MR Assessment of Acute Pathologic Process after Myocardial Infarction in a Permanent Ligation Mouse Model: Role of Magnetic Nanoparticle-Contrasted MRI

We evaluated the relationship between myocardial infarct size and inflammatory response using cardiac magnetic resonance imaging (CMR) in an acute myocardial infarction (AMI) mouse model. Myocardial infarction (MI) was induced in 14 mice by permanent ligation of the left anterior descending artery. Late gadolinium enhancement (LGE), manganese-enhanced MRI (MEMRI), and magnetofluorescent nanoparticle MRI (MNP-MRI) were performed 1, 2, and 3 days after MI, respectively. The size of the enhanced lesion was quantitatively determined using Otsu’s thresholding method in area-based and sector-based approaches and was compared statistically. Linear correlation between the enhanced lesion sizes was evaluated by Pearson’s correlation coefficients. Differences were compared using Bland-Altman analysis. The size of the inflammatory area determined by MNP-MRI (57.1 ± 10.1%) was significantly larger than that of the infarct area measured by LGE (40.8 ± 11.7%, P<0.0001) and MEMRI (44.1 ± 14.9%, P<0.0001). There were significant correlations between the sizes of the infarct and inflammatory lesions (MNP-MRI versus LGE: r=0.3418, P=0.0099; MNP-MRI versus MEMRI: r=0.4764, P=0.0002). MNP-MRI provides information about inflammatory responses in a mouse model of AMI. Thus, MNP-MRI associated with LGE and MEMRI may play an important role in monitoring the disease progression in MI.

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Abstract 145: Apelin Reduces Myocardial Infarction Size and Promotes Angiogenesis by Increasing SDF-1/CXCR4 and AKT/eNOS/VEGF Pathways

Circulation Research ◽

10.1161/res.111.suppl_1.a145 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Lanfang Li ◽

Heng Zeng ◽

Jian-xiong Chen

Keyword(s):

Myocardial Infarction ◽

Myocardial Ischemia ◽

Molecular Mechanisms ◽

Myocardial Infarct ◽

Ischemia Reperfusion ◽

Border Zone ◽

Heart Weight ◽

Tunel Staining ◽

Myocardial Infarct Size

Background: Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and is emerging as a key player in the regulation of angiogenesis as well as ischemia/reperfusion injury. So far, little is known about the functional role of apelin in myocardial ischemia. We investigated the potential intracellular molecular mechanisms and protective role of apelin during myocardial ischemic injury. Methods and Results: Myocardial ischemia was achieved by ligation of the left anterior descending coronary artery (LAD) for 24 hours and 14 days. Myocardial apoptosis was detected by TUNEL staining. Akt, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), SDF-1 and CXCR4 expression were measured by western blot. The CD133+/cKit+/Sca1+, CD133/SDF-1+ and cKit/CXCR4+ cells were determined by immunostaining. Myocardial capillary and arteriole densities were analyzed in the border zone of infarcted myocardium at 14 d of ischemia. Treatment of C57BL/6J mice with apelin-13 (1 mg/Kg.d) by i.p. injection for 3 days before surgery results in significant decreases in TUNEL positive cells and myocardial infarct size at 24 hours of ischemia. Treatment with apelin increases the phosphorylation of AKT and eNOS and upregulates VEGF expression in the ischemic heart. Furthermore, treatment with apelin leads to the expression of SDF-1 and CXCR4 and increases in the number of CD133+/cKit+/Sca1+, CD133/SDF-1+ and cKit/CXCR4+ cells in ischemic hearts. Treatment with apelin also significantly increases myocardial capillary densities and arteriole formation together with a significant decrease in the ratio of heart weight to body weight at 14 days of ischemia. This is accompanied by a significant improvement of cardiac function after 14 days of ischemia. Conclusions: Our data demonstrate that apelin contributes to the protection of myocardial infarction and angiogenesis by the mechanisms involving in upregulation of SDF-1/CXCR4 and AKT/eNOS/VEGF pathways.

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Role of cellular proteinases in acute myocardial infarction II. influence of in vivo suppression of myocardial proteolysis by antipain, leupeptin and pepstatin on myocardial infarct size in the rat

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(83)80308-8 ◽

1983 ◽

Vol 2 (4) ◽

pp. 681-688 ◽

Cited By ~ 11

Author(s):

Roberto Bolli ◽

Richard O. Cannon ◽

Edith Speir ◽

Robert E. Goldstein ◽

Stephen E. Epstein

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Infarct Size ◽

Myocardial Infarct ◽

Myocardial Infarct Size

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Phosphatidylserine Supplementation as a Novel Strategy for Reducing Myocardial Infarct Size and Preventing Adverse Left Ventricular Remodeling

International Journal of Molecular Sciences ◽

10.3390/ijms22094401 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4401

Author(s):

David Schumacher ◽

Adelina Curaj ◽

Mareike Staudt ◽

Franziska Cordes ◽

Andreea R. Dumitraşcu ◽

...

Keyword(s):

Myocardial Infarction ◽

Infarct Size ◽

Ventricular Remodeling ◽

Heart Function ◽

Myocardial Infarct ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Myocardial Infarct Size ◽

Novel Strategy

Phosphatidylserines are known to sustain skeletal muscle activity during intense activity or hypoxic conditions, as well as preserve neurocognitive function in older patients. Our previous studies pointed out a potential cardioprotective role of phosphatidylserine in heart ischemia. Therefore, we investigated the effects of phosphatidylserine oral supplementation in a mouse model of acute myocardial infarction (AMI). We found out that phosphatidylserine increases, significantly, the cardiomyocyte survival by 50% in an acute model of myocardial ischemia-reperfusion. Similar, phosphatidylserine reduced significantly the infarcted size by 30% and improved heart function by 25% in a chronic model of AMI. The main responsible mechanism seems to be up-regulation of protein kinase C epsilon (PKC-ε), the main player of cardio-protection during pre-conditioning. Interestingly, if the phosphatidylserine supplementation is started before induction of AMI, but not after, it selectively inhibits neutrophil’s activation, such as Interleukin 1 beta (IL-1β) expression, without affecting the healing and fibrosis. Thus, phosphatidylserine supplementation may represent a simple way to activate a pre-conditioning mechanism and may be a promising novel strategy to reduce infarct size following AMI and to prevent myocardial injury during myocardial infarction or cardiac surgery. Due to the minimal adverse effects, further investigation in large animals or in human are soon possible to establish the exact role of phosphatidylserine in cardiac diseases.

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Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01250.2007 ◽

2008 ◽

Vol 294 (6) ◽

pp. H2547-H2557 ◽

Cited By ~ 44

Author(s):

Qin-hui Tuo ◽

Heng Zeng ◽

Amanda Stinnett ◽

Heidi Yu ◽

Judy L. Aschner ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Ischemia ◽

Infarct Size ◽

Myocardial Infarct ◽

Critical Role ◽

Myocardial Infarct Size ◽

Vascular Integrity ◽

Impaired Angiogenesis

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are the two ligands of the Tie-2 receptor, a receptor tyrosine kinase that is expressed on the endothelium. A balanced angiopoietin/Tie-2 system is critical for the maintenance of vascular integrity. We investigated the potential role of a disrupted angiopoietin/Tie-2 system on hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Using streptozotocin (STZ) mice subjected to myocardial ischemia, we examined the effects of shifting the Ang-2-to-Ang-1 ratio on myocardial infarction size, apoptosis, bone marrow (BM) cell-endothelial progenitor cell (EPC) differentiation, and angiogenesis. In control mice, myocardial ischemia increased expression of both Ang-2 and Tie-2. In STZ mice, Ang-2 expression was elevated, whereas Tie-2 expression was reduced, and neither was significantly altered by ischemia. Myocardial infarct size and apoptosis were increased in STZ compared with control mice. Using in vivo administration of an adenovirus containing Ang-1 or Ang-2, we found that shifting the Ang-2-to-Ang-1 ratio to favor Ang-1 reduced myocardial apoptosis and infarct size in STZ mice, while shifting the Ang-2-to-Ang-1 ratio to favor Ang-2 resulted in a significant increase in myocardial infarct size and apoptosis in control mice. Myocardial ischemia-stimulated BM cell-EPC differentiation was inhibited and myocardial angiogenesis was reduced in STZ mice. Systemic administration of Ad-Ang-1 restored BM cell-EPC differentiation and increased myocardial VEGF expression and angiogenesis in STZ mice. Our data demonstrate that disturbed angiopoietin/Tie-2 signaling contributes to the hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Restoration of the Ang-2-to-Ang-1 ratio may be a novel therapeutic strategy for the treatment of diabetic myocardial ischemic diseases.

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Relation of Pre-Event Use of Inhibitors of the Renin-Angiotensin System With Myocardial Infarct Size in Patients Presenting With a First ST-Segment Elevation Myocardial Infarction

The American Journal of Cardiology ◽

10.1016/j.amjcard.2010.04.017 ◽

2010 ◽

Vol 106 (5) ◽

pp. 646-649 ◽

Cited By ~ 9

Author(s):

Nasir Shariff ◽

Christina Dunbar ◽

Martin E. Matsumura

Keyword(s):

Myocardial Infarction ◽

Infarct Size ◽

Myocardial Infarct ◽

Renin Angiotensin System ◽

Myocardial Infarct Size ◽

Angiotensin System ◽

Renin Angiotensin ◽

St Segment Elevation ◽

Segment Elevation Myocardial Infarction ◽

St Segment

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Cardioprotection with esmolol-based cardioplegia for non-infarcted and infarcted rat hearts

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezab117 ◽

2021 ◽

Author(s):

Alexander B Veitinger ◽

Audrey Komguem ◽

Lena Assling-Simon ◽

Martina Heep ◽

Julia Schipke ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Infarct Size ◽

Myocardial Infarct ◽

Lactate Production ◽

Left Ventricular ◽

Myocardial Infarct Size ◽

Cardioplegic Arrest ◽

Blood Cardioplegia ◽

Rat Hearts

Abstract OBJECTIVES Esmolol-based cardioplegic arrest offers better cardioprotection than crystalloid cardioplegia but has been compared experimentally with blood cardioplegia only once. We investigated the influence of esmolol crystalloid cardioplegia (ECCP), esmolol blood cardioplegia (EBCP) and Calafiore blood cardioplegia (Cala) on cardiac function, metabolism and infarct size in non-infarcted and infarcted isolated rat hearts. METHODS Two studies were performed: (i) the hearts were subjected to a 90-min cardioplegic arrest with ECCP, EBCP or Cala and (ii) a regional myocardial infarction was created 30 min before a 90-min cardioplegic arrest. Left ventricular peak developed pressure (LVpdP), velocity of contractility (dLVP/dtmax), velocity of relaxation over time (dLVP/dtmin), heart rate and coronary flow were recorded. In addition, the metabolic parameters were analysed. The infarct size was determined by planimetry, and the myocardial damage was determined by electron microscopy. RESULTS In non-infarcted hearts, cardiac function was better preserved with ECCP than with EBCP or Cala relative to baseline values (LVpdP: 100 ± 28% vs 86 ± 11% vs 57 ± 7%; P = 0.002). Infarcted hearts showed similar haemodynamic recovery for ECCP, EBCP and Cala (LVpdP: 85 ± 46% vs 89 ± 55% vs 56 ± 26%; P = 0.30). The lactate production with EBCP was lower than with ECCP (0.6 ± 0.7 vs 1.4 ± 0.5 μmol/min; P = 0.017). The myocardial infarct size and (ECCP vs EBCP vs Cala: 16 ± 7% vs 15 ± 9% vs 24 ± 13%; P = 0.21) the ultrastructural preservation was similar in all groups. CONCLUSIONS In non-infarcted rat hearts, esmolol-based cardioplegia, particularly ECCP, offers better myocardial protection than Calafiore. After an acute myocardial infarction, cardioprotection with esmolol-based cardioplegia is similar to that with Calafiore.

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