Myocardial Conditioning

Abstract

Myocardial conditioning is an endogenous cardioprotective phenomenon that profoundly limits infarct size in experimental models. The current challenge is to translate this paradigm from the laboratory to the clinic. Accordingly, our goal in this review is to provide a critical summary of the progress toward, opportunities for, and caveats to, the successful clinical translation of postconditioning and remote conditioning, the 2 conditioning strategies considered to have the broadest applicability for real-world patient care. In the majority of phase II studies published to date, postconditioning evoked a ≈35% reduction of infarct size in ST-segment–elevation myocardial infarction patients. Essential criteria for the successful implementation of postconditioning include the appropriate choice of patients (ie, those with large risk regions and negligible collateral flow), timely application of the postconditioning stimulus (immediately on reperfusion), together with proper choice of end points (infarct size, with concomitant assessment of risk region). Remote conditioning has been applied in planned ischemic events (including cardiac surgery and elective percutaneous coronary intervention) and in ST-segment–elevation myocardial infarction patients during hospital transport. Controversies with regard to efficacy have emerged, particularly among surgical trials. These disparate outcomes in all likelihood reflect the remarkable heterogeneity within and among studies, together with a deficit in our understanding of the impact of these variations on the infarct-sparing effect of remote conditioning. Ongoing phase III trials will provide critical insight into the future role of postconditioning and remote conditioning as clinically relevant cardioprotective strategies.

A vital role for complement in heart disease

“…However, reperfusion of the ischemic myocardium may itself cause damage to the heart. This ischemiareperfusion injury involves direct cardiomyocyte death and also myocardial 8 stunning, arrhythmias and the "no reflow" phenomenon (Gerczuk and Kloner, 2012;Jennings 2013;Ovize et al, 2013). Several approaches including pre-, post-, and remote-ischemic conditioning and several pharmacological therapies including immune modulation have been promising in both preclinical and clinical models.…”

Time to Give Up on Cardioprotection?

“…[10][11][12] Therefore, additional interventions and treatments on top of timely reperfusion are still needed to reduce infarct size and improve the clinical outcome of patients with AMI. [13][14][15][16][17][18][19][20] Apart from acute STEMI (type 1 myocardial infarction), additional cardioprotection is also sought in elective PCI with the aim to reduce periprocedural myocardial infarction (type 4a) and in surgical coronary revascularization with the aim to reduce perioperative myocardial infarction (type 5) 21 ; in some studies, cardioprotection was also sought in major cardiovascular surgery other than coronary artery bypass grafting (CABG).…”

“…The translation of cardioprotection by the conditioning phenomena and by drugs that recruit part of their signaling to the clinical arena has been difficult to date. [13][14][15][16][17][18][19] Although there are several positive proof-of-concept studies for each of the conditioning phenomena, no phase III study has yet reported a better clinical outcome as the primary end point. With the neutral results of 2 recent phase III trial in cardiosurgical patients, that is, ERICCA (Effect of Remote Ischemic Preconditioning on Clinical Outcomes in CAGB Surgery) 37 and RIPHeart (Remote Ischemic Preconditioning in Heart Surgery), 38 and also a number of recent neutral trials which used drugs to recruit signaling steps of the conditioning phenomena in patients with AMI, that is, CIRCUS (Does Cyclosporine Improve Clinical Outcome in ST Elevation Myocardial Infarction Patients) 39 and CYCLE (Cyclosporine A in Reperfused Myocardial Infarction), 40 disappointment and frustration prevail.…”

Acute Myocardial Injury: A Perspective on Lethal Reperfusion Injury

“…Low-pressure reperfusion (variant of post-conditioning) at the time of reperfusion also merits consideration for post-ischemic myocyte protection [143]. However, cytoprotection potential of these interventions in humans remains controversial [144,145].…”