SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Histochemistry and immunocytochemistry using an antibody to adult rat slow-type myosin demonstrated that about 10% of the fibers in the mouse extensor digitorum longus and semimembranosus muscles contain slow myosin during the first month after birth. In adult animals, these muscles have only t&0.8% slow myosin-containing fibers. These results demonstrate a developmentally linked disappearance of an adult-type myosin, and show that the adult phenotype of muscle fibers is not necessarily determined before birth as previously suggested. Histochemistry Immunocytochemistry

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High-resolution, serial, spin-echo images were obtained for an antigen-induced knee arthritis in six rabbits. The animals were imaged prior to intra-articular challenge and at various time points up to 14 weeks after challenge. Extensive high-signal inflammatory changes were seen at Day 1 in the lymph node, capsule, and surrounding muscle. The muscle and lymph node response decreased rapidly after the first week. The capsule high-signal area reached a maximum at Day 10, but was still extensive at Day 39. The infrapatellar fat pad was replaced more slowly by high signal and the appearance of high signal in both the tibia and femur was a late change. Terminal histological examination showed that the capsule and fat pad high-signal areas corresponded to fibrous and synovial proliferation. The bone changes were a result of edema and cyst formation. The separation of the various time courses of the inflammatory changes may be of value in understanding the model and evaluating potential anti-arthritic drugs.