Remote Ischemic Conditioning a Work in Progress with Great Future Potential
JACC in a Flash | The concept of remote ischemic conditioning (RIC) used to protect remote tissue and organs against ischemia and reperfusion has been researched and developed for several decades; however, to date, researchers have struggled to successfully translate successful laboratory experiments to the clinic.
In an article published recently in JACC, Gerd Heusch, MD, of the University of Essen Medical School, Germany, and his colleagues discussed the current status of RIC as a useful cardioprotective strategy.
“A general consensus regarding RIC has emerged: with rare exceptions, there is consistent evidence among diverse models and species that brief ischemia/reperfusion applied in a remote tissue or organ confers cytoprotection against ischemia/reperfusion injury,” Heusch and colleagues wrote. “When the heart is the target organ, the gold standard of RIC-induced protection is reduction of myocardial infarct size.”
A wide variety of approaches to RIC have been studied, including the use of either interorgan or intracardiac conditioning, and the use of preconditioning, perconditioning (during occlusion) and postconditioning (at the time of reperfusion). Both perconditioning and postconditioning seem to hold the most potential for successful clinical translation.
Large clinical trials have shown that remote ischemic preconditioning has resulted in a reduction of major cardiovascular events as much as 4 years after undergoing coronary artery bypass grafting (CABG) and 6 years after percutaneous coronary intervention (PCI). In contrast, another study randomly assigned patients undergoing elective cardiac surgery to pre- and postconditioning or control and found that two cycles of 5 minutes of ischemia and reperfusion on the upper arm given before and immediately after surgery resulted in no measurable difference in a composite endpoint of major adverse outcomes that included death, MI, arrhythmia, stroke, coma, renal damage, respiratory failure, gastrointestinal complications, and multiorgan failure.
“Although RIC is thought to have systemic protective effects on various distal organs, the results are debatable because the composite endpoint differs from other studies yielding beneficial results,” the authors wrote.
Overall though, evidence from recent meta-analyses and single-center trials points to the fact that RIC has a clinical benefit to patients undergoing CABG and PCI. In addition, several studies have shown that the use of RIC can increase the number of patients with STEMI achieving complete ST-segment resolution and reduce occurrence of major cardiovascular events up to 4 years later when applied in the ambulance during transportation to primary PCI.
However, large multicenter studies will be needed to clarify the extent to which RIC can have a clinical benefit and will need to address the use of RIC in patients with comorbidities commonly seen in association with cardiac disease.
The author pointed out though, that cardioprotective pharmaceuticals have largely been abandoned by pharmaceutical companies because of the one-time use in acute ischemia/reperfusion compared with ongoing use in other cardiac conditions. Therefore, continued exploration of RIC’s cardioprotective benefit is warranted, and RIC “may then, indeed, be the future of cardioprotection.”
Heusch G, Botker HE, Przyklenk K, et al. J Am Coll Cardiol.2014;65:177-95.
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