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Cardiovascular Research May 2007Transforming Growth Factor (TGF)-beta is markedly induced and rapidly activated in the infarcted myocardium. However, understanding of the exact role of TGF-beta... (Review)
Review
Transforming Growth Factor (TGF)-beta is markedly induced and rapidly activated in the infarcted myocardium. However, understanding of the exact role of TGF-beta signaling in the infarcted and remodeling heart has been hampered by the complex and unusual biology of TGF-beta activation and by the diversity of its effects eliciting multiple, and often opposing cellular responses. Experimental studies suggest that TGF-beta signaling may be crucial for repression of inflammatory gene synthesis in healing infarcts mediating resolution of the inflammatory infiltrate. In addition, TGF-beta may play an important role in modulating fibroblast phenotype and gene expression, promoting extracellular matrix deposition in the infarct by upregulating collagen and fibronectin synthesis and by decreasing matrix degradation through induction of protease inhibitors. TGF-beta is also a key mediator in the pathogenesis of hypertrophic and dilative ventricular remodeling by stimulating cardiomyocyte growth and by inducing interstitial fibrosis. In this review we summarize the current knowledge on the role of TGF-beta in infarct healing and cardiac remodeling.
Topics: Animals; Fibroblasts; Humans; Leukocytes; Myocardial Infarction; Signal Transduction; Transforming Growth Factor beta; Ventricular Remodeling
PubMed: 17109837
DOI: 10.1016/j.cardiores.2006.10.002 -
Postgraduate Medical Journal Sep 1995Greater understanding of the underlying pathophysiology of acute myocardial infarction (AMI) has led to more aggressive management and lower mortality, both in-hospital... (Review)
Review
Greater understanding of the underlying pathophysiology of acute myocardial infarction (AMI) has led to more aggressive management and lower mortality, both in-hospital and long term. AMI results mainly from thrombotic occlusion of the infarct-related coronary artery. The ensuing necrosis evolves over a 6-12 h period providing a time window for interventions designed to reduce eventual infarct size. The most appropriate interventions are those which restore coronary artery patency and hence myocardial blood flow as soon as possible. Occasionally, disruption of the occluding thrombus and compression of the underlying atheromatous lesion is best achieved by direct percutaneous transluminal coronary angioplasty. For the vast majority however, revascularisation by drug therapy is more appropriate. As soon as possible, all patients without contraindications should be offered oral aspirin and intravenous thrombolysis, usually with streptokinase but occasionally with tissue plasminogen activator. Patients in whom these agents are contraindicated should be considered for intravenous beta-blockade using atenolol or metoprolol to reduce myocardial demand and hence infarct size. Patients with large infarcts, impaired ventricular function, left ventricular failure or hypertension should be considered for early angiotensin-converting enzyme inhibitor therapy. Other agents may be valuable symptomatically, but have no proven role in reducing infarct size or mortality. After the first 24 h, the main aims of management are to assess the likelihood of later ischaemic events or death (risk stratification) and hence to choose appropriate long term secondary prophylaxis.
Topics: Adrenergic beta-Antagonists; Angioplasty, Balloon, Coronary; Aspirin; Fibrinolytic Agents; Humans; Myocardial Infarction; Myocardial Reperfusion; Thrombolytic Therapy
PubMed: 7479465
DOI: 10.1136/pgmj.71.839.534 -
Stroke Oct 2014Infarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Infarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar infarcts and vascular risk factors and outcomes.
METHODS
We studied 1679 participants in the Secondary Prevention of Small Subcortical Stroke trial with a lacunar infarct visualized on diffusion-weighted imaging. Infarct volume was measured planimetrically, and shape was classified based on visual analysis after 3-dimensional reconstruction of axial MRI slices.
RESULTS
Infarct shape was ovoid/spheroid in 63%, slab in 12%, stick in 7%, and multicomponent in 17%. Median infarct volume was smallest in ovoid/spheroid relative to other shapes: 0.46, 0.65, 0.54, and 0.90 mL, respectively (P<0.001). Distributions of vascular risk factors were similar across the 4 groups except that patients in the ovoid/spheroid and stick groups were more often diabetic and those with multicomponent had significantly higher blood pressure at study entry. Intracranial stenosis did not differ among groups (P=0.2). Infarct volume was not associated with vascular risk factors. Increased volume was associated with worse functional status at baseline and 3 months. Overall, 162 recurrent strokes occurred during an average of 3.4 years of follow-up with no difference in recurrent ischemic stroke rate by shape or volume.
CONCLUSIONS
In patients with recent lacunar stroke, vascular risk factor profile was similar among the different infarct shapes and sizes. Infarct size correlated with worse short-term functional outcome. Neither shape nor volume was predictive of stroke recurrence.
CLINICAL TRIAL REGISTRATION URL
http://www.clinicaltrials.gov. Unique identifier: NCT00059306.
Topics: Aged; Cerebral Infarction; Diffusion Magnetic Resonance Imaging; Female; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Platelet Aggregation Inhibitors; Recovery of Function; Recurrence; Secondary Prevention; Stroke, Lacunar
PubMed: 25190442
DOI: 10.1161/STROKEAHA.114.005211 -
Journal of Cardiovascular Magnetic... Jan 2017Knowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and...
BACKGROUND
Knowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and post-infarction electromechanical functioning of the heart. Accurate imaging of infarct microstructure necessitates imaging techniques that produce high image spatial resolution and high signal-to-noise ratio (SNR). The aim of this study is to provide detailed reconstruction of 3D chronic infarcts in order to characterize the infarct microstructural remodeling in porcine and human hearts.
METHODS
We employed a customized diffusion tensor imaging (DTI) technique in conjunction with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) on a 3T clinical scanner to image, at submillimeter resolution, myofiber orientation and scar structure in eight chronically infarcted porcine hearts ex vivo. Systematic quantification of local microstructure was performed and the chronic infarct remodeling was characterized at different levels of wall thickness and scar transmurality. Further, a human heart with myocardial infarction was imaged using the same DTI sequence.
RESULTS
The SNR of non-diffusion-weighted images was >100 in the infarcted and control hearts. Mean diffusivity and fractional anisotropy (FA) demonstrated a 43% increase, and a 35% decrease respectively, inside the scar tissue. Despite this, the majority of the scar showed anisotropic structure with FA higher than an isotropic liquid. The analysis revealed that the primary eigenvector orientation at the infarcted wall on average followed the pattern of original fiber orientation (imbrication angle mean: 1.96 ± 11.03° vs. 0.84 ± 1.47°, p = 0.61, and inclination angle range: 111.0 ± 10.7° vs. 112.5 ± 6.8°, p = 0.61, infarcted/control wall), but at a higher transmural gradient of inclination angle that increased with scar transmurality (r = 0.36) and the inverse of wall thickness (r = 0.59). Further, the infarcted wall exhibited a significant increase in both the proportion of left-handed epicardial eigenvectors, and in the angle incoherency. The infarcted human heart demonstrated preservation of primary eigenvector orientation at the thinned region of infarct, consistent with the findings in the porcine hearts.
CONCLUSIONS
The application of high-resolution DTI and LGE-CMR revealed the detailed organization of anisotropic infarct structure at a chronic state. This information enhances our understanding of chronic post-infarction remodeling in large animal and human hearts.
Topics: Aged, 80 and over; Animals; Anisotropy; Chronic Disease; Contrast Media; Diffusion Tensor Imaging; Disease Models, Animal; Female; Fibrosis; Gadolinium DTPA; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Myocardial Infarction; Myocardium; Predictive Value of Tests; Sus scrofa; Ventricular Remodeling
PubMed: 28122618
DOI: 10.1186/s12968-016-0317-3 -
Journal of Molecular and Cellular... Mar 2010The dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also... (Review)
Review
The dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also directly modulate the inflammatory and reparative response. During the inflammatory phase of healing, rapid activation of Matrix Metalloproteinases (MMP) causes degradation of the cardiac extracellular matrix. Matrix fragments exert potent pro-inflammatory actions, while MMPs process cytokines and chemokines altering their biological activity. In addition, vascular hyperpermeability results in extravasation of fibronectin and fibrinogen leading to formation of a plasma-derived provisional matrix that serves as a scaffold for leukocyte infiltration. Clearance of the infarct from dead cells and matrix debris is essential for resolution of inflammation and marks the transition to the proliferative phase. The fibrin-based provisional matrix is lysed and cellular fibronectin is secreted. ED-A fibronectin, mechanical tension and Transforming Growth Factor (TGF)-beta are essential for modulation of fibroblasts into myofibroblasts, the main collagen-secreting cells in the wound. The matricellular proteins thrombospondin-1 and -2, osteopontin, tenascin-C, periostin, and secreted protein acidic and rich in cysteine (SPARC) are induced in the infarct regulating cellular interactions and promoting matrix organization. As the infarct matures, matrix cross-linking results in formation of a dense collagen-based scar. At this stage, shielding of fibroblasts from external mechanical tension by the mature matrix network may promote deactivation and cellular quiescence. The components of the extracellular matrix do not passively follow the pathologic alterations of the infarcted heart but critically modulate inflammatory and reparative pathways by transducing signals that affect cell survival, phenotype and gene expression.
Topics: Animals; Extracellular Matrix; Humans; Matrix Metalloproteinases; Models, Biological; Myocardial Infarction; Wound Healing
PubMed: 19631653
DOI: 10.1016/j.yjmcc.2009.07.015 -
Revista Portuguesa de Cardiologia :... Oct 2017The role of endothelial dysfunction (ED) in patients with ST-elevation myocardial infarction (STEMI) is poorly understood. Peripheral arterial tonometry (PAT) allows...
INTRODUCTION AND OBJECTIVES
The role of endothelial dysfunction (ED) in patients with ST-elevation myocardial infarction (STEMI) is poorly understood. Peripheral arterial tonometry (PAT) allows non-invasive evaluation of ED, but has never been used for this purpose early after primary percutaneous coronary intervention (P-PCI). Our purpose was to analyze the relation between ED assessed by PAT and both the presence of microvascular obstruction (MVO) and infarct extension in STEMI patients.
METHODS
ED was assessed by the reactive hyperemia index (RHI), measured by PAT and defined as RHI <1.67. Infarct extension was assessed by troponin I (TnI) release and contrast-enhanced cardiac magnetic resonance (ceCMR). MVO was assessed by ceCMR and by indirect angiographic and ECG indicators. An echocardiogram was also performed in the first 12 h.
RESULTS
We included 38 patients (mean age 60.0±13.7 years, 29 male). Mean RHI was 1.87±0.60 and 16 patients (42.1%) had ED. Peak TnI (median 118 mg/dl, IQR 186 vs. 67/81, p=0.024) and AUC of TnI (median 2305, IQR 2486 vs. 1076/1042, p=0.012) were significantly higher in patients with ED, who also showed a trend for more transmural infarcts (63.6% vs. 22.2%, p=0.06) and larger infarct mass on ceCMR (median 17.5%, IQR 15.4 vs. 10.1/10.3, p=0.08). Left ventricular ejection fraction (LVEF) was lower and wall motion score index (WMSI) was higher on both echocardiogram and ceCMR in patients with ED. On ceCMR, MVO was more frequent in patients with RHI <1.67 (54.5% vs. 11.1%, p=0.03). ECG and angiographic indicators of MVO all showed a trend toward worse results in these patients.
CONCLUSIONS
The presence of ED assessed by PAT 24 h after P-PCI in patients with STEMI is associated with larger infarcts, lower LVEF, higher WMSI and higher prevalence of MVO.
Topics: Endothelium, Vascular; Female; Humans; Male; Microvessels; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; ST Elevation Myocardial Infarction; Time Factors; Vascular Diseases
PubMed: 29033166
DOI: 10.1016/j.repc.2017.01.006 -
BMC Cardiovascular Disorders Jun 2020Atrioventricular plane displacement (AVPD) reflects longitudinal left ventricular (LV) systolic function, and wall thickening (WT) regional radial LV function. The... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Atrioventricular plane displacement (AVPD) reflects longitudinal left ventricular (LV) systolic function, and wall thickening (WT) regional radial LV function. The temporal evolution of these measures after STEMI with CMR has not been evaluated. We aimed to investigate how AVPD and WT are affected globally and regionally from the sub-acute to the chronic phase after ST-elevation myocardial infarction (STEMI).
METHODS
Healthy volunteers without cardiovascular disease and medication (controls, n = 20) and patients from the CHILL-MI study ( NCT01379261 ) prospectively underwent magnetic resonance imaging (MRI) 2-6 days and 6 months after STEMI (n = 77). CHILL-MI randomized STEMI-patients to cooling therapy initiated before reperfusion or standard of care. AVPD was measured at six points in three long axis cine images and wall thickening in short axis cine images. Infarction was quantified using late gadolinium enhancement (LGE) and used to define infarct and remote segments.
RESULTS
There were no difference in AVPD either at acute or chronic phase (p = 0.90 and p = 0.40) or WT (p = 0.85 and p = 0.99) between patients randomized to cooling therapy and standard of care. Therefore, the results are presented for the pooled cohort. Global AVPD was decreased in both the sub-acute (12 ± 2 mm, p < 0.001) and the chronic phase (13 ± 2 mm, p < 0.001) compared to controls (15 ± 2 mm) with a partial recovery of AVPD (p < 0.001) in the chronic phase. Patients with left anterior descending (LAD) and right coronary artery (RCA) infarcts had decreased AVPD in the chronic phase in both infarcted and remote segments. Mean WT was decreased in patients with LAD infarction both in the sub-acute and the chronic phase in both infarcted and remote segments. The decrease in WT in patients with RCA and left circumflex (LCx) infarcts was more affected in the infarcted segments, especially in the chronic phase.
CONCLUSION
AVPD was a global rather than regional marker of cardiac function in this STEMI study and this may explain the prognostic importance of local measurements of mitral annular plane systolic excursion (MAPSE). The decrease in WT in remote myocardium even in the chronic phase needs to be taken into consideration when combining functional measurements with infarct quantification for diagnosis of post-ischemic stunning and hibernation.
Topics: Aged; Female; Humans; Hypothermia, Induced; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome; Ventricular Function, Left
PubMed: 32600336
DOI: 10.1186/s12872-020-01540-y -
Journal of Chemical Neuroanatomy Dec 2021Transient cerebral ischemia followed by reperfusion in an infarcted brain comes with predictable acute and chronic morphological alterations in neuronal and non-neuronal...
Transient cerebral ischemia followed by reperfusion in an infarcted brain comes with predictable acute and chronic morphological alterations in neuronal and non-neuronal cells. An accurate delineation of the cerebral infarct is not a simple task due to the complex shapes and indistinct borders of the infarction. Thus, an exact macroscopic histological approach for infarct volume estimation can lead to faster and more reliable preclinical research results. This study investigated the effect(s) of confounding factors such as fixation and tissue embedding on the quality of macroscopic visualization of focal cerebral ischemia by anti-microtubule-associated-protein-2 antibody (MAP2) with conventional Hematoxylin and Eosin (HE) staining serving as the control. The aim was to specify the most reliable macroscopic infarct size estimation method after sub-acute focal cerebral ischemia based on the qualitative investigation. Our results showed that the ischemic area on the MAP2-stained sections could be identified macroscopically on both cryo-preserved and paraffin-embedded sections from both immersion- and perfusion-fixed brains. The HE staining did not clearly depict an infarct area for macroscopic visualization. Therefore both immersion-fixed and perfused-fixed-MAP2 stained sections can be used reliably to quantify cerebral infarcts.
Topics: Animals; Brain Ischemia; Cerebral Infarction; Histological Techniques; Immunohistochemistry; Infarction, Middle Cerebral Artery; Ischemic Attack, Transient; Male; Microtubule-Associated Proteins; Perfusion; Rats; Rats, Wistar; Reperfusion; Staining and Labeling; Tissue Embedding; Tissue Fixation
PubMed: 34592321
DOI: 10.1016/j.jchemneu.2021.102034 -
Stroke Nov 2013Lacunar infarction is attributable to a perforating arteriolar abnormality. Possible causes include embolism, atheromatosis, or intrinsic disease. We examined whether...
BACKGROUND AND PURPOSE
Lacunar infarction is attributable to a perforating arteriolar abnormality. Possible causes include embolism, atheromatosis, or intrinsic disease. We examined whether the size, shape, or location of the lacunar infarct varied with embolic sources, systemic atheroma, or vascular risk factors.
METHODS
We examined data from 3 prospective studies of patients with clinical and diffusion-weighted imaging-positive symptomatic lacunar infarction who underwent full clinical assessment and investigation for stroke risk factors. Lacunar infarct sizes (maximum diameter; shape, oval/tubular; location, basal ganglia/centrum semiovale/brain stem) were coded blind to clinical details.
RESULTS
Among 195 patients, 48 infarcts were tubular, 50 were 15 to 20 mm in diameter, and 97 and 74 were located in the basal ganglia and the centrum semiovale, respectively. There was no association between infarct size or shape and any of the risk factors. Centrum semiovale infarcts were less likely to have a potential relevant embolic source (4% versus 11%; odds ratio, 0.16; 95% confidence interval, 0.03-0.83) and caused a lower National Institute of Health Stroke Scale score (2 versus 3; odds ratio, 0.78; 95% confidence interval, 0.62-0.98) than basal ganglia infarcts. There were no other differences by infarct location.
CONCLUSIONS
Lacunar infarcts in the basal ganglia caused marginally severer strokes and were 3 times more likely to have a potential embolic source than those in the centrum semiovale, but the overall rate of carotid or known cardiac embolic sources (11%) was low. We found no evidence that other risk factors differed with location, size, or shape, suggesting that most lacunar infarcts share a common intrinsic arteriolar pathology.
Topics: Aged; Basal Ganglia; Carotid Arteries; Cerebral Infarction; Diffusion Magnetic Resonance Imaging; Embolism; Female; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Radiography; Risk Factors; Stroke; Stroke, Lacunar
PubMed: 24008573
DOI: 10.1161/STROKEAHA.113.002227 -
British Journal of Haematology Sep 2015Sickle cell disease induces specific brain alterations that involve both the macrocirculation and the microcirculation. The main overt neurovascular complications in... (Review)
Review
Sickle cell disease induces specific brain alterations that involve both the macrocirculation and the microcirculation. The main overt neurovascular complications in children are infarctive stroke, transient ischaemic attack and cerebral haemorrhage. Silent cerebral infarction, cognitive dysfunction and recurrent headache are also common. Cerebrovascular disease selectively affects children with the HbSS or HbS-β(0) genotypes (i.e. sickle cell anaemia). The incidence of stroke peaks between 2 and 5 years of age (1·02/100 patient-years) and increases with the severity of the anaemia. Most strokes can be prevented by annual transcranial Doppler screening from 2 to 16 years of age and providing chronic blood transfusion when this investigation shows elevated blood-flow velocities. The role for hydroxycarbamide in children with abnormal transcranial Doppler findings is under investigation. After a stroke, chronic blood transfusion is very strongly recommended, unless haematopoietic stem cell transplantation can be performed. Routine magnetic resonance imaging shows that more than one-third of children have silent cerebral infarction, which is associated with cognitive impairments. Screening for silent infarcts seems legitimate, since their presence may lead to supportive treatments. The role for more aggressive interventions such as hydroxycarbamide or chronic blood transfusion is debated.
Topics: Adolescent; Allografts; Anemia, Sickle Cell; Blood Transfusion; Brain Infarction; Cerebrovascular Circulation; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Stroke; Ultrasonography, Doppler, Transcranial
PubMed: 25944412
DOI: 10.1111/bjh.13477