Remote ischaemic preconditioning of the lung: from bench to bedside-are we there yet?
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SUBMITTER: Weber NC
PROVIDER: S-EPMC5863186 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDespite advances in perioperative care, elective major vascular surgical procedures still carry a significant risk of morbidity and mortality. Remote ischaemic preconditioning (RIPC) is the temporary blocking of blood flow to vascular beds remote from those targeted by surgery. It has the potential to provide local tissue protection from further prolonged periods of ischaemia. However, the efficacy and safety of RIPC in people undergoing major vascular surgery remain unknown. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of RIPC versus no RIPC in people undergoing elective major vascular and endovascular surgery.Search methodsThe Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov to 1 April 2022.Selection criteriaWe included all randomised controlled trials that evaluated the role of RIPC in reducing perioperative mortality and morbidities in people undergoing elective major vascular or endovascular surgery.Data collection and analysisWe collected data on the characteristics of the trial, methodological quality, and the remote ischaemic preconditioning stimulus used. Our primary outcome was perioperative mortality, and secondary outcomes included myocardial infarction, renal impairment, stroke, hospital stay, limb loss, and operating time or total anaesthetic time. We analysed the data using random-effects models. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) based on an intention-to-treat analysis. In addition, we used GRADE to assess the certainty of the evidence for each outcome.Main resultsWe included 14 trials which randomised a total of 1295 participants (age range: 64.5 to 76 years; 84% male; study periods ranged from 2003 to 2019). In general, the included studies were at low to unclear risk of bias for most risk of bias domains. The certainty of evidence of main outcomes was moderate due to imprecision of results, moderate heterogeneity, or possible publication bias. We found that RIPC made no clear difference in perioperative mortality compared with no RIPC (RR 1.41, 95% CI 0.59 to 3.40; I2 = 0%; 10 studies, 965 participants; moderate-certainty evidence). Similarly, we found no clear difference between the two groups for myocardial infarction (RR 0.82, 95% CI 0.49 to 1.40; I2 = 7%; 11 studies, 1001 participants; moderate-certainty evidence), renal impairment (RR 1.07, 95% CI 0.62 to 1.86; I2 = 40%; 12 studies, 1054 participants; moderate-certainty evidence), stroke (RR 0.33, 95% CI 0.04 to 3.15; I2 = 0%; 4 studies, 392 participants; moderate-certainty evidence), limb loss (RR 0.74, 95% CI 0.05 to 10.61; I2 = 32%; 3 studies, 322 participants; low-certainty evidence), hospital stay (MD -0.94 day, 95% CI -1.95 to 0.07; I2 = 17%; 7 studies, 569 participants; moderate-certainty evidence), and operating time or total anaesthetic time (MD 5.76 minutes, 95% CI -3.25 to 14.76; I2 = 44%; 10 studies, 803 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Overall, compared with no RIPC, RIPC probably leads to little or no difference in perioperative mortality, myocardial infarction, renal impairment, stroke, hospital stay, and operating time, and may lead to little or no difference in limb loss in people undergoing elective major vascular and endovascular surgery. Adequately powered and designed randomised studies are needed, focusing in particular on the clinical endpoints and patient-centred outcomes.
| S-EPMC9841888 | biostudies-literature
Project description:Despite advances in surgery support there are unmet needs for cardiopulmonary bypass (CPB) patients being at risk of perioperative ischemia. Remote ischemic preconditioning (RIPC) is considered as adjuvant therapy, but its effects are still underexplored. Thus, we monitored transcriptomic responses from the RIPC procedure during and after cardiac surgery in a pilot study, comprising 34 samples and 10 for validation from patients. We systematically compared the response between CTRL and RIPC including individual effects and dynamics. We gratefully acknowledge the support from the study participants as part of the clinical trial (ClinicalTrials.gov ID: NCT01067703). Different individual and time-resolved patterns were found for preconditioned patients (RIPC) comprising alternated cytokine, ribosomal and stress related genes. This was confirmed by a tailored method for ranking candidates by integrating variance and expression changes at once.
2017-09-01 | GSE58270 | GEO
Project description:Remote ischemic conditioning (RIC) is a therapeutic strategy for protecting organs or tissue against the detrimental effects of acute ischemia-reperfusion injury (IRI). It describes an endogenous phenomenon in which the application of one or more brief cycles of non-lethal ischemia and reperfusion to an organ or tissue protects a remote organ or tissue from a sustained episode of lethal IRI. Although RIC protection was first demonstrated to protect the heart against acute myocardial infarction, its beneficial effects are also seen in other organs (lung, liver, kidney, intestine, brain) and tissues (skeletal muscle) subjected to acute IRI. The recent discovery that RIC can be induced non-invasively by simply inflating and deflating a standard blood pressure cuff placed on the upper arm or leg, has facilitated its translation into the clinical setting, where it has been reported to be beneficial in a variety of cardiac scenarios. In this review article we provide an overview of RIC, the potential underlying mechanisms, and its potential as a novel therapeutic strategy for protecting the heart and other organs from acute IRI.
| S-EPMC3282534 | biostudies-literature
Project description:PURPOSE:Remote ischaemic preconditioning (RIPC) refers to the protection conferred to tissues and organs via brief periods of ischaemia in a remote vascular territory, including the brain. Recent studies in humans report that RIPC provides neuroprotection against recurrent (ischaemic) stroke. To better understand the ability of RIPC to improve brain health, the present study explored the potential for RIPC to acutely improve cerebrovascular function. METHODS:Eleven young healthy (females n?=?6, age; 28.1?±?3.7 years) and 9 older individuals (females n?=?4, age 52.5?±?6.7 years) at increased risk for stroke (cardiovascular disease risk factors) underwent assessments of cerebrovascular function, assessed by carbon dioxide (CO2) reactivity and cerebral autoregulation during normo- and hypercapnia (5% CO2) following 40 mins of bilateral arm RIPC or a sham condition. Squat-to-stand manoeuvres were performed to induce changes in blood pressure to assess cerebral autoregulation (0.10 Hz) and analysed via transfer function. RESULTS:We found no change in middle cerebral artery velocity or blood pressure across 40 mins of RIPC. Application of RIPC resulted in no change in CO2 reactivity slopes (sham vs RIPC, 1.97?±?0.88 vs 2.06?±?0.69 cm/s/mmHg P?=?0.61) or parameters of cerebral autoregulation during normocapnia (sham vs RIPC, normalised gain%, 1.27?±?0.25 vs 1.22?±?0.35, P?=?0.46). CONCLUSION:This study demonstrates that a single bout of RIPC does not influence cerebrovascular function acutely in healthy individuals, or those at increased cardiovascular risk. Given the previously reported protective role of RIPC on stroke recurrence in humans, it is possible that repeated bouts of RIPC may be necessary to impart beneficial effects on cerebrovascular function.
| S-EPMC7042189 | biostudies-literature
Project description: Not available
| S-EPMC3846100 | biostudies-literature
Project description:AimsAnthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC.Methods and resultsForty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs.ConclusionIn a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.
| S-EPMC7983009 | biostudies-literature
Project description:Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. Keywords: genomics, diagnosis, microarray, calprotectin
2006-08-29 | GSE5663 | GEO
Project description:Whether oxygen should be administered acutely during ST-segment elevation myocardial infarction is debated. Despite this controversy, the possible influence of supplementary oxygen on animal models of ischaemia-reperfusion injury or cardioprotection is rarely considered. We used an in vivo mouse model of ischaemia and reperfusion to investigate the effect of ventilation with room air versus 100% oxygen. The coronary artery of anaesthetized mice was occluded for 40 min. followed by 2-hrs reperfusion. Infarct size was measured by tetrazolium staining and expressed as a percentage of area at risk, determined using Evan's blue. Unexpectedly, infarct size in mice ventilated with 100% oxygen was significantly smaller than in those ventilated with room air (33 ± 5% versus 46 ± 3%; n = 6; P < 0.01). We tested a standard protocol of 3 × 5 min. cycles of remote ischaemic preconditioning (RIPC) and found this was unable to protect mice ventilated with 100% oxygen. RIPC protocols using 2.5- or 10-min. occlusion were similarly ineffective in mice ventilated with oxygen. Similar disparate results were obtained with direct cardiac ischaemic preconditioning. In contrast, pharmacological protection using bradykinin administered at reperfusion was effective even in mice ventilated with 100% oxygen, reducing infarct size from 33 ± 5% to 21 ± 3% (n = 4-6; P < 0.01). Laser speckle contrast imaging of blood flow and direct pO2 measurements were made in the hindlimb, but these measurements did not correlate with protection. In conclusion, ventilation protocol can have a major influence on infarct size and ischaemic preconditioning protocols in mice.
| S-EPMC5618711 | biostudies-literature
Project description:Background: Ischaemic reperfusion injury (IRI) after tourniquet release during total knee arthroplasty (TKR) is related to postoperative cerebral complications. Remote ischaemic preconditioning (RIPC) is known to minimise IRI in previous studies. Thus, we evaluated the effect of RIPC on regional cerebral oxygenation after tourniquet release during TKR. Methods: Patients undergoing TKR were randomly allocated to not receive RIPC (control group) and to receive RIPC (RIPC group). Regional cerebral oxygenation and pulmonary oxygenation were assessed up to 24 h postoperatively. The changes in serum cytokine and lactate dehydrogenase (LDH) levels were assessed and arterial blood gas analysis was performed. Total transfusion amounts and postoperative bleeding were also examined. Results: In total, 72 patients were included in the final analysis. Regional cerebral oxygenation (P < 0.001 in the left side, P = 0.003 in the right side) with pulmonary oxygenation (P = 0.001) was significantly higher in the RIPC group. The serum LDH was significantly lower in the RIPC group at 1 h and 24 h postoperatively (P < 0.001). The 24 h postoperative transfusion (P = 0.002) and bleeding amount (P < 0.001) were significantly lower in the RIPC group. Conclusions: RIPC increased cerebral oxygenation after tourniquet release during TKR by improving pulmonary oxygenation. Additionally, RIPC decreased the transfusion and bleeding amount with the serum LDH level.
| S-EPMC5332839 | biostudies-literature
Project description:IntroductionCerebral small vessel disease (cSVD) accounts for 20%-25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60-85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13-24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.
| S-EPMC7559076 | biostudies-literature