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‘Gaps’ in targeted ischaemic injury therapies in ST-elevation myocardial infarction
  1. Scott R Johnstone1,
  2. Brant E Isakson1,2
  1. 1Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  2. 2Department of Molecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, Virginia, USA
  1. Correspondence to Dr Brant E Isakson, Robert M Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA; brant{at}virginia.edu

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ST-elevation myocardial infarction (STEMI) is a medical emergency, resulting from blockade of one or several conduit arteries supplying the myocardium. Early and rapid intervention limits ischaemic time, tissue damage and infarct size and is a major determinant of patient prognosis. In principle, restoration of oxygenated blood flow via percutaneous coronary intervention (PCI) and stent placement should limit the damage to the affected myocardium. However, ischaemia-reperfusion injury after restoration of flow can account for 50% of infarct size.

Multiple factors reportedly affect the extent of injury including types of occlusion, failed reperfusion of tissues resulting from haemorrhage, thrombosis, microvascular obstruction (MVO) and cellular generation of free radicals. Recently, a number of proposed therapeutic modalities have been the subject of clinical trials. These include ischaemic preconditioning/postconditioning therapies, cooling strategies and pharmacological interventions. While some studies have reported patient benefits and improved outcomes, these are controversial, with larger studies generally reflecting no overall patient benefit.1 Thus, at present, there are currently no clinically available tools that are specifically indicated to reduce ischaemic-reperfusion injury in patients.

In their recent phase 2 clinical trial, Engstrom et al report on the outcomes of the trial of a novel peptide therapeutic, danegaptide, aimed at limiting ischaemia-reperfusion injury in patients with STEMI.2 Danegaptide (ZP1609) is an analogue of rotigaptide (ZP123), Gap-134 and of the antiarrhythmic peptide (AAP10) first identified as a naturally occurring peptide in bovine serum.3 The various iterations of this peptide (AAP10→rotagaptide→danegaptide) have increased in vivo peptide stability and efficacy. Both AAP10 and rotigaptide have been demonstrated in multiple preclinical studies to limit ischaemia-induced cardiac damage and arrhythmias. Similar studies have demonstrated effects for danegaptide in reducing ischaemia-induced infarct size in canine and porcine models.4 5

Patients with clinical …

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