Doppler Assessment of Diastolic Function Reflect the Severity of Injury in Rats With Chronic Heart Failure

Sanchez, Pablo; Lancaster, Jordan J.; Weigand, Kyle; Mohran, Saffie; Goldman, Steven; Juneman, Elizabeth

doi:10.1016/j.cardfail.2017.08.446

Cited by 5 publications

(17 citation statements)

References 44 publications

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“…Healthy rats commonly showed fusion of the two diastolic waves unless the anesthesia protocol depressed the HR to lower than 300 bpm. By contrast, Sanchez et al (2017) recorded separation of E and A waves at HR over 300 bpm, even when using injection anesthesia. Therefore, both HR and anesthesia protocols play key roles in changing mitral inflow patterns (Stypmann et al, 2009).…”

Section: Discussionmentioning

confidence: 86%

Echocardiographic parameters in different age and sex of Sprague-Dawley rats under isoflurane anesthesia

Kitpipatkun

Sukwan

2021

VIS

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Echocardiography is a useful technique for diagnosing cardiovascular disease that is safe, reproducible and accurate. A comprehensive understanding of echocardiographic parameters in different age and sex is useful for cardiovascular study. Thirty Sprague-Dawley rats of both sexes at different age underwent repetitive echocardiography. The characteristics of early and late diastolic waves through the mitral inflow depend on the heart rate. The rats had fast heart rates, with early and late diastolic Doppler flows commonly fused. Several parameters in male rats were higher than in females except for ejection fraction, fractional shortening, isovolumetric relaxation time, pre-ejection fraction and ejection time that did not differ. Different age, sex, breed and anesthesia protocol can all cause diverse results. Rat echocardiography can be potentially used as a model for human cardiovascular research. Results revealed changes in echocardiographic parameters in different age and sex to better understand normal cardiovascular functions in rat model

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Section: Discussionmentioning

confidence: 86%

Echocardiographic parameters in different age and sex of Sprague-Dawley rats under isoflurane anesthesia

Kitpipatkun

Sukwan

2021

VIS

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“…The important findings of this study were that the TE patchtreated rats decreased LV-end diastolic pressure and the time constant of LV relaxation (Tau), increased anterior wall thickness in diastole, improved echocardiographic-derived indices of diastolic function E/e' [ratio of early peak flow velocity to early peak LV velocity] and e'/a' [ratio of early to late peak LV velocity]. The graft-treated rats have a pressure/volume filling curve shifted back towards SHAM and a lower LV enddiastolic operating volume, consistent with reversal of maladaptive remodeling related to compliance [16][17][18] [Figures 2-4].…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 84%

“…All rats remained in sinus rhythm with synchronized contraction through the patch area documented by transthoracic echocardiography. Transplanted hiPSC-CMs were observed at 7 days but not at 21 days after implantation; despite this LV function improved [16,18] . The patch increased gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction a-1 protein (connexin 43), β-myosin heavy chain 7, and insulin growth factor-1 expression in the infarcted heart after treatment [16] .…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 92%

“…Transplanted hiPSC-CMs were observed at 7 days but not at 21 days after implantation; despite this LV function improved [16,18] . The patch increased gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction a-1 protein (connexin 43), β-myosin heavy chain 7, and insulin growth factor-1 expression in the infarcted heart after treatment [16] . In more recent work, we have characterized the hiPSC-CMs in-vitro prior to implantation by defining their responses to adrenergic stimulation.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 92%

“…Our laboratory utilized the development of iPSCs by seeding hiPSC-CMs onto our fibroblast embedded patch. Thus, we had a human patch containing a "cell payload" that we could test in animal models of CHF and eventually use in patients [16] . Our work showed that the combination of fibroblasts and cardiomyocytes improved cardiac function in rats with CHF.…”

Section: Induced Pluripotent Stem Cellsmentioning

confidence: 99%

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Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial

Goldman¹,

Traverse²,

Zile³

et al. 2022

Vessel Plus

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This perspective focuses on the development of tissue engineered (TE) cell-based therapies to treat left ventricular (LV) dysfunction and chronic heart failure (CHF). The development of induced pluripotent stem cells enabled investigators to seed or co-culture human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) alone and in combination with other cells onto bioengineered scaffolds applied to the epicardial surface of the damaged left ventricle. Using our work as an example, we show how a xenograft implant of a bioengineered scaffold embedded with human neonatal fibroblasts and seeded with hiPSC-CMs partially reversed maladaptive LV remodeling and improved LV systolic/diastolic function in an immune-competent rat model of CHF. The fibroblasts lay down an extracellular matrix and secrete growth factors that increase myocardial blood flow. This approach provides an improved cell payload that covers a larger area of the damaged left ventricle as opposed to direct cell injections into the heart or down the coronary arteries. These studies combined with ongoing studies in immune-competent Yucatan mini swine treated with the same xenograft led to the preliminary design of a proposed Phase I clinical trial that will be presented to the Federal Drug Administration. For the proposed Phase I clinical, this TE patch will be implanted onto the epicardial surface of non-immunosuppressed patients undergoing elective Coronary Artery Bypass Grafting with Ejection Fractions ≥ 20% and ≤ 45%. The primary endpoints will be adverse events/severe adverse events associated with placing the TE patch on the heart. While Phase I trials are primarily safety trials, this proposed trial is designed to obtain some potential efficacy endpoints to help with the design of future Phase II/III clinical trials. These endpoints include changes in LV remodeling that were seen in the pre-clinical animal models as well as including endpoints that focus on patient well-being.

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Cardiovascular Research

et al. 2020

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Objectives: To examine the role of TNF alpha (TNFc~) in cardiac transplant rejection by simultaneous analysis of protein expression and its messenger RNA within serum and grafted tissue. Methods: 54 endomyocardial biopsy specimens were taken from 19 patients at various times after transplantation. TNFa messenger RNA was localised using a digoxygenin labelled complementary DNA probe. An anti-TNFa antibody was used to immunohistochemically label the protein product. Serum TNFc~ levels at the time of biopsy were analysed using a specific enzyme-linked immunosorbent assay. Results: TNFa mRNA was present in 22/34 endomyocardial biopsies. Eight also contained TNFc~ protein. None had protein alone. Expression did not relate to the grade of rejection in the present or subsequent biopsies. Serum TNFc~ was undetectable (assay sensitivity 30-330 pg/ml) for the majority of specimens. In the nine cases with elevated serum levels, eight samples were from cases within the first 30 days post transplant (r =-0.379; P < 0.05). Conclusions: Neither tissue TNFa mRNA, tissue protein, nor serum TNFc~ relate to the grade of rejection. Furthermore, TNFc~ expression within endomyocardial biopsies is not reflected in the serum. These findings argue against the use of serum analysis as an indicator of cytokine profiles within cardiac tissue allografts. The demonstration of a trend in the early expression of TNFct after transplantation suggests that its release may not be specific to the process of rejection.

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Doppler Assessment of Diastolic Function Reflect the Severity of Injury in Rats With Chronic Heart Failure

Cited by 5 publications

References 44 publications

Echocardiographic parameters in different age and sex of Sprague-Dawley rats under isoflurane anesthesia

Echocardiographic parameters in different age and sex of Sprague-Dawley rats under isoflurane anesthesia

Perspective on the development of a bioengineered patch to treat heart failure: rationale and proposed design of phase I clinical trial

Cardiovascular Research

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