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Book ChapterDOI

Ventricular Remodeling after Myocardial Infarction

TL;DR: The extent of ventricular enlargement after infarction is related to the magnitude of the initial damage to the myocardium and, although an increase in cavity size tends to restore stroke volume despite a persistently depressed ejection fraction, ventricular dilation has been associated with a reduction in survival.
Abstract: Acute transmural myocardial infarction initiates a series of changes in left ventricular (LV) volume, regional function and geometry. This process, known as postinfarction LV remodeling, may continue for months or years following the initial ischemic event. To characterize the components of late ventricular remodeling, biplane left ventriculography was performed in 52 patients at 3 weeks and repeated at 1 year after first anterior myocardial infarction. Biplane circumference and contractile and noncontractile segment lengths were measured. Global geometry was evaluated by calculating a sphericity index and regional geometry was assessed by measurement of endocardial curvature. End-diastolic (ED) volume was increased at 3 weeks and enlarged further at one year. This late enlargement was accompanied by an increase in the length of the contractile segment and an increase in sphericity, whereas the length of the noncontractile segment decreased. Curvature analysis revealed that this late increase in sphericity resulted from flattening of regions of presumably high tension negative curvature at the infarct border zone and from less bulging of the infarcted anterior wall. Even in patients selected for late ventricular enlargement (change in ED volume > 20 ml, n = 19), this increase in volume resulted from both lengthening of the contractile segment and an increase in sphericity without a change in the noncontractile segment length. Thus, late ventricular enlargement after anterior myocardial infarction results from an increase in contractile segment length and a change in ventricular geometry and is not a result of progressive infarct expansion.
Citations
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Journal ArticleDOI
05 Apr 2001-Nature
TL;DR: It is indicated that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.
Abstract: Myocardial infarction leads to loss of tissue and impairment of cardiac performance The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time1 Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation2,3,4,5; these events promote structural and functional repair6,7,8 This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein9 by fluorescence-activated cell sorting on the basis of c-kit expression10 Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct Here we report that newly formed myocardium occupied 68% of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells The developing tissue comprised proliferating myocytes and vascular structures Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease

5,331 citations

Journal ArticleDOI
TL;DR: Left ventricular end-diastolic and end-systolic volume and ejection fraction data provide support for the beneficial effects of therapeutic agents such as angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents on the remodeling process.

2,215 citations


Cites background from "Ventricular Remodeling after Myocar..."

  • ...Patients with asymptomatic LV dysfunction and milder forms of HF are still at increased risk of sudden cardiac death (29,81)....

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  • ...Relatively small increases in ventricular volume are associated with a major independent increase in the risk of death in patients with coronary artery disease, recent MI or HF (29,80,81)....

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Journal Article
TL;DR: There remains a substantial subgroup of patients who manifest clinical evidence of heart failure despite the first two of these treatments, despite survival after acute myocardial infarction being enhanced by treatment with thrombolytic agents, aspirin, and Beta -adrenoceptor blockade.

1,958 citations

Journal ArticleDOI
TL;DR: This work identifies two distinct phases of monocyte participation after MI and proposes a model that reconciles the divergent properties of these cells in healing and identifies new therapeutic targets that can influence healing and ventricular remodeling after MI.
Abstract: Healing of myocardial infarction (MI) requires monocytes/macrophages These mononuclear phagocytes likely degrade released macromolecules and aid in scavenging of dead cardiomyocytes, while mediating aspects of granulation tissue formation and remodeling The mechanisms that orchestrate such divergent functions remain unknown In view of the heightened appreciation of the heterogeneity of circulating monocytes, we investigated whether distinct monocyte subsets contribute in specific ways to myocardial ischemic injury in mouse MI We identify two distinct phases of monocyte participation after MI and propose a model that reconciles the divergent properties of these cells in healing Infarcted hearts modulate their chemokine expression profile over time, and they sequentially and actively recruit Ly-6Chi and -6Clo monocytes via CCR2 and CX3CR1, respectively Ly-6Chi monocytes dominate early (phase I) and exhibit phagocytic, proteolytic, and inflammatory functions Ly-6Clo monocytes dominate later (phase II), have attenuated inflammatory properties, and express vascular–endothelial growth factor Consequently, Ly-6Chi monocytes digest damaged tissue, whereas Ly-6Clo monocytes promote healing via myofibroblast accumulation, angiogenesis, and deposition of collagen MI in atherosclerotic mice with chronic Ly-6Chi monocytosis results in impaired healing, underscoring the need for a balanced and coordinated response These observations provide novel mechanistic insights into the cellular and molecular events that regulate the response to ischemic injury and identify new therapeutic targets that can influence healing and ventricular remodeling after MI

1,895 citations

Journal ArticleDOI
TL;DR: The potential paracrine mechanisms involved in adult stem cell signaling and therapy are reviewed: cytokines and growth factors can induce cytoprotection and neovascularization, and cardiac remodeling, contractility, and metabolism may also be influenced in aParacrine fashion.
Abstract: Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and the number of newly generated cardiomyocytes and vascular cells, either by transdifferentiation or cell fusion, appear too low to explain the significant cardiac improvement described. Accordingly, we and others have advanced an alternative hypothesis: the transplanted stem cells release soluble factors that, acting in a paracrine fashion, contribute to cardiac repair and regeneration. Indeed, cytokines and growth factors can induce cytoprotection and neovascularization. It has also been postulated that paracrine factors may mediate endogenous regeneration via activation of resident cardiac stem cells. Furthermore, cardiac remodeling, contractility, and metabolism may also be influenced in a paracrine fashion. This article reviews the potential paracrine mechanisms involved in adult stem cell signaling and therapy.

1,855 citations

References
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Journal ArticleDOI
TL;DR: The hypothesis that hypertrophy develops to normalize systolic but not diastolic wall stress is suggested, and it is proposed that increased syStolic tension development by myocardial fibers results in fiber thickening just sufficient to return the systolics stress (force per unit cross-sectional area) to normal.
Abstract: It is generally recognized that chronic left ventricular (LV) pressure overload results primarily in wall thickening and concentric hypertrophy, while chronic LV volume overload is characterized by chamber enlargement and an eccentric pattern of hypertrophy. To assess the potential role of the hemodynamic factors which might account for these different patterns of hypertrophy, we measured LV wall stresses throughout the cardiac cycle in 30 patients studied at the time of cardiac catheterization. The study group consisted of 6 subjects with LV pressure overload, 18 with LV volume overload, and 6 with no evidence of heart disease (control). LV pressure, meridional wall stress (sigman), wall thickness (h), and radius (R) were measured in each patient throughout the cardiac cycle. For patients with pressure overload, LV peak systolic and end diastolic pressures were significantly increased (220 plus or minus 6/23 plus or minus 3 mm Hg) compared to control (117 plus or minus 7/10 plus or minus 1 mm Hg, P less than 0.01 for each). However, peak systolic and end diastolic (sigman) were normal (161 plus or minus 24/23 plus or minus 3 times 10-3 dyn/cm-2) compared to control (151 plus or minus 14/17 plus or minus 2 times 10-3 dyn/cm-2, NS), reflecting the fact that the pressure overload was exactly counterbalanced by increased wall thickness (1.5 plus or minus 0.1 cm for pressure overload vs. 0.8 plus or minus 0.1 cm for control, P less than 0.01). For patients with volume overload, peak systolic (sigman) was not significantly different from control, but end diastolic (sigmam) was consistently higher than normal (41 plus or minus 3 times 10-3 dyn/cm-2 for volume overload, 17 plus or minus 2 times 10-3 dyn/cm-2 for control, P less than 0.01). LV pressure overload was associated with concentric hypertrophy, and an increased value for the ratio of wall thickness to radius (h/R ratio). In contrast, LV volume overload was associated with eccentric hypertrophy, and a normal h/R ratio. These data suggest the hypothesis that hypertrophy develops to normalize systolic but not diastolic wall stress. We propose that increased systolic tension development by myocardial fibers results in fiber thickening just sufficient to return the systolic stress (force per unit cross-sectional area) to normal. In contrast, increased resting or diastolic tension appears to result in gradual fiber elongation or lengthening which improves efficiency of the ventricular chamber but cannot normalize the diastolic wall stress.

2,307 citations

Journal ArticleDOI
TL;DR: Volume, ejection fractions, and severity of coronary arterial occlusions and stenoses in 605 male patients under 60 years of age at 1 to 2 months after a first or recurrent myocardial infarction showed that end-systolic volume had greater predictive value for survival than end-diastolic volume or ejection fraction.
Abstract: Impairment of left ventricular function is the major predictor of mortality after acute myocardial infarction, but it is not known whether this is best described by ejection fraction or by end-systolic or end-diastolic volume. We measured volumes, ejection fractions, and severity of coronary arterial occlusions and stenoses in 605 male patients under 60 years of age at 1 to 2 months after a first (n = 443) or recurrent (n = 162) myocardial infarction and followed these patients for a mean of 78 months for survivors (range 15 to 165 months). There were 101 cardiac deaths, 71 (70%) of which were sudden (instantaneous or found dead). Multivariate analysis with log rank testing and the Cox proportional hazards model showed that end-systolic volume (chi 2 = 82.9) had greater predictive value for survival than end-diastolic volume (chi 2 = 59.0) or ejection fraction (chi 2 = 46.6), whereas stepwise analysis showed that once the relationship between survival and end-systolic volume had been fitted, there was no additional significant predictive information in either end-diastolic volume or ejection fraction. Severity of coronary occlusions and stenoses showed additional prediction of only borderline significance (p = .04 in one analysis), but continued cigarette smoking did remain an independent risk factor after stepwise analysis. For a subset of patients (n = 200) who had taken part in a randomized trial of coronary artery surgery after recovery from infarction, surgical "intention to treat" showed no predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

2,305 citations

Journal ArticleDOI
TL;DR: In this model of histologically healed myocardial infarction, the impairment of left ventricular function was directly related to the loss of myocardium, and the entire spectrum of postinfarction ventricularfunction was observed, from no detectable impairment to congestive failure.
Abstract: To define the relationship between infarct size and ventricular performance, we performed hemodynamic studies in rats 21 days after left coronary artery occlusion. Ventricular performance was assessed under ether anesthesia by measurements of baseline hemodynamics and stressed performance as determined by the peak cardiac output and stroke volume obtained during intravenous volume loading and by the peak left ventricular developed pressure obtained during occlusion of the ascending aorta. Infarct size was determined by planimetry of the endocardial circumference of each of four histological slices of the left ventricle. Rats with small (4-30%) myocardial infarctions had no discernible impairment in either baseline hemodynamics or peak indices of pumping and pressure-generating ability when compared to the sham-operated, noninfarcted rats. Rats with moderate (31-46%) infarctions had normal baseline hemodynamics but reduced peak flow indices and developed pressure. Rats with infarctions greater than 46% had congestive heart failure, with elevated filling pressures, reduced cardiac output, and a minimal capacity to respond to pre- and after load stresses. The entire spectrum of postinfarction ventricular function was observed, from no detectable impairment to congestive failure. In this model of histologically healed myocardial infarction, the impairment of left ventricular function was directly related to the loss of myocardium.

1,324 citations

Journal ArticleDOI
TL;DR: Desc descriptions of a technique and of a type of optical myograph suitable for such studies and an analysis of the changes in optical myograms which follow clamping of a large coronary vessel are concerned.
Abstract: Many students of the coronary circulation must have noted that the ventricular zone affected by ligating a large coronary branch not only appears cyanotic and dilated, but that it seems to alter in its mode of contraction. The detailed and sequential changes in contraction are not easily followed by the unaided eye and so far have not been recorded myographically. The reasons for this were the lack of an adequate and suitable myograph and a technic for the application of one to a limited ventricular surface so that records obtained represent, at least reasonably well, changes in muscle length and not predominantly artefacts due to position changes, thrusts and vibrations of the vigorously beating ventricle. This communication concerns itself with descriptions of a technique and of a type of optical myograph suitable for such studies and an analysis of the changes in optical myograms which follow clamping of a large coronary vessel. APPARATUS. After preliminary efforts to obtain satisfactory ventricular myograms with the segment myograph used by one of us (Wiggers, 1916) to study auricular contraction, it became obvious that in order to overcome the distortions produced by twists and thrusts of the beating ventricle an instrument was needed in which the movable lever arm operates in fixed bearings. A suitable myograph which retains the compactness, lightness and efficiency of the earlier form is illustrated in figure 1. The body of the instrument consists of a small receiving tambour, E, (2.5 cm. in diameter) from which a tube leads off at right angles for connection with an optical segment capsule. The lever arms which are of aluminum are spaced 1.5 cm. apart. The rigid arm, A, is attached solidly to the back of the tambour and the movable one, B, is pivoted in jewel bearings, C, as indicated in the insert sketch. The total weight of the myograph is only

1,139 citations


"Ventricular Remodeling after Myocar..." refers background in this paper

  • ...baseline (1), to 2-3 days (2), and at 10 days (3) after...

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Journal ArticleDOI
TL;DR: It is indicated that after anterior myocardial infarction, ventricular enlargement is progressive and that captopril may attenuate this process, reduce filling pressures, and improve exercise tolerance.
Abstract: We conducted a double-blind, placebo-controlled trial to determine whether ventricular dilatation continues during the late convalescent phase after myocardial infarction and whether therapy with captopril alters this process. Fifty-nine patients with a first anterior myocardial infarction and a radionuclide ejection fraction of 45 percent or less underwent cardiac catheterization 11 to 31 days after infarction, when they were not in overt congestive heart failure. They were randomly assigned to placebo or captopril and were followed for one year. A repeat catheterization was performed to evaluate interval changes in hemodynamic function and left ventricular volume. Thirty-eight male patients were evaluated with maximal-exercise treadmill tests every three months. No differences were detected at base line in clinical, hemodynamic, or quantitative ventriculographic variables. During one year of follow-up, the end-diastolic volume of the left ventricle increased by a mean [±SEM] of 21 ±8 ml (P<0.02...

1,080 citations