New insights into the pathological role of TNF-α in early cardiac dysfunction and subsequent heart failure after infarction in rats

2004 ◽  
Vol 287 (1) ◽  
pp. H340-H350 ◽  
Author(s):  
C. Berthonneche ◽  
T. Sulpice ◽  
F. Boucher ◽  
L. Gouraud ◽  
J. de Leiris ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Diastolic Pressure ◽  
Subsequent Development ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Direct Role ◽  
Volume Curve ◽  
Tnf Α

A marked increase in plasma TNF-α has been described in patients with chronic heart failure (CHF). Nevertheless, little is known about the direct role of this cytokine early after myocardial infarction (MI) and its possible effects on the subsequent development of CHF. Wistar rats were subjected to permanent in vivo coronary artery ligation. At 5, 7, and 9 days after MI, cardiac function, passive compliance of the left ventricle (LV), and cardiac geometry were evaluated. The same model was used to perform pharmacological studies 7 days and 10 wk after MI in rats treated with monomeric recombinant human soluble TNF-α receptor type II (sTNF-RII, 40 μg/kg iv) or a placebo on day 3. Maximal alterations of cardiac function and geometry occurred 7 days after MI, which correlated chronologically with a peak of cardiac and serum TNF-α, as shown by immunohistochemistry and ELISA, respectively. sTNF-RII improved LV end-diastolic pressure under basal conditions and after volume overload 7 days and 10 wk after MI. Moreover, a significant leftward shift of the pressure-volume curve in the sTNF-RII-treated group 7 days after MI indicated a preservation of LV volume. Infarct expansion index was also significantly improved by sTNF-RII 7 days after MI ( P < 0.01). Nevertheless, 10 wk after MI, geometric indexes and passive pressure-volume curves were not significantly improved by the treatment. In conclusion, TNF-α plays a major role in cardiac alterations 7 days after MI in rats and contributes to hemodynamic derangement, but not to cardiac remodeling, in subsequent CHF.

Abstract P237: Is Ischemia/Reperfusion an Efficient Method for Producing Heart Failure in Rats?

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Ana Carolina M Omoto ◽  
Fábio N Gava ◽  
Mauro de Oliveira ◽  
Carlos A Silva ◽  
Rubens Fazan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Histopathological Examination ◽  
Ischemia Reperfusion ◽  
Mitral Annulus ◽  
Mortality Rates ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Artery Ligation

Myocardium infarction (MI) elicited by coronary artery ligation (CAL) is commonly used to induce chronic heart failure (HF) in rats. However, CAL shows high mortality rates. Given that ischemia-reperfusion (IR) may cause the development of HF, this approach may be useful for obtaining a model of HF with low mortality rates. Therefore, it was compared the model of CAL vs. IR in rats, evaluating the mortality and cardiac morphological and functional aspects. The IR consisted of 30 minutes of cardiac ischemia. Wistar rats were assigned into three groups: CAL: n=18; IR: n=7; SHAM (fictitious IR): n=7. After four weeks of CAL, the subjects were evaluated by echocardiography and ventriculography as well. The statistical analysis consisted of ANOVA combined with Tukey’s posthoc test (p<0.05). There were no deaths in the IR and SHAM groups, whereas in the CAL group the mortality rate was 33.33% (6 out of 18). In the CAL group echocardiography showed increased left ventricular (LV) cavity during systole (8.3 ± 1mm) and diastole (10.5 ± 1mm); decreased LV free wall during systole (1.4 ± 0.5 mm); increased left atrium/aorta (2.3 ± 0.4) ratio. These changes were not significant in IR (4.8 ± 0.5mm, 7.6 ± 0.6mm, 2.6 ± 0.3 mm, 1.6 ± 0.2) and SHAM (4.6 ± 0.6 mm, 7.7 ± 0.8mm, 2.8 ± 0.4mm, 1.5 ± 0.2) groups. There was also the reduction in the ejection fraction in the CAL group (41 ± 12 %) when compared with IR (65 ± 9%) and SHAM (69 ± 7%) groups. The tissue Doppler analysis from the lateral mitral annulus showed reduction in E′ in CAL (-29 ± 8 mm/s) and IR (-31± 9 mm/s) groups when compared with the SHAM (-48 ± 11 mm/s) group. The ventriculography in the CAL group showed smaller maximum dP/dt (6519 ± 1062) and greater end-diastolic pressure (33 ± 8 mmHg) when compared with IR (8716 ± 756 mmHg/s; 9 ± 9 mmHg) and SHAM (7989 ± 1230 mmHg/s; 9 ± 7 mmHg) groups. The CAL group presented transmural infarct size of 40% of the left ventricular wall, measured under histopathological examination. In conclusion, IR for 30 minutes caused only small changes in LV diastolic function, assessed by tissue Doppler; however, the IR was not effective for promoting HF, as observed with CAL. Thus, it is possible that prolonged IR is necessary for promoting significant HF in rats.

Central mineralocorticoid receptor blockade decreases plasma TNF-α after coronary artery ligation in rats

2003 ◽  
Vol 284 (2) ◽  
pp. R328-R335 ◽  
Author(s):  
Joseph Francis ◽  
Robert M. Weiss ◽  
Alan Kim Johnson ◽  
Robert B. Felder
Keyword(s):  
Heart Failure ◽  
Central Nervous System ◽  
Nervous System ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Evaluation Study ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Tnf Α ◽  
The Central Nervous System

The Randomized Aldactone Evaluation Study (RALES) demonstrated a substantial clinical benefit to blocking the effects of aldosterone (Aldo) in patients with heart failure. We recently demonstrated that the enhanced renal conservation of sodium and water in rats with heart failure can be reduced by blocking the central nervous system effects of Aldo with the mineralocorticoid receptor (MR) antagonist spironolactone (SL). Preliminary data from our laboratory suggested that central MR might contribute to another peripheral mechanism in heart failure, the release of proinflammatory cytokines. In the present study, SL (100 ng/h for 21 days) or ethanol vehicle (Veh) was administered via the 3rd cerebral ventricle to one group of rats after coronary ligation (CL) or sham CL (Sham) to induce congestive heart failure (CHF). In Veh-treated CHF rats, tumor necrosis factor-α (TNF-α) levels increased during day 1 and continued to increase throughout the 3-wk observation period. In CHF rats treated with SL, started 24 h after CL, TNF-α levels rose initially but retuned to control levels by day 5 after CL and remained low throughout the study. These findings suggest that activation of MR in the central nervous system plays a critical role in regulating TNF-α release in heart failure rats. Thus some of the beneficial effect of blocking MR in heart failure could be due at least in part to a reduction in TNF-α production.

Abstract 17163: Prolonged Increase in Endothelium-Specific NOX2-Derived Cytosolic Oxidants Exacerbates Maladaptive Cardiac Remodeling in Ischemic Myocardium

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rayane Brinck Teixeira ◽  
Melissa Pfeiffer ◽  
Catherine Karbasiafshar ◽  
Frank W Sellke ◽  
Ruhul Abid
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Left Ventricle ◽  
Wall Thickness ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Left Ventricle Mass

Introduction: Global increase in reactive oxygen species (ROS) in endothelial cells (EC) plays major roles in cardiovascular disease (CVD). However, the precise role of ROS within specific compartments of ECs are not yet known. This study aims to address the role of endothelium-derived cytosolic ROS in myocardial infarction (MI). Hypothesis: We hypothesized that an extended exposure to increased NADPH oxidase 2 (NOX2)-derived cytosolic ROS in EC would result in a worse post-MI outcome. Methods: Binary conditional transgenic mice expressing NOX2 in an EC-specific manner (NOX2VE) were studied. NOX2VE mice were assigned to tetracycline (Tet)-ON (control) to turn off transgene, or without Tet as Tet-OFF, i.e. NOX2- O ver E xpressing (NOX2VE-OE) groups. After 15 weeks of Tet-ON/OFF treatment, all mice were subjected to left anterior descending (LAD) coronary artery ligation that mimics acute MI (n=10/group). Left ventricle function was assessed by echocardiography 28 days post LAD. Ejection fraction (EF), fractional shortening (FS), left ventricle mass, wall thickness, heart rate, chamber diameter and volume at systole and diastole were analyzed by Student’s t-test. Results: Echocardiographic data showed that mice subjected to an increased NOX2-derived ROS in EC (NOX2VE-OE) presented with 19.3 ± 7.7% and 20.8 ± 7.9% decrease in EF and FS, respectively (p<0.05) compared to control (NOX2VE, Tet-ON). NOX2VE-OE mice showed an increase (by 14.1 ± 3.4%, p<0.01) in diastolic posterior wall thickness (DPWT) suggesting ventricular stiffness. NOX2VE-OE group also showed increased cardiac mass (by 14.0 ± 5.4%, p<0.05), which, along with DPWT indicates hypertrophy with a likelihood to develop heart failure. Interestingly, heart rate, systolic and diastolic chamber volume and diameters, stroke volume, and cardiac output showed no differences between the groups (p>0.05). Conclusions: Together, these results suggest that prolonged exposure to increased cytosolic ROS in coronary EC results in worse cardiac performance and myocardial stiffness, leading to a higher propensity to heart failure after MI. Currently, in vivo signaling studies are being carried out to understand molecular mechanisms by which NOX2-derived ROS in ECs result in impaired cardiac function.

TNF-α blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure rats

2007 ◽  
Vol 293 (1) ◽  
pp. H599-H609 ◽  
Author(s):  
Anuradha Guggilam ◽  
Masudul Haque ◽  
Edmund Kenneth Kerut ◽  
Elizabeth McIlwain ◽  
Pamela Lucchesi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Paraventricular Nucleus ◽  
Coronary Artery Ligation ◽  
Tei Index ◽  
Artery Ligation ◽  
Tnf Α ◽  
Mrna And Protein Expression ◽  
Necrosis Factor ◽  
Renal Sympathetic

Oxidative stress plays an important role in the pathophysiology of cardiovascular disease. Recent evidence suggests that cytokines induce oxidative stress and contribute to cardiac dysfunction. In this study, we investigated whether increased circulating and tissue levels of tumor necrosis factor (TNF)-α in congestive heart failure (CHF) modulate the expression of NAD(P)H oxidase subunits, Nox2 and its isoforms, in the paraventricular nucleus (PVN) of the hypothalamus and contribute to exaggerated sympathetic drive in CHF. Heart failure was induced in Sprague-Dawly rats by coronary artery ligation and was confirmed using echocardiography. Pentoxifylline (PTX) was used to block the production of cytokines for a period of 5 wk. CHF induced a significant increase in the production of reactive oxygen species (ROS) in the left ventricle (LV) and in the PVN. The mRNA and protein expression of TNF-α, Nox1, Nox2, and Nox4 was significantly increased in the LV and PVN of CHF rats. CHF also decreased ejection fraction, increased Tei index, and increased circulating catecholamines (epinephrine and norepinephrine) and renal sympathetic activity (RSNA). In contrast, treatment with PTX in CHF rats completely blocked oxidative stress and decreased the production of TNF-α and Nox2 isoforms both in the LV and PVN. PTX treatment also decreased catecholamines and RSNA and prevented further decrease in cardiac function. In summary, TNF-α blockade attenuates ROS and sympathoexcitation in CHF. This study unveils new mechanisms by which cytokines play a role in the pathogenesis of CHF, thus underscoring the importance of targeting cytokines in heart failure.

Validation of echocardiographic methods for assessing left ventricular dysfunction in rats with myocardial infarction

2004 ◽  
Vol 287 (5) ◽  
pp. H2049-H2053 ◽  
Author(s):  
Eric E. Morgan ◽  
Michael D. Faulx ◽  
Tracy A. McElfresh ◽  
Theodore A. Kung ◽  
Michael S. Zawaneh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Index ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Artery Ligation ◽  
Peak Rate ◽  
Fractional Shortening

The rat infarct model is widely used in heart failure research, but few echocardiographic indexes of left ventricular (LV) function are validated in this model. Accordingly, the objective of this study was to validate a 13-segment LV wall motion score index (WMSI) and the myocardial performance index (MPI) in infarcted rats. Twenty-nine male Wistar rats underwent left coronary artery ligation or sham operation and were evaluated with two-dimensional and Doppler flow echocardiography 8 wk later. After echocardiography, invasive indexes were obtained using a high-fidelity catheter. WMSI and MPI were correlated with the invasive and noninvasive measurements of LV function. WMSI and MPI significantly correlated directly with end-diastolic pressure ( r = 0.72 and 0.42 for WMSI and MPI, respectively) and the time constant of isovolumic relaxation ( r = 0.68 and 0.48) and inversely with peak rate of rise of LV pressure (+dP/d t; r = −0.68 and −0.50), peak rate of decline in LV pressure ( r = −0.57 and −0.44), LV developed pressure ( r = −0.58 and −0.42), area fractional shortening ( r = −0.85 and −0.53), and cardiac index ( r = −0.74 and −0.74). Stepwise linear regression analyses revealed that LV end-diastolic pressure, +dP/d t, area fractional shortening, and cardiac index were independent determinants of WMSI ( r = 0.994) and that cardiac index and +dP/d t were independent determinants of MPI ( r = 0.781). We conclude that the 13-segment WMSI and MPI are reproducible and correlate strongly with established echocardiographic and invasive indexes of systolic and diastolic function. These findings support the use of WMSI and MPI as indexes of global LV function in the rat infarction model of heart failure.

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.

Role of renal nerves in sodium retention of cirrhosis and congestive heart failure

1991 ◽  
Vol 260 (2) ◽  
pp. R298-R305 ◽  
Author(s):  
G. F. DiBona ◽  
L. L. Sawin
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Renal Denervation ◽  
Bile Duct Ligation ◽  
Renal Nerves ◽  
Coronary Artery Ligation ◽  
Common Bile Duct Ligation ◽  
Artery Ligation ◽  
Duct Ligation

To define the role of renal nerves in renal Na retention of cirrhosis and congestive heart failure (CHF), experiments were done in rats with cirrhosis due to common bile duct ligation (CBDL) and CHF due to myocardial infarction from left coronary artery ligation. Two weeks after induction of CBDL or CHF, diseased and sham diseased (Sham) rats were subjected to bilateral renal denervation (DNX) or sham renal denervation (innervated, INN). Five days after DNX or INN, 26-day metabolic balance studies were carried out in all rats. Daily dietary Na intake averaged 2.0-3.0 meq/day on days 1-6 and 22-26 and averaged 0.120 meq/day on days 7-21. Cumulative Na balance was greater in CBDL and CHF rats, INN or DNX, than in Sham/CBDL or CHF rats throughout the study. On day 6 at the end of the normal dietary Na intake period (days 0-6), cumulative Na balance was not affected by renal denervation in Sham/CBDL or CHF rats (INN, 2.02 +/- 0.19 meq, n = 10; DNX, 2.04 +/- 0.17 meq, n = 11), CBDL rats (INN, 4.21 +/- 0.39 meq, n = 10; DNX, 3.78 +/- 0.37 meq, n = 10), or CHF rats (INN, 3.74 +/- 0.72 meq, n = 9; DNX, 3.22 +/- 0.55 meq, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

2163Molecular imaging of cardiac and neuroinflammation early after myocardial infarction and in progressive heart failure

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Borchert ◽  
A Hess ◽  
M Lukacevic ◽  
T L Ross ◽  
F M Bengel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Translocator Protein ◽  
Whole Body ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Macrophage Depletion ◽  
Progressive Heart Failure

Abstract Background/Introduction Myocardial infarction (MI) triggers local inflammation to support endogenous healing and repair. Recent imaging studies of the macrophage- and microglia-expressed mitochondrial translocator protein (TSPO) identified concurrent neuroinflammation after acute MI and in chronic heart failure. The source of this neuroinflammation and its relationship to cardiac function early and late after MI are unknown. Purpose We aimed to characterize the cellular basis of the TSPO PET signal by modulating early inflammation via clodronate-mediated macrophage depletion, and modifying late mitochondrial function using the TSPO inhibitor PK11195. Methods C57BL/6 mice underwent permanent coronary artery ligation (n=47) or sham surgery (n=9). Subgroups were treated 24h prior surgery with clodronate liposomes (n=18) to deplete peripheral macrophages or continuously with the cardioprotective TSPO inhibitor PK11195 (n=13). Cardiac and neuroinflammation were evaluated by whole-body PET using the TSPO ligand 18F-GE180 at 1wk, 4wk and 8wk after surgery. Cardiac function and perfusion were assessed by ECG-gated 99mTc-sestamibi SPECT. Results Untreated MI mice showed elevated TSPO signal in the infarct territory compared to sham at 1wk post-MI (ID/g, 10.5±2.9 vs 7.2±1.6, p<0.001), and elevated remote myocardial TSPO signal at 8wk (ID/g, 9±1.9 vs 7±1.6, p=0.003). TSPO signal in brain of MI mice was also increased compared to sham at 1wk (ID/g, 2.1±0.3 vs 1.8±0.2, p=0.006) and 8wk (ID/g, 2.0±0.3 vs 1.8±0.2, p=0.033), reflecting neuroinflammation. Clodronate macrophage depletion lowered the infarct territory TSPO signal at 1wk compared to untreated (ID/g, 4.9±1 vs 10.5±3, p<0.001), consistent with lack of peripheral macrophage recruitment. Conversely, brain TSPO remained elevated (ID/g, 2.7±0.3 vs 2.2±0.3, p<0.001), suggesting resident microglial activation as the source of cerebral PET signal. Late signal at 8wk was comparable between clodronate and untreated (p=NS). TSPO inhibition by PK11195 treatment did not affect acute TSPO signal in heart or brain compared to untreated (p=NS). At 8wk, remote myocardial signal was reduced (ID/g, 7.4±1 vs 9.0±2, p=0.040) in parallel with attenuated cardiac dysfunction in PK11195 treated mice (%EF, 49.8±6 vs 37.3±5, p<0.001). Late brain TSPO signal at 8wk was comparable between PK11195 treatment and untreated (p=NS). Consistently, cardiac and brain TSPO signal were proportional (r=0.637, p<0.001), and neuroinflammation was correlated to cardiac function at 8wk after MI (r=−0.345, p=0.005). Conclusions Cardiac TSPO signal reflects acute macrophage activity and chronic mitochondrial dysfunction in heart failure. Neuroinflammation derives from resident microglia, and is proportional to cardiac function at late stages. As such, TSPO PET provides insight into inflammation and mitochondrial dysfunction in progressive heart failure, and may guide novel therapies such as cardioprotection via TSPO inhibition.

Abstract 567: Ivabradine Improved Cardiac Function, Fibrosis And Hyperexcitability In Rat Post-myocardial Infarction Severe Heart Failure.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Milliez ◽  
Johnny Nehme ◽  
Estelle Robidel ◽  
Camille Rodriguez ◽  
JaneLise Samuel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Sinus Node ◽  
Severe Heart Failure ◽  
Lv Function ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Adult Rats ◽  
Beneficial Effects ◽  
Lv Dysfunction

The selective sinus node I f current inhibitor Ivabradine (Iva) reduces heart rate (HR) without any other hemodynamic effects. We investigated in a rat model of post-MI severe heart failure, the effects of a chronic Iva administration on LV function, structure and electrical remodelling. Methods . MI was induced by coronary artery ligation in adult rats: echocardiography and Holter ECG were performed 2 months (m) after MI i.e. before randomization (n=12/group) into MI and MI+Iva (10 mg/kg/d) groups, and 3 m later. In ventricles, collagen was quantified after Sirius red staining of section and ACE and AT1-receptor mRNA expression (normalized to GAPDH) was assayed by RT-PCR. Results : 2m-post MI, all rats displayed severe decreased LVEF, and increased LVEDP compared to sham-operated (28%±3 vs 66%±5 and 32±2 vs 10±1 mmHg, respectively; p<0.05). In 5m-post-MI, LVEF and LVEDP were stabilized with Iva (31±1% and 24±2 mmHg), while they were worsened in MI groups (21±3% and 38±2mmHg). Blood pressure, body and heart weights were similar in MI and MI+Iva. Iva reduced HR (RR: 201±5 vs 179±3 ms in MI; p<0.05) and ventricular premature beats (514±152 vs 4717±1363/day for MI; p<0.05), and improved HR variability (SDRR: 5±1.5 vs 3.9± 0.6 for MI; p<0.05). There were no effects of Iva on duration (ms) of PR (45±3 vs 44±3), QRS (51±3 vs 46±3) and QT (106±7 vs 99±6, for MI and MI+Iva, respectively). The increased ventricular collagen in MI (4.0±0.1 vs 0.8±0.2 % in sham; p<0.05) was markedly reduced in MI+Iva (1.8±0.1%, p<0.0001 vs MI). The increases in ventricular gene expression of ACE and AT-1 receptor in MI rats (2.5 and 6 folds versus sham operated, respectively, p<0.05) were completely blunted by Iva treatment. Conclusion: Iva treatment of the post-MI heart failure: 1- markedly reduced HR and ventricular excitability and without harmful effects on conduction; 2- prevented worsening of LV dysfunction and remodelling, and 3- induced a downregulation of cardiac RAAS transcripts. Thus, through its negative chronotropic effects, Iva allowed the maintenance of cardiac function below the threshold for a tissular RAAS stimulation even in severe post-MI cardiac failure. Such beneficial effects of Iva on cardiac remodelling open new perspectives for the treatment of severe heart failure

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.

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