The effect of short-term remote ischemic preconditioning on endothelial function of patients with chronic kidney disease: A randomized pilot study.

AIM: Patients with chronic kidney disease (CKD) are more susceptible to endothelial dysfunction and cardiovascular disease (CV). Remote ischemic preconditioning (rIPC) has been proven efficient in improving endothelial function and lowering the risk of CV. However, the safety and effect of rIPC on endothelial function in patients with CKD have not been effectively assessed. METHODS: 45 patients with CKD (average estimated glomerular filtration rate: 48.4 mL/min/1.73 m2) were randomly allocated to either 7-day daily upper-arm rIPC (4 × 5 min 200 mmHg, interspaced by 5-min reperfusion) or control (4 × 5 min 60 mmHg, interspaced by 5-min reperfusion). Vascular endothelial function was assessed by natural log-transformed reactive hyperemia index (LnRHI) before and after a 7-day intervention. Arterial elasticity was assessed by augmentation index (AI). RESULTS: The results showed that LnRHI could be improved by rIPC treatment (Pre = 0.57 ± 0.04 vs. Post = 0.67 ± 0.04, p = .001) with no changes relative to control (Pre = 0.68 ± 0.06 vs. Post = 0.64 ± 0.05, p = .470). Compared with the control group, the improvement of LnRHI was greater after rIPC treatment (rIPC vs. Control: 0.10 ± 0.03 vs. -0.04 ± 0.06, between-group mean difference, -0.15 [95% CI, -0.27 to -0.02], p = .027), while there was no significant difference in the change of AI@75 bpm (p = .312) between the two groups. CONCLUSION: RIPC is safe and well tolerated in patients with CKD. This pilot study suggests that rIPC seems to have the potential therapeutic effect to improve endothelial function. Of note, further larger trials are still warranted to confirm the efficacy of rIPC in improving endothelial function in CKD patients.

[Cytosteatonecrosis after breast reconstruction by fat flap with or without ischemic preconditioning]. / Cytostéatonécrose après reconstruction mammaire par lambeau graisseux avec ou sans préconditionnement ischémique.

INTRODUCTION: Cytosteatonecrosis (CTN) is a frequent postoperative complication after breast autologous reconstruction using DIEP (deep inferior epigastric perforator) flap. CTN radiological diagnostic reveals different types of lesions, as nodes or extended fat necrosis, which become in some cases infected, or pass for tumor recurrence after breast cancer treatment. CTN is caused by intraoperative ischemia of the flap, and no current method can prevent postoperative CTN development after DIEP breast reconstruction. Mechanical ischemic preconditioning, consisting in intraoperative briefs consecutive cycles of ischemia reperfusion using vascular clamp upon the graft pedicle, is used in transplantation surgery. This procedure improves the graft tolerance towards ischemic surgical lesions. The aim of this retrospective observational study was to assess PCIM effects on CTN development after DIEP surgery, comparing CTN occurrence after breast reconstruction using DIEP flap with or without intraoperative PCIM. MATERIAL AND METHODS: All patients breats reconstructed using DIEP flap between novembre 2020 and may 2022, presenting 6 months postoperative breast echography were retrospectively included. Primary outcome was the ultrasonic existence of CTN, according to the Wagner classification. Clinical data, postoperative outcomes such as infection, hematoma or surgical revision, and length of stay in hospital were also recorded. RESULTS: Twenty nine patients among which 8 PCIM were included. CTN occurrence rate after PCIM (25%) was quite lower than CTN rate without PCIM (71,4%), although the difference was not significant (P=0,088). Other postoperative complications rates were not significantly different with or without PCIM. CONCLUSION: PCIM seems to improve CTN occurrence after DIEP breast reconstruction, improving fat flap tolerance to ischemic perioperative lesions. Those preliminary results need to be confirmed with clinical prospective study.

Short-term Outcomes of Different Techniques for Gastric Ischemic Preconditioning Before Esophagectomy: A Network Meta-analysis.

BACKGROUND: Ischemia at the anastomotic site plays a critical role determinant in the development of anastomosis-related complications after esophagectomy. Gastric ischemic conditioning (GIC) before esophagectomy has been described to improve the vascular perfusion at the tip of the gastric conduit with a potential effect on anastomotic leak (AL) and stenosis (AS) risk minimization. Laparoscopic (LapGIC) and angioembolization (AngioGIC) techniques have been reported. PURPOSE: Compare short-term outcomes among different GIC techniques. MATERIALS AND METHODS: Systematic review and network meta-analysis. One-step esophagectomy (noGIC), LapGIC, and AngioGIC were compared. Primary outcomes were AL, AS, and gastric conduit necrosis (GCN). Risk ratio (RR) and weighted mean difference (WMD) were used as pooled effect size measures, whereas 95% credible intervals (CrIs) were used to assess relative inference. RESULTS: Overall, 1760 patients (14 studies) were included. Of those, 1028 patients (58.4%) underwent noGIC, 593 (33.6%) LapGIC, and 139 (8%) AngioGIC. AL was reduced for LapGIC versus noGIC (RR=0.68; 95% CrI 0.47-0.98) and AngioGIC versus noGIC (RR=0.52; 95% CrI 0.31-0.93). Similarly, AS was reduced for LapGIC versus noGIC (RR=0.32; 95% CrI 0.12-0.68) and AngioGIC versus noGIC (RR=1.30; 95% CrI 0.65-2.46). The indirect comparison, assessed with the network methodology, did not show any differences for LapGIC versus AngioGIC in terms of postoperative AL and AS risk. No differences were found for GCN, pulmonary complications, overall complications, hospital length of stay, and 30-day mortality among different treatments. CONCLUSIONS: Compared to noGIC, both LapGIC and AngioGIC before esophagectomy seem equivalent and associated with a reduced risk for postoperative AL and AS.

Prospective Evaluation of a Universally Applied Laparoscopic Gastric Ischemic Preconditioning Protocol Prior to Esophagectomy with Comparison with Historical Controls.

BACKGROUND: Anastomotic leak after esophagectomy is associated with significant morbidity and mortality. Our institution began performing laparoscopic gastric ischemic preconditioning (LGIP) with ligation of the left gastric and short gastric vessels prior to esophagectomy in all patients presenting with resectable esophageal cancer. We hypothesized that LGIP may decrease the incidence and severity of anastomotic leak. METHODS: Patients were prospectively evaluated following the universal application of LGIP prior to esophagectomy protocol in January 2021 until August 2022. Outcomes were compared with patients who underwent esophagectomy without LGIP from a prospectively maintained database from 2010 to 2020. RESULTS: We compared 42 patients who underwent LGIP followed by esophagectomy with 222 who underwent esophagectomy without LGIP. Age, sex, comorbidities, and clinical stage were similar between groups. Outpatient LGIP was generally well tolerated, with one patient experiencing prolonged gastroparesis. Median time from LGIP to esophagectomy was 31 days. Mean operative time and blood loss were not significantly different between groups. Patients who underwent LGIP were significantly less likely to develop an anastomotic leak following esophagectomy (7.1% vs. 20.7%, p = 0.038). This finding persisted on multivariate analysis [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.03-0.42, p = 0.029]. The occurrence of any post-esophagectomy complication was similar between groups (40.5% vs. 46.0%, p = 0.514), but patients who underwent LGIP had shorter length of stay [10 (9-11) vs. 12 (9-15), p = 0.020]. CONCLUSIONS: LGIP prior to esophagectomy is associated with a decreased risk of anastomotic leak and length of hospital stay. Further, multi-institutional studies are warranted to confirm these findings.

Effects of remote ischaemic preconditioning on myocardial injury after major abdominal surgery in patients at high risk for cardiovascular adverse events in China (RIPC-MAS): protocol for a randomised, sham-controlled, observer-blinded trial.

INTRODUCTION: Myocardial injury after non-cardiac surgery (MINS) caused by an ischaemic mechanism is common and is associated with adverse short-term and long-term prognoses. However, MINS is a recent concept, and few studies have prospectively used it as a primary outcome. Remote ischaemic preconditioning (RIPC) is a non-invasive procedure that induces innate cardioprotection and may reduce MINS. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled, observer-blinded trial. Patients with a high clinical risk of cardiovascular events who are scheduled to undergo major abdominal surgery will be enrolled. A total of 766 participants will be randomised (1:1 ratio) to receive RIPC or control treatment before anaesthesia. RIPC will comprise four cycles of cuff inflation for 5 min to 200 mm Hg and deflation for 5 min. In the controls, an identical-looking cuff will be placed around the arm but will not be actually inflated. The primary outcome will be MINS, defined as at least one postoperative cardiac troponin (cTn) concentration above the 99th percentile upper reference limit of the cTn assay as a result of a presumed ischaemic mechanism. This trial will test the concentration of high-sensitivity cardiac troponin T (hs-cTnT). The secondary outcomes will be hs-cTnT levels reaching/above the prognostically important thresholds, peak hs-cTnT and total hs-cTnT release during the initial 3 days after surgery, length of hospital stay after surgery, length of stay in the intensive care unit, myocardial infarction, major adverse cardiovascular events, cardiac-related death, all-cause death within 30 days, 6 months, 1 year and 2 years after surgery, and postoperative complications and adverse events within 30 days after surgery. ETHICS AND DISSEMINATION: This study protocol (version 5.0 on 7 April 2023) was approved by the Ethics Committee of Sixth Affiliated Hospital of Sun Yat-sen University. The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05733208.

Efficacy and safety of remote ischemic conditioning for acute ischemic stroke: A comprehensive meta-analysis from randomized controlled trials.

BACKGROUND AND PURPOSE: Remote ischemic conditioning (RIC) is a remote, transient, and noninvasive procedure providing temporary ischemia and reperfusion. However, there is no comprehensive literature investigating the efficacy and safety of RIC for the treatment of acute ischemic stroke. In the present study, we performed a comprehensive meta-analysis of the available studies. METHODS: MEDLINE, Embase, the Cochrane Library database (CENTRAL), and ClinicalTrials.gov were searched before Sep 7, 2022. The data were analyzed using Review Manager 5.4.1 software, Stata version 16.0 software, and R 4.2.0 software. Odds ratio (OR), mean difference (MD), and corresponding 95% CIs were pooled using fixed-effects meta-analysis. RESULTS: We pooled 6392 patients from 17 randomized controlled trials. Chronic RIC could reduce the recurrence of ischemic stroke at the endpoints (OR 0.67, 95% CI [0.51, 0.87]). RIC could also improve the prognosis of patients at 90 days as assessed by mRS score (mRS 0-1: OR 1.29, 95% CI [1.09, 1.52]; mRS 0-2: OR 1.22, 95% CI [1.01, 1.48]) and at the endpoints assessed by NIHSS score (MD -0.99, 95% CI [-1.45, -0.53]). RIC would not cause additional adverse events such as death (p = 0.72), intracerebral hemorrhage events (p = 0.69), pneumonia (p = 0.75), and TIA (p = 0.24) but would inevitably cause RIC-related adverse events (OR 26.79, 95% CI [12.08, 59.38]). CONCLUSIONS: RIC could reduce the stroke recurrence and improve patients' prognosis. Intervention on bilateral upper limbs, 5 cycles, and a length of 50 min in each intervention might be an optimal protocol for RIC at present. RIC could be an effective therapy for patients not eligible for reperfusion therapy. RIC would not cause other adverse events except for relatively benign RIC-related adverse events.

Time from Onset to Remote Ischemic Conditioning and Clinical Outcome After Acute Moderate Ischemic Stroke.

OBJECTIVE: We conducted a post hoc exploratory analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to determine whether early remote ischemic conditioning (RIC) initiation after stroke onset was associated with clinical outcome in patients with acute moderate ischemic stroke. METHODS: In RICAMIS, patients receiving RIC treatment in the intention-to-treat analysis were divided into 2 groups based on onset-to-treatment time (OTT): early RIC group (OTT ≤ 24 hours) and late RIC group (OTT 24-48 hours). Patients receiving usual care without RIC treatment from intention-to-treat analysis were assigned as the control group. The primary outcome was excellent functional outcome at 90 days. RESULTS: Among 1,776 patients from intention-to-treat analysis, 387 were in the early RIC group, 476 in the late RIC group, and 913 in the control group. In the post hoc exploratory analysis, a higher proportion of excellent functional outcome was found in the early RIC versus control group (adjusted absolute difference = 8.1%, 95% confidence interval [CI] = 2.5%-13.8%, p = 0.005), but no difference in outcomes was detected in the late RIC versus control group (adjusted absolute difference = 3.3%, 95% CI = -2.1% to 8.6%, p = 0.23), or in the early RIC versus late RIC group (adjusted absolute difference = 5.0%, 95% CI = -1.3% to 11.2%, p = 0.12). Similar results were found in the per-protocol analysis. INTERPRETATION: Among patients with acute moderate ischemic stroke who are not candidates for intravenous thrombolysis or endovascular therapy, early RIC initiation within 24 hours of onset may be associated with higher likelihood of excellent clinical outcome. ANN NEUROL 2023;94:561-571.

Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial.

Resuscitation induced ischemia/reperfusion predisposes trauma patients to systemic inflammation and organ dysfunction. We investigated the effect of remote ischemic conditioning (RIC), a treatment shown to prevent ischemia/reperfusion injury in experimental models of hemorrhagic shock/resuscitation, on the systemic immune-inflammatory profile in trauma patients in a randomized trial. We conducted a prospective, single-centre, double-blind, randomized, controlled trial involving trauma patients sustaining blunt or penetrating trauma in hemorrhagic shock admitted to a Level 1 trauma centre. Patients were randomized to receive RIC (four cycles of 5-min pressure cuff inflation at 250 mmHg and deflation on the thigh) or a Sham intervention. The primary outcomes were neutrophil oxidative burst activity, cellular adhesion molecule expression, and plasma levels of myeloperoxidase, cytokines and chemokines in peripheral blood samples, drawn at admission (pre-intervention), 1 h, 3 h, and 24 h post-admission. Secondary outcomes included ventilator, ICU and hospital free days, incidence of nosocomial infections, 24 h and 28 day mortality. 50 eligible patients were randomized; of which 21 in the Sham group and 18 in the RIC group were included in the full analysis. No treatment effect was observed between Sham and RIC groups for neutrophil oxidative burst activity, adhesion molecule expression, and plasma levels of myeloperoxidase and cytokines. RIC prevented significant increases in Th2 chemokines TARC/CCL17 (P < 0.01) and MDC/CCL22 (P < 0.05) at 24 h post-intervention in comparison to the Sham group. Secondary clinical outcomes were not different between groups. No adverse events in relation to the RIC intervention were observed. Administration of RIC was safe and did not adversely affect clinical outcomes. While trauma itself modified several immunoregulatory markers, RIC failed to alter expression of the majority of markers. However, RIC may influence Th2 chemokine expression in the post resuscitation period. Further investigation into the immunomodulatory effects of RIC in traumatic injuries and their impact on clinical outcomes is warranted.ClinicalTrials.gov number: NCT02071290.

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.

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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Role of caveolin-eNOS platform and mitochondrial ATP-sensitive potassium channel in abrogated cardioprotective effect of ischemic preconditioning in postmenopausal women

Abstract Caveolin, the protein of the caveolar membrane, interacts and binds with endothelial nitric oxide synthase (eNOS), forming a caveolin-eNOS complex leading to suppression of the eNOS activity. Caveolin, therefore, maintains eNOS in the inactivated state leading to reduced nitric oxide (NO) production. Ischemic preconditioning disrupts the caveolin-eNOS complex leading to activation of the eNOS and thus results in cardioprotection. During ischemic preconditioning, NO produces cardioprotection by the opening of the KATP channel, and the caveolin forms a suitable signalling platform facilitating the interaction of NO with the KATP channel. Estrogen deficiency has been reported to upregulate caveolin-1 expression. The article aims to review the various mechanisms that placed the women at the risk of coronary artery diseases after postmenopausal estrogen deficiency and their role in the cardioprotective effect of ischemic preconditioning.

Limb Remote Ischemic Preconditioning Applied During Sevoflurane Anesthesia Does Not Protect the Lungs in Patients Undergoing Adult Heart Valve Surgery.

BACKGROUND: Two consistent overall cell protective preconditioning treatments should provide more protection. We hypothesized that limb remote ischemic preconditioning (RIPC, second preconditioning stimulus) applied during sevoflurane inhalation (first preconditioning stimulus) would provide more protection to the lungs of patients undergoing adult heart valve surgery. METHODS: In this randomized, placebo-controlled, double-blind trial, 50 patients were assigned to the RIPC group or the placebo group (1:1). Patients in the RIPC group received three 5-min cycles of 300 mmHg cuff inflation/deflation of the left-side lower limb before aortic cross-clamping. Anesthesia consisted of opioids and propofol for induction and sevoflurane for maintenance. The primary end point was comparison of the postoperative arterial-alveolar oxygen tension ratio (a/A ratio) between groups. Secondary end points included comparisons of pulmonary variables, postoperative morbidity and mortality and regional and systemic inflammatory cytokines between groups. RESULTS: In the RIPC group, the a/A ratio and other pulmonary variables exhibited no significant differences throughout the study period compared with the placebo group. No significant differences in either plasma or bronchoalveolar lavage levels of TNF- α were noted between the groups at 10 min after anesthetic induction and 1 h after cross-clamp release. The percentage of neutrophils at 12 h postoperation was significantly increased in the RIPC group compared with the placebo group (91.34±0.00 vs. 89.42±0.10, P = 0.023). CONCLUSIONS: Limb RIPC applied during sevoflurane anesthesia did not provide additional significant pulmonary protection following adult valvular cardiac surgery.

Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac Surgery: A Network Meta-Analysis.

BACKGROUND AND OBJECTIVES: AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed. RESULTS: Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of <57% relative risk reduction with remote ischemic preconditioning. Nonetheless, the network meta-analysis was unable to demonstrate any significant differences among the examined treatments, including also acetaminophen, aminophylline, levosimendan, milrinone, and normothermic cardiopulmonary bypass. Surface under the cumulative ranking curve probabilities showed that milrinone (76%) was most likely to result in the lowest risk of AKI, followed by dexmedetomidine (70%), levosimendan (70%), aminophylline (59%), normothermic cardiopulmonary bypass (57%), and remote ischemic preconditioning (55%), although all showing important overlap. CONCLUSIONS: Current evidence from randomized controlled trials does not support the efficacy of most strategies to prevent AKI in the pediatric population, apart from limited evidence for dexmedetomidine and remote ischemic preconditioning.

Deleterious Effects of Remote Ischaemic Per-conditioning During Lower Limb Ischaemia-Reperfusion in Mice.

OBJECTIVE: The aim of this study was to investigate whether remote ischaemic per-conditioning might protect skeletal muscle during lower limb ischaemia-reperfusion (IR). METHODS: Twenty-three male C57BL/6 mice were randomised into three groups: sham group (n = 7), IR group (unilateral tourniquet induced three hours of ischaemia followed by 24 hours of reperfusion, n = 8), and remote ischaemic per-conditioning group (RIPerC) (three cycles of 10 minute IR episodes on the non-ischaemic contralateral hindlimb, n = 8). Oxygraphy, spectrofluorometry, and electron paramagnetic resonance spectroscopy were performed in order to determine mitochondrial respiratory chain complexes activities, mitochondrial calcium retention capacity (CRC) and reactive oxygen species (ROS) production in skeletal muscle. RESULTS: IR impaired mitochondrial respiration (3.66 ± 0.98 vs. 7.31 ± 0. 54 µmol/min/g in ischaemic and sham muscles, p = .009 and p = .003 respectively) and tended to impair CRC (2.53 ± 0.32 vs. 3.64 ± 0.66 µmol/mg in ischaemic and sham muscles respectively, p = .066). IR did not modify ROS production (0.082 ± 0.004 vs. 0.070 ± 0.004 µmol/min/mg in ischaemic and sham muscles respectively, p = .74). RIPerC failed to restore mitochondrial respiration (3.82 ± 0.40 vs. 3.66 ± 0.98 µmol/min/g in ischaemic muscles from the RIPerC group and the IR group respectively, p = .45) and CRC (2.76 ± 0.3 vs. 2.53 ± 0.32 µmol/mg in ischaemic muscles from the RIPerC group and the IR group respectively, p = .25). RIPerC even impaired contralateral limb mitochondrial respiration (3.85 ± 0.34 vs. 7.31 ± 0. 54 µmol/min/g in contralateral muscles and sham muscles respectively, -47.3%, p = .009). CONCLUSION: RIPerC failed to protect ischaemic muscles and induced deleterious effects on the contralateral non-ischaemic muscles. These data do not support the concept of RIPerC.

Cardiac autonomic recovery following traditional and augmented remote ischemic preconditioning.

PURPOSE: While the possible ergogenic benefits of remote ischemic preconditioning (RIPC) make it an attractive training modality, the mechanisms of action remain unclear. Alterations in neural tone have been demonstrated in conjunction with circulatory occlusion, yet investigation of the autonomic nervous system following RIPC treatment has received little attention. We sought to characterize alterations in autonomic balance to both RIPC and augmented RIPC (RIPCaug) performed while cycling, using acute and sustained autonomic indices. METHODS: Thirteen participants (8M:5F) recorded baseline waking heart rate variability (HRV) for 5 days prior to treatment. Participants then completed control exercise (CON), RIPC, and RIPCaug interventions in a randomized cross-over design. Cardiovascular measurements were recorded immediately before and after each intervention at rest, and during an orthostatic challenge. Waking HRV was repeated the morning after each intervention. RESULTS: RIPC resulted in acutely reduced resting heart rates (HR) (∆ - 4 ± 6 bpm, P = 0.02) and suppressed HR 30 s following the orthostatic challenge compared to CON (64 ± 10 vs 74 ± 9 bpm, P = 0.003). RIPCaug yielded elevated HRs compared to CON and RIPC prior to (P = 0.003) and during the orthostatic challenge (P = 0.002). RIPCaug reduced LnSDNN (Baseline 4.39 ± 0.27; CON 4.44 ± 0.39; RIPC 4.41 ± 0.34; RIPCaug 4.22 ± 0.29, P = 0.02) and LnHfa power (Baseline 7.82 ± 0.54; CON 7.73 ± 1.11; RIPC 7.89 ± 0.78; RIPCaug 7.23 ± 0.87, P = 0.04) the morning after treatment compared to all other conditions. CONCLUSIONS: Our data suggest that RIPC may influence HR acutely, possibly through a reduction in cardiac sympathetic activity, and that RIPCaug reduces HRV through cardiac vagal withdrawal or increased cardiac sympathetic modulation, with alterations persisting until the following morning. These findings imply a dose-response relationship with potential for optimization of performance.

Effect of remote ischaemic conditioning on platelet reactivity and endogenous fibrinolysis in ST-elevation myocardial infarction: a substudy of the CONDI-2/ERIC-PPCI randomized controlled trial.

AIMS: Remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in animal models of myocardial infarction. Platelet thrombus formation is a critical determinant of outcome in ST-segment elevation myocardial infarction (STEMI). Whether the beneficial effects of RIC are related to thrombotic parameters is unclear. METHODS AND RESULTS: In a substudy of the Effect of Remote Ischaemic Conditioning on clinical outcomes in STEMI patients undergoing Primary Percutaneous Coronary Intervention (ERIC-PPCI) trial, we assessed the effect of RIC on thrombotic status. Patients presenting with STEMI were randomized to immediate RIC consisting of an automated autoRIC™ cuff on the upper arm inflated to 200 mmHg for 5 min and deflated for 5 min for four cycles (n = 53) or sham (n = 47). Venous blood was tested at presentation, discharge (48 h) and 6-8 weeks, to assess platelet reactivity, coagulation, and endogenous fibrinolysis using the Global Thrombosis Test and thromboelastography. Baseline thrombotic status was similar in the two groups. At discharge, there was some evidence that the time to in vitro thrombotic occlusion under high shear stress was longer with RIC compared to sham (454 ± 105 s vs. 403 ± 105 s; mean difference 50.1 s; 95% confidence interval 93.7-6.4, P = 0.025), but this was no longer apparent at 6-8 weeks. There was no difference in clot formation or endogenous fibrinolysis between the study arms at any time point. CONCLUSION: RIC may reduce platelet reactivity in the first 48 h post-STEMI. Further research is needed to delineate mechanisms through which RIC may reduce platelet reactivity, and whether it may improve outcomes in patients with persistent high on-treatment platelet reactivity.

Acute cardiovascular response to unilateral, bilateral, and alternating resistance exercise with blood flow restriction.

AIM: Blood flow restriction (BFR) exercise is a common alternative to traditional high-load resistance exercise used to increase muscle size and strength. Some populations utilizing BFR at a low load may wish to limit their cardiovascular response to exercise. Different contraction patterns may attenuate the cardiovascular response, but this has not been compared using BFR. PURPOSE: To compare the cardiovascular response to unilateral (UNI), bilateral (BIL), and alternating (ALT) BFR exercise contraction patterns. METHODS: Twenty healthy participants performed four sets (30 s rest) of knee extensions to failure, using 30% one-repetition maximum, 40% arterial occlusion pressure, and each of the three contraction patterns (on different days, at the same time of day, separated by 2-10 days, randomized). Cardiovascular responses, presented as pre- to post-exercise mean changes (SD), were measured using pulse wave analysis and analyzed with Bayesian RMANOVA. RESULTS: ALT caused greater changes in: aortic systolic [ΔmmHg: ALT = 21(8); UNI = 13(11); BIL = 15(8); BF10 = 29.599], diastolic [ΔmmHg: ALT = 13(8); UNI = 7(11); BIL = 8(8); BF10 = 5.175], and mean arterial [ΔmmHg: ALT = 19(8); UNI = 11(11); BIL = 13(7); BF10 = 48.637] blood pressures. Aortic [ΔmmHg bpm: ALT = 4945(2340); UNI = 3294(1408); BIL = 3428 (1461); BF10 = 113.659] and brachial [ΔmmHg bpm: ALT = 6134(2761); UNI = 4300(1709); BIL = 4487(1701); BF10 = 31.845] rate pressure products, as well as heart rate [Δbpm: ALT = 26(14); UNI = 19(8); BIL = 19(11); BF10 = 5.829] were greatest with ALT. Augmentation index [Δ%: UNI = -6(13); BIL = - 7(11); ALT = - 5(16); BF10 = 0.155] and wave reflection magnitude [Δ%: UNI = - 5(9); BIL = - 4(7); ALT = - 4(7); BF10 = 0.150] were not different. CONCLUSION: Those at risk of a cardiovascular event may choose unilateral or bilateral BFR exercise over alternating until further work determines the degree to which it can be tolerated.

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.

Irisin and troponin I expression in dialysis patients submitted to remote ischemic preconditioning: a pilot study / Expressão de irisina e troponina I em pacientes em diálise submetidos a pré-condicionamento isquêmico remoto: um estudo piloto

ABSTRACT Background: Renal replacement therapy continues to be related to high hospitalization rates and poor quality of life. All-cause morbidity and mortality in renal replacement therapy in greater than 20% per year, being 44 times greater when diabetes is present, and over 10 times that of the general population. Regardless of treatment, the 5-year survival is 40%, surpassing many types of cancers. Irisin is a hormone that converts white adipose tissue into beige adipose tissue, aggregating positive effects like fat mass control, glucose tolerance, insulin resistance, prevention of muscle loss, and reduction in systemic inflammation. Objectives: To determine the serum levels of troponin I in hemodialysis patients submitted to remote ischemic preconditioning (RIPC) associated with irisin expression. Methods: This was a prospective, randomized, double-blind clinical trial with patients with chronic kidney disease submitted to hemodialysis for a 6-month period. Troponin I, IL-6, urea, TNF-α, and creatinine levels were determined from blood samples. The expressions of irisin, thioredoxin, Nf-kb, GPX4, selenoprotein and GADPH were also evaluated by RT-PCR. Results: Samples from 14 hypertensive patients were analyzed, 9 (64.3%) of whom were type 2 diabetics, aged 44-64 years, and 50% of each sex. The difference between pre- and post-intervention levels of troponin I was not significant. No differences were verified between the RIPC and control groups, except for IL-6, although a significant correlation was observed between irisin and troponin I. Conclusion: Remote ischemic preconditioning did not modify irisin or troponin I expression, independent of the time of collection.

RESUMO Introdução: A terapia de substituição renal continua associada a altas taxas de hospitalização e baixa qualidade de vida. A morbimortalidade por todas as causas na terapia de substituição renal é superior a 20% ao ano, sendo 44 vezes maior quando a diabetes está presente e mais de 10 vezes a da população em geral. Independentemente do tratamento, a sobrevida em 5 anos é de 40%, superando muitos tipos de câncer. A irisina é um hormônio que converte tecido adiposo branco em tecido adiposo bege, agregando efeitos positivos como o controle de massa gorda, tolerância à glicose, resistência à insulina, prevenção de perda muscular e redução da inflamação sistêmica. Objetivos: Determinar os níveis séricos de troponina I em pacientes em hemodiálise submetidos ao pré-condicionamento isquêmico remoto (PCIR) associado à expressão da irisina. Métodos: Estudo clínico prospectivo, randomizado, duplo-cego, com pacientes com doença renal crônica submetidos à hemodiálise por um período de 6 meses. Os níveis de troponina I, IL-6, uréia, TNF-α e creatinina foram determinados a partir de amostras de sangue. As expressões de irisina, tioredoxina, Nf-kb, GPX4, selenoproteína e GADPH foram também avaliadas por RT-PCR. Resultados: Foram analisadas amostras de 14 pacientes hipertensos, 9 (64,3%) dos quais eram diabéticos tipo 2, com idades entre 44 e 64 anos e 50% de cada gênero. A diferença entre os níveis pré e pós-intervenção de troponina I não foi significativa. Não houve diferenças entre os grupos PCIR e controle, exceto pela IL-6, embora tenha sido observada correlação significativa entre irisina e troponina I. Conclusão: O pré-condicionamento isquêmico remoto não modificou a expressão de irisina ou troponina I, independentemente do tempo de coleta.