SD: 41.2) U/ml, p = .001), were noted. The trans-cardiac gradients of RNase1 and eRNA before and after ischemia were not significantly different (p = .158 and p = .221; p = .397 and p = .683, respectively). Likewise, the trans-cardiac gradient of TNF-α was similar before and after ischemia. During the first 48h after the surgery, RNase1 activity rose significantly and exceeded baseline values (135.7 (SD: 40.6) U/ml before and 279.2 (SD: 85.6) U/ml after surgery, p = .001) as did eRNA levels (148,6 (SD: 35.4) ng/ml before and 396.5 (SD: 154.5) ng/ml after surgery, p = .005), whereas TNF-α levels decreased significantly (91.7 (SD: 47.7) pg/ml before and 35.7 (SD: 36.9) pg/ml after surgery, p = .001). Six RIP cycles increased the RNase1 levels significantly above those observed with four cycles. More clinical data are required to show whether this translates into a benefit for patients.

Negative interaction between nitrates and remote ischemic preconditioning in patients undergoing cardiac surgery: the ERIC-GTN and ERICCA studies

Remote ischaemic preconditioning (RIPC) using transient limb ischaemia failed to improve clinical outcomes following cardiac surgery and the reasons for this remain unclear. In the ERIC-GTN study, we evaluated whether concomitant nitrate therapy abrogated RIPC cardioprotection. We also undertook a post-hoc analysis of the ERICCA study, to investigate a potential negative interaction between RIPC and nitrates on clinical outcomes following cardiac surgery. In ERIC-GTN, 185 patients undergoing cardiac surgery were randomized to: (1) Control (no RIPC or nitrates); (2) RIPC alone; (3); Nitrates alone; and (4) RIPC + Nitrates. An intravenous infusion of nitrates (glyceryl trinitrate 1 mg/mL solution) was commenced on arrival at the operating theatre at a rate of 2–5 mL/h to maintain a mean arterial pressure between 60 and 70 mmHg and was stopped when the patient was taken off cardiopulmonary bypass. The primary endpoint was peri-operative myocardial injury (PMI) quantified by a 48-h area-under-the-curve high-sensitivity Troponin-T (48 h-AUC-hs-cTnT). In ERICCA, we analysed data for 1502 patients undergoing cardiac surgery to investigate for a potential negative interaction between RIPC and nitrates on clinical outcomes at 12-months. In ERIC-GTN, RIPC alone reduced 48 h-AUC-hs-cTnT by 37.1%, when compared to control (ratio of AUC 0.629 [95% CI 0.413–0.957], p = 0.031), and this cardioprotective effect was abrogated in the presence of nitrates. Treatment with nitrates alone did not reduce 48 h-AUC-hs-cTnT, when compared to control. In ERICCA there was a negative interaction between nitrate use and RIPC for all-cause and cardiovascular mortality at 12-months, and for risk of peri-operative myocardial infarction. RIPC alone reduced the risk of peri-operative myocardial infarction, compared to control, but no significant effect of RIPC was demonstrated for the other outcomes. When RIPC and nitrates were used together they had an adverse impact in patients undergoing cardiac surgery with the presence of nitrates abrogating RIPC-induced cardioprotection and increasing the risk of mortality at 12-months post-cardiac surgery in patients receiving RIPC.

Cardioprotective Properties of Humoral Factors Released after Remote Ischemic Preconditioning in CABG Patients with Propofol-Free Anesthesia-A Translational Approach from Bedside to Bench.

The cardioprotective effect of remote ischemic preconditioning (RIPC) is well detectable in experimental studies but not in clinical trials. Propofol, a commonly used sedative, is discussed to negatively influence the release of humoral factors after RIPC. Further, results from experimental and clinical trials suggest various comorbidities interact with inducible cardioprotective properties of RIPC. In the present study, we went back from bedside to bench to investigate, in male patients undergoing CABG surgery, whether (1) humoral factors are released after RIPC during propofol-free anesthesia and/or (2) DM interacts with plasma factor release. Blood samples were taken from male patients with and without DM undergoing CABG surgery before (control) and after RIPC (RIPC). To investigate the release of cardioprotective humoral factors into the plasma, isolated perfused hearts of young rats (n = 5 per group) were used as a bioassay. The hearts were perfused with patients’ plasma without (Con) and with RIPC (RIPC) for 10 min (1% of coronary flow) before global ischemia and reperfusion. In additional groups, the plasma of patients with DM was administered (Con DM, RIPC DM). Infarct size was determined by TTC staining. Propofol-free RIPC plasma of male patients without DM showed an infarct size of 59 ± 5% compared to 61 ± 13% with Con plasma (p = 0.973). Infarct sizes from patients with DM showed similar results (RIPC DM: 55 ± 3% vs. Con DM: 56 ± 4%; p = 0.995). The release of humoral factors into the blood after RIPC in patients receiving propofol-free anesthesia undergoing CABG surgery did not show any cardioprotective properties independent of a pre-existing diabetes mellitus.

Evaluation of systemic inflammation in response to remote ischemic preconditioning in patients undergoing transcatheter aortic valve replacement (TAVR)

Systemic inflammation can occur after transcatheter aortic valve replacement (TAVR) and correlates with adverse outcome. The impact of remote ischemic preconditioning (RIPC) on TAVR associated systemic inflammation is unknown and was focus of this study. We performed a prospective controlled trial at a single center and included 66 patients treated with remote ischemic preconditioning (RIPC) prior to TAVR, who were matched to a control group by propensity score. RIPC was applied to the upper extremity using a conventional tourniquet. Definition of systemic inflammation was based on leucocyte count, C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), assessed in the first 5 days following the TAVR procedure. Mortality was determined within 6 months after TAVR. RIPC group and matched control group showed comparable baseline characteristics. Systemic inflammation occurred in 66% of all patients after TAVR. Overall, survival after 6 months was significantly reduced in patients with systemic inflammation. RIPC, in comparison to control, did not significantly alter the plasma levels of leucocyte count, CRP, PCT or IL-6 within the first 5 days after TAVR. Furthermore, inflammation associated survival after 6 months was not improved by RIPC. Of all peri-interventional variables assessed, only the amount of the applied contrast agent was connected to the occurrence of systemic inflammation. Systemic inflammation frequently occurs after TAVR and leads to increased mortality after 6 months. RIPC neither reduces the incidence of systemic inflammation nor improves inflammation associated patient survival within 6 months.

Circulating platelet‐derived extracellular vesicles are decreased after remote ischemic preconditioning in patients with coronary disease: A randomized controlled trial

BackgroundBrief nonharmful ischemia, remote ischemic preconditioning (RIPC) has been proposed to confer benefit to patients with coronary artery disease via unknown mechanisms. ObjectivesWe aimed to investigate the effect of RIPC on circulating levels of extracellular vesicles (EVs) and global coagulation and fibrinolytic factors in patients with coronary disease. Patients/MethodsBlood samples were taken from 60 patients presenting for coronary angiography enrolled in a randomized, controlled trial before and after RIPC (3 × 5 min administration of 200 mmHg sphygmomanometer on the arm, n = 31) or sham (n = 29) treatment. Most patients (n = 48) had significant coronary artery disease and all were taking at least one antiplatelet agent. ResultsRemote ischemic preconditioning significantly decreased circulating levels of EVs expressing platelet markers CD41 and CD61 detected by flow cytometry in plasma, whereas no such effect was found on EVs expressing phosphatidylserine, CD62P, CD45, CD11b, CD144, CD31+/CD41–, or CD235a. RIPC had no effect on the overall hemostatic potential assay or circulating antigen levels of tissue plasminogen activator, urokinase, plasminogen activator inhibitor‐1, or plasminogen. Sham treatment had no effect on any studied parameter. Statin use inhibited the effect of RIPC on CD61+ EVs, diabetes modified the effect of RIPC on CD45+ and CD11b+ EVs, and hypertension modified the effect of RIPC on CD235a+ EVs. ConclusionsRemote ischemic preconditioning decreased circulating levels of platelet‐derived EVs in patients with coronary disease taking conventional antiplatelet therapy. This may reflect increased EV clearance/uptake or change in production. Clinical variables may alter the effectiveness of RIPC.

MHRT expression during remote ischemic preconditioning in patients with coronary artery disease

MHRT expression during remote ischemic preconditioning in patients with coronary artery disease

Effects of intense remote ischemic preconditioning in patients undergoing elective off-pump coronary artery bypass graft surgery: a pilot study

Effects of intense remote ischemic preconditioning in patients undergoing elective off-pump coronary artery bypass graft surgery: a pilot study

Remote Ischemic Pre-conditioning in Subarachnoid Hemorrhage: A Prospective Pilot Trial.

Cerebral injury from aneurysmal subarachnoid hemorrhage (aSAH) is twofold. The initial hemorrhage causes much of the injury; secondary injury can occur from delayed cerebral ischemia (DCI). Remote ischemic preconditioning (RIPC) is a mechanism of organ protection in response to transient ischemia within a distant organ. This pilot trial sought to apply RIPC in patients with aSAH to evaluate its effect on secondary cerebral injury and resultant outcomes. Patients were randomized to the high-pressure occlusion group (HPO) or the low-pressure occlusion group (LPO). Lower extremity RIPC treatment was initiated within 72h of symptom onset and every other day for 14days or until Intensive Care Unit (ICU) discharge. In HPO, each treatment consisted of 4 five-minute cycles of manual blood pressure cuff inflation with loss of distal pulses. LPO received cuff inflation with lower pressures while preserving distal pulses. Retrospectively matched controls were also analyzed. Efficacy of treatment was measured by total days spent in vasospasm out of study enrollment days, hospital and ICU length of stay (LOS), cerebral infarction, one and six month modified Rankin score, and mortality. The final analysis included 33 patients with 11 in each group. Patient demographics, aneurysm location, admission airway status, Glasgow Coma Scale (GCS), modified Rankin score, Hunt and Hess score, modified Fisher Score and aneurysm management were not significantly different between groups. Hospital and ICU LOS was shorter in LPO compared to the control (p = 0·0468 and p = 0·0409, respectively). Total vasospasm days/study enrollment days, cerebral infarction, one and six month modified Rankin score, and mortality were not significantly different between the groups. This pilot trial did demonstrate feasibility and safety. The shortened LOS in the LPO may implicate a protective role of RIPC and warrants future study.

Peripheral Artery Disease in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy; Results From the MR CLEAN Registry

Background and Purpose: Though peripheral artery disease (PAD) is a well-known risk factor for ischemic events, better outcomes have been described in acute ischemic stroke patients with co-existing PAD. This paradoxical association has been attributed to remote ischemic preconditioning (RIPC) and might be related to better collateral blood flow. The aim of this study is to compare outcomes after endovascular thrombectomy (EVT) in acute stroke patients with and without PAD and to assess the relation between PAD and collateral grades.Methods: We analyzed acute ischemic stroke patients treated with EVT for an anterior circulation large artery occlusion, included in the Dutch, prospective, multicenter MR CLEAN Registry between March 2014 and November 2017. Collaterals were scored on CT angiography, using a 4-point collateral score. We used logistic regression analysis to estimate the association of PAD with collateral grades and functional outcome, assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included mortality at 90 days, symptomatic intracranial hemorrhage, and stroke progression.Results: We included 2,765 patients for analysis, of whom 254 (9.2%) had PAD. After adjustment for potential confounders, multivariable regression analysis showed no association of PAD with functional outcome [mRS cOR 0.90 (95% CI, 0.7–1.2)], collateral grades (cOR 0.85, 95% CI 0.7–1.1), or safety outcomes.Conclusion: In the absence of an association between the presence of PAD and collateral scores or outcomes after EVT, it may be questioned whether PAD leads to RIPC in patients with acute ischemic stroke due to large vessel occlusion.

The efficiency of remote ischemic preconditioning on serum cystatin C-based acute kidney injury in patients undergoing coronary angiography; a randomized controlled trial

Introduction: Contrast-induced acute kidney injury (CI-AKI) is a known complication of cardiac interventions. Remote ischemic preconditioning (RIPC) is a non-pharmacological method which has a nephroprotective effect. Serum cystatin C (CysC) is a suitable biomarker for the early diagnosis of AKI. Objectives: This study aimed to evaluate the incidence of CI-AKI after RIPC in patients undergoing coronary angiography, through assessment of CysC. Patients and Methods: Around 140 patients with stable coronary artery disease undergoing angiography were randomly allocated to two groups of RIPC and control groups. In each group, the following biomarkers were assessed: serum creatinine (Cr) and CysC at baseline, 24-hour and 48-hour serum Cr and 24-hour CysC. The endpoint was the development of AKI based on either the KDIGO criteria or a 15% increase in serum CysC. Results: No significant difference was observed between two groups regarding the incidence of AKI according to either KIDIGO criteria or by the increase of serum CysC (P =0.116 and P =0.392, respectively). Moreover, a 46.99% increase in CysC level was observed among patients with AKI during the first 24 hours after the procedure, while at the same interval, it increased only 16.01% in patients without AKI. Conclusion: RIPC with three cycles of 5-minute ischemia and 5-minute reperfusion, did not decrease serum CysC based CI-AKI or alter renal biomarkers course in patients with low risk, who underwent coronary angiography.

90 days impacts of remote ischemic preconditioning on patients undergoing open total aortic arch replacement: a post-hoc analysis of previous trial

BackgroundIn the previous randomized controlled trial by our research group, we evaluated the effect of remote ischemic preconditioning (RIPC) in 130 patients (65 per arm) on acute kidney injury (AKI) within 7 days of open total aortic arch replacement. Significantly fewer RIPC-treated patients than sham-treated patients developed postoperative AKI, and, epically, RIPC significantly reduced serious AKI (stage II–III). However, the long-term effect of RIPC in patients undergoing open total aortic arch replacement is unclear.MethodsThis study was a post-hoc analysis. We aimed to assess the roles of RIPC in major adverse kidney events (MAKE), defined as consisting persistent renal dysfunction, renal replacement therapy and mortality, within 90 days after surgery in patients receiving open total aortic arch replacement.ResultsIn this 90-day follow-up study, data were available for all study participants. We found that RIPC failed to improve the presence of MAKE within 90 days after surgery (RIPC: 7 of 65[10.8%]) vs sham: 15 of 65[23.1%]; P = 0.061). In those patients who developed AKI after surgery, we found that the rate of MAKE within 90 days after surgery differed between the RIPC group and the sham group (RIPC: 4 of 36[11.2%]; sham: 14 of 48[29.2%]; P = 0.046).ConclusionsAt 90 days after open total aortic arch replacement, we failed to find a difference between the renoprotective effects of RIPC and sham treatment. The effectiveness or ineffectiveness of RIPC should be further investigated in a large randomized sham-controlled trial.Trial registrationThis study was approved by the Ethics Committee of Fuwai Hospital (No. 2016–835) and our previous study was registered at clinicaltrials.gov before patient enrollment (NCT03141385; principal investigator: G.W.; date of registration: March 5, 2017).

Remote Ischaemic Preconditioning Reduces Kidney Injury Biomarkers in Patients Undergoing Open Surgical Lower Limb Revascularisation: A Randomised Trial.

Background and Aims Perioperative kidney injury affects 12.7% of patients undergoing lower limb revascularisation surgery. Remote ischaemic preconditioning (RIPC) is a potentially protective procedure against organ damage and consists of short nonlethal episodes of ischaemia. The main objective of this substudy was to evaluate the effect of RIPC on kidney function, inflammation, and oxidative stress in patients undergoing open surgical lower limb revascularisation. Materials and Methods. This is a subgroup analysis of a randomised, sham-controlled, double-blinded, single-centre study. A RIPC or a sham procedure was performed noninvasively along with preparation for anaesthesia in patients undergoing open surgical lower limb revascularisation. The RIPC protocol consisted of 4 cycles of 5 minutes of ischaemia, with 5 minutes of reperfusion between every episode. Blood was collected for analysis preoperatively, 2, 8, and 24 hours after surgery, and urine was collected preoperatively and 24 hours after surgery. Results Data of 56 patients were included in the analysis. Serum creatinine, cystatin C, and beta-2 microglobulin increased, and eGFR decreased across all time points significantly more in the sham group than in the RIPC group (p = 0.021, p = 0.021, p = 0.021, p = 0.021, p = 0.021, Conclusions Our finding of reduced release of kidney injury biomarkers may indicate the renoprotective effect of RIPC in patients undergoing open surgical lower limb revascularisation. The trial is registered with ClinicalTrials.gov NCT02689414.

Remote Ischemic Pre-Conditioning in Subarachnoid Hemorrhage: A Prospective Randomized Pilot Trial

Background: Remote ischemic preconditioning (RIPC) is an innate mechanism of organ protection in response to transient ischemia in a distant organ. This pilot trial looks to apply RIPC in patients with aneurysmal subarachnoid hemorrhage (aSAH) to gauge its effect on clinical outcomes. Methods: Patients were randomized to the high pressure occlusion group (HPO) or the low pressure occlusion group (LPO). Retrospectively matched controls were also analyzed. The HPO under went lower extremity RIPC treatments on non-consecutive days. Each treatment was 4 five-minute cycles of manual blood pressure cuff inflation with loss of a distal pulse. LPO received cuff inflation but with pulses present, all other procedures were same as HPO. Primary outcome of vasospasm was measured with neurological change and confirmed with radiological study. Findings: The final analysis was done on 33 patients with 11 in each group. Patient demographics, aneurysm location, admission intubation, GCS, mRankin score, Hunt and Hess score, Fisher Grade and aneurysm management were not significantly different between groups. Vasospasm was not different between groups. Secondary outcome of hospital length of stay (LOS) was shorter in LPO compared to the control (p=0·0400). ICU LOS was also shorter in LPO compared to the control (p= 0·0354). DCI, one and six month mRankin score, and mortality were not significantly different between the groups. Interpretation: A difference in vasospasm was not noted between groups but there was decreased hospital and ICU LOS in the LPO compared to the control group. It has been previously noted that vasospasm do not correlate well with DCI or outcomes. Although DCI was not statistically significant between groups there was increased DCI in the control group compared to LPO. This may be the reason for the LOS improvement. Future studies should focus on DCI and outcome measures to evaluate efficacy of RIPC. Clinical Trial Registration Number: Registered on Clinicaltrials.gov, number NCT02381522. Funding Statement: This study was departmentally funded. No external funding source. Declaration of Interests: All authors have no conflicts of interest. Ethics Approval Statement: Approval was obtained from our University’s Institutional Review Board (#5150015).

Effect of remote ischemic preconditioning in patients with STEMI during primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

Remote ischemic conditioning is usually associated with cardioprotective intervention against ischemia-reperfusion. However, the effect of remote ischemic preconditioning (RIC-pre) completed before myocardial reperfusion with intermittent limb ischemia-reperfusion in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) is unclear. PubMed, EMBASE, and the Cochrane Library were fully searched from the beginning of each database up to September 2019 to find seven RCTs, a total of 2796 patients with STEMI undergoing PPCI with RIC-pre and 2818 patients with STEMI undergoing PPCI alone. No significant discrepancy in cardiac death was observed between RIC-pre and control groups (RR 1.03, 95% CI [0.76-1.41], P = 0.83, I2 = 40%). The incidences of hospitalization for heart failure (RR 1.03, 95% CI [0.85-1.25], P = 0.77, I2 = 0%), myocardial infarction (RR 0.86, 95% CI [0.59-1.26], P = 0.44, I2 = 0%), and stroke (RR 1.04, 95% CI [0.62-1.77], P = 0.87, I2 = 0%) were not decreased in RIC-pre group when compared with control group. Subgroup analysis revealed similar risk in clinical adverse events at long- and short-term follow-up between two groups. However, peak of creatine kinase-myocardial band (CK-MB) was reduced in RIC-pre group (SWD -0.42, 95% CI [-0.77, -0.07], P = 0.02, I2 = 34%). RIC-pre tended to a low peak of CK-MB in patients with STEMI undergoing PPCI, but lacked significant beneficial effects on improving clinical outcomes at long- and short-term follow-up.

Remote ischemic preconditioning in patients undergoing coronary bypass grafting following acute coronary syndrome without ST elevation

Background/Aim. A protection of heart and other organs from ischemic-reperfusion injuries can be provided by remote ischemic preconditioning (RIPC) by brief episodes of ischemia and reperfusion in distant tissues. The aim of this study was to assess effects of RIPC on early outcomes in patients underwent coronary bypass surgery (CABG) following acute coronary syndrome without persistent ST segment elevation (NSTEMI ACS). Methods. This trial included 42 patients randomized into two groups: the group 1 received RIPC and the group 2 was without RIPC (control group). Pre-, intra- and postoperative parameters were compared but primary endpoint was myocardial injury reflected as value of troponin I measured preoperatively and 1, 6, 12, 24, 48 and 72 h postoperatively. The secondary endpoints were hemodynamic parameters, blood loss, intensive care unit stay, mortality etc. Results. The groups 1 and 2 were similar in preoperative characteristics including age, New York Heart Association (NYHA) class, EuroSCORE II, left ventricular ejection fraction. The only significant difference between groups was for triple vessel coronary disease with dominance in the RIPC group [20 (100%) vs. 17 (77.3%), p = 0.049]. Cardiopulmonary bypass time [mean (? standard deviation): 83.0 (22.9) vs. 67.0 (17.4) minutes, p = 0.015], cross clamp time [57.9 (15.4) vs. 44.3 (14.3) minutes, p = 0.005] and number of conduits [median (25?75th percentile): 23.5(3?4) vs. 3(2?3), p = 0.002] were different. Other intra- and postoperative variables did not differ between groups. There were no differences in C reactive protein levels and postoperative hemodynamic parameters. Average troponin values in all time points revealed no significant differences between groups (p0h = 0.740, p1h = 0.212, p6h = 0.504, p12h = 0.597, p24h = 0.562, p48h = 0.465 and p72h = 0.715, respectively). Furthermore, there were no significant differences in adverse events, hospital stay and mortality between groups. Conclusion. Treatment with RIPC during CABG following NSTEMI ACS did not provide better myocardial protection and hemodynamics characteristics but further larger randomized studies are needed t. prove its real value.