Live from the ACC in Orlando: Prehospital Remote Ischemic Perconditioning

Danish study shows that Prehospital Remote Ischemic Perconditioning Reduces Infarct Size in Patients with Evolving Myocardial Infarction Undergoing Primary Percutaneous Intervention

Topics: Acute Coronary Syndromes (ACS)

Date: 31 Mar 2009

Live from the 58th Annual Scientific Session of the American College of Cardiology in Orlando:

Prof Hans Erik Bøtker, Aarhus, presented a study where patients with STEMI had been randomized to either inflation of a blood pressure cuff on the arm or no inflation during transport for primary angioplasty. The patients in the group with limb ischaemia developed smaller infarcts.

The studies show that it is possible to activate endogenous protection mechanisms and this may have great potential for the therapy of STEMI patients.

The size of a myocardial infarct is determined by the ischemic damage which can be reduced by rapid restoration of myocardial blood flow with primary PCI. However, recent studies have indicated that a part of the infarct may rather be triggered by reperfusion injury than caused by ischemia itself. If so, modification of reperfusion may reduce injury and harness the full benefit of reperfusion. Modification of reperfusion injury leading to cardioprotection has been demonstrated by local and remote ischemic preconditioning in predictable ischemia and by postconditioning and pharmacological intervention with cyclosporin during reperfusion after unpredictable ischemia.

Remote ischemic preconditioning mediated by brief ischemic periods of a distant organ before index ischemia reduces myocardial reperfusion injury. Because acute myocardial infarction is an unpredictable event, application of the conditioning stimulus before ischemia is not achievable for this disease entity. Hence, we introduced a new concept when we changed the timing of the condition stimulus from before ischemia to the period of ongoing myocardial ischemia. We call this concept remote ischemic perconditioning (rIPerC), which is intermittent limb ischemia during evolving ST-elevation myocardial infarction (STEMI). In the present study we tested whether rIPerC whether rIPerC performed in the ambulance during transportation to primary PCI reduces myocardial reperfusion injury and infarct size in patients with a first STEMI.

In a prospective randomized single-blinded single-center trial, 246 consecutive patients with first STEMI admitted for primary PCI were assigned to either control or rIPerC applied as upper limb ischemia with four cycles of 5-minute inflation (200 mmHg)/deflation using a standard blood pressure cuff and initiated in-ambulance during transfer to hospital. Area at risk (AAR) was determined using 99mTc-sestamibi injected before coronary intervention and SPECT imaging within 8 h. Final infarct size was determined by SPECT after 30 days.

Patients treated with ischemic conditioning while en route to the hospital had a significantly higher salvage ratio than those who underwent PCI without remote conditioning. Final infarct size assessed by nuclear scintigraphy was significantly less among those who underwent conditioning. Interestingly, the benefit appeared driven by infarcts caused by left anterior descending (LAD) lesions. Patients with LAD infarcts also had a trend towards improved left ventricular ejection fraction after perconditioning.

Conclusion Remote ischemic perconditioning during evolving ST-elevation myocardial infarction is feasible, increases myocardial salvage and reduces final infarct size with primary PCI. The mechanisms of benefit are not exactly known, but it is likely that a compound or a series of compounds, as part of a generalized endogenous protective system, is released during ischemia to reduce infarct size. This simple and safe intervention has the potential to reduce mortality and morbidity in STEMI patients and merits a larger trial powered to detect these clinical endpoints.

Authors: Hans Erik Botker, Rajesh Kharbanda, Michael R. Schmidt, Morten Bottcher, Anne K. Kaltoft, Christian J. Terkelsen, Kim Munk, Niels H. Andersen, Troels M. Hansen, Sven Trautner, Jens F. Lassen, Evald H. Christiansen, Lars R. Krusell, Steen D. Kristensen, Leif Thuesen, Soren S. Nielsen, Michael Rehling, Andrew N. Redington, Torsten T. Nielsen, Aarhus University Hospital Skejby, Aarhus N, Denmark, University of Oxford, UK, University of Toronto, Canada.