Surgical and physiological challenges in the development of left and right heart failure in rat models

Katz, Michael G.; Fargnoli, Anthony S.; Gubara, Sarah M.; Chepurko, Elena; Bridges, Charles R.; Hajjar, Roger J.

doi:10.1007/s10741-019-09783-4

Cited by 16 publications

(10 citation statements)

References 141 publications

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“…Right heart catheterization four weeks after PAH creation in rats demonstrated increase in the mean PA pressure to 30.4±2.13 mmHg from 10.4±1.65 mmHg, which was consistent with de nition of PAH in humans and in our previous rodents study [24,25]. Also, at this time point, we documented a signi cant increase in PVR (6.13±0.46 mm Hg, as compared with sham subjects displaying 2.78±0.044 mm Hg, p< 0.0001.…”

Section: Acid Ceramidase Gene Therapy Improved Cardio-pulmonary Hemod...supporting

confidence: 89%

Acid Ceramidase Gene Therapy Ameliorates Pulmonary Arterial Hypertension with Right Heart Dysfunction

Katz

Hadas

Vincek

et al. 2022

Preprint

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BackgroundUp-regulation of ceramides in pulmonary arterial hypertension (PAH), contributing to perturbations in sphingolipid homeostasis and the transition of cells to a senescence state. We assessed the safety, feasibility, and efficiency of acid ceramidase gene transfer in a rodent PAH model.MethodsA model of PAH was created by the combination of pneumonectomy and injection of Sugen toxin. Magnetic resonance imaging and right heart catheterization confirmed development of PAH. Animals were subjected to intratracheal administration of synthetic adeno-associated viral vector (Anc80L65) carrying the acid ceramidase (Anc80L65.AC), an empty capsid vector, or saline. Therapeutic efficacy was evaluated 8 weeks after gene delivery.ResultsHemodynamic assessment four weeks after PAH model creation demonstrated an increase in the mean pulmonary artery pressure to 30.4 ± 2.13 mmHg versus 10.4 ± 1.65 mmHg in sham (p < 0.001), which was consistent with the definition of PAH. We documented a significant increase in pulmonary vascular resistance in the saline-treated (6.79 ± 0.85 mm Hg) and empty capsid (6.94 ± 0.47 mm Hg) groups, but not in animals receiving Anc80L65.AC (4.44 ± 0.71 mm Hg, p < 0.001). Morphometric analysis demonstrated an increase in medial wall thickness in control groups in comparison to those treated with acid ceramidase. After acid ceramidase gene delivery, a significant decrease of pro-inflammatory factors, interleukins, and senescence markers was observed.ConclusionGene delivery of acid ceramidase provided tropism to pulmonary tissue and ameliorated vascular remodeling with right ventricular dysfunction in pulmonary arterial hypertension.

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Section: Acid Ceramidase Gene Therapy Improved Cardio-pulmonary Hemod...supporting

confidence: 89%

Acid Ceramidase Gene Therapy Ameliorates Pulmonary Arterial Hypertension with Right Heart Dysfunction

Katz

Hadas

Vincek

et al. 2022

Preprint

Self Cite

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“…The Frank–Starling mechanism is responsible for maintaining a high output status in the early stages following the development of the AV shunt. This variable represents an abrupt increase in wall stress caused by volume overload, whereas changes in LV end-diastolic pressure indicate that the development of cardiac hypertrophy and dilation of the cardiac chamber tend to regulate wall stress ( 6 ).…”

Section: Surgical Modelsmentioning

confidence: 99%

“…In compensated AR, the LV first responds to volume overload by eccentric hypertrophy, preserving LV diastolic compliance and allowing LV filling pressures to stay normal or mildly elevated despite a substantial regurgitation volume. Decompensated AR is defined as LV systolic dysfunction and poor LV diastolic compliance as a result of hypertrophy and fibrosis, resulting in excessive filling pressures and HF ( 6 , 134 ).…”

Section: Surgical Modelsmentioning

confidence: 99%

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A review on experimental surgical models and anesthetic protocols of heart failure in rats

et al. 2023

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Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative treatments. The development of novel HF treatments requires the testing of potential therapeutic procedures in appropriate animal models of HF. During the past decades, murine models have been extensively used in fundamental and translational research studies to better understand the pathophysiological mechanisms of HF and develop more effective methods to prevent and control congestive HF. Proper surgical approaches and anesthetic protocols are the first steps in creating these models, and each successful approach requires a proper anesthetic protocol that maintains good recovery and high survival rates after surgery. However, each protocol may have shortcomings that limit the study's outcomes. In addition, the ethical regulations of animal welfare in certain countries prohibit the use of specific anesthetic agents, which are widely used to establish animal models. This review summarizes the most common and recent surgical models of HF and the anesthetic protocols used in rat models. We will highlight the surgical approach of each model, the use of anesthesia, and the limitations of the model in the study of the pathophysiology and therapeutic basis of common cardiovascular diseases.

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“…Cardiac fibrosis is a typical phenomenon that occurs during cardiac muscle remodeling due to various heart diseases such as myocardial infarction (MI) and cardiac hypertrophy. Many experimental mouse models, such as permanent or temporary coronary occlusion, are commonly used in the field of cardiovascular research to increase cardiac fibrosis in the myocardium 12. In these models, myocardial remodeling occurs as MI progresses.…”

Section: Introductionmentioning

confidence: 99%

Effects of Fimasartan/Amlodipine Fixed-Dose Combination on Left Ventricular Systolic Function and Infarct Size in Rat Myocardial Infarction Model

et al. 2019

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The aim of this study was to evaluate the effects of fimasartan/amlodipine fixed-dosed combination (F/A) on left ventricle (LV) systolic function and infarct size in the rat myocardial infarction (MI) model. We induced MI in 20 rats by ligation of the left anterior descending coronary artery and they were divided into two groups [MI group (n=10) vs. MI+F/A 10 mg/kg group (n=10)]. F/A was administered for 28 days between day-7 and day-35 in the MI+F/A group and echocardiography was performed at day-7 and at day-35 after the induction of MI. Picrosirius red staining was performed to confirm the fibrotic tissue and infarct size was measured using image analysis program for Image J. At the 35-day follow-up, the LV ejection fraction (EF) was significantly higher (38.10±3.92% vs. 29.86±4.56%, p<0.001) and delta (day-35 minus day-7) EF was significantly higher (0.14±2.66% vs. −8.53±2.66%. p<0.001) in the MI+F/A group than the MI group. Systolic blood pressure was significantly lower in the MI+F/A group than the MI group (103.23±13.35 mmHg vs. 123.43±14.82 mmHg, p<0.01). The MI+F/A group had a smaller infarct size (26.84±5.31% vs. 36.79±3.10%, p<0.01) than the MI group at the 35-day follow-up. Oral administration of F/A 10 mg/kg could improve LV systolic function and reduce infarct size in a rat MI model.

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Surgical and physiological challenges in the development of left and right heart failure in rat models

Cited by 16 publications

References 141 publications

Acid Ceramidase Gene Therapy Ameliorates Pulmonary Arterial Hypertension with Right Heart Dysfunction

Acid Ceramidase Gene Therapy Ameliorates Pulmonary Arterial Hypertension with Right Heart Dysfunction

A review on experimental surgical models and anesthetic protocols of heart failure in rats

Effects of Fimasartan/Amlodipine Fixed-Dose Combination on Left Ventricular Systolic Function and Infarct Size in Rat Myocardial Infarction Model

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