Left ventricular wall stress normalization in chronic pressure-overloaded heart: a mathematical model study

2000 ◽  
Vol 279 (3) ◽  
pp. H1120-H1127 ◽  
Author(s):  
Patrick Segers ◽  
Nikos Stergiopulos ◽  
Jan J. Schreuder ◽  
Berend E. Westerhof ◽  
Nico Westerhof
Keyword(s):  
Blood Pressure ◽  
Wall Thickness ◽  
Alternative Hypothesis ◽  
Pressure Overload ◽  
Wall Stress ◽  
Quantitative Agreement ◽  
Left Ventricular ◽  
Lumped Parameter Model ◽  
Model Parameters

It is generally accepted that the left ventricle (LV) hypertrophies (LVH) to normalize systolic wall stress (ςs) in chronic pressure overload. However, LV filling pressure (Pv) may be elevated as well, supporting the alternative hypothesis of end-diastolic wall stress (ςd) normalization in LVH. We used an LV time-varying elastance model coupled to an arterial four-element lumped-parameter model to study ventricular-arterial interaction in hypertension-induced LVH. We assessed model parameters for normotensive controls and applied arterial changes as observed in hypertensive patients with LVH (resistance +40%, compliance −25%) and assumed 1) no cardiac adaptation, 2) normalization of ςs by LVH, and 3) normalization of ςs by LVH and increase in Pv, such that ςd is normalized as well. In patients, systolic and diastolic blood pressures increase by ∼40%, cardiac output (CO) is constant, and wall thickness increases by 30–55%. In scenarios 1 and 2, blood pressure increased by only 10% while CO dropped by 20%. In scenario 2, LV wall thickness increased by only 10%. The predictions of scenario 3 were in qualitative and quantitative agreement with in vivo human data. LVH thus contributes to the elevated blood pressure in hypertension, and cardiac adaptations include an increase in Pv, normalization of ςs, and preservation of CO in the presence of an impaired diastolic function.

Heart size-independent analysis of myocardial function in murine pressure overload hypertrophy

2002 ◽  
Vol 282 (6) ◽  
pp. H2190-H2197 ◽  
Author(s):  
Hideyuki Takaoka ◽  
Giovanni Esposito ◽  
Lan Mao ◽  
Hiroyuki Suga ◽  
Howard A. Rockman
Keyword(s):  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Lv Function ◽  
Compensatory Mechanism ◽  
Compensatory Response ◽  
Myocardial Stiffness ◽  
Stiffness Constant

Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress (ς)-strain (ɛ) relations in normal and hypertrophied mice. LV volume was measured using two pairs of miniature omnidirectional piezoelectric crystals implanted orthogonally in the endocardium and one crystal placed on the anterior free wall to measure instantaneous wall thickness. Highly linear ς-ε relations were obtained in control ( n = 7) and hypertrophied mice produced by 7 days of transverse aortic constriction (TAC; n = 13). Administration of dobutamine in control mice significantly increased the load-independent measure of LV contractility, systolic myocardial stiffness. In TAC mice, systolic myocardial stiffness was significantly greater than in control mice (3,156 ± 1,433 vs. 1,435 ± 467 g/cm2, P < 0.01), indicating enhanced myocardial contractility with pressure overload. However, despite the increased systolic performance, both active (time constant of LV pressure decay) and passive (diastolic myocardial stiffness constant) diastolic properties were markedly abnormal in TAC mice compared with control mice. These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload.

Abstract 16018: Impaired Intrinsic Myocardial Shortening in Both Two Directions and Compensatory Mechanism to Maintain Left Ventricular Ejection Fraction in Patients With Hypertensive Heart Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Satoshi Yamada ◽  
Kazunori Okada ◽  
Hisao Nishino ◽  
Hiroyuki Iwano ◽  
Daisuke Murai ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ejection Fraction ◽  
Wall Thickness ◽  
Circumferential Strain ◽  
Hypertensive Heart Disease ◽  
Wall Stress ◽  
Left Ventricular ◽  
Relative Wall Thickness ◽  
Left Ventricular Ejection ◽  
Compensatory Mechanism

Background: Longitudinal myocardial shortening is known to be reduced even if left ventricular (LV) ejection fraction (EF) is preserved in patients with hypertensive heart disease (HHD). However, the compensatory mechanism remains to be elucidated. Thus layer-specific longitudinal and circumferential strain as well as stress-strain relationship was observed in HHD patients. Methods: In 46 HHD patients with preserved EF (>50%) and 29 age-matched control subjects, global longitudinal strain (LS) and layer-specific circumferential strain (CS) were measured from the apical 4-chamber view and mid-ventricular short-axis view, respectively, by using speckle tracking echocardiography. LS was measured at innermost LV wall layer, and CS at innermost, midwall, and outermost layers. Layer-specific end-systolic circumferential wall stress (CWS) according to Mirsky’s formula and endocardial meridional wall stress (MWS) were calculated. Results: Systolic blood pressure (147±20 mm Hg), interventricular septal thickness (13±2 mm), and LV dimension (48±4 mm) were greater in HHD than controls, whereas EF was comparable (66±8 vs 66±5%). LS was smaller in HHD than controls (-13±3 vs -17±3%, p<0.001) in spite of reduced MWS (520±141 vs 637±164 dyn·mm -2 , p<0.01), suggesting impaired longitudinal myocardial function in HHD. Similarly, CS was smaller in HHD than controls at outer layer (-6.8±2.2 vs -8.8±2.2%, p<0.01) and at midwall (-11.3±3.4 vs -13.9±3.2%, p<0.01) in spite of reduced CWS (outer: 238±82 vs 336±110 dyn·mm -2 , p<0.001; mid: 360±107 vs 473±131 dyn·mm -2 , p<0.001). In contrast, at the innermost layer, both CS (-26±5 vs -25±5%, p=0.41) and CWS (979±153 vs 992±139 dyn·mm -2 , p=0.72) were comparable between groups. Furthermore, the difference of CS between inner and outer layers significantly correlated with relative wall thickness (r=-0.33, p<0.01). Finally, CS at inner layer significantly correlated with EF (r=-0.43, p<0.001), whereas LS did not. Conclusions: In patients with HHD, intrinsic myocardial shortening was impaired both longitudinally and circumferentially. Some compensatory mechanism associated with increased relative wall thickness might work to maintain subendocardial CS, resulting in preserved EF.

Abstract 313: STIM1 Silencing Reverses Pressure-overload Induced Cardiac Hypertrophy In Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ludovic O Bénard ◽  
Daniel S Matasic ◽  
Mathilde Keck ◽  
Anne-Marie Lompré ◽  
Roger J Hajjar ◽  
...  
Keyword(s):  
Ventricular Hypertrophy ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Aortic Banding ◽  
Cross Section Area ◽  
Abdominal Aortic ◽  
Section Area

STromal Interaction Molecule 1 (STIM1), a membrane protein of the sarcoplasmic reticulum, has recently been proposed as a positive regulator of cardiomyocyte growth by promoting Ca2+ entry through the plasma membrane and the activation of Ca2+-mediated signaling pathways. We demonstrated that STIM1 silencing prevented the development of left ventricular hypertrophy (LVH) in rats after abdominal aortic banding. Our aim was to study the role of STIM1 during the transition from LVH to heart failure (HF). For experimental timeline, see figure. Transverse Aortic Constriction (TAC) was performed in C57Bl/6 mice. In vivo gene silencing was performed using recombinant Associated AdenoVirus 9 (AAV9). Mice were injected with saline or with AAV9 expressing shRNA control or against STIM1 (shSTIM1) (dose: 1e+11 viral genome), which decreased STIM1 cardiac expression by 70% compared to control. While cardiac parameters were similar between the TAC groups at weeks 3 and 6, shSTIM1 animals displayed a progressive and total reversion of LVH with LV walls thickness returning to values observed in sham mice at week 8. This reversion was associated with the development of significant LV dilation and severe contractile dysfunction, as assessed by echography. Hemodynamic analysis confirmed the altered contractile function and dilation of shSTIM1 animals. Immunohistochemistry showed a trend to more fibrosis. Despite hypertrophic stimuli, there was a significant reduction in cardiac myocytes cross-section area in shSTIM1-treated animals as compared to other TAC mice. This study showed that STIM1 is essential to maintain compensatory LVH and that its silencing accelerates the transition to HF.

Abstract 285: Cardiac Inflammation and Fibrosis Induced by Heart Failure Are Reversed by Short-Duration Estrogen Therapy

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Andrea Iorga ◽  
Rangarajan Nadadur ◽  
Salil Sharma ◽  
Jingyuan Li ◽  
Mansoureh Eghbali
Keyword(s):  
Heart Failure ◽  
Estrogen Therapy ◽  
Pressure Overload ◽  
Decompensated Heart Failure ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
In Vivo Model ◽  
Anti Inflammatory

Heart failure is generally characterized by increased fibrosis and inflammation, which leads to functional and contractile defects. We have previously shown that short-term estrogen (E2) treatment can rescue pressure overload-induced decompensated heart failure (HF) in mice. Here, we investigate the anti-inflammatory and anti-fibrotic effects of E2 on reversing the adverse remodeling of the left ventricle which occurs during the progression to heart failure. Trans-aortic constriction procedure was used to induce HF. Once the ejection fraction reached ∼30%, one group of mice was sacrificed and the other group was treated with E2 (30 αg/kg/day) for 10 days. In vitro, co-cultured neonatal rat ventricular myocytes and fibroblasts were treated with Angiotensin II (AngII) to simulate cardiac stress, both in the presence or absence of E2. In vivo RT-PCR showed that the transcript levels of the pro-fibrotic markers Collagen I, TGFβ, Fibrosin 1 (FBRS) and Lysil Oxidase (LOX) were significantly upregulated in HF (from 1.00±0.16 to 1.83±0.11 for Collagen 1, 1±0.86 to 4.33±0.59 for TGFβ, 1±0.52 to 3.61±0.22 for FBRS and 1.00±0.33 to 2.88±0.32 for LOX) and were reduced with E2 treatment to levels similar to CTRL. E2 also restored in vitro AngII-induced upregulation of LOX, TGFβ and Collagen 1 (LOX:1±0.23 in CTRL, 6.87±0.26 in AngII and 2.80±1.5 in AngII+E2; TGFβ: 1±0.08 in CTRL, 3.30±0.25 in AngII and 1.59±0.21 in AngII+E2; Collagen 1: 1±0.05 in CTRL.2±0.01 in AngII and 0.65±0.02 (p<0.05, values normalized to CTRL)). Furthermore, the pro-inflammatory interleukins IL-1β and IL-6 were upregulated from 1±0.19 to 1.90±0.09 and 1±0.30 to 5.29±0.77 in the in vivo model of HF, respectively, and reversed to CTRL levels with E2 therapy. In vitro, IL-1β was also significantly increased ∼ 4 fold from 1±0.63 in CTRL to 3.86±0.14 with AngII treatment and restored to 1.29±0.77 with Ang+E2 treatment. Lastly, the anti-inflammatory interleukin IL-10 was downregulated from 1.00±0.17 to 0.49±0.03 in HF and reversed to 0.67±0.09 in vivo with E2 therapy (all values normalized to CTRL). This data strongly suggests that one of the mechanisms for the beneficial action of estrogen on left ventricular heart failure is through reversal of inflammation and fibrosis.

Dose-dependent effect of ANG II-receptor antagonist on myocyte remodeling in rat cardiac hypertrophy

1997 ◽  
Vol 273 (4) ◽  
pp. H1824-H1831 ◽  
Author(s):  
Masakazu Obayashi ◽  
Masafumi Yano ◽  
Michihiro Kohno ◽  
Shigeki Kobayashi ◽  
Taketo Tanigawa ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Receptor Antagonist ◽  
Pressure Overload ◽  
Wall Stress ◽  
Treated Group ◽  
Left Ventricular ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
And Function ◽  
Vehicle Treated Group

The goal of this study was to examine the effect of an angiotensin II type 1 (AT1)-receptor antagonist (TCV-116) on left ventricular (LV) geometry and function during the development of pressure-overload LV hypertrophy. A low (LD; 0.3 mg ⋅ kg−1 ⋅ day−1) or a high (HD; 3.0 mg ⋅ kg−1 ⋅ day−1) dose of TCV-116 was administered to abdominal aortic-banded rats over 4 wk, and hemodynamics and morphology were then evaluated. In both LD and HD groups, peak LV pressures were decreased to a similar extent compared with the vehicle-treated group but stayed at higher levels than in the sham-operated group. In the LD group, both end-diastolic wall thickness (3.08 ± 0.14 mm) and myocyte width (13.3 ± 0.1 μm) decreased compared with those in the vehicle-treated group (3.67 ± 0.19 mm and 15.3 ± 0.1 μm, respectively; both P < 0.05). In the HD group, myocyte length was further decreased (HD: 82.6 ± 2.6, LD: 94.1 ± 2.9 μm; P < 0.05) in association with a reduction in LV midwall radius (HD: 3.36 ± 0.12, LD: 3.60 ± 0.14 mm; P < 0.05) and peak midwall fiber stress (HD: 69 ± 8, LD: 83 ± 10 × 103dyn/cm2; P < 0.05). There was no significant difference in cardiac output among all groups. The AT1-receptor antagonist TCV-116 induced an inhibition of the development of pressure-overload hypertrophy. Morphologically, not only the width but also the length of myocytes was attenuated with TCV-116, leading to a reduction of midwall radius and hence wall stress, which in turn may contribute to a preservation of cardiac output.

Severe myocardial dysfunction induced by ventricular remodeling in aging rat hearts

1990 ◽  
Vol 259 (4) ◽  
pp. H1086-H1096 ◽  
Author(s):  
J. M. Capasso ◽  
T. Palackal ◽  
G. Olivetti ◽  
P. Anversa
Keyword(s):  
Ventricular Remodeling ◽  
Volume Fraction ◽  
Diastolic Pressure ◽  
Structural Characteristics ◽  
Myocardial Dysfunction ◽  
Pressure Rise ◽  
Wall Stress ◽  
Left Ventricular ◽  
Cross Sectional

To determine if aging engenders alterations in the functional properties of the myocardium and ventricular remodeling, the hemodynamic performance and structural characteristics of the left ventricle of male Fischer 344 rats at 4, 12, 20, and 29 mo of age were studied by quantitative physiology and morphology. In vivo assessment of cardiac pump function showed no change up to 20 mo, whereas left ventricular end-diastolic pressure was increased at 29 mo. Moreover, peak rates of pressure rise and decay, stroke volume, ejection fraction, and cardiac output were depressed at the later age interval, demonstrating the presence of ventricular failure at this time. The measurements of chamber size and wall thickness showed that ventricular end-diastolic and end-systolic volumes progressively increased with age with the greatest change occurring at 20-29 mo. Aging was also accompanied by a marked augmentation in the volume fraction of fibrotic areas in the ventricular myocardium that was due to an increase in their number and cross-sectional area with time. These architectural rearrangements, in combination with the abnormalities in ventricular function, resulted in an elevation in the volume of wall stress throughout the cardiac cycle. Wall stress increased by 64, 44, and 50% from 4 to 12, 12 to 20, and 20 to 29 mo of age. In conclusion, aging leads to a continuous rise in wall stress that is not normalized by ventricular remodeling. These two independent processes appear to be responsible for the onset of heart failure in the senescent rat.

scholarly journals Interrelation between Exercise Heart Rate, Post-Run Systolic Blood Pressure, and Myocardial Structure in Distance Runners

2018 ◽  
Vol 3 (66) ◽  
Author(s):  
Tomas Venckūnas ◽  
Birutė Mažutaitienė ◽  
Arvydas Stasiulis
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Wall Thickness ◽  
Myocardial Hypertrophy ◽  
Pressure Overload ◽  
Exercise Heart Rate ◽  
Training Volume ◽  
Distance Runners ◽  
Myocardial Wall

Endurance running is an exercise practiced by athletes in many sports. Being benefi cial to health, it is also under-taken by a great number of non-athletic individuals. Rigorous endurance training frequently induces symmetric (i. e. both ventricular chamber dilation and wall thickening) myocardial hypertrophy, which is a physiological adapta-tion. Although distance running is a sport associated with haemodynamic volume rather than pressure overload, in addition to enlarged cardiac output, systolic arterial blood pressure also considerably increases during running. The extent of the cardiac hypertrophy was shown to be correlated with peak blood pressure measured during laboratory exercise. However, the predominant type of myocardial hypertrophy (the ratio between the myocardial wall thickness and chamber size) in endurance runners remains contradictory, and the majority of the responsible factors are still to be determined. The aim of this study was to determine possible correlations between post-run systolic blood pressure and myocardial hypertrophy in endurance runners.Standard transthoracic two-dimensional M-mode echocardiography was performed in white adult male distance runners (n = 49) of national level within four weeks of treadmill testing, which was a non-continuous incremental exercise test employed for the determination of the heart rate as well as post-exertional systolic blood pressure re-sponse. Runners’ training volume (evaluated as the average number of hours per week spent training averaged over the past four weeks) correlated (p < 0.05) positively with the left ventricular (LV) wall thickness but not with the cavity size or LV mass (p > 0.05). Training volume also positively correlated with systolic blood pressure response to exercise (p < 0.05), but negatively with submaximal exercise heart rate (p < 0.01). Post-run systolic blood pressure correlated positively with LV wall thickness and LV concentricity (namely, the ratio between the myocardial wall thick-ness and chamber size) (p < 0.05), but no signifi cant correlation of any of the LV size parameters with resting heart rate, blood pressure, or systolic blood pressure in 2 to 4 min during the recovery period was revealed. Submaximal and maximal heart rate correlated signifi cantly and negatively with LV wall thickness, LV mass, and systolic blood pressure measured immediately after running (p < 0.05).Training volume and post-run systolic blood pressure have been found to correlate positively with LV wall thickness and concentricity in white adult male distance runners. Negative correlation of exercise heart rate has been found with the post-exercise systolic blood pressure, LV wall thickness, and LV mass.Keywords: myocardial hypertrophy, pressure overload, echocardiography, athlete’s heart.

PYK2 expression and phosphorylation increases in pressure overload-induced left ventricular hypertrophy

2002 ◽  
Vol 283 (2) ◽  
pp. H695-H706 ◽  
Author(s):  
Allison L. Bayer ◽  
Maria C. Heidkamp ◽  
Nehu Patel ◽  
Michael J. Porter ◽  
Steven J. Engman ◽  
...  
Keyword(s):  
Pressure Overload ◽  
Left Ventricular ◽  
Cellular Growth ◽  
Mitogen Activated Protein Kinase ◽  
Cardiomyocyte Hypertrophy ◽  
Sprague Dawley ◽  
Aortic Banding ◽  
Tyrosine Kinase 2 ◽  
High Degree

Proline-rich tyrosine kinase 2 (PYK2) is a member of the focal adhesion kinase (FAK) family of nonreceptor protein tyrosine kinases. PYK2 has been implicated in linking G protein-coupled receptors to activation of mitogen-activated protein kinase cascades and cellular growth in a variety of cell types. To determine whether PYK2 expression and phosphorylation is altered in left ventricular (LV) myocardium undergoing LV hypertrophy (LVH) and heart failure in vivo, suprarenal abdominal aortic coarctation was performed in 160-g male Sprague-Dawley rats. Immunohistochemistry and Western blotting were performed on LV tissue 1, 8, and 24 wk after aortic banding. Aortic banding produced sustained hypertension and gradually developing LVH. PYK2 levels were increased 1.8 ± 0.2-, 2.7 ± 0.6-, and 2.0 ± 0.2-fold in 1-, 8-, and 24-wk banded animals compared with their respective sham-operated controls. The increase in PYK2 expression was paralleled by an increase in PYK2 phosphorylation, both of which preceded the development of LVH. Immunohistochemistry revealed that enhanced PYK2 expression occurred predominantly in the cardiomyocyte population. Furthermore, there was a high degree of correlation ( R = 0.75; P< 0.001) between the level of PYK2 and the degree of LVH in 24-wk sham and banded animals. In contrast, FAK levels and FAK phosphorylation were not increased before the development of LVH. However, there was a high degree of correlation (R = 0.68; P < 0.001) between the level of FAK and the degree of LVH in 24-wk sham and banded rats. There was also a significant increase in the ratio of phosphospecific anti-FAK to FAK at this time point. These data are consistent with a role for PYK2 in the induction of pressure overload-induced cardiomyocyte hypertrophy, and suggest that PYK2 and FAK have distinctly different roles in LVH progression.

Myocardial mechanical alterations during gradual onset long-term hypertension in rats

1981 ◽  
Vol 241 (3) ◽  
pp. H435-H441 ◽  
Author(s):  
J. M. Capasso ◽  
J. E. Strobeck ◽  
E. H. Sonnenblick
Keyword(s):  
Blood Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Left Renal Artery ◽  
Ventricular Performance ◽  
Time To Peak ◽  
Gradual Onset ◽  
Significant Depression ◽  
Female Wistar Rats

Although a suddenly produced load leads to depressed myocardial contractility, the effects of a slowly induced physiological overload have not been defined. Therefore, a more gradual pressure overload was produced in female Wistar rats by hypertension due to constriction of the left renal artery. Hypertension (systolic blood pressure greater than or equal to 150 mmHg) developed within 3 wk, and blood pressure continued to increase for the next 5 wk. Heart weights in hypertensive animals were elevated by 34% after the onset of hypertension. Isometric and isotonic contractions from left ventricular papillary muscles were recorded at 5, 10, 20, and 30 wk after the onset of hypertension. Total and actively developed isometric tension at all initial muscle lengths were significantly greater in hypertensive animals throughout the 30-wk period. Time to peak tension and time to half relaxation were significantly prolonged. Force-velocity curves demonstrated a significant depression in velocity of shortening at all relative loads in hypertensive muscles that progressed with the duration of hypertension. These studies suggest that myocardial hypertrophy may impart the ability to maintain ventricular performance in terms of force development while speed of shortening decays.

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