scholarly journals Relation between right ventricular wall stress, fibrosis, and function in right ventricular pressure loading

2020 ◽  
Vol 318 (2) ◽  
pp. H366-H377
Author(s):  
Jonathan Gold ◽  
Yohei Akazawa ◽  
Mei Sun ◽  
Kendall S. Hunter ◽  
Mark K. Friedberg
Keyword(s):  
Pulmonary Artery ◽  
Right Ventricular ◽  
Computer Model ◽  
Computational Models ◽  
Rabbit Model ◽  
Wall Stress ◽  
Free Wall ◽  
Pressure Loading ◽  
Hinge Point ◽  
And Function

Right ventricle (RV) pressure loading can lead to RV fibrosis and dysfunction. We previously found increased RV, septal hinge-point and left ventricle (LV) fibrosis in experimental RV pressure loading. However, the relation of RV wall stress to biventricular fibrosis and dysfunction is incompletely defined. Rabbits underwent progressive pulmonary artery banding (PAB) over 3 wk with hemodynamics, echocardiography, and myocardial samples obtained at a terminal experiment at 6 wk. An additional group received PAB and treatment with an endothelin receptor antagonist. The endocardial and epicardial borders of short-axis echo images were traced and analyzed with invasive pressures to yield regional end-diastolic (ED) and end-systolic (ES) wall stress. To increase clinical translation, computer model-derived wall stress was compared with Laplace wall stress. The relation of wall stress with fibrosis (picrosirius red staining) and ventricular function was analyzed. ED wall stress in all regions and RV and LV free-wall ES wall stress were increased in PAB rabbits versus sham animals. Laplace wall stress correlated well with computational models. In PAB, fibrosis was highest in the RV free wall, then septal hinge regions, and lowest in the septum and LV free wall. Fibrosis was moderately related to ED ( r = 0.47, P = 0.0011), but not ES wall stress. RV ED wall stress was strongly related to echo indexes of function (strain rate: r = 0.71, P = 0.048; E′, r = −0.75, P = 0.0077; tricuspid annular plane systolic excursion: r = 0.85, P = 0.0038) and RV fractional area change ( r = 0.77, P = 0.027). ED, more than ES, wall stress is related moderately to fibrosis and strongly to function in experimental RV pressure loading, especially at the septal hinge-point regions, where fibrosis is prominent. This suggests that wall stress partially links RV pressure loading, fibrosis, and dysfunction and may be useful to follow clinically. NEW & NOTEWORTHY Biventricular fibrosis and dysfunction impact outcomes in RV pressure loading, but their relation to wall stress is poorly defined. Using a pulmonary artery band rabbit model, we entered echocardiography and catheter data into a computer model to yield regional end-diastolic (EDWS) and end-systolic (ESWS) wall stress. EDWS, more than ESWS, correlated with fibrosis and dysfunction, especially at the fibrosis-intense septal hinge-point regions. Thus, wall stress may be clinically useful in linking RV pressure loading to regional fibrosis and dysfunction.

scholarly journals Serial MRI-based right ventricular mechanical wall stress measurements and their association with right ventricle function in patients with repaired Tetralogy of Fallot

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
SCS Minderhoud ◽  
A Hirsch ◽  
F Marin ◽  
I Kardys ◽  
JW Roos-Hesselink ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Right Ventricular ◽  
Computational Models ◽  
Wall Stress ◽  
Patient Specific ◽  
Apical Region ◽  
Free Wall ◽  
Time Points ◽  
Over Time

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Stichting Hartekind en Thorax Foundation Background Optimal timing of pulmonary valve replacement (PVR) in Tetralogy of Fallot (TOF) patients remains challenging. Wall stress is considered to be a possible early marker of right ventricular (RV) dysfunction. With patient-specific computational models, wall stress can be determined regionally and with high accuracy, especially in complex shaped ventricles such as in TOF patients. We aimed to 1) develop patient-specific computational models to assess RV diastolic wall stresses and 2) investigate the association of wall stresses and their change over time with functional parameters in TOF patients. Methods Repaired TOF patients with at least moderate pulmonary regurgitation (PR) and prior to PVR were included. MRI-based patient-specific computational ventricular models were created (figure). The ventricular geometry was created by stacking endo- and epicardial contours traced on short axis SSFP cine images. Pressure in the right ventricle was estimated from echocardiography. Mid-diastolic wall stress in the RV free wall was analysed globally and regionally (basal, mid, apical, anterior, lateral and posterior) at two time points. RV ejection fraction (RVEF), NT-proBNP and exercise tests (% maximum predicted workload) were used as outcomes for RV function. Associations between wall stresses and outcomes were investigated using linear mixed models adjusted for follow-up duration. Results Five males and five females were included with an age at baseline of 24 (IQR 16-28) years and RV end-diastolic volume of 140 (IQR 127-144) ml/m2. The period between the two time points was 7.0 (IQR 5.8-7.3) years. Global wall stress of the RV free wall combining both time points was 5.8 kPa (IQR 5.2-7.2). There was no statistical difference between baseline and follow-up global wall stress. The mean wall stresses in the mid region was 1.69 kPa (p < 0.01) higher than in the basal region and was 1.05 kPa (p = 0.03) higher than in the apical region cross-sectionally. The wall stress also increased more in the mid region compared to basal and apical region, corrected for duration of follow-up. Patients with more severe PR at baseline demonstrated a higher increase of global wall stress over time (p = 0.02), especially in lateral free wall. Higher global free wall stresses were cross-sectionally independently associated with lower RVEF, adjusted for LVEF and RVEDV (β=-1.29 % RVEF per kPa increase in wall stress, p = 0.01). This association was most prominent in the anterior, basal and mid part. No statistically significant association was found between wall stress, NT-proBNP, and exercise capacity. Conclusions This study generated a novel MRI-based method to calculate wall stress in geometrically complex ventricles. Wall stress associated negatively with RVEF in patients with TOF and PR. This promising tool for RV wall stress analysis can be used in future larger studies to validate these preliminary findings and to assess the predictive value of wall stress in TOF. Abstract Figure.

scholarly journals Right ventricular myocardial oxygen tension is reduced in monocrotaline-induced pulmonary hypertension in the rat and restored by myo-inositol trispyrophosphate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marta Oknińska ◽  
Zuzanna Zambrowska ◽  
Karolina Zajda ◽  
Aleksandra Paterek ◽  
Klaudia Brodaczewska ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Oxygen Tension ◽  
Systolic Pressure ◽  
Wall Stress ◽  
Saline Control ◽  
Oxygen Balance ◽  
Important Target ◽  
Oxygen Dissociation

AbstractPulmonary hypertension (PH) initially results in compensatory right ventricular (RV) hypertrophy, but eventually in RV failure. This transition is poorly understood, but may be triggered by hypoxia. Measurements of RV oxygen tension (pO2) in PH are lacking. We hypothesized that RV hypoxia occurs in monocrotaline-induced PH in rats and that myo-inositol trispyrophosphate (ITPP), facilitating oxygen dissociation from hemoglobin, can relieve it. Rats received monocrotaline (PH) or saline (control) and 24 days later echocardiograms, pressure–volume loops were obtained and myocardial pO2 was measured using a fluorescent probe. In PH mean pulmonary artery pressure more than doubled (35 ± 5 vs. 15 ± 2 in control), RV was hypertrophied, though its contractility was augmented. RV and LV pO2 was 32 ± 5 and 15 ± 8 mmHg, respectively, in control rats. In PH RV pO2 was reduced to 18 ± 9 mmHg, while LV pO2 was unchanged. RV pO2 correlated with RV diastolic wall stress (negatively) and LV systolic pressure (positively). Acute ITPP administration did not affect RV or LV pO2 in control animals, but increased RV pO2 to 26 ± 5 mmHg without affecting LV pO2 in PH. RV oxygen balance is impaired in PH and as such can be an important target for PH therapy. ITPP may be one of such potential therapies.

Right ventricular free wall pacing improves cardiac pump function in severe pulmonary arterial hypertension: a computer simulation analysis

2009 ◽  
Vol 297 (6) ◽  
pp. H2196-H2205 ◽  
Author(s):  
Joost Lumens ◽  
Theo Arts ◽  
Bernard Broers ◽  
Karin A. Boomars ◽  
Pieter van Paassen ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Free Wall ◽  
Pump Function ◽  
Cardiac Pump Function ◽  
Pulmonary Arterial

In pulmonary arterial hypertension (PAH), duration of myofiber shortening is prolonged in the right ventricular (RV) free wall (RVfw) compared with that in the interventricular septum and left ventricular free wall. This interventricular mechanical asynchrony eventually leads to right heart failure. We investigated by computer simulation whether, in PAH, early RVfw pacing may improve interventricular mechanical synchrony and, hence, cardiac pump function. A mathematical model of the human heart and circulation was used to simulate left ventricular and RV pump mechanics and myofiber mechanics. First, we simulated cardiovascular mechanics of a healthy adult at rest. Size and mass of heart and blood vessels were adapted so that mechanical tissue load was normalized. Second, compensated PAH was simulated by increasing mean pulmonary artery pressure to 32 mmHg while applying load adaptation. Third, decompensated PAH was simulated by increasing mean pulmonary artery pressure further to 79 mmHg without further adaptation. Finally, early RVfw pacing was simulated in severely decompensated PAH. Time courses of circumferential strain in the ventricular walls as simulated were similar to the ones measured in healthy subjects (uniform strain patterns) and in PAH patients (prolonged RVfw shortening). When simulating pacing in decompensated PAH, RV pump function was best upon 40-ms RVfw preexcitation, as evidenced by maximal decrease of RV end-diastolic volume, reduced RVfw myofiber work, and most homogeneous distribution of workload over the ventricular walls. Thus our simulations indicate that, in decompensated PAH, RVfw pacing may improve RV pump function and may homogenize workload over the ventricular walls.

Cardiac Assist With a Twist: Apical Torsion as a Means to Improve Failing Heart Function

2011 ◽  
Vol 133 (10) ◽  
Author(s):  
Dennnis R. Trumble ◽  
Walter E. McGregor ◽  
Roy C. P. Kerckhoffs ◽  
Lewis K. Waldman
Keyword(s):  
Stroke Volume ◽  
Computer Model ◽  
Computational Models ◽  
Heart Function ◽  
Imaging Techniques ◽  
Wall Stress ◽  
Similar Proportion ◽  
Stroke Work ◽  
Drug Induced

Changes in muscle fiber orientation across the wall of the left ventricle (LV) cause the apex of the heart to turn 10–15 deg in opposition to its base during systole and are believed to increase stroke volume and lower wall stress in healthy hearts. Studies show that cardiac torsion is sensitive to various disease states, which suggests that it may be an important aspect of cardiac function. Modern imaging techniques have sparked renewed interest in cardiac torsion dynamics, but no work has been done to determine whether mechanically augmented apical torsion can be used to restore function to failing hearts. In this report, we discuss the potential advantages of this approach and present evidence that turning the cardiac apex by mechanical means can displace a clinically significant volume of blood from failing hearts. Computational models of normal and reduced-function LVs were created to predict the effects of applied apical torsion on ventricular stroke work and wall stress. These same conditions were reproduced in anesthetized pigs with drug-induced heart failure using a custom apical torsion device programmed to rotate over various angles during cardiac systole. Simulations of applied 90 deg torsion in a prolate spheroidal computational model of a reduced-function pig heart produced significant increases in stroke work (25%) and stroke volume with reduced fiber stress in the epicardial region. These calculations were in substantial agreement with corresponding in vivo measurements. Specifically, the computer model predicted torsion-induced stroke volume increases from 13.1 to 14.4 mL (9.9%) while actual stroke volume in a pig heart of similar size and degree of dysfunction increased from 11.1 to 13.0 mL (17.1%). Likewise, peak LV pressures in the computer model rose from 85 to 95 mm Hg (11.7%) with torsion while maximum ventricular pressures in vivo increased in similar proportion, from 55 to 61 mm Hg (10.9%). These data suggest that: (a) the computer model of apical torsion developed for this work is a fair and accurate predictor of experimental outcomes, and (b) supra-physiologic apical torsion may be a viable means to boost cardiac output while avoiding blood contact that occurs with other assist methods.

scholarly journals Early versus late cardiac remodeling during right ventricular pressure load and impact of preventive versus rescue therapy with endothelin-1 receptor blockers

2018 ◽  
Vol 124 (5) ◽  
pp. 1349-1362 ◽  
Author(s):  
Sara Roldan Ramos ◽  
Guido Pieles ◽  
Mei Sun ◽  
Cameron Slorach ◽  
Wei Hui ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Right Ventricular ◽  
Time Course ◽  
Rabbit Model ◽  
Systolic Pressure ◽  
Pulmonary Artery Banding ◽  
Receptor Blockade ◽  
Apoptotic Cells ◽  
Early Therapy ◽  
Endothelin 1

Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction, biventricular fibrosis, and apoptosis, which are attenuated by endothelin-1 receptor blockade (ERB). Little is known about the time course of remodeling and whether early versus late ERB confers improved outcome. PAB was performed in five groups of rabbits: Shams, 3-wk PAB (3W), 6-wk PAB (6W), 6-wk PAB + ERB administered from day 1 (6WERB1), and 6-wk PAB + ERB administered from day 21 (6WERB21). Biventricular development of profibrotic molecular signaling, fibrosis, apoptosis, and conductance catheter and echocardiography function were studied. Thirty-three rabbits [ n = 6–7 per group; 3.00 (0.23) kg, mean (SD)] developed half to full systemic RV pressures. Biventricular profibrotic signaling and collagen deposition [RV collagen: Shams 3.8 (0.58) vs. 3W 8.69 (2.52) vs. 6W 8.83 (4.02)%, P < 0.005] and apoptosis [RV: Shams 8.32 (3.2) vs. 3W 55.95 (47.55) vs. 6W 38.85 (17.26) apoptotic cells per microfield, P < 0.0005] increased with PAB. Early and late ERB attenuated fibrosis [RV: 6WERB1 5.55 (1.18), 6WERB21 5.63 (0.72)%] and apoptosis [RV: 6WERB1 11.1 (5.25), 6WERB21 20.24 (7.16) apoptotic cells per microfield, P < 0.0001 vs. 6W]. RV dimensions progressively increased at 3W and 6W and decreased with early ERB [end-diastolic dimensions: Shams 0.4 (0.13) vs. 3W 0.55 (0.78) vs. 6W 0.78 (0.25) vs. 6WERB1 0.71 (0.26) vs. 6WERB21 0.49 (0.23) cm, P < 0.05]. Despite increased RV contractility with PAB [RV end-systolic pressure-volume relationship: Shams 3.76 (1.76) vs. 3W 12.21 (3.44) vs. 6W 19.4 (6.88) mmHg/ml], biventricular function and cardiac output [Shams 196.1 (39.73) vs. 3W 149.9 (34.82) vs. 6W 151 (31.69) ml/min] worsened in PAB groups and improved with early and late ERB [6WERB1 202.8 (26.8), 6WERB21 194.8 (36.93) ml/min, P < 0.05 vs. PAB]. In conclusion, RV pressure overload induces early biventricular fibrosis, apoptosis, remodeling, and dysfunction that worsens with persistent RV hypertension. This remodeling is attenuated by early and late ERB. NEW & NOTEWORTHY Our results in a rabbit model of progressive right ventricular (RV) pressure loading indicate that biventricular fibrosis, apoptosis, and dysfunction are already present when RV hypertension is reached at 3 wk of progressive pulmonary artery banding. These findings worsen with persistent RV hypertension to 6 wk and are attenuated with both early and late endothelin-1 receptor blockade, with some advantages to early therapy. These findings highlight the role of endothelin-1 in driving biventricular remodeling secondary to RV hypertension and suggest that early therapy with an endothelin-1 receptor blocker may be beneficial in attenuating biventricular remodeling but that late therapy is also effective.

Changes in pulmonary structure and function induced by monocrotaline intoxication

1981 ◽  
Vol 240 (2) ◽  
pp. H149-H155 ◽  
Author(s):  
F. Ghodsi ◽  
J. A. Will
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Pyrrolizidine Alkaloid ◽  
Histological Study ◽  
Right Ventricular Hypertrophy ◽  
Laboratory Animals ◽  
Functional Relationships ◽  
And Function

Monocrotaline, a pyrrolizidine alkaloid derived from Crotalaria spectabilis, is known to be toxic to a variety of domestic and laboratory animals and to humans. Major pathological effects induced by monocrotaline poisoning include hepatic cirrhosis and megalocytosis, venocclusive disease, pulmonary hypertension, and right ventricular hypertrophy. The present investigation explored the structural and functional relationships that exist between pulmonary artery pressure, small pulmonary artery medial thickness, and right ventricular hypertrophy. The results of this physiological and histological study on monocrotaline-intoxicated rats has demonstrated that there is a positive correlation between progressive pulmonary hypertension, thickening of the medical wall of small pulmonary vessels, and right ventricular hypertrophy as a function of time.

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