Abstract 5907: Development of Left Ventricular Dysfunction During Progression of Infant Right Ventricular Hypertrophy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kazuo Kitahori ◽  
Huamei He ◽  
Douglas B Cowan ◽  
Ingeborg Friehs ◽  
Pedro J Nido ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Ex Vivo ◽  
Late Complication ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Lv Function ◽  
Lv Dysfunction ◽  
Lv Remodeling ◽  
Point Total

Background: Progressive left ventricular (LV) dysfunction can be a major late complication in patients with chronic right ventricular (RV) pressure overload (e.g. tetralogy of Fallot). The mechanisms remains unclear. We therefore examined LV function (serial echocardiography and ex vivo Langendorff) and histology in a model of infant pressure-load RV hypertrophy (RVH). Methods and Results: Ten-day-old rabbits (N=6 per time point, total =48) underwent pulmonary artery banding (PAB), were sacrificed at 2–8 weeks after PAB, and compared to age-matched sham controls. Both RV and LV performance (myocardial performance index, MPI; fractional area change, FAC), measured by echocardiography, decreased during the progression of RVH (Table ). In addition, RVH caused significant septal displacement, reduced septal contractility, and decreased LV end-systolic (LVDs) and diastolic (LVDd) dimensions. Significant septal and LV free wall apoptosis (myocyte-specific TUNEL and activated caspase-3), fibrosis (Masson’s Trichrome), and reduced capillary density (CD31 immunostaining) occurred in the left ventricles of the PAB group after 6 – 8 wks (all p<0.05). Conclusion: This study for the first time shows that pressure overload resulting in RVH causes LV dysfunction by both mechanical and molecular effects upon the septum and LV myocardium. In particular, the development of RVH is associated with septal and LV apoptosis, pathologic LV remodeling, and reduced LV capillary density. Potential mediators and mechanisms (e.g. paracrine vs. circulating stimuli) merit further investigation LV performance during the progression of RVH

Abstract 14952: Hemodynamic Comparison of Left Ventricular Function in Pressure Overload- versus Volume Overload-Induced Heart Failure Models by Invasive Pressure-Volume Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mihály Ruppert ◽  
Christian Karime ◽  
Alex A Sayour ◽  
Attila Oláh ◽  
Dávid Nagy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Function ◽  
Pressure Overload ◽  
Volume Overload ◽  
Detailed Comparison ◽  
Left Ventricular ◽  
Lv Function ◽  
Arterial Elastance ◽  
Lv Remodeling ◽  
Av Shunt

Introduction: Both sustained left ventricular (LV) pressure overload (PO) and volume overload (VO) induces LV remodeling and eventually development of heart failure (HF). Using rat models, the present study aimed to provide a detailed comparison of distinct aspects of LV function in PO- and VO-induced HF. Methods: PO and VO was induced by transverse aortic constriction (TAC, n=12) and aortocaval shunt (AV-shunt, n=12) creation respectively. Controls underwent corresponding sham operations (n=11). LV remodeling was characterized by echocardiography, histology, qRT PCR, and western blot. LV function was assessed by invasive pressure-volume (P-V) analysis. Results: Both sustained PO and VO resulted in the development of HF, as evidenced by increased LV BNP mRNA expression, pulmonary edema, and characteristic symptoms. While the extent of LV hypertrophy was comparable between the HF models, PO induced concentric while VO evoked eccentric LV remodeling. P-V analysis revealed impaired systolic function in both HF models. Accordingly, decreased ejection fraction and impaired ventriculo-arterial coupling (calculated as the ratio of arterial elastance/LV contractility [VAC]: 0.38±0.05 vs. 1.30±0.13, ShamTAC vs. TAC and 0.52±0.08 vs. 1.17±0.13, ShamAV-Shunt vs. AV-shunt; p<0.05) was detected in both HF models. However, in case of VO the severely reduced LV contractility (slope of end-systolic P-V relationship: 1.79±0.19 vs. 0.52±0.06, ShamAV-Shunt vs. AV-shunt, p<0.05 and 2.14±0.28 vs. 2.03±0.21, ShamTAC vs. TAC p>0.05) underpinned the contractility-afterload mismatch, while in case of PO the increased afterload (arterial elastance: 0.77±0.07 vs. 2.64±0.28, ShamTAC vs. TAC and 0.80±0.07 vs. 0.54±0.05, ShamAV-Shunt vs. AV-shunt; p<0.05) was the main determinant. Furthermore, prolongation of active relaxation occurred to a greater extent in case of PO. In addition, increased myocardial stiffness was only observed in PO-induced HF. Conclusion: Systolic function was reduced in both HF models. However, different factors underpinned the impaired VAC in case of VO (reduced LV contractility) and PO (increased arterial elastance). Furthermore, although diastolic function deteriorated in both models, it occurred to a greater extent in case of PO.

scholarly journals Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure

2008 ◽  
Vol 295 (5) ◽  
pp. H2149-H2155 ◽  
Author(s):  
Sharad Rastogi ◽  
Victor G. Sharov ◽  
Sudhish Mishra ◽  
Ramesh C. Gupta ◽  
Brent Blackburn ◽  
...  
Keyword(s):  
Heart Failure ◽  
Oral Treatment ◽  
Capillary Density ◽  
Cellular Level ◽  
Left Ventricular ◽  
Lv Function ◽  
Systolic Volume ◽  
Moderate Heart Failure ◽  
Beneficial Effects ◽  
Lv Dysfunction

Acute intravenous infusion of ranolazine (Ran), an anti-ischemic/antiangina drug, was previously shown to improve left ventricular (LV) ejection fraction (EF) without a concomitant increase in myocardial oxygen consumption in dogs with chronic heart failure (HF). This study examined the effects of treatment with Ran alone and in combination with metoprolol (Met) or enalapril (Ena) on LV function and remodeling in dogs with HF. Dogs ( n = 28) with microembolization-induced HF were randomized to 3 mo oral treatment with Ran alone [375 mg twice daily (bid); n = 7], Ran (375 mg bid) in combination with Met tartrate (25 mg bid; n = 7), Ran (375 mg bid) in combination with Ena (10 mg bid; n = 7), or placebo (PL; Ran vehicle bid; n = 7). Ventriculographic measurements of LV end-diastolic volume (EDV) and end-systolic volume (ESV) and LV EF were obtained before treatment and after 3 mo of treatment. In PL-treated dogs, EDV and ESV increased significantly. Ran alone prevented the increase in EDV and ESV seen in the PL group and significantly increased EF, albeit modestly, from 35 ± 1% to 37 ± 2%. When combined with either Ena or Met, Ran prevented the increase in EDV, significantly decreased ESV, and markedly increased EF compared with those of PL. EF increased from 35 ± 1% to 40 ± 1% with Ran + Ena and from 34 ± 1% to 41 ± 1% with Ran + Met. Ran alone or in combination with Ena or Met was also associated with beneficial effects at the cellular level on histomorphometric parameters such as hypertrophy, fibrosis, and capillary density as well as the expression for pathological hypertrophy and Ca2+ cycling genes. In conclusion, Ran prevented progressive LV dysfunction and global and cellular myocardial remodeling, and Ran in combination with Ena or Met improved LV function beyond that observed with Ran alone.

Sepiapterin prevents left ventricular hypertrophy and dilatory remodeling induced by pressure overload in rats

2015 ◽  
Vol 309 (10) ◽  
pp. H1782-H1791 ◽  
Author(s):  
Kei Yoshioka ◽  
Hajime Otani ◽  
Takayuki Shimazu ◽  
Masanori Fujita ◽  
Toshiji Iwasaka ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Interstitial Fibrosis ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Salvage Pathway ◽  
Aortic Constriction ◽  
Beneficial Effects ◽  
Lv Remodeling

Uncoupling of nitric oxide (NO) synthase (NOS) has been implicated in left ventricular (LV) hypertrophy (LVH) and dilatory remodeling induced by pressure overload. We investigated whether administration of sepiapterin, a substrate of the salvage pathway of tetrahydrobiopterin synthesis, prevents LVH and dilatory LV remodeling by inhibiting NOS uncoupling and increasing bioavailable NO. Pressure overload was induced in rats by transverse aortic constriction (TAC). Concentric LVH developed during 8 wk after TAC, and dilatory LV remodeling and dysfunction developed between 8 and 16 wk after TAC associated with a decrease in capillary density. Oral administration of sepiapterin or the superoxide/peroxynitrite scavenger N-(2-mercaptopropionyl)-glycine for 8 wk after TAC inhibited oxidative stress, but only sepiapterin increased bioavailable NO and inhibited cardiomyocyte hypertrophy associated with a further increase in capillary density. When sepiapterin was administered between 8 and 16 wk after TAC, cardiomyocyte hypertrophy was regressed and capillary density was restored. This was associated with the inhibition of interstitial fibrosis and dilatory LV remodeling. N-nitro-l-arginine methyl ester abrogated all the beneficial effects of sepiapterin in rats with TAC. These results suggest that sepiapterin prevents concentric LVH and dilatory remodeling after TAC primarily by increasing the bioavailability of NO.

scholarly journals Pregnancy mitigates cardiac pathology in a mouse model of left ventricular pressure overload

2016 ◽  
Vol 311 (3) ◽  
pp. H807-H814 ◽  
Author(s):  
Hong Xu ◽  
Elza D. van Deel ◽  
Mark R. Johnson ◽  
Petra Opić ◽  
Bronwen R. Herbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Disease ◽  
Interstitial Fibrosis ◽  
Experimental Studies ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Capillary Density ◽  
Left Ventricular ◽  
Lv Function ◽  
Lung Weight

In Western countries heart disease is the leading cause of maternal death during pregnancy. The effect of pregnancy on the heart is difficult to study in patients with preexisting heart disease. Since experimental studies are scarce, we investigated the effect of pressure overload, produced by transverse aortic constriction (TAC) in mice, on the ability to conceive, pregnancy outcome, and maternal cardiac structure and function. Four weeks of TAC produced left ventricular (LV) hypertrophy and dysfunction with marked interstitial fibrosis, decreased capillary density, and induced pathological cardiac gene expression. Pregnancy increased relative LV and right ventricular weight without affecting the deterioration of LV function following TAC. Surprisingly, the TAC-induced increase in relative heart and lung weight was mitigated by pregnancy, which was accompanied by a trend towards normalization of capillary density and natriuretic peptide type A expression. Additionally, the combination of pregnancy and TAC increased the cardiac phosphorylation of c-Jun, and STAT1, but reduced phosphoinositide 3-kinase phosphorylation. Finally, TAC did not significantly affect conception rate, pregnancy duration, uterus size, litter size, and pup weight. In conclusion, we found that, rather than exacerbating the changes associated with cardiac pressure overload, pregnancy actually attenuated pathological LV remodeling and mitigated pulmonary congestion, and pathological gene expression produced by TAC, suggesting a positive effect of pregnancy on the pressure-overloaded heart.

scholarly journals Apoptosis in severe, compensated pressure overload predominates in nonmyocytes and is related to the hypertrophy but not function

2011 ◽  
Vol 300 (3) ◽  
pp. H1062-H1068 ◽  
Author(s):  
Ricardo J. Gelpi ◽  
Misun Park ◽  
Shumin Gao ◽  
Sunil Dhar ◽  
Dorothy E. Vatner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Lv Dysfunction ◽  
The Face ◽  
Canine Models

It is widely held that myocyte apoptosis in left ventricular hypertrophy (LVH) contributes to left ventricle (LV) dysfunction and heart failure. The main goal of this investigation was to determine if there is a statistical relationship among LV hypertrophy, apoptosis and LV function, and importantly whether the apoptosis occurs in myocytes or nonmyocytes in the heart. We used both rat and canine models of severe LVH induced by chronic thoracic aortic banding with resultant LV-aortic pressure gradients 145–155 mmHg and increases in LV/body weight of 58 and 70%. These models also provided the ability to examine transmural apoptosis in LVH. In both models, the overwhelming majority (88%) of apoptotic cells were nonmyocytes. The regressions for apoptosis vs. LVH were stronger for nonmyocytes than myocytes and also stronger in the subendocardium than the subepicardium. Importantly, LV systolic and diastolic wall stresses were normal, indicating that the apoptosis could not be attributed to LV stretch or heart failure. In addition, there was no relationship between the extent of apoptosis and LV ejection fraction, which actually increased ( P < 0.05), in the face of elevated LV systolic pressure, indicating that greater apoptosis did not result in a decrease in LV function. Thus, in response to chronic, severe pressure overload, LVH in the absence of LV dilation, and elevated LV wall stress, apoptosis occurred predominantly in nonmyocytes in the myocardial interstitium, more in the subendocardium than the subepicardium. The extent of apoptosis was linearly related to the amount of LV hypertrophy, but not to LV function.

scholarly journals Adverse Consequences of Right Ventricular Apical Pacing and Novel Strategies to Optimize Left Ventricular Systolic and Diastolic Function

2019 ◽  
Vol 15 (2) ◽  
pp. 145-155 ◽  
Author(s):  
Mohammad Reeaze Khurwolah ◽  
Jing Yao ◽  
Xiang-Qing Kong
Keyword(s):  
Right Ventricular ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Lv Function ◽  
Ventricular Dyssynchrony ◽  
Lv Dysfunction ◽  
Rv Pacing ◽  
Systolic And Diastolic Function

Several studies have focused on the deleterious consequences of Right Ventricular Apical (RVA) pacing on Left Ventricular (LV) function, mediated by pacing-induced ventricular dyssynchrony. Therapeutic strategies to reduce the detrimental consequences of RVA pacing have been proposed, that includes upgrading of RVA pacing to Cardiac Resynchronization Therapy (CRT), alternative Right Ventricular (RV) pacing sites, minimal ventricular pacing strategies, as well as atrial-based pacing. In developing countries, single chamber RV pacing still constitutes a majority of cases of permanent pacing, and assessment of the optimal RV pacing site is of paramount importance. In chronically-paced patients, it is crucial to maintain as close and normal LV physiological function as possible, by minimizing ventricular dyssynchrony, reducing the chances for heart failure and other complications to develop. This review provides an analysis of the deleterious immediate and long-term consequences of RVA pacing, and the most recent available evidence regarding improvements in pacing options and strategies to optimize LV diastolic and systolic function. Furthermore, the place of advanced echocardiography in the identification of patients with pacing-induced LV dysfunction, the potential role of a new predictor of LV dysfunction in RV-paced subjects, and the long- term outcomes of patients with RV septal pacing will be explored.

Changes in left ventricular function and remodeling after myocardial infarction in hypothyroid rats

2010 ◽  
Vol 298 (1) ◽  
pp. H259-H262 ◽  
Author(s):  
Yue-Feng Chen ◽  
Rebecca A. Redetzke ◽  
Suleman Said ◽  
April J. Beyer ◽  
A. Martin Gerdes
Keyword(s):  
Myocardial Infarction ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Lv Function ◽  
Sprague Dawley ◽  
Lv Dysfunction ◽  
Long Term Effect ◽  
Sprague Dawley Rats ◽  
Lv Remodeling

It has been shown that hypothyroidism may lead to delayed wound healing after experimental myocardial infarction (MI) in rats and increased infarct size in dogs. However, the long-term effect of hypothyroidism on left ventricular (LV) remodeling after MI has not been determined. Adult female Sprague-Dawley rats with and without surgical thyroidectomy (TX) were used in the study. Four weeks after TX, MI or sham MI was performed on TX and non-TX rats. Rats from all groups were examined 4 wk later. Four weeks after TX, hypothyroid-induced LV dysfunction was confirmed by echocardiography. In terminal experiments 4 wk after MI, TX sham-MI rats showed smaller hearts and impaired LV function compared with non-TX sham-MI controls. TX + MI rats showed smaller hearts with bigger infarct areas, higher LV end-diastolic pressures, and greater impairment of relaxation (−dP/d t) compared with non-TX MI rats. Relative changes after MI between TX and non-TX rats for most other hemodynamic and echocardiographic indexes were similar. These results suggest that preexisting hypothyroidism exaggerates post-MI remodeling and worsens LV function, particularly diastolic function.

Left ventricular dimensions and function during right ventricular pressure overload

1982 ◽  
Vol 242 (4) ◽  
pp. H611-H618 ◽  
Author(s):  
F. R. Badke
Keyword(s):  
Right Ventricular ◽  
Diastolic Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Lv Function ◽  
Free Wall ◽  
Inflatable Cuff ◽  
Left Ventricular Dimensions ◽  
And Function ◽  
Ventricular Dimensions

The effects of right ventricular (RV) pressure overload on left ventricular (LV) function is controversial. Therefore, we examined LV dimensions and shortening after acute and chronic pulmonary artery (PA) constriction in six conscious dogs, preinstrumented with LV and RV catheters, an LV micromanometer, a PA inflatable cuff occluder, and ultrasonic crystals to measure an LV anteroposterior, a septal-lateral, and a free wall segment chord. Studies were performed before, immediately after, and 2, 4, and 6 wk after PA constriction. With acute cuff inflation, RV systolic- and end-diastolic pressures rose, but LV end-diastolic pressure fell. Both septal-lateral end-diastolic length and systolic shortening declined 4.1 +/- 0.7 mm and 5.9 +/- 2.3% respectively (P less than 0.01), whereas the anteroposterior and segment chords were unaffected. With chronic RV pressure overload septal-lateral shortening but not end-diastolic length returned to control levels. Also the first derivative of LV pressure (LV dP/dt) fell 540 +/- 164 mmHg/s by 6 wk compared with control, but this decline was reversed by volume expansion with dextran. We conclude that RV pressure overload displaces the septum toward the LV free wall; acutely this displacement is primarily at end diastole, but chronically it occurs at end systole as well, maintaining the septal contribution to LV ejection. Thus chronic RV pressure overload is associated with significant changes in LV diastolic shape but maintenance of normal LV function.

Urine Albumin to Creatinine Ratio and Echocardiographic Left Ventricular Structure and Function in Patients with Essential Hypertension

2011 ◽  
Vol 9 (2) ◽  
pp. 90 ◽  
Author(s):  
Rohola Hemmati ◽  
Mojgan Gharipour ◽  
Hasan Shemirani ◽  
Alireza Khosravi ◽  
Elham Khosravi ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Peak Velocity ◽  
Left Ventricular ◽  
Lv Function ◽  
Creatinine Ratio ◽  
Uncomplicated Hypertension ◽  
Urine Albumin ◽  
Lv Dysfunction ◽  
Mitral Annulus Velocity ◽  
Lv Mass

Background:Appearance of microalbuminuria, particularly in patients with hypertension, might be associated with a higher prevalence of left ventricular (LV) dysfunction and geometric abnormalities. This study was undertaken to determine whether high urine albumin to creatinine ratio (UACR) as a sensitive marker for microalbuminuria can be associated with LV hypertrophy (LVH) and systolic and diastolic LV dysfunction.Methods:The study population consisted of 125 consecutive patients with essential uncomplicated hypertension. Urine albumin and creatinine concentration was determined by standard methods. LVH was defined as a LV mass index >100 g/m2 of body surface area in women and >130 g/m2 in men. Echocardiographic LV systolic and diastolic parameters were measured.Results:The prevalence of microalbuminuria in patients with essential hypertension was 5.6 %. UACR was significantly no different in patients with LVH than in patients with normal LV geometry (21.26 ± 31.55 versus 17.80 ± 24.52 mg/mmol). No significant correlation was found between UACR measurement and systolic and diastolic function parameters, including early to late diastolic peak velocity (E/A) ratio (R=-0.192, p=0.038), early diastolic peak velocity to early mitral annulus velocity (E/E') ratio (R=-0.025, p=0.794), LV ejection fraction (R=0.008, p=0.929), and LV mass (R=-0.132, p=0.154). According to the receiver operator characteristic (ROC) curve analysis, UACR measurement was not an acceptable indicator of LVH with areas under the ROC curves 0.514 (95 % confidence interval 0.394–0.634). The optimal cut-off value for UACR for predicting LVH was identified at 9.4, yielding a sensitivity of 51.6 % and a specificity of 48.3 %.Conclusion:In patients with uncomplicated essential hypertension, abnormal systolic and diastolic LV function and geometry cannot be effectively predicted by the appearance of microalbuminuria.

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