Abstract 104: Sex-specific Impact Of S-nitrosoglutathione Reductase (gsnor) On Ventricular Remodeling And Function Following Myocardial Infarction In Mice.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Shathiyah Kulandavelu ◽  
Ellena Paulino ◽  
Lauro Takeuchi ◽  
Rosemeire Kanashiro-Takeuchi ◽  
Wayne Balkan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Myocardial Injury ◽  
Ventricular Remodeling ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Left Ventricular Volumes ◽  
Myocardial Infarct Size ◽  
Cardiac Protection ◽  
Ventricular Volumes

Introduction: Female hearts are less susceptible to myocardial injury following myocardial infarction (MI) and estrogen working through the nitric oxide (NO) pathway is thought to play a role. S-nitrosylation of cysteine thiols is a major signaling pathway through which NO exerts its action and mice with targeted deletion of S-nitrosoglutathione reductase (GSNOR), a denitrosylase that regulates S-nitrosylation, show increased levels of nitrosylated proteins. Male GSNOR -/- mice show a more favorable outcome after MI as compared to wild-type (WT), including reduced myocardial infarct size, improved ejection fraction and preserved left ventricular volumes. Whether female GSNOR -/- mice show gender-related cardiac protection following MI was not known and thus investigated. Methods & Results: MI was induced in male and female GSNOR -/- mice and their respective controls, C57Bl/6J, at 3-5 months via left anterior descending coronary artery occlusion. Serial echocardiography was performed prior to MI and after 1- and 4-weeks post-MI to assess ejection fraction (EF) and left ventricular volume both at diastole (end-diastolic volume, EDV) and systole (end-systolic volume, ESV). Compared to WT, GSNOR -/- males showed less dilation in both EDV (98.6 ± 9.3 mm vs. 140.6 ± 7.4 mm in WT, P<0.001) and ESV (73.1 ± 9.2 vs. 112.7 ± 7.3 mm in WT, P<0.05) at 4 weeks post-MI. Whereas, GSNOR -/- females showed greater dilation in both EDV (162.2 ± 13 vs. 83.8 ± 12 mm in WT, P<0.001) and ESV (141.8 ± 13 vs. 65.6 ± 12 mm in WT, P<0.001) as compared to WT females. EF decreased (P<0.001) in all groups post-MI, but at 4 weeks post-MI, it was significantly worse in GSNOR -/- females compared to GSNOR -/- males (14 ± 4% vs. 28 ± 3%, P<0.05). Conclusion: GSNOR -/- females exhibit significantly lower EF and greater dilation of left ventricular volumes both at diastole and systole following MI than any of the other groups suggesting that S-nitrosylation plays an important role in gender-related cardiac protection following myocardial injury. These findings suggest the importance of taking gender into account when exploring novel therapeutic treatments for myocardial injury.

Abstract 16538: Circulating Ketone Levels are Associated With Myocardial Infarct Size and Left Ventricular Function in Patients Presenting With St-Elevation Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Marie Sophie L de Koning ◽  
B. D Westenbrink ◽  
Solmaz Assa ◽  
Dirk J van Veldhuisen ◽  
Robin P Dullaart ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Left Ventricular Function ◽  
Infarct Size ◽  
Ventricular Function ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
St Elevation Myocardial Infarction ◽  
Myocardial Infarct Size ◽  
St Elevation

Background: Circulating ketone bodies (KB) are increased in patients with heart failure, corresponding with increased utilization of KB as a cardiac fuel. Whether circulating KB are increased in patients presenting with ST-elevation myocardial infarction (STEMI) and whether this is associated with infarct size is unknown. Methods: KB were measured in 379 non-diabetic participants of the Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction (GIPS) III trial (Clinicaltrial.gov Identifier: NCT01217307). Non-fasting plasma concentrations of the KB beta-hydroxybutyrate, acetoacetate, acetone were measured at presentation, 24 hours and 4 months after STEMI presentation using nuclear magnetic resonance spectroscopy. Associations of circulating KB with myocardial infarct size and left ventricular ejection fraction (both detected with MRI at 4 months after STEMI) were determined using multivariable linear regression analyses. Results: Circulating KB were higher at baseline (total KB 520 [315-997](median [IQR], μmol/L), compared to 206 [174-246] at 24 hours and 166 [143-201] at 4 months ( P <0.001 for all)). KB at 24 hours were positively associated with enzymatic infarct size, HbA1C and beta-blocker use. KB at 24 hours were independently associated with MRI outcomes at 4 months. Higher KB was associated with larger myocardial infarct size (total KB: standardized β=0.17, 95%-confidence interval (CI) (0.04-0.31), P =0.012) and lower ejection fraction (standardized β=-0.15, 95%-CI (-0.29- -0.009), P =0.037). Conclusion: Circulating KB are increased in patients with STEMI and are independently associated with myocardial infarct size and left ventricular function after 4 months of follow-up. The increase in circulating KB may reflect maladaptive changes of myocardial metabolism during the acute phase.

Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction

2015 ◽  
Vol 21 (4) ◽  
pp. 363-367 ◽  
Author(s):  
Robert A. Kloner ◽  
Wangde Dai ◽  
Sharon L. Hale ◽  
Jianru Shi
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Myocardial Infarct ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Structure And Function ◽  
Myocardial Infarct Size ◽  
Cardiac Structure And Function ◽  
And Function

While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function.

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

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.

scholarly journals High-resolution imaging of murine myocardial infarction with delayed-enhancement cine micro-CT

2007 ◽  
Vol 292 (6) ◽  
pp. H3172-H3178 ◽  
Author(s):  
Matthias Nahrendorf ◽  
Cristian Badea ◽  
Laurence W. Hedlund ◽  
Jose-Luiz Figueiredo ◽  
David E. Sosnovik ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Ventricular Remodeling ◽  
Ex Vivo ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Delayed Enhancement ◽  
Constant Infusion ◽  
Mouse Heart ◽  
Myocardial Infarct Size

The objective of this study was to determine the feasibility of delayed-enhancement micro-computed tomography (μCT) imaging to quantify myocardial infarct size in experimental mouse models. A total of 20 mice were imaged 5 or 35 days after surgical ligation of the left coronary artery or sham surgery ( n = 6 or 7 per group). We utilized a prototype μCT that covers a three-dimensional (3D) volume with an isotropic spatial resolution of 100 μm. A series of image acquisitions were started after a 200 μl bolus of a high-molecular-weight blood pool CT agent to outline the ventricles. CT imaging was continuously performed over 60 min, while an intravenous constant infusion with iopamidol 370 was started at a dosage of 1 ml/h. Thirty minutes after the initiation of this infusion, signal intensity in Hounsfield units was significantly higher in the infarct than in the remote, uninjured myocardium. Cardiac morphology and motion were visualized with excellent contrast and in fine detail. In vivo CT determination of infarct size at the midventricular level was in good agreement with ex vivo staining with triphenyltetrazolium chloride [5 days post-myocardial infarction (MI): r2 = 0.86, P < 0.01; 35 days post-MI: r2 = 0.92, P < 0.01]. In addition, we detected significant left ventricular remodeling consisting of left ventricular dilation and decreased ejection fraction. 3D cine μCT reliably and rapidly quantifies infarct size and assesses murine anatomy and physiology after coronary ligation, despite the small size and fast movement of the mouse heart. This efficient imaging tool is a valuable addition to the current phenotyping armamentarium and will allow rapid testing of novel drugs and cell-based interventions in murine models.

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