The Patent Infarct-Related Artery HypothesisThe open artery hypothesis: Potential mechanisms of action☆
Section snippets
Late infarct-related artery reperfusion and infarct expansion
Infarct expansion, defined by Hutchins and Bulkley11 as “an acute dilatation of and thinning of the area of infarction not explained by additional myocardial necrosis,” forms one of the earliest morphological sequelae of postinfarction ventricular remodeling. Although the precise mechanisms leading to infarct expansion are unknown, it seems likely that extracellular matrix remodeling including the breakdown of intercellular collagen struts is implicated (see later). The cellular basis of
Collagen breakdown
The myocardium consists of a tough 3-dimensional scaffold of type 1 and type III collagen fibers.22 Within this framework is a finer lattice of fibronectin to which parenchymal components and latent metalloprotinases (MMPs) are anchored.23 The geometric alignment of the extracellular matrix is responsible for much of the tensile strength and elasticity of the myocardium.22 Disruption of the matrix (which occurs after myocardial infarction) leads to a vulnerable segment of softened tissue liable
Inflammation and late reperfusion
The relationship between inflammation and infarct healing is interesting and may account for some of the favorable effects associated with delayed reperfusion. After infarction, endothelial cells play a crucial role in the regional inflammatory response.24 Inflammatory mediators (eg, bradykinin, prostaglandins, and chemokines) are released, endothelial cell permeability is increased, and the interstitium becomes edematous.32 The result includes recruitment of phagocytes that lyse and clear
Mechanical effects associated with late reperfusion
In addition to promoting an acute inflammatory response and local edema, reperfusion of an infarct-related coronary artery with blood at an arterial perfusion pressure increases tissue turgor. It is possible, therefore, that engorgement of the coronary vascular tree can have a scaffolding effect on the vulnerable infarcted bed, which increases tissue stiffness, to resist early infarct expansion.
The effect of reperfusion on tissue stiffness has been investigated in a canine study involving left
Global ventricular dilatation and late reperfusion
In the first few days after myocardial infarction, infarct expansion accounts for most of the geometric changes and increases in left ventricular chamber volume.15 Initially, ventricular dilatation can be considered beneficial because it maintains stroke volume through the Frank Starling mechanism. At the same time, however, the dilating ventricle also proves detrimental because it exerts further demands on the surviving myocardium through increases in wall tension (Fig 5).16 Despite
The arrhythmic substrate and late reperfusion
The electrical substrate of the myocardium is altered after myocardial infarction.50 Electrically neutral scar tissue, for example, predisposes to reentrant arrhythmias,51 while in other areas, automaticity is increased.51 Analysis of 24-hour Holter recordings taken approximately 11 days after myocardial infarction from patients participating in the Multicentre Post-Infarction Programme, for example, revealed that at least 11% of patients had runs of nonsustained ventricular tachycardia.52
Autonomic function and late reperfusion
The relationship between autonomic tone and postinfarction arrhythmogenesis may be another mechanism by which late reperfusion of an infarct-related artery may favorably influence prognosis.63 The sympathetic system is among the first of the neurohormones to be activated after infarction.64 In the initial postinfarction period, increased intracellular cyclic AMP (through activation of myocyte adrenoceptors) results in positive chronotropic and inotropic effects that help maintain cardiac
Conclusion
In patients receiving reperfusion therapy late, and in which the opportunity for myocardial salvage has been missed, there still appear to be additional mechanisms of benefit. Caution, however, must be exercised when interpreting the results of experimental studies examining the open artery hypothesis. In animals, the open artery hypothesis can be tested in its purest sense. The clinical situation, however, is more complex, often with acute-on-chronic coronary artery occlusion in the presence
Acknowledgements
Z.R.Y. and M.S.M. are funded in part by the British Heart Foundation.
The magnetic resonance images in Fig 4 were kindly provided by Dr N. Bellenger and Dr D. Pennell (MRI Unit, The Royal Brompton and Harefield Hospitals).
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Cited by (22)
Predictors of Left Ventricular Remodeling After Myocardial Infarction in Patients With a Patent Infarct Related Coronary Artery After Percutaneous Coronary Intervention (from the Post-Myocardial Infarction Remodeling Prevention Therapy [PRomPT] Trial)
2018, American Journal of CardiologyCitation Excerpt :Reperfusion of ischemic myocardium may help deliver blood products necessary for clearing necrotic cells and formation of healthy scar tissue. IRA patency may also provide a scaffolding function for collateral circulation to develop and allow perfusion to peri-infarct myocardium in hibernation.26 Despite these putative benefits, randomized trials have reached mixed conclusions regarding the benefits of late reperfusion.
Guidelines for percutaneous coronary interventions
2005, Revista Espanola de CardiologiaLate intervention after anterior myocardial infarction: Effects on left ventricular size, function, quality of life, and exercise tolerance: Results of the open artery trial (TOAT study)
2002, Journal of the American College of CardiologyCitation Excerpt :Left ventricular ESV is a sensitive measure of post-infarction LV remodeling and one of the most powerful predictors of long-term prognosis after MI (13). Furthermore, attenuation of post-infarction LV dilation is thought to be an important contributing mechanism to the open artery hypothesis (2). The Open Artery Trial was therefore designed to compare LV ESV between the two study groups of patients at highest risk of adverse LV remodeling (transmural anterior MI).
Comparison of time of reperfusion during anterior wall acute myocardial infarction to left ventricular volume one month and 20 months later
2002, American Journal of CardiologyCitation Excerpt :Our previous results also suggest that late reperfusion has a preventive effect on LV dilatation without infarct size reduction.5 These preventive effects of late reperfusion on LV dilatation could be explained by the proposed mechanism as suggested by previous published reports.3,20,21 In contrast, the long-term beneficial effect of very late reperfusion has not been demonstrated in either animal models or in clinical settings.
Left ventricular aneurysm formation after acute myocardial infarction
2002, International Journal of Cardiology
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Address reprint requests to Professor Michael S. Marber, PhD, FRCP, FACC, Department of Cardiology, The Rayne Institute, St Thomas' Hospital, Kings College London, London, SE1 7EH, United Kingdom; e-mail: [email protected].