Hyperhomocysteinemia leads to pathological ventricular hypertrophy in normotensive rats

2003 ◽  
Vol 285 (2) ◽  
pp. H679-H686 ◽  
Author(s):  
Jacob Joseph ◽  
Lija Joseph ◽  
Nawal S. Shekhawat ◽  
Sulochana Devi ◽  
Junru Wang ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Ventricular Hypertrophy ◽  
Ventricular Remodeling ◽  
Systolic Function ◽  
Left Ventricular ◽  
Lv Function ◽  
Wall Thickening ◽  
Cardiovascular Morbidity And Mortality ◽  
And Function

A recent report indicated that hyperhomocysteinemia (Hhe), in addition to its atherothrombotic effects, exacerbates the adverse cardiac remodeling seen in response to hypertension, a powerful stimulus for pathological ventricular hypertrophy. The present study was undertaken to determine whether Hhe has a direct effect on ventricular remodeling and function in the absence of other hypertrophic stimuli. Male Wistar-Kyoto rats were fed either an amino acid-defined control diet or an intermediate Hhe-inducing diet. After 10 wk of dietary treatment, rats were subjected to echocardiographic assessment of left ventricular (LV) dimensions and systolic function. Subsequently, blood was collected for plasma homocysteine measurements, and the rats were killed for histomorphometric and biochemical assessment of cardiac remodeling and for in vitro cardiac function studies. Significant LV hypertrophy was detected by echocardiographic measurements, and in vitro results showed hypertrophy with significantly increased myocyte size in the LV and right ventricle (RV). LV and RV remodeling was characterized by a disproportionate increase in perivascular and interstitial collagen, coronary arteriolar wall thickening, and myocardial mast cell infiltration. In vitro study of LV function demonstrated abnormal diastolic function secondary to decreased compliance because the rate of relaxation did not differ between groups. LV systolic function did not vary between groups in vitro. In summary, in the absence of other hypertrophic stimuli short-term intermediate Hhe caused pathological hypertrophy and remodeling of both ventricles with diastolic dysfunction of the LV. These results demonstrate that Hhe has direct adverse effects on cardiac structure and function, which may represent a novel direct link between Hhe and cardiovascular morbidity and mortality, independent of other risk factors.

Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice

2001 ◽  
Vol 281 (5) ◽  
pp. H1938-H1945 ◽  
Author(s):  
Chari Y. T. Hart ◽  
John C. Burnett ◽  
Margaret M. Redfield
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Systolic Function ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Lv Function ◽  
Ketamine Anesthesia ◽  
The Difference ◽  
And Function ◽  
Derivatives Of

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (τ), and the first derivatives of LV pressure rise and fall (dP/d t max and dP/d t min, respectively). During echocardiography, HR was lower in XK than AV mice (250 ± 14 beats/min in XK vs. 453 ± 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 ± 0.08 mm in XK vs. 3.8 ± 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 ± 1.2% in XK vs. 40 ± 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 ± 24 beats/min) and XK (342 ± 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 ± 5 vs. 6.2 ± 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/d t max: 4,402 ± 798 vs. 8,250 ± 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (τ: 23 ± 2 vs. 14 ± 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.

Abstract 3435: Left Ventricular Hypertrophy is Resistant to Inhibition of Expression of the R403Q Alpha-Myosin Heavy Chain Cardiac Hypertrophy-Inducing Mutant Protein

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Leah Cannon ◽  
Tadeusz Marciniec ◽  
Bryony Mearns ◽  
Robert M Graham ◽  
Diane Fatkin
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Interstitial Fibrosis ◽  
Myocardial Dysfunction ◽  
Left Ventricular ◽  
Familial Hypertrophic Cardiomyopathy ◽  
Lv Function ◽  
Dependent Manner ◽  
Cardiovascular Morbidity And Mortality ◽  
Lv Mass

Left ventricular hypertrophy (LVH) develops as a compensatory response to myocardial dysfunction due to diverse causes, but is nonetheless a major risk factor for premature cardiovascular morbidity and mortality. It is thus unclear if regressing LVH is beneficial or may worsen patient outcome. To evaluate the effects of LVH regression, we developed a transgenic mouse model in which the expression of a familial hypertrophic cardiomyopathy (FHC)-inducing mutation (R403Q alpha-MHC) can be regulated in a temporal and dose-dependent manner. In this model, transgene expression can be shut off by feeding with a tetracycline analogue (doxycycline). Serial echocardiography and histology studies were performed in a cohort of mice expressing the FHC mutant (“gene-on”) and in wildtype (WT) littermates. A second cohort of WT and 403/+ mice was randomised to placebo or doxycycline (“gene off”) from 6 (Dox6) or 20 weeks (Dox20) and evaluated at 40 weeks of age. Compared to WT littermates, “gene on” 403/+ mice showed increased LV mass, LV end-diastolic diameter (LVDD) and left atrial diameter (LAD), and reduced fractional shortening (LVFS), with changes evident from 12 weeks of age. LV sections from 403/+ mice showed typical features of FHC: myofibre disarray and interstitial fibrosis. LV mass, LV function and myocardial histology were unchanged in both male and female placebo- vs Dox6 or Dox20 mice at 40 weeks (Table 1 ). Thus, consistent with the major LV thickening in FHC humans occurring in adolescence, overexpression of R403Q for only 6 weeks is sufficient to trigger the complete LVH phenotypic response. Moreover, switching off the genetic trigger for LVH in 403/+ mice at 6 weeks (prior to overt disease manifestation) or 20 weeks (established disease) does not induce regression of LVH or exacerbate contractile dysfunction. Interventions to induce LVH regression may, therefore, need to be directed at downstream factors in hypertrophic pathways. Table 1. Echo data for male WT and 403/+ mice aged 40 weeks

Structural and functional changes in left ventricle during normotensive and preeclamptic pregnancy

2002 ◽  
Vol 283 (4) ◽  
pp. H1627-H1633 ◽  
Author(s):  
Lisa A. Simmons ◽  
Adrian G. Gillin ◽  
Richmond W. Jeremy
Keyword(s):  
Cardiac Remodeling ◽  
Inverse Relationship ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cardiac Work ◽  
Functional Changes ◽  
Lv Mass ◽  
Lv Systolic Function ◽  
And Function ◽  
Normotensive Pregnancy

Increased cardiac output in pregnancy is associated with cardiac remodeling and possible reduction in contractility, which may worsen in preeclampsia. Left ventricular (LV) geometry and function were compared between nonpregnant controls ( n = 12) and normotensive ( n = 44) and preeclamptic ( n = 15) pregnant women using echocardiography. Load-independent comparisons of LV systolic function compared end-systolic stress (ESS) and rate-corrected velocity of circumferential fiber shortening ( VCFC). Mean arterial pressures were 101 ± 14 mmHg in preeclampsia, 76 ± 6 mmHg in normotensive pregnancy, and 78 ± 6 mmHg in controls ( P < 0.005 vs. preeclampsia). LV mass increased during normotensive pregnancy (66 ± 13 to 76 ± 16 g/m2; P < 0.05; controls, 65 ± 10 g/m2; P < 0.05) and was greater in preeclampsia (90 ± 18 g/m2; P < 0.05). In normotensive pregnancy, ESS decreased (59 ± 9 to 52 ± 11 g/cm2; P < 0.05; controls, 66 ± 14 g/cm2; P < 0.005). ESS was greater in preeclampsia (60 ± 14 g/cm2; P < 0.05). In controls, there was an inverse relationship between ESS and VCFC( r = −0.78). The ESS- VCFCrelationships in normotensive and preeclamptic pregnancy were unchanged from controls. We conclude that LV hypertrophy in normotensive and preeclamptic pregnancy matches changes in cardiac work, and LV contractility is preserved.

scholarly journals Carotid Occlusion Accentuates Aortic Stenosis and Cardiac Remodeling With Preserved Systolic Function in LDL Receptor-Deficient Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Yandong Liu ◽  
Jiawei Cai ◽  
Lefeng Qu
Keyword(s):  
Aortic Stenosis ◽  
Ventricular Remodeling ◽  
Systolic Function ◽  
Ldl Receptor ◽  
Left Ventricular ◽  
Carotid Occlusion ◽  
Plaque Burden ◽  
Control Group ◽  
Internal Diameter ◽  
And Function

Background: Carotid atherosclerotic disease is associated with aortic stenosis and reduced cardiac function. The causality between carotid and cardiac pathologies is unknown. We aim to explore the effects of carotid stenosis or occlusion on cardiac pathology and function.Methods and Results: We produced carotid obstruction or stenosis in 36 atherogenic mice with 150- or 300-μm tandem surgery or sham surgery. The structure and function of the heart were assessed by histology and animal ultrasound. The 150-μm group had larger plaque burden and thicker valve leaflets in the aortic root than did the control group. Also, the two surgery groups had a thicker left ventricular posterior wall and smaller internal diameter compared with controls. Increased myocardial fibrosis was also found in the 150-μm group compared with controls, although the surgery groups had preserved systolic function compared with that of controls.Conclusions: In a mouse model, carotid occlusion accentuated the formation of aortic stenosis and promoted ventricular remodeling without impairing systolic function. Carotid atherosclerotic plaque may be a pathogenic factor for aortic stenosis and ventricular remodeling.

Heart rate reduction improves myocardial ischemia in swine: role of interventricular blood flow redistribution

1991 ◽  
Vol 261 (3) ◽  
pp. H910-H917 ◽  
Author(s):  
C. Indolfi ◽  
B. D. Guth ◽  
S. Miyazaki ◽  
T. Miura ◽  
R. Schulz ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Left Ventricular ◽  
Regional Myocardial Blood Flow ◽  
Lv Function ◽  
Wall Thickening ◽  
Regional Dysfunction ◽  
Electrical Pacing ◽  
And Function

Regional myocardial blood flow (MBF) distribution and function upon slowing the heart rate (HR) during ischemia were studied in anesthetized swine, a species without coronary collaterals. Perfusion of the left anterior descending artery by a pump allowed controlled production of regional ischemia. Slowing tachycardia by electrical pacing (127 to 87 beats/min) caused marked improvement of regional dysfunction [% wall thickening (WTh) from 9 to 27%] and increased subendocardial MBF [from 0.31 to 0.55 ml.min-1.g-1 (P less than 0.001)] without change of subepicardial MBF. Total left ventricular (LV) MBF increased, whereas right ventricular (RV) MBF fell by 18% (P less than 0.02). The mechanism of MBF changes during slowed HR was assessed by surgically excluding the RV and comparing findings with previous experiments with RV intact when HR was slowed from 96 to 60 beats/min. A similar improvement of regional LV function occurred (8% vs. 30% WTh) with the RV excluded, but without a change in total flow to the LV bed, whereas subendocardial MBF increased and subepicardial MBF fell, indicating transmural redistribution only. These findings show that the RV vascular bed can contribute to LV perfusion in swine during ischemia, and they document the potential for “reverse RV steal” during slowed heart rate in this setting.

Abstract 2180: Relationship of Left Ventricular Systolic Function to Persistence or Development of Electrocardiographic Left Ventricular Hypertrophy in Hypertensive Patients: Implications for the Development of New Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Peter M Okin ◽  
Kristian Wachtell ◽  
Eva Gerdts ◽  
Kurt Boman ◽  
Markku S Nieminen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Diastolic Pressure ◽  
Systolic Function ◽  
Left Ventricular ◽  
Lv Function ◽  
Increased Risk ◽  
Cornell Product

Background : We have previously demonstrated that persistence or development of ECG left ventricular hypertrophy (LVH) by Cornell product criteria are associated with an increased risk of developing heart failure (HF) compared with regression or continued absence of LVH. We postulated that this relationship might be in part mediated via worse LV systolic function in patients with new and persistent LVH. Methods : Baseline and year-3 ECG LVH and LV midwall shortening (MWS) were examined in 725 patients in the LIFE echocardiographic substudy. MWS was measured and considered abnormal if <14.2%; stress-corrected MWS (scMWS) was considered abnormal if 2440 mm-msec. Results : Between baseline and 3 years follow-up, there was continued absence (n=260) or regression (n=167) of LVH in 427 patients and persistence (n=259) or development (n=39) of ECG LVH in 298 patients. Although there was no difference in baseline prevalence of abnormal MWS (23.4 vs 26.5%, p=0.389) or abnormal scMWS (24.6 vs 26.4%, p=0.663) between groups, after 3 years follow-up persistence or development of new LVH was associated with significantly lower mean MWS and scMWS and with higher prevalence and odds of abnormal MWS and scMWS than continued absence or regression of LVH (Table ). After controlling for differences in age, gender, race, treatment group, baseline and change from baseline to year-3 of heart rate, Sokolow-Lyon voltage, systolic and diastolic pressure and baseline severity of LVH by Cornell product, persistent or new ECG LVH remained associated with a >2-fold increased risk of abnormal MWS or scMWS at year 3. Conclusions : Persistence or development of new ECG LVH during antihypertensive therapy is associated with an increased risk of LV systolic dysfunction after 3 years of follow-up. These findings provide insight into a possible mechanism by which changes in ECG LVH are associated with changing risk of developing HF. < Midwall LV Function in Relation to Persistence or Development of ECG LVH Between Baseline and Year-3

PATHOGENETIC ROLE OF MYOCARDIAL FIBROSIS: FOCUS ON EXTRACELLULAR MATRIX

2020 ◽  
pp. 21-24
Author(s):  
T. M. Ambrosova ◽  
T. V. Ashcheulova
Keyword(s):  
Extracellular Matrix ◽  
Left Ventricular Hypertrophy ◽  
Myocardial Fibrosis ◽  
Cardiac Remodeling ◽  
Heart Muscle ◽  
Ventricular Hypertrophy ◽  
Collagen Type ◽  
Left Ventricular ◽  
And Function

The main cardiovascular diseases affect the processes of myocardial remodeling, which further contributes to the formation of systolic or diastolic heart dysfunction. The formation of myocardial dysfunction is primarily associated with left ventricular hypertrophy when under hemodynamic loading, firstly, wall rigidity increases, secondly, myocardial fibrosis is formed. The latter is one of the key factors of the hypertrophic process caused by the accumulation of collagen, which leads to a aggravation of the left ventricle relaxation processes. Cardiac remodeling is defined as a group of molecular, cellular, and interstitial changes that are clinically manifested by alterations in the size, shape, and function of heart as a result of the heart muscle injury. It has been determined that fibrosis is an early morphological sign of injury in patients with left ventricular overload, as well as a factor in the development of diastolic and systolic dysfunctions. Compensatory left ventricular hypertrophy transforms into heart failure due to the fibrosis development. In hypertrophy the content of elastic collagen type III decreases and rigid collagen type I increases. The essential role of the extracellular matrix in myocardial fibrosis formation is emphasized. Cardiac fibrosis is a process of pathological remodeling of the extracellular matrix, which leads to abnormalities in its composition and dysfunction of the heart muscle. The extracellular matrix plays a key role in organogenesis and post−traumatic healing in tissue injuries. The study of intercellular interactions of the extracellular matrix will provide a better understanding of the mechanisms of changes in geometry and function of the heart, and investigation of the activity of matrix components will open new opportunities for targeted therapeutic effects on molecular mechanisms of cardiac remodeling. Key words: diastolic dysfunction, extracellular matrix, myocardial fibrosis, cardiomyocytes, fibroblasts.

Effect of repeated episodes of reversible myocardial ischemia on myocardial blood flow and function in humans

2002 ◽  
Vol 282 (5) ◽  
pp. H1603-H1608 ◽  
Author(s):  
Edward Barnes ◽  
David P. Dutka ◽  
Masood Khan ◽  
Paolo G. Camici ◽  
Roger J. Hall
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Myocardial Blood Flow ◽  
Systolic Function ◽  
Peak Stress ◽  
Left Ventricular ◽  
Lv Function ◽  
Positron Emission ◽  
Artery Disease ◽  
And Function

Nine patients with coronary artery disease and normal left ventricular (LV) function underwent two episodes of dobutamine-induced ischemia to determine whether repeated episodes of ischemia lead to cumulative stunning. Positron emission tomography (PET) and oxygen 15-labeled H2O was used to assess myocardial blood flow (MBF) at baseline, peak stress, and after stress for each ischemic episode. Quantitative echocardiographic assessment of global ejection fraction (EF) and regional systolic function (SF) was performed at rest and regular intervals after dobutamine. SF was assessed for regions subtended by a coronary artery with a >70% diameter stenosis. Both EF and SF were more severely impaired 45 min after the second episode of stress compared with 45 min after the first (both P < 0.01), despite no difference in duration of the two dobutamine infusions or MBF at peak stress (1.72 vs. 1.69). After both episodes of ischemia, when LV function was impaired but subsequently recovered, MBF (1.15 ± 0.39 and 1.20 ± 0.43, respectively) was no different to baseline MBF (1.02 ± 0.35), confirming that repeated episodes of dobutamine-induced ischemia lead to cumulative myocardial stunning.

scholarly journals Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise

2017 ◽  
Vol 313 (3) ◽  
pp. H459-H468 ◽  
Author(s):  
Maria Sanz-de la Garza ◽  
Cira Rubies ◽  
Montserrat Batlle ◽  
Bart H. Bijnens ◽  
Lluis Mont ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Diastolic Function ◽  
Cardiac Remodeling ◽  
Ventricular Remodeling ◽  
Contractile Function ◽  
Systolic Function ◽  
Training Model ◽  
Left Ventricular ◽  
Physiological Adaptation ◽  
Exercise Load

Arrhythmogenic right ventricular (RV) remodeling has been reported in response to regular training, but it remains unclear how exercise intensity affects the presence and extent of such remodeling. We aimed to assess the relationship between RV remodeling and exercise load in a long-term endurance training model. Wistar rats were conditioned to run at moderate (MOD; 45 min, 30 cm/s) or intense (INT; 60 min, 60 cm/s) workloads for 16 wk; sedentary rats served as controls. Cardiac remodeling was assessed with standard echocardiographic and tissue Doppler techniques, sensor-tip pressure catheters, and pressure-volume loop analyses. After MOD training, both ventricles similarly dilated (~16%); the RV apical segment deformation, but not the basal segment deformation, was increased [apical strain rate (SR): −2.9 ± 0.5 vs. −3.3 ± 0.6 s−1, SED vs. MOD]. INT training prompted marked RV dilatation (~26%) but did not further dilate the left ventricle (LV). A reduction in both RV segments' deformation in INT rats (apical SR: −3.3 ± 0.6 vs. −3.0 ± 0.4 s−1 and basal SR: −3.3 ± 0.7 vs. −2.7 ± 0.6 s−1, MOD vs. INT) led to decreased global contractile function (maximal rate of rise of LV pressure: 2.53 ± 0.15 vs. 2.17 ± 0.116 mmHg/ms, MOD vs. INT). Echocardiography and hemodynamics consistently pointed to impaired RV diastolic function in INT rats. LV systolic and diastolic functions remained unchanged in all groups. In conclusion, we showed a biphasic, unbalanced RV remodeling response with increasing doses of exercise: physiological adaptation after MOD training turns adverse with INT training, involving disproportionate RV dilatation, decreased contractility, and impaired diastolic function. Our findings support the existence of an exercise load threshold beyond which cardiac remodeling becomes maladaptive. NEW & NOTEWORTHY Exercise promotes left ventricular eccentric hypertrophy with no changes in systolic or diastolic function in healthy rats. Conversely, right ventricular adaptation to physical activity follows a biphasic, dose-dependent, and segmentary pattern. Moderate exercise promotes a mild systolic function enhancement at the right ventricular apex and more intense exercise impairs systolic and diastolic function.

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.

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