scholarly journals Variability in coronary artery anatomy affects consistency of cardiac damage after myocardial infarction in mice

2017 ◽  
Vol 313 (2) ◽  
pp. H275-H282 ◽  
Author(s):  
Jiqiu Chen ◽  
Delaine K. Ceholski ◽  
Lifan Liang ◽  
Kenneth Fish ◽  
Roger J. Hajjar
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Left Coronary Artery ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Fluorescent Imaging ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Functional Parameters

Low reliability and reproducibility in heart failure models are well established. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. MI was induced by left coronary artery (LCA) ligation. The coronary artery was casted with resin and visualized with fluorescent imaging ex vivo. LCA characteristics and MI size were analyzed individually in each animal, and MI size was correlated with left ventricular (LV) function by echocardiography. Coronary anatomy varies widely in mice, posing challenges for surgical ligation and resulting in inconsistent MI size postligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches are unique in each animal. When the main LCA trunk is ligated, this results in a large MI, but when a single branch is ligated, MI size is variable due to differing levels of LCA ligation and area supplied by the branches. During the ligation procedure, nearly 40% of LCAs are not grossly visible to the surgeon. In these situations, the surgeon blindly sutures a wider and deeper area of tissue in an attempt to catch the LCA. Paradoxically, these situations have greater odds of resulting in smaller MIs. In conclusion, variation in MI size and LV function after LCA ligation in mice is difficult to avoid. Anatomic diversity of the LCA in mice leads to inconsistency in MI size and functional parameters, and this is independent of potential technical modifications made by the operator. NEW & NOTEWORTHY In the present study, we demonstrate that left coronary artery diversity in mice is one of the primary causes of variable myocardial infarction size and cardiac functional parameters in the left coronary artery ligation model. Recognition of anatomic diversity is essential to improve reliability and reproducibility in heart failure research.

Abstract 130: The Diversity of Coronary Artery and Myocardial Infarction in Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jiqiu Chen ◽  
Delaine K Ceholski ◽  
Lifan Liang ◽  
Roger Hajjar
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Ex Vivo ◽  
Fluorescent Imaging ◽  
Lv Function ◽  
Coronary Anatomy ◽  
Arterial Trunk ◽  
Heart Failure Model ◽  
Number Of Branches

Low reliability and reproducibility in heart failure research has been a major concern. The purpose of the present study is to explore factors that affect model consistency of myocardial infarction (MI) in mice. Methods: MI was induced by left coronary artery (LCA) ligation. Echocardiography was used to measure cardiac function after MI. The coronary artery was casted with resin and visualized with fluorescent imaging in ex vivo. LCA characteristics and MI size were analyzed individually in each animal. MI size was correlated with LV function by echocardiography. Results: Coronary anatomy varies widely amongst animals, posing challenges for surgical ligation and resulting in inconsistent MI size data post-ligation. The length of coronary arterial trunk, level of bifurcation, number of branches, and territory supplied by these branches were unique in every animal. When the main LCA trunk was ligated, this resulted in a large MI, but when a single branch was ligated, MI size varied significantly due to differing levels of LCA ligation and differing amounts of territory supplied by the branches. During the ligation procedure, nearly 40% of LCAs were not grossly visible to the surgeon. In these situations, the surgeon commonly blindly sutures a wider and deeper area of tissue in an attempt to ensure that the LCA is caught and ligated. Paradoxically, these situations have greater odds of resulting in smaller MIs. Conclusion: The current study offers evidence of anatomical LCA diversity and the problems this poses for creating a consistent heart failure model by LCA ligation in mice. Carefully recognizing the inevitable individual variation of coronary anatomy in mice is essential to restoring reliability of the LCA ligation model of heart failure.

Abstract 57: Platelet Extracellular-signal-regulated Kinase 5 is a Redox Switch which Regulates Myocardial Infarct Expansion via Matrix Metalloproteinases

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Scott J Cameron ◽  
Sara K Ture ◽  
Deanne Mickelsen ◽  
Enakshi Chakrabarti ◽  
Kristina L Modjeski ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Ex Vivo ◽  
Myocardial Infarct ◽  
Left Ventricular ◽  
Fluorescent Imaging ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Dependent Manner ◽  
Platelet Receptor

Background: Dysregulated platelet activation in an ischemic microvascular environment may play a role in myocardial infarction (MI). Platelet receptor signaling is well-characterized, but mechanisms of receptor-independent activation, such as by reactive oxygen species (ROS) generated in ischemic conditions, are less well understood. We discovered that ERK5, a nuclear protein which is ROS-activated in others cells, is abundantly present in platelets. We investigated whether ERK5 could regulate platelet activation and thrombosis in healthy and diseased states. Methods: Human and mouse platelets were stimulated with agonists including ADP, U46619, TRAP, convulxin, or ROS (H 2 O 2 or 5% O 2 ). ERK5 activity was assessed by immunoblotting. Platelet activation was assessed via fluorescent-activated cell sorting (FACS) for P-selectin or activated GPIIb/IIIa. Intravascular thrombus (pulmonary embolus) or mesenteric thrombus (oxidative injury) formation was assessed by ex vivo fluorescent imaging and in vivo intravital microscopy, respectively. MI was performed in wild-type (WT) and in platelet specific ERK5 deficient (ERK5 -/- ) mice by LAD coronary artery ligation. Left ventricular (LV) function was determined by echocardiography. Matrix metalloproteinase (MMP) activity was determined by in-gel zymography. Results: Human and platelet ERK5 was activated by ROS and via the thrombin and thromboxane receptors, but not via the purinergic or collagen receptors. Murine in vivo thrombosis was regulated by platelet ERK5 only if the injury involved oxidative stress. MI in mice promoted sustained platelet activation over one week in an ERK5-dependent manner. Following MI, platelet ERK5 -/- mice had less reactive platelets, less platelet MMP activity and thromboxane production, attenuated MMP activity in the LV, less remodeling with smaller infarcts, and enhanced myocardial systolic performance. Conclusions: ERK5 is an ischemic sensor in platelets which regulates ongoing platelet activation after MI as well as remodeling via myocardial microvasculature. These observations may explain ischemic microvascular aberrations like the no-reflow phenomenon following percutaneous coronary intervention, suggesting a novel pharmacologic target.

scholarly journals Clofibrate Treatment Decreases Inflammation and Reverses Myocardial Infarction-Induced Remodelation in a Rodent Experimental Model

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 270 ◽  
Author(s):  
Luz Ibarra-Lara ◽  
María Sánchez-Aguilar ◽  
Elizabeth Soria-Castro ◽  
Jesús Vargas-Barrón ◽  
Francisco Roldán ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Ex Vivo ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Cardiac Damage ◽  
Artery Ligation ◽  
Apoptotic Proteins

Myocardial infarction (MI) initiates an inflammatory response that promotes both beneficial and deleterious effects. The early response helps the myocardium to remove damaged tissue; however, a prolonged later response brings cardiac remodeling characterized by functional, metabolic, and structural pathological changes. Current pharmacological treatments have failed to reverse ischemic-induced cardiac damage. Therefore, our aim was to study if clofibrate treatment was capable of decreasing inflammation and apoptosis, and reverse ventricular remodeling and MI-induced functional damage. Male Wistar rats were assigned to (1) Sham coronary artery ligation (Sham) or (2) Coronary artery ligation (MI). Seven days post-MI, animals were further divided to receive vehicle (V) or clofibrate (100 mg/kg, C) for 7 days. The expression of IL-6, TNF-α, and inflammatory related molecules ICAM-1, VCAM-1, MMP-2 and -9, nuclear NF-kB, and iNOS, were elevated in MI-V. These inflammatory biomarkers decreased in MI-C. Also, apoptotic proteins (Bax and pBad) were elevated in MI-V, while clofibrate augmented anti-apoptotic proteins (Bcl-2 and 14-3-3ε). Clofibrate also protected MI-induced changes in ultra-structure. The ex vivo evaluation of myocardial functioning showed that left ventricular pressure and mechanical work decreased in infarcted rats; clofibrate treatment raised those parameters to control values. Echocardiogram showed that clofibrate partially reduced LV dilation. In conclusion, clofibrate decreases cardiac remodeling, decreases inflammatory molecules, and partly preserves myocardial diameters.

Abstract 249: Chronic Neuregulin-1β Treatment Mitigates the Progression of Post-myocardial Infarction Heart Failure in the Setting of Type 1 Diabetes Mellitus

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Manisha Gupte ◽  
Hind Lal ◽  
Firdos Ahmad ◽  
Lin Zhong ◽  
Douglas B Sawyer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 1 Diabetes ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Aim: Neuregulin-1β (NRG-1β), a growth factor critical for cardiac development as well as maintenance of heart function after injury has been shown to significantly improve heart function in preclinical rodent models. Importantly, number of studies are ongoing to test the efficacy of NRG-1β as a treatment for patients with chronic heart failure. However, the efficacy of recombinant NRG-1β in a typ1 diabetic model of heart failure due to myocardial infarction (MI) has not been investigated. The aim of the present study was to determine the efficacy of exogenous NRG-1β to improve residual cardiac function after MI in type1 diabetic rats. Methods and Results: Sprague Dawley rats were induced type 1 diabetes by a single injection of streptozotocin (STZ) (65 mg/kg). Two weeks after induction of type 1 diabetes, rats underwent left coronary artery ligation to induce MI. STZ-diabetic rats were treated with saline or NRG-1β (100 ug/kg) twice a week for 7 weeks, starting two weeks prior to experimental MI. Residual left ventricular (LV) function was significantly greater in the NRG-1β-treated STZ-diabetic MI group compared to the vehicle-treated STZ-diabetic MI group 5 weeks after MI as assessed by high-resolution echocardiography. Furthermore, NRG-1β treatment in STZ-diabetic MI rats reduced myocardial fibrosis and apoptosis as well as decreased gene expression of key oxidant-producing enzymes. Conclusion: This study demonstrates that augmentation of NRG-1β signaling in STZ-diabetic post-MI rats via therapy with exogenous recombinant NRG-1β will alleviate subsequent HF through improvements in residual LV function via protection against adverse remodeling and apoptosis.

Na+/H+ exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats

2001 ◽  
Vol 280 (2) ◽  
pp. H738-H745 ◽  
Author(s):  
Keiji Kusumoto ◽  
James V. Haist ◽  
Morris Karmazyn
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery ◽  
Hydrogen Exchange ◽  
Diastolic Pressure ◽  
Control Diet ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Large Infarct

We investigated the effect of sodium/hydrogen exchange inhibition (NHE-1) on hypertrophy and heart failure after coronary artery ligation (CAL) in the rat. Animals were subjected to occlusion (or sham) of the left main coronary artery and immediately administered a control diet or one consisting of the NHE-1 inhibitor cariporide for 13–15 wk. Hearts were separated by small [≤30% of left ventricle (LV)] and large (>30% of LV) infarcts. CAL depressed change in left ventricular increase in pressure over time (LV +dP/d t) in small and large infarct groups by 18.8% ( P < 0.05) and 34% ( P < 0.01), respectively, whereas comparative values for the cariporide groups were 8.7% (not significant) and 23.1% ( P < 0.01), respectively. LV end-diastolic pressure was increased by 1,225% in the control large infarct group but was significantly reduced to 447% with cariporide. Cariporide also significantly reduced the degree of LV dilation in animals with large infarcts. Hypertrophy, defined by tissue weights and cell size, was reduced by cariporide, and shortening of surviving myocytes was preserved. Infarct sizes were unaffected by cariporide, and the drug had no influence on either blood pressure or the depressed inotropic response of infarcted hearts to dobutamine. These results suggest an important role for NHE-1 in the progression of heart failure after myocardial infarction.

Abstract 16091: Cardioprotective Actions of the N-Terminal-Derived Annexin-A1 Peptide, Ac2-26, Against Myocardial Infarction in vivo

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rebecca H Ritchie ◽  
Chengxue Qin ◽  
Renming Li ◽  
Jane E Bourke ◽  
Helen Kiriazis ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Western World ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Annexin A1

Myocardial infarction (MI) is the major cause of heart failure and death in the Western world. Annexin-A1 is an endogenous, glucocorticoid-regulated anti-inflammatory protein. We have previously shown that this protein plays an important protective role in preserving left ventricular (LV) viability and function in vitro, actions that are reproduced by treatment with its N-terminal-derived peptide, Ac2-26. Little is known however about its cardioprotective actions in vivo, particularly beyond its early anti-necrotic actions in the first few hours of reperfusion. We now test the hypothesis that exogenous Ac2-26 limits multiple aspects of MI injury, over both the short and longer-term in vivo. In the first study, adult C57BL/6 mice were subjected to ischemia-reperfusion (left arterial descending coronary artery ligation, with 1-7 days reperfusion), and Ac2-26 was administered at 1mg/kg i.v. every 24h commencing 5mins before reperfusion. In the second study, mice were subjected to permanent coronary artery occlusion, with Ac2-26 administered 1mg/kg/day i.p. via osmotic pump inserted at time of surgery. As shown in the Table, Ac2-26 reduced cardiac necrosis after 24h reperfusion (infarct size, plasma troponin I levels), systemic and cardiac inflammation after 48h reperfusion (neutrophil and macrophage infiltration) and cardiac fibrosis after 7 days reperfusion. These protective actions at the level of cardiac morphology were associated with preservation of LV function 4wks after permanent occlusion, as determined on fractional shortening and velocity of circumferential fiber shortening. Taken together, our data is the first evidence of Ac2-26 cardioprotection beyond the first few hours of reperfusion in vivo, and importantly, the first to report Ac2-26-induced preservation of LV function in the heart post MI in vivo.

Abstract 48: Differentiation of Moderate and Severe Ischemic Heart Failure by Invasive and Non-invasive Assessments of Diastolic Function in a Rat Model of Chronic Heart Failure

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Saffie Mohran ◽  
Jordan Lancaster ◽  
Pablo Sanchez ◽  
Steven Goldman ◽  
Elizabeth Juneman
Keyword(s):  
Heart Failure ◽  
Coronary Artery ◽  
Diastolic Function ◽  
Left Coronary Artery ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Dead Volume ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Hemodynamic Measurements

Background: This work is designed to determine if specific left ventricle (LV) pressure-volume relations, hemodynamic, and echo derived parameters of diastolic function are able to separate severe from moderate CHF in rats with left coronary artery occlusion. Hypothesis: Echocardiographic indices of diastolic function, end-diastolic pressure (EDP), dead volume, stiffness constants (k), and pressure volume relations predict the severity of CHF in infarcted rats. Methods: Male Sprague Dawley rats (N=14) were randomized to undergo left coronary artery ligation or sham operation. Echocardiography was performed at 3 and 6 weeks post coronary ligation. The rats were categorized into moderate or severe CHF according to their LVEDP at 6 weeks post ligation. Invasive hemodynamic measurements with solid state micro manometer pressure catheters as well as diastolic pressure-volume relation values were obtained at the 6 week end point. Results: Moderate and severe CHF rats had significantly (P<0.05) elevated left ventricular (LV) end-diastolic pressure (LV EDPs), prolonged time constants of LV relaxation (tau), and decreased peak development pressures. When moderate versus severe CHF rats were separated based on LV EDP, early diastolic anterior wall radial relaxation velocity as well as e’, and E/e’ had strong correlations with invasive hemodynamic measurements of diastolic functions. There was a trend towards decreased compliance as measured by stiffness constants in severe heart failure group. Differences (P<0.05) in dead volume, mean arterial pressure (MAP), tau, and ejection fraction (EF) were also displayed. End diastolic pressure-volume analyses illustrated significant differences in plot positioning and curvature. Conclusion: While it is possible to separate rats with moderate and severe CHF in the rat coronary artery ligation model, the separation is not simply based on a specific EF value. This work may be useful in deciding whether there is a differential effect of new treatments for severe versus moderate CHF.

scholarly journals Hydrogen Sulfide Therapy Suppresses Cofilin-2 and Attenuates Ischemic Heart Failure in a Mouse Model of Myocardial Infarction

2020 ◽  
Vol 25 (5) ◽  
pp. 472-483
Author(s):  
Khoa Nguyen ◽  
Vinh Q. Chau ◽  
Adolfo G. Mauro ◽  
David Durrant ◽  
Stefano Toldo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Hydrogen Sulfide ◽  
Saline Group ◽  
Left Ventricular ◽  
Ischemic Heart ◽  
Saline Control ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Ischemic Heart Failure

Aims: Hydrogen sulfide (H2S) protects against ischemic and inflammatory injury following myocardial ischemia via induction of microRNA (miR)-21. We sought to determine whether H2S attenuates ischemic heart failure with reduced ejection fraction (HFrEF) and interrogate the role of cofilin-2, a target of miR-21, in this protective process. Methods and Results: Adult male mice underwent myocardial infarction (MI) by coronary artery ligation after baseline echocardiography. Following MI, mice were treated with Na2S (100 μg/kg/day; intraperitoneal [IP]) or saline up to 28 days. End-diastolic pressure, measured by Millar catheter, was significantly increased ( P < .05 vs sham) at 3 days post-MI in the saline group, which was attenuated with Na2S. Left ventricular (LV) fractional shortening decreased significantly at 28 days post-MI in the saline group but was preserved with Na2S and LV infarct scar size was smaller in Na2S group as compared to control. Apoptotic signaling, measured by Bcl-2/Bax ratio, was significantly increased in the saline group but was mitigated with Na2S. Survival rate was 2-fold higher in Na2S group compared to saline control ( P < .05). Proteomic analysis and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (TOF)/TOF tandem mass spectrometry identified significant changes in proapoptotic cofilin-2 expression, a specific target of miR-21, between saline- and sodium sulfide -treated mice at 28 days post-MI. Western blot analysis confirmed a significant increase in cofilin-2 after MI, which was suppressed with Na2S treatment. Chronic Na2S treatment also attenuated inflammasome formation and activation leading to reduction of maladaptive signaling. Conclusion: Na2S treatment after MI preserves LV function and improves survival through attenuation of inflammasome-mediated adverse remodeling. We propose H2S donors as promising therapeutic tools for ischemic HFrEF.

Blockade of AT1 receptors and Na+/H+exchanger and LV dysfunction after myocardial infarction in rats

1999 ◽  
Vol 277 (2) ◽  
pp. H610-H616 ◽  
Author(s):  
Marcel Ruzicka ◽  
Baoxue Yuan ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Ang Ii ◽  
Artery Ligation ◽  
Volume Load ◽  
Lv Dysfunction

Mechanical stretch, ANG II, and α1-receptor stimulation may contribute to cardiac remodeling after myocardial infarction (MI). Each of these mechanisms involves different signaling pathways for the cellular hypertrophic response. All three also activate the Na+/H+exchanger. In the present study we evaluated the hypothesis that activation of the Na+/H+exchanger is involved in parallel with other signaling mechanisms for ANG II. Three days before coronary artery ligation, rats were randomly allocated to no treatment or treatment with amiloride, losartan, or amiloride and losartan in combination. Four weeks after coronary artery ligation, left ventricular (LV) function was assessed from in vivo resting cardiac pressures, hemodynamic responses to cardiac volume and pressure load, and cardiac remodeling by in vitro pressure-volume curves and LV and right ventricle (RV) weight. Amiloride and losartan given alone to a similar extent attenuated the shift of the pressure-volume curve to the right. This effect was significantly more pronounced with amiloride and losartan in combination. Each drug alone to a minor extent improved LV responses to pressure and volume load. However, with amiloride and losartan in combination, close-to-normal responses to pressure and volume load were observed. Losartan and amiloride alone had only a small effect on development of RV hypertrophy after MI but in combination completely prevented the RV hypertrophy. Amiloride and losartan appear to be complementary in prevention of cardiac remodeling and LV dysfunction after MI. This finding suggests that, besides ANG II, other mechanisms activating the Na+/H+exchanger contribute to cardiac remodeling after MI.

Regulation of components of the brain and cardiac renin-angiotensin systems by 17β-estradiol after myocardial infarction in female rats

2006 ◽  
Vol 291 (1) ◽  
pp. R155-R162 ◽  
Author(s):  
Stephanie A. Dean ◽  
Junhui Tan ◽  
Roselyn White ◽  
Edward R. O’Brien ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular ◽  
Female Rats ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Brain Nuclei ◽  
Renin Angiotensin ◽  
Lv Dysfunction ◽  
17Β Estradiol ◽  
The Brain

The present study tested the hypothesis that 17β-estradiol (E2) inhibits increases in angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT1R) in the brain and heart after myocardial infarction (MI) and, thereby, inhibits development of left ventricular (LV) dysfunction after MI. Age-matched female Wistar rats were treated as follows: 1) no surgery (ovary intact), 2) ovariectomy + subcutaneous vehicle treatment (OVX + Veh), or 3) OVX + subcutaneous administration of a high dose of E2 (OVX + high-E2). After 2 wk, rats were randomly assigned to coronary artery ligation (MI) and sham operation groups and studied after 3 wk. E2 status did not affect LV function in sham rats. At 2–3 wk after MI, impairment of LV function was similar across MI groups, as measured by echocardiography and direct LV catheterization. LV ACE mRNA abundance and activity were increased severalfold in all MI groups compared with respective sham animals and to similar levels across MI groups. In most brain nuclei, ACE and AT1R densities increased after MI. Unexpectedly, compared with the respective sham groups the relative increase was clearest (20–40%) in OVX + high-E2 MI rats, somewhat less (10–15%) in ovary-intact MI rats, and least (<10–15%) in OVX + Veh MI rats. However, because in the sham group brain ACE and AT1R densities increased in the OVX + Veh rats and decreased in the OVX + high-E2 rats compared with the ovary-intact rats, actual ACE and AT1R densities in most brain nuclei were modestly higher (<20%) in OVX + Veh MI rats than in the other two MI groups. Thus E2 does not inhibit upregulation of ACE in the LV after MI and amplifies the percent increases in ACE and AT1R densities in brain nuclei after MI, despite E2-induced downregulation in sham rats. Consistent with these minor variations in the tissue renin-angiotensin system, during the initial post-MI phase, E2 appears not to enhance or hinder the development of LV dysfunction.

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