Experimental myocardial infarction

Vokonas, Pantel; Pirzada, Farouk A.; Hood, William B.

doi:10.1016/0002-9149(76)90109-0

Cited by 62 publications

(6 citation statements)

References 30 publications

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“…They concluded that acute infarct expansion resulted predominantly from permanent myocyte slippage and rearrangement. A number of other studies across a variety of species have since supported these early findings of an abrupt circumferential dilation of the injured zone within the first few hours after the induction of infarction (28, 66, 132, 157, 178, 195, 271, 273). …”

Section: Scar Formation and Remodeling Following Myocardial Infarctionmentioning

confidence: 78%

“…However, it has proven remarkably difficult to test this hypothesis directly. In vivo measurements of pressure-segment length curves (211, 257, 258, 264, 273), two-dimensional strains (107), and three-dimensional strains (271) consistently show a shift to longer segment lengths during ischemia. However, this shift could reflect the fact that systolic stresses are now acting on passive myocardium and stretching it to longer lengths, or could in part reflect a shift in the myocardial stress-strain curve itself.…”

Section: Mechanical Implications Of Scar Structurementioning

confidence: 91%

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Physiological Implications of Myocardial Scar Structure

Richardson

Clarke

Quinn

et al. 2015

Comprehensive Physiology

241

201

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Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following an MI, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction.

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Section: Scar Formation and Remodeling Following Myocardial Infarctionmentioning

confidence: 78%

Section: Mechanical Implications Of Scar Structurementioning

confidence: 91%

Physiological Implications of Myocardial Scar Structure

Richardson

Clarke

Quinn

et al. 2015

Comprehensive Physiology

241

201

View full text Add to dashboard Cite

show abstract

“…Among the 46 studies we identified that quantified changes in infarct in-plane dimension in mice, rats, dogs, pigs, sheep, baboons, and patients, the 8 that reported measurements over the first 24 hours consistently reported in-plane expansion (Figure 1A) [5,7,24–29]. By contrast, results from the 40 studies that measured dimensions beyond 24 hours were surprisingly diverse: 20 showed significant in-plane expansion [4,30–48], 9 showed significant compaction [9,14,49–55], and 11 showed no significant change in either direction [5,27,56–64] (Figure 1B).…”

Section: Resultsmentioning

confidence: 99%

“…The balance of reported dimension changes differed when measurements were made in an unloaded (zero cavity pressure) or loaded state. [4,5,7,9,14,24–30,32–64,85]…”

Section: Figmentioning

confidence: 99%

Why Is Infarct Expansion Such an Elusive Therapeutic Target?

Richardson

Holmes

2015

J. of Cardiovasc. Trans. Res.

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Myocardial infarct expansion has been associated with an increased risk of infarct rupture and progression to heart failure, motivating therapies such as infarct restraint and polymer injection that aim to limit infarct expansion. However, an exhaustive review of quantitative studies of infarct remodeling reveals that only half found chronic in-plane expansion, and many reported in-plane compaction. Using a finite-element model, we demonstrate that the balance between scar stiffening due to collagen accumulation and increased wall stresses due to infarct thinning can produce either expansion or compaction in the pressurized heart – potentially explaining variability in the literature – and that loaded dimensions are much more sensitive to changes in thickness than in stiffness. Our analysis challenges the concept that in-plane expansion is a central feature of post-infarction remodeling; rather, available data suggest that radial thinning is the dominant process during infarct healing and may be an attractive therapeutic target.

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“…Prolonged coronary occlusion induces permanent damage within the first hour, and by 6 hours the damaged region begins to stiffen, most likely due to edema. (Pirzada et al, 1976; Vokonas et al, 1976) The first few days post-infarction are a particularly vulnerable time from a mechanical point of view. Damaged myocardium is being resorbed and pre-existing collagen damaged by metalloproteases released by inflammatory cells, (Sato et al, 1983; Takahashi et al, 1990; Zamilpa and Lindsey, 2010) but fibroblasts have not yet infiltrated the infarct and begun depositing substantial amounts of new collagen.…”

Section: Myocardial Infarctionmentioning

confidence: 99%

Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation

Holmes

Laksman

Gepstein

2016

Progress in Biophysics and Molecular Biology

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Following myocardial infarction (MI), damaged myocytes are replaced by collagenous scar tissue, which serves an important mechanical function – maintaining integrity of the heart wall against enormous mechanical forces – but also disrupts electrical function as structural and electrical remodeling in the infarct and borderzone predispose to re-entry and ventricular tachycardia. Novel emerging regenerative approaches aim to replace this scar tissue with viable myocytes. Yet an alternative strategy of therapeutically modifying selected scar properties may also prove important, and in some cases may offer similar benefits with lower risk or regulatory complexity. Here, we review potential goals for such modifications as well as recent proof-of-concept studies employing specific modifications, including gene therapy to locally increase conduction velocity or prolong the refractory period in and around the infarct scar, and modification of scar anisotropy to improve regional mechanics and pump function. Another advantage of scar modification techniques is that they have applications well beyond MI. In particular, ablation treats electrical abnormalities of the heart by intentionally generating scar to block aberrant conduction pathways. Yet in diseases such as atrial fibrillation (AF) where ablation can be extensive, treating the electrical disorder can significantly impair mechanical function. Creating smaller, denser scars that more effectively block conduction, and choosing the location of those lesions by balancing their electrical and mechanical impacts, could significantly improve outcomes for AF patients. We review some recent advances in this area, including the use of computational models to predict the mechanical effects of specific lesion sets and gene therapy for functional ablation. Overall, emerging techniques for modifying scar properties represents a potentially important important set of tools for improving patient outcomes across a range of heart diseases, whether used in place of or as an adjunct to regenerative approaches.

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Experimental myocardial infarction

Cited by 62 publications

References 30 publications

Physiological Implications of Myocardial Scar Structure

Physiological Implications of Myocardial Scar Structure

Why Is Infarct Expansion Such an Elusive Therapeutic Target?

Making better scar: Emerging approaches for modifying mechanical and electrical properties following infarction and ablation

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