scholarly journals Modification of a Volume-Overload Heart Failure Model to Track Myocardial Remodeling and Device-Related Reverse Remodeling

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Egemen Tuzun ◽  
Roger Bick ◽  
Cihan Kadipasaoglu ◽  
Jeffrey L. Conger ◽  
Brian J. Poindexter ◽  
...  
Keyword(s):  
Heart Failure ◽  
Wall Thickness ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Volume Overload ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Sheep Model ◽  
Dystrophin Expression ◽  
Cellular Markers

Purpose. To provide an ovine model of ventricular remodeling and reverse remodeling by creating congestive heart failure (CHF) and then treating it by implanting a left ventricular assist device (LVAD). Methods. We induced volume-overload heart failure in 2 sheep; 20 weeks later, we implanted an LVAD and assessed recovery 11 weeks thereafter. We examined changes in histologic and hemodynamic data and levels of cellular markers of CHF. Results. After CHF induction, we found increases in LV end-diastolic pressure, LV systolic and diastolic dimensions, wall thickness, left atrial diameter, and atrial natriuretic protein (ANP) and endothelin-1 (ET-1) levels; β-adrenergic receptor (BAR) and dystrophin expression decreased markedly. Biopsies confirmed LV remodeling. After LVAD support, LV systolic and diastolic dimensions, wall thickness, and mass, and ANP and ET-1 levels decreased. Histopathologic and hemodynamic markers improved, and BAR and dystrophin expression normalized. Conclusions. We describe a successful sheep model for ventricular and reverse remodeling.

Importance of antioxidant and antiapoptotic effects of β-receptor blockers in heart failure therapy

2004 ◽  
Vol 287 (3) ◽  
pp. H1003-H1012 ◽  
Author(s):  
Keisuke Kawai ◽  
Fuzhong Qin ◽  
Junya Shite ◽  
Weike Mao ◽  
Shuji Fukuoka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Cardiac Pacing ◽  
Left Ventricular ◽  
Beneficial Effects ◽  
Myocyte Apoptosis ◽  
Adrenergic Blocking ◽  
Fractional Shortening

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its β-adrenergic blocking, antioxidant, and/or α-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2′-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension ( r = −0.678, P < 0.0001), fractional shortening ( r = 0.706, P < 0.0001), and apoptotic myocytes ( r = −0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of β-receptors in the treatment of CHF.

Contribution of ventricular remodeling to pathogenesis of heart failure in rats

2001 ◽  
Vol 280 (2) ◽  
pp. H674-H683 ◽  
Author(s):  
Gregory L. Brower ◽  
Joseph S. Janicki
Keyword(s):  
Heart Failure ◽  
Ventricular Remodeling ◽  
Volume Fraction ◽  
Volume Overload ◽  
Left Ventricular ◽  
Morbidity And Mortality ◽  
Compliance Matrix ◽  
Hypertrophic Response ◽  
Lv Volume ◽  
And Function

We previously reported an approximately 50% incidence of rats with symptoms of congestive heart failure (CHF) at 8 wk postinfrarenal aorto-caval fistula. However, it was not clear whether compensatory ventricular remodeling could continue beyond 8 wk or whether the remaining animals would have developed CHF or died. Therefore, the intent of this study was to complete the characterization of this model of sustained volume overload by determining the morbidity and mortality and the temporal response of left ventricular (LV) remodeling and function beyond 8 wk. The findings demonstrate an upper limit to LV hypertrophy and substantial increases in LV volume and compliance, matrix metalloproteinase activity, and collagen volume fraction associated with the development of CHF. There was an 80% incidence of morbidity and mortality following 21 wk of chronic volume overload. These findings indicate that the development of CHF is triggered by marked ventricular dilatation and increased compliance occurring once the myocardial hypertrophic response is exhausted.

Ventricular remodeling induced by acute nonocclusive constriction of coronary artery in rats

1989 ◽  
Vol 257 (6) ◽  
pp. H1983-H1993 ◽  
Author(s):  
J. M. Capasso ◽  
M. W. Jeanty ◽  
T. Palackal ◽  
G. Olivetti ◽  
P. Anversa
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Wall Thickness ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Cell Damage ◽  
Left Ventricular ◽  
Consistent Difference ◽  
Luminal Diameter

To determine the consequence of acute nonocclusive constriction of the epicardial coronary artery on the adaptation of the left ventricle and its impact as a function of age, the left main coronary artery was narrowed in rats 4 and 12 mo of age, and the animals were killed 45 min later. Similar reductions in the luminal diameter, averaging 4%, were obtained in both groups of animals, and this change resulted in an increase in left ventricular end-diastolic pressure and a decrease in positive and negative change in pressure overtime (dP/dt) and in peak-developed ventricular pressure. Left ventricular volume increased by 66% and 56% at 4 and 12 mo because of increases in both the longitudinal and transverse chamber diameters. In contrast, wall thickness decreased by 27% and 35%, whereas sarcomere length increased only by 8.0% and 6.0%, respectively. These changes implied the occurrence of side-to-side slippage of myocytes within the wall to accommodate the larger chamber volume. The alterations in myocardial performance combined with the variations in ventricular size and wall thickness produced a marked elevation in diastolic and systolic wall stress. Moreover, myocyte cell damage in the form of contraction bands and disorganization of the intercalated disc region was seen. No consistent difference was found in any of the parameters measured as a function of age. Measurements of resting coronary blood flow across the left ventricular wall before coronary artery narrowing were comparable with those obtained 45 min after constriction. In conclusion, acute nonocclusive coronary artery stenosis has profound detrimental effects on the function and structure of the myocardium in the absence of an impairment of resting coronary blood flow.

scholarly journals Time-dependent remodeling of transmural architecture underlying abnormal ventricular geometry in chronic volume overload heart failure

2004 ◽  
Vol 287 (5) ◽  
pp. H1994-H2002 ◽  
Author(s):  
Hiroshi Ashikaga ◽  
Jeffrey H. Omens ◽  
James W. Covell
Keyword(s):  
Wall Thickness ◽  
Ventricular Remodeling ◽  
Volume Overload ◽  
Wall Stress ◽  
Anterior Wall ◽  
Left Ventricular ◽  
Ventricular Geometry ◽  
Final Study ◽  
Chronic Volume Overload ◽  
Apical Site

To test the hypothesis that the abnormal ventricular geometry in failing hearts may be accounted for by regionally selective remodeling of myocardial laminae or sheets, we investigated remodeling of the transmural architecture in chronic volume overload induced by an aortocaval shunt. We determined three-dimensional finite deformation at apical and basal sites in left ventricular anterior wall of six dogs with the use of biplane cineradiography of implanted markers. Myocardial strains at end diastole were measured at a failing state referred to control to describe remodeling of myofibers and sheet structures over time. After 9 ± 2 wk (means ± SE) of volume overload, the myocardial volume within the marker sets increased by >20%. At 2 wk, the basal site had myofiber elongation (0.099 ± 0.030; P < 0.05), whereas the apical site did not [ P = not significant (NS)]. Sheet shear at the basal site increased progressively toward the final study (0.040 ± 0.003 at 2 wk and 0.054 ± 0.021 at final; both P < 0.05), which contributed to a significant increase in wall thickness at the final study (0.181 ± 0.047; P < 0.05), whereas the apical site did not ( P = NS). We conclude that the remodeling of the transmural architecture is regionally heterogeneous in chronic volume overload. The early differences in fiber elongation seem most likely due to a regional gradient in diastolic wall stress, whereas the late differences in wall thickness are most likely related to regional differences in the laminar architecture of the wall. These results suggest that the temporal progression of ventricular remodeling may be anatomically designed at the level of regional laminar architecture.

scholarly journals Right versus left ventricular remodeling in heart failure due to chronic volume overload: pressure-volume and proteome analysis

2021 ◽  
Author(s):  
Tereza Havlenova ◽  
Petra Skaroupkova ◽  
Matus Miklovic ◽  
Matej Behounek ◽  
Martin Chmel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Systolic Dysfunction ◽  
Volume Overload ◽  
Left Ventricular ◽  
Cytoskeletal Proteins ◽  
Sham Operation ◽  
Stroke Work ◽  
Specific Regulation

Abstract Mechanisms of right ventricular (RV) dysfunction in heart failure (HF) are poorly understood. RV response to volume overload (VO), a common contributing factor to HF, is rarely studied. The goal was to identify interventricular differences in response to chronic VO. Rats underwent aorto-caval fistula (ACF)/sham operation to induce VO. After 24 weeks, RV and left ventricular (LV) functions, gene expression and proteomics were studied. ACF led to biventricular dilatation, systolic dysfunction and hypertrophy affecting relatively more RV. Increased RV afterload contributed to larger RV stroke work increment compared to LV. Both ACF ventricles displayed upregulation of genes of myocardial stress and metabolism. Most proteins reacted to VO in a similar direction in both ventricles, yet the expression changes were more pronounced in RV. The most upregulated were extracellular matrix (POSTN, NRAP, TGM2, CKAP4), cell adhesion (NCAM, NRAP, XIRP2) and cytoskeletal proteins (FHL1, CSRP3) and enzymes of carbohydrate (PKM) or norepinephrine (MAOA) metabolism. Downregulated were MYH6 and FAO enzymes. Therefore, when exposed to identical VO, both ventricles display similar upregulation of stress and metabolic markers. RV reacts to ACF relatively more than LV due to concomitant pulmonary hypertension. No evidence supports RV chamber-specific regulation of protein expression in response to VO.

Temporal evaluation of left ventricular remodeling and function in rats with chronic volume overload

1996 ◽  
Vol 271 (5) ◽  
pp. H2071-H2078 ◽  
Author(s):  
G. L. Brower ◽  
J. R. Henegar ◽  
J. S. Janicki
Keyword(s):  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Systolic Function ◽  
Left Ventricular Remodeling ◽  
Isolated Heart ◽  
Volume Overload ◽  
Left Ventricular ◽  
Control Value ◽  
Chronic Volume Overload ◽  
And Function

The left ventricle (LV) significantly dilates and hypertrophies in response to chronic volume overload. However, the temporal responses in LV mass, volume, and systolic/diastolic function secondary to chronic volume overload induced by an infrarenal arteriovenous (A-V) fistula in rats have not been well characterized. To this end, LV end-diastolic pressure, size, and function (i.e., isovolumetric pressure-volume relationships in the blood-perfused isolated heart) were assessed at 1, 2, 3, 5, and 8 wk post-A-V fistula and compared with age-matched control animals. Progressive hypertrophy (192% at 8 wk), ventricular dilatation (172% at 8 wk), and a decrease in ventricular stiffness (257% at 8 wk) occurred in the fistula groups. LV end-diastolic pressure increased from a control value of 4.2 +/- 3.1 mmHg to a peak value of 15.7 +/- 3.6 mmHg after 3 wk of volume overload. A subsequent decline in LVEDP to 11.0 +/- 6.0 mmHg together with further LV dilation (169%) corresponded to a significant decrease in LV stiffness (222%) at 5 wk post-A-V fistula. Myocardial contractility, as assessed by the isovolumetric pressure-volume relationship, was significantly reduced in all A-V fistula groups; however, the compensatory remodeling induced by 8 wk of chronic biventricular volume overload tended to preserve systolic function.

scholarly journals Beta-Adrenergic Blockade Therapy for Autonomic Dysfunction is Less Effective for Elderly Patients with Heart Failure and Reduced Left Ventricular Ejection Fraction

2015 ◽  
Vol 6 ◽  
pp. JCM.S30488
Author(s):  
Ken Shimamoto ◽  
Masatoshi Kawana
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Ventricular Remodeling ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Reverse Remodeling ◽  
Adrenergic Blockade ◽  
Beta Adrenergic ◽  
Ventricular Ejection Fraction ◽  
Patients With Heart Failure

Objective Heart rate variability (HRV) has been reported to be an independent predictor of all-cause and sudden cardiac death in patients with heart failure. In the aging heart, however, both autonomic and cardiac functions appear to be altered. We assessed the relationship between aging and responsiveness of HRV and ventricular remodeling to beta-adrenergic blockade therapy in patients with heart failure and reduced ejection fraction (HFREF). Methods Twenty-eight clinically stable patients with chronic heart failure, sinus rhythm, and left ventricular ejection fraction <50% as confirmed by echocardiography were included. At baseline and after carvedilol treatment, 24-hour ambulatory Holter monitor recording was used to analyze HRV indices by the maximum entropy method. Changes in these parameters were compared among three age groups. Results HR decreased in all groups after carvedilol treatment, but was still highest in the youngest group despite the same treatment doses. Time and frequency domain variables improved. The response of time domain variables (the standard deviation of all normal sinus to normal sinus [NN] intervals and the standard deviation of the averages of NN intervals in all 5-minute or 30-minute segments) to carvedilol therapy significantly decreased with increasing age. Ventricular reverse remodeling induced by carvedilol therapy significantly decreased with increasing age. Increases in time domain variables and a low-frequency domain moderately correlated with left ventricular reverse remodeling. Conclusion Beta-adrenergic blockade therapy improved HRV variables and ventricular remodeling in HFREF patients; however, the response tended to be milder in the elderly. HRV improvement was associated with ventricular reverse remodeling.

Hemodynamic and histomorphometric characteristics of heart failure induced by aortic stenosis in the guinea pig: comparison of two constriction sizes

2009 ◽  
Vol 87 (11) ◽  
pp. 908-914 ◽  
Author(s):  
Bruno Laviolle ◽  
Danielle Pape ◽  
Marie-Clémence Verdier ◽  
Audrey Lavenu ◽  
Eric Bellissant
Keyword(s):  
Heart Failure ◽  
Aortic Stenosis ◽  
Wall Thickness ◽  
Guinea Pigs ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Wall Thickening ◽  
Aortic Banding ◽  
Lv Mass

Heart failure induced by aortic stenosis in young guinea pigs could constitute an interesting model for pharmacology, but its natural history needs to be characterized. One hundred five guinea pigs (3–4 weeks old) underwent thoracic aortic banding with 12- (B12G) or 14-gauge (B14G) needles or similar sham operations (S12G, S14G). Animals alive at 7 d (S12G, n = 16; B12G, n = 28; S14G, n = 19; B14G, n = 27) were assessed at 60 or 120 d. At 60 d, compared with sham groups, left ventricular (LV) mass and wall thickness increased in operated groups, but LV systolic pressure and right ventricular (RV) wall thickness only increased in the B14G group. At 120 d, B12G animals still showed signs of compensated hypertrophy with LV and RV wall thickening (+8%, +21%) and LV dilation (+20%), whereas B14G animals showed signs of decompensation with LV end-diastolic pressure increase (+167%) and mean arterial pressure decrease (–28%) associated with LV and RV hypertrophy (+77%, + 51%) and greater increases of LV and RV wall thickening (+19%, + 57%), as well as LV dilation (+43%). A 12G stenosis results in compensated hypertrophy at 60 and 120 d; a 14G stenosis leads to compensated hypertrophy at 60 d and heart failure at 120 d.

scholarly journals Right versus left ventricular remodeling in heart failure due to chronic volume overload

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tereza Havlenova ◽  
Petra Skaroupkova ◽  
Matus Miklovic ◽  
Matej Behounek ◽  
Martin Chmel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
Systolic Dysfunction ◽  
Volume Overload ◽  
Left Ventricular ◽  
Cytoskeletal Proteins ◽  
Sham Operation ◽  
Stroke Work ◽  
Specific Regulation

AbstractMechanisms of right ventricular (RV) dysfunction in heart failure (HF) are poorly understood. RV response to volume overload (VO), a common contributing factor to HF, is rarely studied. The goal was to identify interventricular differences in response to chronic VO. Rats underwent aorto-caval fistula (ACF)/sham operation to induce VO. After 24 weeks, RV and left ventricular (LV) functions, gene expression and proteomics were studied. ACF led to biventricular dilatation, systolic dysfunction and hypertrophy affecting relatively more RV. Increased RV afterload contributed to larger RV stroke work increment compared to LV. Both ACF ventricles displayed upregulation of genes of myocardial stress and metabolism. Most proteins reacted to VO in a similar direction in both ventricles, yet the expression changes were more pronounced in RV (pslope: < 0.001). The most upregulated were extracellular matrix (POSTN, NRAP, TGM2, CKAP4), cell adhesion (NCAM, NRAP, XIRP2) and cytoskeletal proteins (FHL1, CSRP3) and enzymes of carbohydrate (PKM) or norepinephrine (MAOA) metabolism. Downregulated were MYH6 and FAO enzymes. Therefore, when exposed to identical VO, both ventricles display similar upregulation of stress and metabolic markers. Relatively larger response of ACF RV compared to the LV may be caused by concomitant pulmonary hypertension. No evidence supports RV chamber-specific regulation of protein expression in response to VO.

Sign in / Sign up

Export Citation Format

Share Document