Background— Transient limb ischemia administered before a prolonged ischemic insult has systemic protective effects against ischemia-reperfusion (IR) injury (remote ischemic preconditioning [RIPC]). It has been demonstrated that protection from IR can be achieved by brief periods of ischemia applied at a remote site during an injurious ischemic event (remote postconditioning [RPostC]). Using an in vivo model of endothelial IR injury, we sought to determine whether RPostC occurred in humans and whether it shared mechanistic similarities with RIPC. Methods and Results— Endothelial function was assessed by flow-mediated dilation before and after IR (20 minutes of arm ischemia followed by reperfusion). RIPC was induced by conditioning cycles of 5 minutes of ischemia and reperfusion on the contralateral arm or leg before IR. For RPostC induction, conditioning cycles were administered during the ischemic phase of IR. Oral glibenclamide was used to determine the dependence of RIPC and RPostC on K ATP channels. IR caused a significant reduction in flow-mediated dilation in healthy volunteers (baseline, 9.3±1.2% versus post-IR, 3.3±0.7%; P <0.0001) and patients with atherosclerosis (baseline, 5.5±0.6% versus post-IR, 2.3±0.5%; P <0.01). This reduction was prevented by RIPC (post-IR+RIPC: healthy volunteers, 7.2±0.5% [ P <0.0001 versus post-IR]; patients, 4.5±0.3% [ P <0.01 versus post-IR]) and RPostC (post-IR+RPostC: 8.0±0.5%; P <0.0001 versus post-IR). The protective effects of RIPC and RPostC were blocked by glibenclamide. Conclusions— This study demonstrates for the first time in humans that RPostC can be induced by transient limb ischemia and is as effective as RIPC in preventing endothelial IR injury. RIPC and RPostC share mechanistic similarities, with protection being dependent on K ATP channel activation. These results suggest that remote conditioning stimuli could be protective in patients with acute ischemia about to undergo therapeutic reperfusion.

BackgroundNovel cardioprotective strategies are required to improve clinical outcomes in higher-risk patients undergoing coronary artery bypass graft (CABG) with or without valve surgery. Remote ischaemic preconditioning (RIPC) in which brief episodes of non-lethal ischaemia and reperfusion are applied to the arm or leg has been demonstrated to reduce perioperative myocardial injury (PMI) following CABG with or without valve surgery.ObjectiveTo investigate whether or not RIPC can improve clinical outcomes in this setting in the Effect of Remote Ischaemic preconditioning on Clinical outcomes in patients undergoing Coronary Artery bypass graft surgery (ERICCA) study in patients undergoing CABG surgery.DesignMulticentre, double-blind, randomised sham controlled trial.SettingThe study was conducted across 30 cardiothoracic centres in the UK between March 2010 and March 2015.ParticipantsEligible patients were higher-risk adult patients (aged > 18 years of age; additive European System for Cardiac Operative Risk of ≥ 5) undergoing on-pump CABG with or without valve surgery with blood cardioplegia.InterventionsPatients were randomised to receive either RIPC (four 5-minute inflations/deflations of a standard blood pressure cuff placed on the upper arm) or the sham control procedure (simulated RIPC protocol) following anaesthetic induction and prior to surgical incision. Anaesthetic management and perioperative care were not standardised.Main outcome measuresThe combined primary end point was the rate of major adverse cardiac and cerebral events comprising cardiovascular death, myocardial infarction, coronary revascularisation and stroke within 12 months of randomisation. Secondary end points included perioperative myocardial and acute kidney injury (AKI), intensive care unit and hospital stay, inotrope score, left ventricular ejection fraction, changes in quality of life and exercise tolerance.ResultsIn total, 1612 patients (sham control group,n = 811; RIPC group,n = 801) were randomised in 30 cardiac surgery centres in the UK. There was no difference in the primary end point at 12 months between the RIPC group and the sham control group (26.5% vs. 27.7%; hazard ratio 0.95, 95% confidence interval 0.79 to 1.15;p = 0.58). Furthermore, there was no evidence for any differences in either adverse events or the secondary end points of PMI (72-hour area under the curve for serum high-sensitivity troponin T), inotrope score, AKI, intensive therapy unit and hospital stay, 6-minute walk test and quality of life.ConclusionsIn patients undergoing elective on-pump CABG with or without valve surgery, without standardisation of the anaesthetic regimen, RIPC using transient arm ischaemia–reperfusion did not improve clinical outcomes. It is important that studies continue to investigate the potential mechanisms underlying RIPC, as this may facilitate the translation of this simple, non-invasive, low-cost intervention into patient benefit. The limitations of the study include the lack of standardised pre-/perioperative anaesthesia and medication, the level of missing and incomplete data for some of the secondary end points and the incompleteness of the data for the echocardiography substudy.Trial registrationClinicalTrials.gov NCT01247545.FundingThis project was funded by the Efficacy and Mechanism Evaluation programme, a MRC and NIHR partnership, and the British Heart Foundation.

Objective In the United Kingdom, the COVID-19 pandemic has led to the cessation of elective surgery. However, there remains a need to provide urgent and emergency cardiac and thoracic surgery as well as to continue time-critical thoracic cancer surgery. This study describes our early experience of implementing a protocol to safely deliver major cardiac and thoracic surgery in the midst of the pandemic. Methods Data on all patients undergoing cardiothoracic surgery at a single tertiary referral centre in London was prospectively collated during the first 7 weeks of lockdown in the United Kingdom. A comprehensive protocol was implemented to maintain a COVID-19 free environment including the pre-operative screening of all patients, the use of full personal protective equipment in areas with aerosol generating procedures, and separate treatment pathways for patients with and without the virus Results A total of 156 patients underwent major cardiac and thoracic surgery over the study period. Operative mortality was 9% in the cardiac patients and 1.4% in thoracic patients. The pre-operative COVID-19 protocol implemented resulted in 18 patients testing positive for COVID-19 infection and 13 patients having their surgery delayed. No patients who were negative for COVID-19 infection on pre-operative screening tested positive post-operatively. However, one thoracic patient tested positive on intra-operative broncho-alveolar lavage. Conclusion Our early experience demonstrates that it is possible to perform major cardiac and thoracic surgery with low operative mortality and zero development of post-operative COVID-19 infection.

Results obtained from retrospective patient satisfaction surveys indicate high efficacy for PCA as a pain management strategy. The large majority of patients did not seek more medication for pain alleviation and found in-hospital treatment sufficient. Further, all patients agreed that they were adequately informed of pain-risk prior to surgery.