Corticosteroids Are Essential for Maintaining Cardiovascular Function in Male Mice

Activation of the hypothalamic-pituitary-adrenal axis results in the release of hormones from the adrenal glands, including glucocorticoids and mineralocorticoids. The physiological association between corticosteroids and cardiac disease is becoming increasingly recognized; however, the mechanisms underlying this association are not well understood. To determine the biological effects of corticosteroids on the heart, we investigated the impact of adrenalectomy in C57BL/6 male mice. Animals were adrenalectomized (ADX) at 1 month of age and maintained for 3–6 months after surgery to evaluate the effects of long-term adrenalectomy on cardiac function. Morphological evaluation suggested that ADX mice showed significantly enlarged hearts compared with age-matched intact controls. These changes in morphology correlated with deficits in left ventricular (LV) function and electrocardiogram (ECG) abnormalities in ADX mice. Correlating with these functional defects, gene expression analysis of ADX hearts revealed aberrant expression of a large cohort of genes associated with cardiac hypertrophy and arrhythmia. Combined corticosterone and aldosterone replacement treatment prevented the emergence of cardiac abnormalities in ADX mice, whereas corticosterone replacement prevented the effects of adrenalectomy on LV function but did not block the emergence of ECG alterations. Aldosterone replacement did not preserve the LV function but prevented ECG abnormalities. Together, the data indicate that adrenal glucocorticoids and mineralocorticoids either directly or indirectly have selective effects in the heart and their signaling pathways are essential in maintaining normal cardiac function.

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.5.h1938 ◽

2001 ◽

Vol 281 (5) ◽

pp. H1938-H1945 ◽

Cited By ~ 70

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.

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“A CROSS SECTIONAL, DESCRIPTIVE STUDY ON SYSTEMIC ILLNESSES AND CARDIAC FUNCTION ABNORMALITIES IN CHILDREN”

10.36106/paripex/8609339 ◽

2021 ◽

pp. 75-79

Author(s):

Munesh Tomar ◽

Tanvi goel ◽

Raza Faizan ◽

Vijay Jaiswal

Keyword(s):

Cardiac Output ◽

Cardiac Function ◽

Ventricular Dysfunction ◽

Significant Proportion ◽

Descriptive Study ◽

Left Ventricular ◽

The Body ◽

Cross Sectional ◽

Pr Interval ◽

Ecg Abnormalities

Background:There are wide number of diseases of almost every system in the body which can affect heart in a number of different ways including increasing demands on the heart ,ventricular dysfunction ,rhythm abnormalities ,valve abnormalities ,pulmonary pressures and lot more.Cardiac involvement in systemic diseases is usually silent or oligosymptomatic and includes different pathophysiological mechanisms such as myocardial inflammation, infarction ,subendocardial vasculitis,valvular disease and different patterns of fibrosis. Objective : To study association between systemic illnesses (hematological, endocrinal , renal) and cardiac function abnormalities as ventricular function,cardiac dimensions ,pulmonary artery pressure and pericardial effusion,for early diagnosis and treatment to decrease morbidity and mortality in patient with systemic illness. Design/Method:It was a cross sectional,descriptive study The present study was conducted in the Department of Pediatrics, LLRM Medical College,Meerut,Uttar Pradesh over a period of 1 year (June 2019-June 2020) Results: Cardiac findings in all three groups show ECG abnormalities and echocardiographic changes compared to general population. ECG abnormalities were prolonged PR interval and sinus tachycardia while echocardiographic changes mainly left ventricular(LV) dilatation and hypertrophy ,increased cardiac output ,ventricular dysfunction and pulmonary arterial hypertension(PAH),were noted in a significant proportion of patients. Conclusion:Systemic illnesses affect cardiac parameters in various ways including prolonged PR interval,cardiac dilatation,chamber hypertrophy ,high cardiac output,high cardiac index ,PAH and ventricular dysfunction.

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Impact of Valve Surgery on Serum Osteopontin Levels in Patients with Mitral Regurgitation

Cardiology ◽

10.1159/000368299 ◽

2015 ◽

Vol 130 (2) ◽

pp. 82-86

Author(s):

H.M. Gunes ◽

G.B. Guler ◽

E. Guler ◽

G.G. Demir ◽

S. Hatipoglu ◽

...

Keyword(s):

Mitral Regurgitation ◽

Left Ventricular ◽

Valve Surgery ◽

Lv Function ◽

Vena Contracta ◽

Atherosclerotic Lesions ◽

Lv Dysfunction ◽

Echocardiographic Parameters ◽

Artery Disease ◽

The Impact

Objective: Osteopontin (OPN), a sialoprotein present within atherosclerotic lesions, especially in calcified plaques, is linked to the progression of coronary artery disease and heart failure. We assessed the impact of valve surgery on serum OPN and left ventricular (LV) function in patients with mitral regurgitation (MR). Methods: Thirty-two patients with severe MR scheduled for surgery were included in the study. Echocardiography markers were assessed preoperatively and at 3 months following the surgery and matched with the serum OPN levels. Results: Valve surgery was associated with a reduction of the ejection fraction (EF) from 55.2 ± 6.3 to 48.8 ± 7.1% after surgery, p < 0.001. Following surgery, the OPN level was significantly higher than preoperatively (mean 245, range 36-2,284 ng/ml vs. 76, 6-486 ng/ml, p = 0.007). Preoperative OPN exhibited a slight negative correlation with the EF (r = -0.35, p = 0.04), and a moderate correlation with vena contracta (r = -0.38, p = 0.02). There were no other meaningful correlations between conventional echocardiographic parameters and OPN. Conclusion: Following valve surgery due to severe MR, patients exhibited a decrease in EF and an increase in OPN levels. The assessment of preoperative OPN failed to strongly predict probable LV dysfunction.

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Abstract 15172: Murf1 Inhibitor Embl205 is a New Approach for Treatment of Heart Failure With Preserved Ejection Fraction in an Animal Model

Circulation ◽

10.1161/circ.142.suppl_3.15172 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Anett Jannasch ◽

Antje Schauer ◽

Virginia Kirchhoff ◽

Runa Draskowsi ◽

Claudia Dittfeld ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Diastolic Pressure ◽

Posterior Wall ◽

Left Ventricular ◽

Skeletal Muscle Atrophy ◽

Lv Function ◽

Preserved Ejection Fraction ◽

The Impact ◽

Peak Gradient

Background: The novel MuRF1 inhibitor EMBL205 attenuates effectively developing skeletal muscle atrophy and dysfunction in animals with heart failure with preserved ejection fraction (HFpEF, ZSF1 rat model). The impact of EMBL205 on myocardial function in the HFpEF setting is currently unknown and was evaluated in ZSF1 rats. Methods: 20 wks-old female obese ZSF1 rats received EMBL205 (12 wks, conc. of 0.1% in chow; HFpEF-EMBL205). Age-matched untreated lean (con) and obese (HFpEF) ZSF1 rats served as controls. At 32 wks of age left ventricular (LV)-, aortic valve (AV) function and LV end diastolic pressure (LVEDP) was determined by echocardiography and invasive hemodynamic measurements. LV expression of collagen 1A (Col1A) and 3A (Col3A) was assessed by qRT-PCR, MMP2 expression was obtained by zymography and perivascular fibrosis was quantified in histological sections. Results: Development of HFpEF in ZSF1 obese animals is associated with cardiac enlargement and hypertrophy, as evident by increased myocardial weight, an increase in end diastolic volume (EDV) and LV anterior and posterior wall diameters. Diastolic LV-function is disturbed with elevation of E/é, an increased LVEDP and a preserved LV ejection fraction. AV peak velocity and peak gradient are significantly increased and AV opening area (AVA) significantly decreased. Col1A and Col3A expression are increased in HFpEF animals. EMBL205 treatment results in a significant reduction of myocardial weight and a trend towards lower EDV compared to HFpEF group. EMBL205 attenuates the increase in E/é, LVEDP, AV peak gradient and the decrease of AVA. EMBL205 significantly reduces Col3A expression and a trend for Col1A expression is seen. Increased perivascular fibrosis and MMP2 expression in HFpEF is extenuated by EMBL205 treatment (table 1). Conclusions: Application of EMBL205 attenuated the development of pathological myocardial alterations associated with HFpEF in ZSF1rats due to antifibrotic effects.

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Dietary Calanus oil recovers metabolic flexibility and rescues postischemic cardiac function in obese female mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00191.2019 ◽

2019 ◽

Vol 317 (2) ◽

pp. H290-H299 ◽

Cited By ~ 3

Author(s):

Kirsten M. Jansen ◽

Sonia Moreno ◽

Pablo M. Garcia-Roves ◽

Terje S. Larsen

Keyword(s):

Fatty Acid ◽

Cardiac Function ◽

Glucose Oxidation ◽

Myocardial Metabolism ◽

Dietary Supplementation ◽

Left Ventricular ◽

Lv Function ◽

Marine Oil ◽

Normal Chow ◽

Postischemic Recovery

The aim of this study was to find out whether dietary supplementation with Calanus oil (a novel marine oil) or infusion of exenatide (an incretin mimetic) could counteract obesity-induced alterations in myocardial metabolism and improve postischemic recovery of left ventricular (LV) function. Female C57bl/6J mice received high-fat diet (HFD, 45% energy from fat) for 12 wk followed by 8-wk feeding with nonsupplemented HFD, HFD supplemented with 2% Calanus oil, or HFD plus exenatide infusion (10 µg·kg−1·day−1). A lean control group was included, receiving normal chow throughout the whole period. Fatty acid and glucose oxidation was measured in ex vivo perfused hearts during baseline conditions, while LV function was assessed with an intraventricular fluid-filled balloon before and after 20 min of global ischemia. HFD-fed mice receiving Calanus oil or exenatide showed less intra-abdominal fat deposition than mice receiving nonsupplemented HFD. Both treatments prevented the HFD-induced decline in myocardial glucose oxidation. Somewhat surprising, recovery of LV function was apparently better in hearts from mice fed nonsupplemented HFD relative to hearts from mice fed normal chow. More importantly however, postischemic recovery of hearts from mice receiving HFD with Calanus oil was superior to that of mice receiving nonsupplemented HFD and mice receiving HFD with exenatide, as expressed by better pressure development, contractility, and relaxation properties. In summary, dietary Calanus oil and administration of exenatide counteracted obesity-induced derangements of myocardial metabolism. Calanus oil also protected the heart from ischemia, which could have implications for the prevention of obesity-related cardiac disease. NEW & NOTEWORTHY This article describes for the first time that dietary supplementation with a low amount (2%) of a novel marine oil (Calanus oil) in mice is able to prevent the overreliance of fatty acid oxidation for energy production during obesity. The same effect was observed with infusion of the incretin mimetic, exanatide. The improvement in myocardial metabolism in Calanus oil-treated mice was accompanied by a significantly better recovery of cardiac performance following ischemia-reperfusion. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/dietary-calanus-oil-energy-metabolism-and-cardiac-function/ .

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P1603 Changes of cardiac function in cirrhotic patients after liver transplantation

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.1021 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

H M Kim ◽

H K Kim ◽

J H Lee ◽

E A Park ◽

J B Park ◽

...

Keyword(s):

Liver Transplantation ◽

Mr Imaging ◽

Cardiac Function ◽

Speckle Tracking ◽

Speckle Tracking Echocardiography ◽

Left Ventricular ◽

Lv Function ◽

Qtc Interval ◽

Cardiac Mr ◽

Cirrhotic Patients

Abstract Funding Acknowledgements This study was supported by the grant of CJ healthcare 2016 research fund. Background Liver cirrhosis (LC) has been known to affect cardiovascular performance. Limited study have evaluated the alteration of myocardial function in patients with LC after liver transplantation (LT). Purpose The aim of study was to evaluate changes of cardiac function in patients with cirrhosis following LT using conventional and speckle-tracking echocardiography and late gadolinium enhancement (LGE) of cardiac magnetic resonance (MR). Methods Thirty-five patients with cirrhosis (mean age, 57.1 ± 9.0; male, 75%) who were listed for LT were prospectively enrolled. Patients underwent conventional, speckle-tracking echocardiography, and cardiac MR imaging with LGE. Echocardiography and cardiac MR were performed at pre and 1 year after LT. Cirrhotic patients were compared with normal control (n = 20, mean age, 65.0 ± 14.8; men, 11(55%)) and echocardiographic and cardiac MR data were compared pre and post LT. Results Conventional and speckle-tracking echocardiography and Cardiac MR imaging demonstrated hyperdynamic left ventricular (LV) function in patients with cirrhosis (LV ejection fraction (EF) with cardiac MR 67.8 ± 7.0% in LC vs. 63.4 ± 6.4% in control, P = 0.028; global longitudinal strain (GLS) -24.3 ± 2.6% in LC vs. -18.6 ± 2.2% in control, P < 0.001). There were no LGE in patients with cirrhosis and no significant differences in LV size, LV wall thickness, LV mass index, and diastolic function between cirrhotic patients and control group (all P > 0.1). Corrected QT interval (QTc) in electrocardiogram was prolonged in LC patients (P < 0.001). One-year after LT, LV end-diastolic diameter and LV end-diastolic volume significantly decreased (P = 0.016 and 0.022, respectively). Although LVEF showed no significant changes 1 year post-LT (P = 0.362), LV-GLS (from -24.7 ± 1.8% to -20.8 ± 3.4%, P < 0.001) significantly decreased. QTc interval also decreased 1 year after LT (from 470.4 ± 29.6msec to 428.2 ± 31.6msec, P = 0.001). Conclusions The present study demonstrated that cirrhotic patients showed hyperdynamic circulation and prolonged QTc interval compared with normal controls. After 1 year LT, LV size reduced and augmented LV function was normalized. Given that no LGE in cardiac MR and normalized GLS and QTc after LT, cardiac dysfunction in LC patients could be reversed by LT.

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Increased cholinergic activity under conditions of low estrogen leads to adverse cardiac remodeling

AJP Cell Physiology ◽

10.1152/ajpcell.00142.2020 ◽

2020 ◽

Author(s):

Vanessa P. Teixeira ◽

Kiany Miranda ◽

Sergio Scalzo ◽

Cibele Rocha-Resende ◽

Mário Morais Silva ◽

...

Keyword(s):

Cardiac Function ◽

Postmenopausal Women ◽

Ventricular Myocytes ◽

Left Ventricular ◽

Genetically Engineered ◽

Cardiac Response ◽

Cholinesterase Inhibition ◽

Functional Changes ◽

Concentric Hypertrophy ◽

The Impact

Cholinesterase inhibitors are used in postmenopausal women for the treatment of neurodegenerative diseases. Despite their widespread use in the clinical practice, little is known about the impact of augmented cholinergic signaling on cardiac function under reduced estrogen conditions. To address this gap, we subjected a genetically engineered murine model of systemic vesicular acetylcholine transporter overexpression (Chat-ChR2) to ovariectomy and evaluated cardiac parameters. Left-ventricular function was similar between Chat-ChR2 and wild-type (WT) mice. Following ovariectomy, WT mice showed signs of cardiac hypertrophy. Conversely, ovariectomized (OVX) Chat-ChR2 mice evolved to cardiac dilation and failure. Transcript levels for cardiac stress markers ANP and BNP were similarly upregulated in WT/OVX and Chat-ChR2/OVX mice. 17β-Estradiol (E2) treatment normalized cardiac parameters in Chat-ChR2/OVX to the Chat-ChR2/SHAM levels, providing a link between E2 status and the aggravated cardiac response in this model. To investigate the cellular basis underlying the cardiac alterations, ventricular myocytes were isolated and their cellular area and contractility were assessed. Myocytes from WT/OVX mice were wider than WT/SHAM, an indicative of concentric hypertrophy, but their fractional shortening was similar. Conversely, Chat-ChR2/OVX myocytes were elongated, and presented contractile dysfunction. E2 treatment again prevented the structural and functional changes in Chat-ChR2/OVX myocytes. We conclude that hypercholinergic mice under reduced estrogen conditions do not develop concentric hypertrophy, a critical compensatory adaptation, evolving towards cardiac dilation and failure. This study emphasizes the importance of understanding the consequences of cholinesterase inhibition, used clinically to treat dementia, for cardiac function in postmenopausal women.

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Comparison of energy supplements during prolonged exercise for maintenance of cardiac function: carbohydrate only versus carbohydrate plus whey or casein hydrolysate

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2015-0491 ◽

2016 ◽

Vol 41 (6) ◽

pp. 674-683 ◽

Cited By ~ 3

Author(s):

Tanja Oosthuyse ◽

Aletta M.E. Millen

Keyword(s):

Cardiac Function ◽

Casein Hydrolysate ◽

Left Ventricular ◽

Doppler Imaging ◽

Energy Deficit ◽

Strenuous Exercise ◽

Lv Function ◽

Time Effects ◽

Systolic Volume ◽

End Systolic Volume

Cardiac function is often suppressed following prolonged strenuous exercise and this may occur partly because of an energy deficit. This study compared left ventricular (LV) function by 2-dimensional echocardiography and tissue Doppler imaging (TDI) before and after ∼2.5 h of cycling (2-h steady-state 60% peak aerobic power output plus 16 km time trial) in 8 male cyclists when they ingested either placebo, carbohydrate-only (CHO-only), carbohydrate-casein hydrolysate (CHO-casein), or carbohydrate-whey hydrolysate (CHO-whey). No treatment-by-time interactions occurred, but pre-to-postexercise time effects occurred selectively. Although diastolic function measured by pulsed-wave Doppler early-to-late (E/A) transmitral blood flow velocity was suppressed in all trials from pre- to postexercise (mean change post-pre exercise: −0.53 (95% CI −0.15 to −0.91)), TDI early-to-late (e′/a′) tissue velocity was significantly suppressed pre- to postexercise only with placebo, CHO-only, and CHO-whey (septal and lateral wall e′/a′ average change: −0.62 (95% CI −1.12 to −0.12); −0.69 (95% CI −1.19 to −0.20); and −0.79 (95% CI −1.28 to −0.29), respectively) but not with CHO-casein (−0.40 (95% CI −0.90 to 0.09)). LV contractility was, or tended to be, significantly reduced pre- to postexercise with placebo, CHO-only, and CHO-whey (systolic blood pressure/end systolic volume change, mm Hg·mL−1: −0.8 (95% CI −1.2 to −0.4), p = 0.0003; −0.5 (95% CI −0.9 to −0.02), p = 0.035; and −0.4 (95% CI −0.8 to 0.04), p = 0.086, respectively), but not with CHO-casein (−0.3 (95% CI −0.8 to 0.1), p = 0.22). However, ejection fraction (EF) and ventricular-arterial coupling were significantly reduced pre- to postexercise only with placebo (placebo change: EF, −4.6 (95% CI −8.4 to −0.7)%; stroke volume/end systolic volume, −0.3 (95% CI −0.6 to −0.04)). Despite no treatment-by-time interactions, pre-to-postexercise time effects observed with specific beverages may be meaningful for athletes. Tentatively, the order of beverages with least-to-most variables displaying a time effect indicating suppression of LV function following exercise was CHO-casein < CHO-only and CHO-whey < placebo, and calls for further verification.

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Impact of Syndecan-2-Selected Mesenchymal Stromal Cells on the Early Onset of Diabetic Cardiomyopathy in Diabetic db/db Mice

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.632728 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kathleen Pappritz ◽

Fengquan Dong ◽

Kapka Miteva ◽

Arpad Kovacs ◽

Muhammad El-Shafeey ◽

...

Keyword(s):

Experimental Model ◽

Mesenchymal Stromal Cells ◽

Diabetic Cardiomyopathy ◽

Stromal Cells ◽

Early Onset ◽

Left Ventricular ◽

Guanosine Monophosphate ◽

Lv Function ◽

Protein Distribution ◽

The Impact

Background: Mesenchymal stromal cells (MSCs) are an attractive cell type for cell therapy given their immunomodulatory, anti-fibrotic, and endothelial-protective features. The heparin sulfate proteoglycan, syndecan-2/CD362, has been identified as a functional marker for MSC isolation, allowing one to obtain a homogeneous cell product that meets regulatory requirements for clinical use. We previously assessed the impact of wild-type (WT), CD362−, and CD362+ MSCs on local changes in protein distribution in left ventricular (LV) tissue and on LV function in an experimental model of early-onset diabetic cardiomyopathy. The present study aimed to further explore their impact on mechanisms underlying diastolic dysfunction in this model.Materials: For this purpose, 1 × 106 WT, CD362−, or CD362+ MSCs were intravenously (i.v.) injected into 20-week-old diabetic BKS.Cg-m+/+Leprdb/BomTac, i.e., db/db mice. Control animals (db+/db) were injected with the equivalent volume of phosphate-buffered saline (PBS) alone. After 4 weeks, mice were sacrificed for further analysis.Results: Treatment with all three MSC populations had no impact on blood glucose levels in db/db mice. WT, CD362−, and CD362+ MSC application restored LV nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels in db/db mice, which correlated with a reduction in cardiomyocyte stiffness. Furthermore, all stromal cells were able to increase arteriole density in db/db mice. The effect of CD362+ MSCs on NO and cGMP levels, cardiomyocyte stiffness, and arteriole density was less pronounced than in mice treated with WT or CD362− MSCs. Analysis of collagen I and III protein expression revealed that fibrosis had not yet developed at this stage of experimental diabetic cardiomyopathy. All MSCs reduced the number of cardiac CD3+ and CD68+ cells in db/db mice, whereas only splenocytes from CD362−- and CD362+-db/db mice exhibited a lower pro-fibrotic potential compared to splenocytes from db/db mice.Conclusion: CD362+ MSC application decreased cardiomyocyte stiffness, increased myocardial NO and cGMP levels, and increased arteriole density, although to a lesser extent than WT and CD362− MSCs in an experimental model of early-onset diabetic cardiomyopathy without cardiac fibrosis. These findings suggest that the degree in improvement of cardiomyocyte stiffness following CD362+ MSC application was insufficient to improve diastolic function.

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Assessment of left ventricular mechanics in right ventricular overload using in silico rat models

European Heart Journal - Digital Health ◽

10.1093/ehjdh/ztab104.3074 ◽

2021 ◽

Vol 2 (4) ◽

Author(s):

H Martinez-Navarro ◽

E K S Espe ◽

O O Odeigah ◽

I Sjaastad ◽

J Sundnes

Keyword(s):

Cardiac Function ◽

Circumferential Strain ◽

Radial Strain ◽

Left Ventricular ◽

Public Institution ◽

Lv Function ◽

Passive Stiffness ◽

Ventricular Mechanics ◽

Longitudinal Strains ◽

Rv Function

Abstract Background To preserve cardiac function in overload conditions, the RV adapts by developing muscular hypertrophy through progressive tissue remodelling. This process may lead to a vicious cycle with detrimental effects on RV diastolic and systolic function, as seen in pulmonary arterial hypertension (PAH) patients [1]. However, how RV overload affects LV function and remodelling remains an open question [2]. Computational models of cardiac physiology offer an opportunity for investigating mechanisms difficult or impossible to analyse otherwise due to the existence of overlapping factors and technical limitations. Aim This study aims to assess the acute effects of RV overload and increased myocardial passive stiffness on the LV mechanical properties in an anatomically-based computational model of healthy rat heart. Methods A computational simulation pipeline of cardiac mechanics based on the Holzapfel-Ogden model has been implemented using MR images from a healthy rat. Whereas LV function was modelled realistically using catheter measurements conducted on the same subject than the MR imaging, RV function was based on representative literature values for healthy and PAH rats with RV overload. The following cases were defined (Fig. 1): CTRL, with normal RV function; PAH1, with 30% increase in RV ESV (end-systolic volume) and 15% increase in RV ESP (end-systolic pressure) in comparison to CTRL; and PAH2, with 60% increase in RV ESV and 30% increase in RV ESP compared to CTRL. The cardiac cycle was simulated for all cases whilst fitting the experimentally measured LV pressure and volume values from a healthy rat, which allowed quantifying the effects of RV overload on LV function. Results The increase of average circumferential strain in the LV correlated with the degree of RV overload simulated (CTRL: −8.7%, PAH1: −8.9%, PAH2: −9.2%), whilst average radial (CTRL: 35.2%, PAH1: 34.8%, PAH2: 30.3%) and longitudinal strains decreased (CTRL: −7.7%, PAH1: −7.4%, PAH2: −6.6%), as seen in Fig.2. However, regional differences in strain were significant: under RV overload conditions, circumferential strain increased in the septum (−3.5% difference in PAH2 vs. CTRL) but lower values were observed in the lateral wall (+1.7% difference in PAH2 vs. CTRL). Cardiac function of case PAH2 was simulated also with increased myocardial passive stiffness (2.67 kPa instead of 1.34 kPa) which presented a mild strain increase in the mid LV ventricle in comparison to PAH2 with normal stiffness (circumferential strain: −0.8%, radial strain: +0.5%, longitudinal strain: −0.2%). Conclusion Our study provides mechanistic evidence on how RV overload and increased passive myocardial stiffness causes a redistribution of strain and fibre stress in the LV, which may play a significant role in LV remodelling and function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): K.G. Jebsen Center for Cardiac Research Figure 1. Pressure – volume loops Figure 2. Mean mid-LV strains

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