Coronary microembolization during early reperfusion: infarct extension, but protection by ischaemic postconditioning

Skyschally, Andreas; Walter, Barbara; Heusch, Gerd

doi:10.1093/eurheartj/ehs434

Cited by 70 publications

(50 citation statements)

References 34 publications

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“…Thrombus aspiration was no confounder of the observed protection, largely excluding coronary microembolization as an important pathomechanism of no-reflow in the present study. Yet, a recent study in pigs demonstrated the extension of myocardial infarction with superimposed coronary microembolization, but protection by ischemic postconditioning from infarction was even more pronounced when there was superimposed microembolization [24]. As previously shown for hypothermia [5], the present study by Mewton et al also suggests a somewhat greater protection by ischemic postconditioning from coronary microvascular obstruction than from myocardial infarction, but still a close correlation between infarct size and size of areas with coronary microvascular obstruction.…”

supporting

confidence: 82%

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

2013

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Timely reperfusion is the only way to rescue ischemic myocardium from impending infarction. However, reperfusion also adds a component of injury to that incurred during ischemia and thus contributes to final infarct size [6,20,28]. It appears that all conditioning strategies which delay infarct size development and/or reduce infarct size act through attenuation of such reperfusion injury [7]. Apart from its contribution to cardiomyocyte necrosis, reperfusion is frequently also characterized by the development of areas of no-reflow within the previously ischemic myocardium [10]. Evidence for microvascular no-reflow by angiography or MRI despite successfully reopened epicardial coronary arteries in patients with myocardial infarction is associated with impaired recovery of ventricular function and worse survival [19].The coexistence of infarcted cardiomyocytes and areas of coronary microvascular no-reflow in reperfused myocardium is well established [13]; however the underlying mechanisms are not really clear. Several mechanisms can initiate no-reflow in previously ischemic myocardium: (a) embolization of particulate atherosclerotic debris from the culprit lesion into the coronary microcirculation, both after mechanical or thrombolytic reopening of epicardial coronary arteries The analysis of temporal and spatial relationships between infarcted myocardium and no-reflow is largely limited by methodological restraints. By definition, infarcted myocardium and no-reflow are confined to the previously ischemic area at risk. This appears trivial, but when analyzed by clinical imaging technology, the area at risk is often not determined or not clear. Slow/no-flow phenomena outside the area at risk may also occur but have a different underlying pathophysiology, e.g., reflex-mediated coronary vasoconstriction [4,8]. Myocardial infarction develops progressively during ischemia, and a separate component of irreversible injury is added during early reperfusion; the relative contribution of infarction which develops during ischemia and during reperfusion varies and depends on the duration of ischemia [3]. Even with gold standard technology (TTC staining) in the experiment, infarcted tissue is only recognized as such after several hours of reperfusion, and no distinction between myocardium infarcting during ischemia and during reperfusion is possible. No-reflow, as evidenced by lack of endothelial staining by thioflavin in the experiment [13], develops rapidly during early reperfusion and progresses over time [1,22,23]. Most studies indicate that no-reflow areas are This comment refers to the article available at

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confidence: 82%

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

2013

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“…coronary occlusion with reperfusion 101,103,104 and impair coronary dilator reserve. 105,106 In patients, coronary microembolization is particularly seen with PCIs in saphenous vein bypass grafts, and it is here that protection devices are useful to prevent atherothrombotic debris from embolizing into the microcirculation.…”

Section: Heusch Cardioprotection and Coronary Circulation 1647mentioning

confidence: 99%

The Coronary Circulation as a Target of Cardioprotection

Heusch

2016

Circulation Research

209

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Abstract:The atherosclerotic coronary vasculature is not only the culprit but also a victim of myocardial ischemia/ reperfusion injury. Manifestations of such injury are increased vascular permeability and edema, endothelial dysfunction and impaired vasomotion, microembolization of atherothrombotic debris, stasis with intravascular cell aggregates, and finally, in its most severe form, capillary destruction with hemorrhage. In animal experiments, local and remote ischemic pre-and postconditioning not only reduce infarct size but also these manifestations of coronary vascular injury, as do drugs which recruit signal transduction steps of conditioning. Clinically, no-reflow is frequently seen after interventional reperfusion, and it carries an adverse prognosis. The translation of cardioprotective interventions to clinical practice has been difficult to date. Only 4 drugs (brain natriuretic peptide, exenatide, metoprolol, and esmolol) stand unchallenged to date in reducing infarct size in patients with reperfused acute myocardial infarction; unfortunately, for these drugs, no information on their impact on the ischemic/reperfused coronary circulation is available. (Circ Res.

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“…This maneuver has the potential to enhance thrombus dislodgement and, therefore, distal embolization, which in turn could exacerbate the final myocardial damage. 75 …”

Section: Modalities Of Reperfusion Therapymentioning

confidence: 99%

“…Despite the fact that the Ovize group never observed adverse effects with angioplasty postconditioning, it is not always technically feasible and, as discussed previously, could carry a risk of microembolization if not performed appropriately. 72,74,75,88 In contrast, the use of a safe drug as a postconditioning agent is fairly easy, provided it is available in an intravenous formulation and can be administered in a way to cover the time window for protection against lethal reperfusion injury. The Ovize group has reported that cyclosporine, administered as a single intravenous injection immediately before reperfusion, can reduce infarct size in patients with STEMI, 49,95 and Lønborg et al 96 gov: NCT01311700).…”

Section: Pharmacological Versus Ischemic Postconditioningmentioning

confidence: 99%

Myocardial Conditioning

Ovize

Thibault

Przyklenk

2013

Circulation Research

100

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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.

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Coronary microembolization during early reperfusion: infarct extension, but protection by ischaemic postconditioning

Abstract: Microembolization at reperfusion augments infarct size, but postconditioning in the presence of microembolization still reduces infarct size and attenuates infarct expansion.

Cited by 70 publications

References 34 publications

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

Myocardial infarction and coronary microvascular obstruction: an intimate, but complicated relationship

The Coronary Circulation as a Target of Cardioprotection

Myocardial Conditioning

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