Published: February 13th, 2021
Left ventricular dysfunction constitutes the final common pathway for a host of cardiac disorders. We here provide a detailed protocol of transthoracic dobutamine stress echocardiography approach for comprehensive evaluation of the left ventricular function of mouse models of cardiac disease as well as cardiac phenotyping.
Left ventricular (LV) dysfunction paves the final pathway for a multitude of cardiac disorders. With the non-invasive high-frequency transthoracic dobutamine stress echocardiography in humans, a reductionist investigation approach to unmask subtle changes in cardiac function has become possible. Here, we provide a protocol for using this technique in mice to facilitate expanded analysis of LV architecture and function in physiology and pathology enabling the observation of alterations in models of cardiac disease hidden in unstressed hearts. This investigation can be performed in one and the same animal and allows both, basal and pharmacologically stress-induced measurements. We outline detailed criteria for appropriate anesthesia, imaging-based LV analysis, consideration of intra- and interobserver variability, and obtaining positive inotrope response that can be attained in mice after intraperitoneal injection of dobutamine under near physiological conditions. To recapitulate the characteristics of human physiology and disease in small animal models, we highlight critical pitfalls in evaluation, e.g., a pronounced Bowditch effect in mice. To further meet translational objectives, we compare stress-induced effects in humans and mice. When used in translational studies, attention must be paid to physiological differences between mice and human. Experimental rigor dictates that some parameters assessed in patients can only be used with caution due to restrictions in spatial and temporal resolution in mouse models.
The hallmark of many cardiac diseases in human is a systolic and/or diastolic functional impairment of the left ventricle (LV). For the detection of structural abnormalities, the diagnosis, and the management of systolic heart failure as well as the evaluation of diastolic function in patients with symptoms of heart failure, echocardiography is used as a fundamental assessment modality.
Since the symptoms are unspecific and more than one third of patients with the clinical syndrome of heart failure may not suffer from the actual heart failure, it is important to find an objective echocardiographic correlate for the pat....
All methods and procedures were performed in accordance and compliance with all relevant regulations ('European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes' (Directive 2010/63/EU) and animal care was in accordance with institutional guidelines. Data from human subjects were analyzed in compliance with all institutional, national, and international guidelines for human welfare and was approved by the Local Ethics Committee (20-9218-BO). All experiments ha.......
A physiological unstressed echocardiographic image acquired in PSLAX is shown in Figure 3. In diastole, the ventricle walls appear uniformly (Figure 3A) and thicken to a certain degree (Figure 3B,C). The injection of 5 µg/g body weight dobutamine i.p. leads to a significant increase of the heart rate (positive chronotropic effect)12 and the LVEF (positive.......
Stress-induced evaluation of the cardiac function is widely used in humans in a clinical setting using exercise testing or pharmacological stress testing6,7. Because immediate post-exercise echocardiography of mice is very limited due to the need for sedation, dobutamine-induced stress echocardiography is likely to be the most translational method to assess stress-induced cardiac physiopathology. Reliable information on cardiac function can be obtained using real.......
The authors acknowledge the following funding sources: German Research Foundation (UMEA Junior Clinician Scientist, Stephan Settelmeier; RA 969/12-1, Tienush Rassaf; HE 6317/2-1, Ulrike Hendgen-Cotta), Else-Kroener-Fresenius-Stiftung (2014_A216, Tienush Rassaf).....
|Activated Charcoal Filter
|Aquasonic 100 Ultrasound Transmission Gel
|Chemical Hair removal lotion
|Flowmeter for laboratory animal anesthesia
|Gas Exhaust Unit
|Medical Sharps Container
|MX400 ultrasound transducer (20-46 Mhz)
|Omnican F syringe with needle 1ml
|Signacreme Electrode Cream
|Standard Gauze Pads
|Thermasonic Gel Warmer
|Vaporizer Sigma Delta
|Vevo 3100 high-frequency preclinical ultrasound imaging system
|https://www.visualsonics.com/product/imaging-systems/vevo-3100 * required software package: Cardiovascular package; B-mode, M-mode, pulsed-wave doppler mode
|Vevo Imaging Station with integrated rail system, heated platform and physiological monitoring unit
|VevoLab Analysis Software
|https://www.visualsonics.com/product/software/vevo-lab *required software package: Vevo Strain, LV analysis
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