ArticlesRemote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial
Introduction
ST-elevation myocardial infarction is a leading cause of mortality and morbidity. Infarct size is an important determinant of outcome. Hence reduction of myocardial injury is a therapeutic mainstay, best achieved by early reperfusion through primary percutaneous coronary intervention.1 Patients receiving such treatment will achieve infarct-related vessel patency and reperfusion, but risk sustaining clinically significant myocardial infarction, even when the procedure is done soon after symptom onset.2 Attempts to improve outcomes with adjuvant mechanical treatments such as thrombectomy and distal protection devices show inconsistent benefit.3, 4, 5
An alternative approach for treatment is to exploit innate cytoprotective mechanisms. Findings from recent studies of local postconditioning and targeting of mitochondrial pathways in myocardial infarction have indicated success in reduction of infarct size in patients with occluded left anterior descendent artery.6, 7 Remote ischaemic preconditioning, induced by repeated brief periods of limb ischaemia before index ischaemia,8 reduces myocardial injury in patients exposed to predictable ischaemia.9, 10, 11 Furthermore, remote ischaemic postconditioning, applied in the early reperfusion phase after prolonged ischaemia, seems to be more effective than local postconditioning in experimental myocardial infarction.12 We have shown that conditioning, by intermittent limb ischaemia after the onset of myocardial ischaemia and before reperfusion, reduces infarct size in a porcine model.13 This simple technique can be used during hospital transport.
We used myocardial perfusion imaging to examine whether remote ischaemic conditioning done before primary percutaneous coronary intervention increases myocardial salvage, a predictor of mortality,14 in patients with a first acute and evolving myocardial infarction.
Section snippets
Patients
This prospective, single-centre randomised controlled trial was done during February, 2007–November, 2008 in Aarhus University Hospital Skejby, Aarhus N, Denmark. Eligible patients were aged 18 years or older; presented with chest pain before admission to hospital and within 12 h of onset; had ST-segment elevation of more than 0·1 mV in two contiguous leads in the first electrocardiogram (ECG) recorded on the scene; and were telemedically assigned the clinical decision to receive primary
Results
Figure 1 shows the trial profile. 333 patients were assessed during ambulance transport and randomly allocated to treatment, but 82 patients did not fulfil entry criteria on arrival at the hospital and were excluded. Of the remaining 251 patients, final infarct size was obtained in 110 (88%) patients in the control group and 109 (87%) in the intervention group. A lack of 24-h imaging availability meant that acute myocardial perfusion imaging was not possible in all patients within 8 h after
Discussion
Our study shows that remote ischaemic conditioning, induced by intermittent upper-arm ischaemia and done before primary percutaneous coronary intervention, can attenuate reperfusion injury in patients with evolving myocardial infarction, thereby resulting in increased myocardial salvage. This protective effect seemed to be strongest in patients with totally occluded vessels and with infarcts in the left anterior descending artery—both of which were associated with almost double the area at
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