Contractile force of transplanted cardiomyocytes contributes to heart function after injury

Transplantation of pluripotent stem cell-derived cardiomyocytes represents an innovative therapeutic strategy for heart failure. Studies in small and large animals have demonstrated functional recovery of left ventricular function after cardiomyocyte transplantation, and first clinical studies are currently underway. Yet, the mechanism of action underlying graft-induced benefit is unknown. Here we demonstrate that transplanted cardiomyocytes actively contribute to heart function. We transplanted cardiomyocytes with an optogenetic off-on switch in a guinea pig cardiac injury model. Light-induced inhibition of engrafted cardiomyocyte contractility resulted in a rapid decrease of left ventricular function that was fully reversible with the offset of photostimulation. Hence, our optogenetic approach demonstrated that transplanted cardiomyocytes actively participate in heart function, supporting the hypothesis that the delivery of new force-generating myocardium can serve as a regenerative therapeutic strategy.

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Additional lack of iNOS attenuates diastolic dysfunction in aged ET-1 transgenic miceThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-032 ◽

2008 ◽

Vol 86 (6) ◽

pp. 353-357 ◽

Cited By ~ 4

Author(s):

Philipp Kalk ◽

Dirk Westermann ◽

Sophia Herzfeld ◽

Katharina Relle ◽

Thiemo Pfab ◽

...

Keyword(s):

Transgenic Mice ◽

Left Ventricular Function ◽

Diastolic Dysfunction ◽

Ventricular Function ◽

Cardiac Injury ◽

Systolic Heart Failure ◽

Group Versus ◽

Study Groups ◽

Left Ventricular ◽

Dependent Manner

Endothelin-1 (ET-1) exhibits potent proinflammatory and profibrotic properties. Moreover, inflammation is a potent stimulus for inducible NO synthase (iNOS), which has been shown to contribute to cardiac injury. We thus hypothesized that ET-1-induced cardiac injury is attenuated by concomitant lack of iNOS. We established crossbred animals of ET-1 transgenic mice (ET+/+) and iNOS knockout mice (iNOS−/−). At 13 months of age, mice were allocated according to their genotype to one of 4 study groups: wild type (WT) controls (n = 8); ET-1 transgenic (ET+/+) mice (n = 10); iNOS knockout (iNOS−/−) mice (n = 7); and crossbred (ET+/+ iNOS−/−) mice (n = 15). Left ventricular function was determined in vivo by using a tip catheter. Animals were subsequently euthanized and hearts were harvested for weight assessment and histologic evaluation. No cardiac hypertrophy was present, as evidenced by similar mean cardiac weight and myocyte diameter in all groups. Cardiac perivascular fibrosis was significantly increased in ET+/+ and iNOS−/− groups versus WT, whereas ET+/+ iNOS−/− mice did not differ from WT. Regarding left ventricular function, plasma B-type natriuretic peptide was elevated in ET+/+ and iNOS−/− mice, but again in crossbred animals this effect was blunted. Heart catheterization revealed a significantly increased stiffness constant in both ET-overexpressing groups versus WT, but this increase was significantly attenuated in the ET+/+iNOS−/− group versus the ET+/+ group. Parameters indicating systolic heart failure (EF, cardiac output), however, were not different between all study groups. Our study demonstrates that ET transgenic mice develop left ventricular stiffening with subsequent diastolic dysfunction in a slow, age-dependent manner. Additional knock out of iNOS significantly attenuates cardiac injury. We thus conclude that ET-1-induced cardiac injury is at least partially mediated by iNOS.

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Evaluation of heart function. Evaluation of left ventricular function using echocardiography.

THE JOURNAL OF JAPAN SOCIETY FOR CLINICAL ANESTHESIA ◽

10.2199/jjsca.7.174 ◽

1987 ◽

Vol 7 (2) ◽

pp. 174-185

Author(s):

HARUYUKI KASUDA

Keyword(s):

Left Ventricular Function ◽

Ventricular Function ◽

Heart Function ◽

Left Ventricular ◽

Function Evaluation

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Abstract 696: Cardiosphere-derived Cells Engraft Long-term in Infarcted Mice and Preserve Left Ventricular Function

Circulation ◽

10.1161/circ.116.suppl_16.ii_130 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Rachel R Smith ◽

Michelle K Leppo ◽

Isotta Chimenti ◽

John Terrovitis ◽

Andreas S Barth ◽

...

Keyword(s):

Left Ventricular Function ◽

Ventricular Function ◽

Cardiac Troponin ◽

Troponin I ◽

Heart Function ◽

Single Cells ◽

Left Ventricular ◽

Cardiac Troponin I ◽

Border Zone

Cardiosphere-derived cells (CDCs) were grown from rat hearts and percutaneous endomyocardial adult human biopsy specimens. Rat CDCs plated as single cells formed clones with a doubling time of 42.2 ± 0.7 hours (n = 9). Clones from rat CDCs divided steadily for 27 days before proliferation spontaneously slowed and morphological changes occurred in most cells. After 56 days, rat clonal populations contained a small fraction of c-Kit + cells as determined by flow cytometry, and large subsets of cells expressing cardiac troponin I, α-smooth muscle actin, and von Willebrand factor as determined by immunofluorescence, indicative of their multipotentiality in vitro . To assess therapeutic potential, acute myocardial infarcts (MIs) were created in immunodeficient mice and actively proliferating polyclonal human CDCs were injected into the border zone. Echocardiographic left ventricular function, histological examination, and immunofluorescence served as endpoints. CDC-injected animals showed no significant deterioration in ejection fraction (EF) from 2 days (EF = 45.2 ± 4.8%) to 6 weeks post-MI (EF = 40.2 ± 4.5%, n = 7, p = NS), in contrast to fibroblast-injected control animals (EF = 42.8 ± 4.3% at 2 days vs 27.3 ± 4.0% at 6 weeks, p < 0.01). At the 6 week endpoint, the CDC group had thicker infarct walls as measured histologically compared to the fibroblast group (0.26 ± 0.03mm vs 0.12 ± 0.01mm, n = 5, p < 0.01). CDC engraftment was determined by immunofluorescence using a human-specific antibody. CDCs stably engrafted for up to 6 weeks and could be found distributed primarily throughout the infarct (57 ± 3% of engrafted CDCs, n = 5 animals), as well as the border zone (30 ± 5%) and viable tissue (13 ± 3%). After 6 weeks, CDCs within the infarct had formed small myocytes with little cytoplasmic cardiac troponin I, while CDCs within the viable myocardium had formed large myocytes with well-defined sarcomeric organization. We conclude that CDCs are clonogenic and spontaneously multipotent in vitro and capable of preserving heart function in a mouse infarct model. Functional preservation is presumably due in part to maintenance of infarct wall thickness, likely secondary to stable CDC engraftment within the infarct, as well as the formation of morphologically mature myocytes throughout the non-infarcted tissue.

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Rapid decline in cardiac function in diabetic patients with calcified coronary artery disease undergoing hemodialysis: two case reports

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02076-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hironobu Yamaoka ◽

Taira Yamamoto ◽

Daisuke Endo ◽

Akie Shimada ◽

Satoshi Matsushita ◽

...

Keyword(s):

Coronary Artery ◽

Left Ventricular Function ◽

Ventricular Function ◽

Risk Score ◽

Heart Function ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Diabetic Patients ◽

Ventricular Ejection Fraction ◽

Left Circumflex Artery

Abstract Background Clinical symptoms of patients on dialysis do not match the signs of coronary disease progression, making the prediction of the true progression of their medical condition in clinical settings difficult. Emergency and concomitant surgeries are significant risk factors of mortality following open-heart surgery in patients on hemodialysis. Case presentation We report two cases of successful coronary artery bypass grafting (CABG) in patients on dialysis with a history of cardiac surgery. The first case describes a 65-year-old woman who had undergone aortic valve replacement 2 years ago and was hospitalized urgently, because of a sudden decline in heart function and hypotension. She had moderate mitral regurgitation with right ventricular pressure of 66 mmHg and poor left ventricular function [left ventricular ejection fraction (LVEF), 40%]. Cineangiography revealed an increase in the rate of stenosis in the left main trunk, from 25 to 99% at admission, in addition to 100% occlusion in proximal left anterior descending artery (LAD) and 99% stenosis in the proximal left circumflex artery (LCX). We inserted an intra-aortic balloon pump preoperatively and performed emergency surgery (Euro II risk score, 61.7%; Society of Thoracic Surgeons (STS) risk score, 56.3%). The second case described a 78-year-old man who had undergone surgery for left atrial myxoma 4 years ago and was hospitalized urgently due to dyspnea, chest discomfort, and an LVEF of 44% (Euro II risk score, 40.7%; STS risk score, 33.2%). Cineangiography revealed an increase in the rate of stenosis in the proximal LAD, from 25% (4 years ago) to 90% at admission, in addition to 99% stenosis in proximal LCX and 95% stenosis in the posterolateral branch of LCX. Both patients underwent emergency CABG due to unstable hemodynamics and decreased left ventricular function despite regular dialysis. The surgeries were successful, and the patients were discharged without any complications. Conclusions In patients with multiple comorbidities and those who undergo dialysis treatment, calcified lesions in coronary arteries can progress severely and rapidly without any symptoms, including chest pain. Close outpatient management involving nephrologists and the cardiovascular team is necessary for patients on dialysis.

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Heart failure in pregnancy: what is the long-term impact of pregnancy on cardiac function? A tertiary care centre experience and systematic review

Open Heart ◽

10.1136/openhrt-2021-001587 ◽

2021 ◽

Vol 8 (2) ◽

pp. e001587

Author(s):

Anudeep K Dodeja ◽

Francesca Siegel ◽

Katherine Dodd ◽

Marwan Ma'ayeh ◽

Laxmi S Mehta ◽

...

Keyword(s):

Heart Failure ◽

Left Ventricular Function ◽

Ventricular Function ◽

Heart Function ◽

Tertiary Care ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Major Adverse Cardiovascular Events ◽

Ventricular Ejection Fraction ◽

The Impact

BackgroundWomen with cardiomyopathy (CM) are often advised against pregnancy due to risk for major adverse cardiovascular events (MACE). However, the impact of CM subtype on maternal MACE is not understood, and so we sought to evaluate the influence of CM phenotype on maternal outcomes, as well as the effect on immediate and late left ventricular function.MethodsWe evaluated all pregnant women in our high-risk maternal cardiovascular programme (2009–2019). Composite maternal MACE included: death, inotrope use, left ventricular assist device, orthotopic heart transplant and/or escalation in transplant listing status, acute decompensated heart failure and sustained ventricular arrhythmia.ResultsAmong 875 women followed, 32 had CM (29±7 years old, left ventricular ejection fraction (LVEF) 41%±12%): 3 ischaemic CM (ICM), 10 peripartum CM (PPCM) and 19 non-ICM (NICM). MACE events occurred in 6 (18%) women (PPCM: 2 (33%), NICM: 4 (67%)). There was no difference in LVEF at baseline, however, women with MACE had significantly lower LVEF both early (LVEF: 27±5% vs . 41±2%, p<0.05) and late post partum (LVEF: 28±5% vs . 44±2%, p<0.01).ConclusionsIn this contemporary cohort of women with CM, maternal MACE rates were lower than previously reported, and were less common in PPCM as compared with ICM and NICM. Heart function in women with MACE was negatively impacted immediately after delivery and in late postpartum follow-up, suggesting that pregnancy itself likely has influence on future left ventricular function in women with underlying CM.

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