Time course of right ventricular remodeling in rats with experimental myocardial infarction

2003 ◽  
Vol 284 (1) ◽  
pp. H241-H248 ◽  
Author(s):  
Matthias Nahrendorf ◽  
Kai Hu ◽  
Daniela Fraccarollo ◽  
Karl-Heinz Hiller ◽  
Axel Haase ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Right Ventricular ◽  
Time Course ◽  
Ventricular Remodeling ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Cine Mri ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Artery Ligation

Right ventricular (RV) weight increases dependent on time after myocardial infarction (MI) and on MI size. The sequential changes in RV volume and hemodynamics and their relations to left ventricular (LV) remodeling after MI are unknown. We therefore examined the time course of RV remodeling in rats with LV MI. MI was produced by left coronary artery ligation. Four, eight, and sixteen weeks later, LV and RV hemodynamic measurements were performed and pressure-volume curves were obtained. For serial measurement of RV volumes and performance, cine-MRI was performed 2 and 8 wk after MI. The ratios of β-myosin heavy chain (MHC) to α-MHC and skeletal to cardiac α-actin were determined for the RV and LV after large MI or sham operation. RV weight increased in rats with MI, as did RV volume. RV pressure-volume curves were shifted toward larger volumes 16 wk after large MI. RV systolic pressure increased gradually over time; however, the gain in RV weight was always in excess of RV systolic pressure. The ratios of skeletal to cardiac α-actin and β-MHC to α-MHC were increased after MI in both ventricles in a similar fashion. Because RV wall stress was not increased after infarction, mechanical factors may not conclusively explain hypertrophy, which maintained balanced loading conditions for the RV even after large LV infarction.

Biphasic temporal pattern in exercise capacity after myocardial infarction in the rat: relationship to left ventricular remodeling

2005 ◽  
Vol 288 (1) ◽  
pp. H244-H249 ◽  
Author(s):  
Nathan A. Trueblood ◽  
Patrick R. Inscore ◽  
Daniel Brenner ◽  
Daniel Lugassy ◽  
Carl S. Apstein ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Exercise Capacity ◽  
Time Course ◽  
Ventricular Remodeling ◽  
Contractile Function ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Early Recovery ◽  
Functional Changes ◽  
Lv Remodeling

After myocardial infarction (MI), there is progressive left ventricular (LV) remodeling and impaired exercise capacity. We tested the hypothesis that LV remodeling results in structural and functional changes that determine exercise impairment post-MI. Rats underwent coronary artery ligation ( n = 12) or sham ( n = 11) surgery followed by serial exercise tests and echocardiography for 16 wk post-MI. LV pressure-volume relationships were determined using a blood-perfused Langendorff preparation. Exercise capacity was 60% of shams immediately post-MI ( P < 0.05) followed by a recovery to near normal during weeks 5– 8. Thereafter, there was a progressive decline in exercise capacity to ±40% of shams ( P < 0.01). At both 8 and 16 wk post-MI, fractional shortening (FS) was reduced and end-diastolic diameter (EDD) was increased ( P < 0.01). However, neither FS nor EDD correlated with exercise at 8 or 16 wk ( r2 < 0.12, P > 0.30). LV septal wall thickness was increased at both 8 ( P = 0.17 vs. shams) and 16 wk ( P = 0.035 vs. shams) post-MI and correlated with exercise at both times ( r2 ≥ 0.50 and P ≤ 0.02 at 8 and 16 wk). Neither end-diastolic volume nor maximum LV developed pressure at 16 wk correlated with exercise capacity. Exercise capacity follows a biphasic time course post-MI. An immediate decrease is followed by an early recovery phase that is associated with compensatory LV hypertrophy. Subsequently, there is a progressive decrease in exercise capacity that is independent of further changes in LV volume or contractile function.

scholarly journals Progression of heart failure after myocardial infarction in the rat

2001 ◽  
Vol 281 (5) ◽  
pp. R1734-R1745 ◽  
Author(s):  
J. Francis ◽  
R. M. Weiss ◽  
S. G. Wei ◽  
A. K. Johnson ◽  
R. B. Felder
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Systolic Function ◽  
Left Ventricular Remodeling ◽  
Plasma Renin ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation

This study examined the early neurohumoral events in the progression of congestive heart failure (CHF) after myocardial infarction (MI) in rats. Immediately after MI was induced by coronary artery ligation, rats had severely depressed left ventricular systolic function and increased left ventricular end-diastolic volume (LVEDV). Both left ventricular function and the neurohumoral indicators of CHF underwent dynamic changes over the next 6 wk. LVEDV increased continuously over the study interval, whereas left ventricular stroke volume increased but reached a plateau at 4 wk. Plasma renin activity (PRA), arginine vasopressin, and atrial natriuretic factor all increased, but with differing time courses. PRA declined to a lower steady-state level by 4 wk. Six to 8 wk after MI, CHF rats had enhanced renal sympathetic nerve activity and blunted baroreflex regulation. These findings demonstrate that the early course of heart failure is characterized not by a simple “switching on” of neurohumoral drive, but rather by dynamic fluctuations in neurohumoral regulation that are linked to the process of left ventricular remodeling.

Abstract 15058: Disruption of Extracellular Cytotoxic Chromatin by Acute DNase1 Administration Improves Left Ventricular Remodeling after Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Benjamin Vogel ◽  
Hisahito Shinagawa ◽  
Ullrich Hofmann ◽  
Georg Ertl ◽  
Stefan Frantz
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Pcr Analysis ◽  
Coronary Artery Ligation ◽  
Protective Effects ◽  
Artery Ligation ◽  
High Concentrations

Rationale: Myocardial infarction (MI) leads to necrosis of multinucleated and polyploid myocytes. This causes uncontrolled release of cellular content like chromatin to the infarct area. Chromatin is mainly comprised of histones which are essential for controlling and packing of DNA but paradoxically are also known to be cytotoxic. This makes free chromatin a toxic DNA polymer creating local high concentrations of hazardous histones. Objective: We hypothesized that chromatin from necrotic cells accumulates in ischemic myocardium, creates local high concentrations of cytotoxic histones, and thereby potentiates ischemic damage to the heart after MI. The endonuclease DNase1 is capable of dispersing extracellular chromatin through linker DNA digestion and could decrease local histone concentrations and cytotoxicity. Methods and Results: After permanent coronary artery ligation in mice we found extracellular histones accumulated within the infarcted myocardium. Histone cytotoxicity towards isolated myocytes was confirmed in vitro. To reduce histone related cytotoxicity in vivo DNase1 was injected within the first 6 hours after induction of MI. DNase1 accumulated in the infarcted region of the heart, effectively disrupted extracellular cytotoxic chromatin and thereby reduced high local histone concentration. Animals acutely treated with DNase1 revealed significantly improved left ventricular remodeling as measured by serial echocardiography up to 28 days after MI (e.g. NaCl vs DNase1, papillary end diastolic area [mm 2 ]: 23.26 ± 2.06 vs 18.90 ± 1.24, n=9 vs 10, p<0,05). Treatment did not influence mortality, infarct size or inflammatory parameters as determined by neutrophil infiltration and RTQ-PCR analysis of characteristic cytokines. However improved myocyte survival was discovered within the infarct region which might account for the protective effects in DNase1 treated animals (NaCl vs DNase1: 3.0 ± 0.7% vs 8.3 ± 2.3%; p<0.05; n=7 vs 8). Conclusions: Targeting extracellular cytotoxic chromatin within the infarcted heart by DNase1 is a promising approach to preserve myocytes from histone induced cell death and to conserve left ventricular function after MI. The efficacy of other chromatin degrading agents is now under investigation.

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.

Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction

2010 ◽  
Vol 298 (5) ◽  
pp. H1415-H1425 ◽  
Author(s):  
Sih Min Tan ◽  
Yuan Zhang ◽  
Kim A. Connelly ◽  
Richard E. Gilbert ◽  
Darren J. Kelly
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Dysfunction ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Type I ◽  
Artery Ligation ◽  
Receptor Like Kinase

Following myocardial infarction (MI), the heart undergoes a pathological process known as remodeling, which in many instances results in cardiac dysfunction and ultimately heart failure and death. Transforming growth factor-β (TGF-β) is a key mediator in the pathogenesis of cardiac remodeling following MI. We thus aimed to inhibit TGF-β signaling using a novel orally active TGF-β type I receptor [activin receptor-like kinase 5 (ALK5)] inhibitor (GW788388) to attenuate left ventricular remodeling and cardiac dysfunction in a rat model of MI. Sprague-Dawley rats underwent left anterior descending coronary artery ligation to induce experimental MI and then were randomized to receive GW788388 at a dosage of 50 mg·kg−1·day−1 or vehicle 1 wk after surgery. After 4 wk of treatment, echocardiography was performed before the rats were euthanized. Animals that received left anterior descending coronary artery ligation demonstrated systolic dysfunction, Smad2 activation, myofibroblasts accumulation, collagen deposition, and myocyte hypertrophy (all P < 0.05). Treatment with GW788388 significantly attenuated systolic dysfunction in the MI animals, together with the attenuation of the activated (phosphorylated) Smad2 ( P < 0.01), α-smooth muscle actin ( P < 0.001), and collagen I ( P < 0.05) in the noninfarct zone of MI rats. Cardiomyocyte hypertrophy in MI hearts was also attenuated by ALK5 inhibition ( P < 0.05). In brief, treatment with a novel TGF-β type I receptor inhibitor, GW788388, significantly reduced TGF-β activity, leading to the attenuation of systolic dysfunction and left ventricular remodeling in an experimental rat model of MI.

Pattern of neuronal activation in rats with CHF after myocardial infarction

1998 ◽  
Vol 275 (6) ◽  
pp. H2140-H2146 ◽  
Author(s):  
Faranak Vahid-Ansari ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Sham Group ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Locus Ceruleus ◽  
Coronary Artery Ligation ◽  
Neuronal Activation ◽  
Artery Ligation ◽  
Neuronal Populations

To identify neuronal populations possibly contributing to the sympathetic hyperactivity in rats with congestive heart failure (CHF) after myocardial infarction (MI), immunohistochemical detection of Fra-like immunoreactivity (Fra-LI) was used as a marker of long-term neuronal activation. In adult Wistar rats, 2 and 4 wk after left coronary artery ligation, left ventricular (LV) peak systolic pressure and LV end-diastolic pressure were measured, immediately followed by transcardial perfusion and removal of the heart and brain. The brains were processed using an antibody that recognizes Fos, FosB, Fra-1, and Fra-2 for the detection of Fra-LI and using an antibody that only recognizes Fos-like immunoreactivity (Fos-LI). At both 2 and 4 wk after large MI, LV peak systolic pressure was significantly decreased and LV end-diastolic pressure increased. At 2 wk post-MI or sham surgery, Fra-LI was observed in several areas of either group but was significantly higher in the MI versus the sham group in the magnocellular division of the paraventricular nucleus (PVN), supraoptic nucleus (SON), subfornical organ, and caudal part of the nucleus of the solitary tract. At 4 wk after large MI, Fra-LI was clearly detected in the parvocellular and magnocellular divisions of the PVN, SON, and locus ceruleus. Modest expression was noted in these nuclei in rats with small MI, whereas Fra-like positive immunoreactive neurons were barely detectable in the sham group 4 wk postsurgery. In these nuclei, the extent of expression of Fra-LI correlated significantly with the LV end-diastolic pressure. Fos-LI was only noted in the cerebral cortex. These results indicate clear activation of neurons as identified by Fra-LI in specific cardiovascular control centers in rats with CHF 2 and 4 wk post-MI.

Progressive left ventricular remodeling and apoptosis late after myocardial infarction in mouse heart

2000 ◽  
Vol 279 (1) ◽  
pp. H422-H428 ◽  
Author(s):  
Flora Sam ◽  
Douglas B. Sawyer ◽  
Donny L.-F. Chang ◽  
Franz R. Eberli ◽  
Soeun Ngoy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Remodeling ◽  
Contractile Function ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mouse Heart ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Lv Remodeling

We tested the hypothesis that left ventricular (LV) remodeling late after myocardial infarction (MI) is associated with myocyte apoptosis in myocardium remote from the infarcted area and is related temporally to LV dilation and contractile dysfunction. One, four, and six months after MI caused by coronary artery ligation, LV volume and contractile function were determined using an isovolumic balloon-in-LV Langendorff technique. Apoptosis and nuclear morphology were determined by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) and Hoechst 33258 staining. Progressive LV dilation 1–6 mo post-MI was associated with reduced peak LV developed pressure (LVDP). In myocardium remote from the infarct, there was increased wall thickness and expression of atrial natriuretic peptide mRNA consistent with reactive hypertrophy. There was a progressive increase in the number of TUNEL-positive myocytes from 1 to 6 mo post-MI (2.9-fold increase at 6 mo; P < 0.001 vs. sham). Thus LV remodeling late post-MI is associated with increased apoptosis in myocardium remote from the area of ischemic injury. The frequency of apoptosis is related to the severity of LV dysfunction.

Abstract 14122: Myeloid Cell mPGES-1 Depletion Attenuates Mortality After Myocardial Infarction in Mice

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lihong Chen ◽  
Guangrui Yang ◽  
Garret FitzGerald
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Treatment And Prevention

Selective depletion of microsomal PGE2 synthase (mPGES) -1 in myeloid cells retards atherogenesis and suppresses the vascular proliferative response to injury, while it does not predispose to thrombogenesis or hypertension. However, studies using bone marrow transplants from irradiated mice suggest that myeloid cell mPGES-1 facilitates cardiac remodeling and prolongs survival after experimental myocardial infarction (MI). Here we addressed this question using mice lacking mPGES-1 in myeloid cells, particularly macrophages (Mac-mPGES-1 KO), generated by crossing mPGES-1 floxed mice with LysMCre mice, and subjecting them to coronary artery ligation. Cardiac structure and function were assessed by morphometric analysis, echocardiography, and invasive hemodynamics 7 and 28 days after MI. Despite a similar infarct size, in contrast to the prior report, the post-MI survival rate was markedly improved in the Mac-mPGES-1 KO mice compared to WT controls (92.9% vs. 55.6%, p=0.03). Left ventricular systolic (reflected by ejection fraction, fractional shortening, end systolic pressure, and +dP/dt) and diastolic function (reflected by end diastolic pressure, -dP/dt, and Tau), cardiac hypertrophy (reflected by LV dimensions) and staining for fibrosis did not differ between the groups. In conclusion, Cre-loxP mediated deletion of mPGES-1 in myeloid cells has favorable effects on post-MI survival, with no detectable adverse influence on post-MI remodeling. These results add to evidence that targeting macrophage mPGES-1 may represent a safe and efficacious approach to the treatment and prevention of cardiovascular inflammatory disease.

Time course of hemodynamic changes in rats with healed severe myocardial infarction

1989 ◽  
Vol 257 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
A. DeFelice ◽  
R. Frering ◽  
P. Horan
Keyword(s):  
Myocardial Infarction ◽  
Blood Flow ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Male Rats ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Functional Changes

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.

Cardiac adaptations to endurance training in rats with a chronic myocardial infarction

1989 ◽  
Vol 66 (2) ◽  
pp. 712-719 ◽  
Author(s):  
T. I. Musch ◽  
R. L. Moore ◽  
P. G. Smaldone ◽  
M. Riedy ◽  
R. Zelis
Keyword(s):  
Myocardial Infarction ◽  
Endurance Training ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Coronary Artery Ligation ◽  
Maximal Heart Rate ◽  
Chronic Myocardial Infarction ◽  
Artery Ligation ◽  
Training Paradigm ◽  
Myosin Isozyme

The hemodynamic response to maximal exercise was determined in sedentary and trained rats with a chronic myocardial infarction (MI) produced by coronary artery ligation and in rats that underwent sham operations (SHAM). Infarct size in the MI groups of rats comprised 28–29% of the total left ventricle and resulted in both metabolic and hemodynamic changes that suggested that these animals had moderate compensated heart failure. The training regimen used in the present study produced significant increases in maximal O2 uptake (VO2max) when expressed in absolute terms (ml/min) or when normalized for body weight (ml.min-1.kg-1) and consisted of treadmill running at work loads that were equivalent to 70–80% of the animal's VO2max for a period of 60 min/day, 5 days/wk over an 8- to 10-wk interval. This training paradigm produced two major cardiocirculatory adaptations in the MI rat that had not been elicited previously when using a training paradigm of a lower intensity. First, the decrement in the maximal heart rate response to exercise (known as “chronotropic incompetence”) found in the sedentary MI rat was completely reversed by endurance training. Second, the downregulation of cardiac myosin isozyme composition from the fast ATPase V1 isoform toward the slower ATPase (V2 and V3) isoforms in the MI rat was partially reversed by endurance training. These cardiac adaptations occurred without a significant increase in left ventricular pump function as an increase in maximal cardiac output (Qmax) and maximal stroke volume (SVmax) did not occur in the trained MI rat.(ABSTRACT TRUNCATED AT 250 WORDS)

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