Cardiovascular Imaging in Mice

Phoon, Colin K.L.; Turnbull, Daniel H.

doi:10.1002/9780470942390.mo150122

Cited by 24 publications

(17 citation statements)

References 113 publications

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“…Mouse models are an alternative, but it is challenging to create consistent MIs in mice; and their smaller size relative to rats pose additional difficulties for imaging studies (higher heart rates, much smaller size, etc.) [ 14 ]. To address these limitations, we investigated the specific conditions which could enable creation of a murine (rat) model of hemorrhagic MI.…”

Section: Introductionmentioning

confidence: 99%

Reperfused hemorrhagic myocardial infarction in rats

et al. 2020

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Background Intramyocardial hemorrhage following reperfusion is strongly associated with major adverse cardiovascular events in myocardial infarction (MI) patients; yet the mechanisms contributing to these outcomes are not well understood. Large animal models have been used to investigate intramyocardial hemorrhage, but they are exorbitantly expensive and difficult to use for mechanistic studies. In contrast, rat models are widely used to investigate mechanistic aspects of cardiovascular physiology, but a rat model that consistently recapitulates the characteristics of an hemorrhagic MI does not exist. To bridge this gap, we investigated the physiological conditions of MI that would create intramyocardial hemorrhage in rats so that a reliable model of hemorrhagic MI would become available for basic research. Methods & results Sprague-Dawley rats underwent either a 90-minute (90-min) ischemia and then reperfusion (I/R) (n = 22) or 30-minute (30-min) I/R (n = 18) of the left anterior descending coronary artery. Sham rats (n = 12) were used as controls. 90-min I/R consistently yielded hemorrhagic MI, while 30-min I/R consistently yielded non-hemorrhagic MI. Twenty-four hours post-reperfusion, ex-vivo late-gadolinium-enhancement (LGE) and T2* cardiac MRI performed on excised hearts from 90-min I/R rats revealed colocalization of iron deposits within the scarred tissue; however, in 30-min I/R rats scar was evident on LGE but no evidence of iron was found on T2* CMR. Histological studies verified tissue damage (H&E) detected on LGE and the presence of iron (Perl’s stain) observed on T2*-CMR. At week 4 post-reperfusion, gene and protein expression of proinflammatory markers (TNF-α, IL-1β and MMP-9) were increased in the 90-min I/R group when compared to 30-min I/R groups. Further, transmission electron microscopy performed on 90-min I/R myocardium that were positive for iron on T2* CMR and Perl’s stain showed accumulation of granular iron particles within the phagosomes. Conclusion Ischemic time prior to reperfusion is a critical factor in determining whether a MI is hemorrhagic or non-hemorrhagic in rats. Specifically, a period of 90-min of ischemia prior to reperfusion can produce rat models of hemorrhagic MI, while 30-minutes of ischemia prior to reperfusion can ensure that the MIs are non-hemorrhagic. Hemorrhagic MIs in rats result in marked increase in iron deposition, proinflammatory burden and adverse left—ventricular remodeling compared to rats with non-hemorrhagic MIs.

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Section: Introductionmentioning

confidence: 99%

Reperfused hemorrhagic myocardial infarction in rats

et al. 2020

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“…5,6 The majority of the immunized animals then develop a CD4+ cell-mediated experimental autoimmune myocarditis (EAM) peaking 21 days after the first immunization, despite no apparent clinical symptoms of heart failure. 11 Since echocardiographic parameters, such as LV systolic function, have been used as outcome parameters for interventional studies in EAM before, and previous studies reported diverging echocardiographic findings in this setting, we performed serial TTE examinations throughout the course of the disease to establish imaging standards and reference values for future examiners. 9,10 To improve the feasibility of the examination, TTE is frequently conducted under continuous anaesthesia (eg with isoflurane), which can affect haemodynamics and LV systolic function.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, close monitoring of the depth of anaesthesia is essential to obtain valid and reliable results. 11 Since echocardiographic parameters, such as LV systolic function, have been used as outcome parameters for interventional studies in EAM before, and previous studies reported diverging echocardiographic findings in this setting, we performed serial TTE examinations throughout the course of the disease to establish imaging standards and reference values for future examiners.…”

Section: Introductionmentioning

confidence: 99%

Autoimmune myocarditis is not associated with left ventricular systolic dysfunction

Mirna

Paar

Kraus

et al. 2019

Eur J Clin Investigation

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Background Experimental autoimmune myocarditis (EAM) is a common animal model for the investigation of the pathophysiology of myocarditis. Because of diverging findings from previous studies, we performed serial echocardiographic examinations throughout the course of the disease and investigated the dimensions of the murine heart and left ventricular (LV) systolic function. Materials and Methods Experimental autoimmune myocarditis was induced in male Balb/c mice by subcutaneous injection of a fragment of the α‐myosin heavy chain (MyHC‐α 614‐629: Ac‐SLKLMATLFSTYASAD). Transthoracic echocardiography was performed on days 0, 7 and 21 in healthy animals and mice with EAM. Results Experimental autoimmune myocarditis was associated with a reduction in LV systolic function and an increase in LV internal diameter in diastole (LVIDd) and systole (LVIDs) 7 days postimmunization. After 21 days, EAM led to a significant increase in LV‐thickness (1.3‐fold increase in LV anterior wall diameter in diastole [LVAWDd]), but there was no difference in LV systolic function between immunized animals and healthy controls. LV‐thickness correlated well with the severity of myocarditis in the histopathological examination (LVAWDd: rs = 0.603, P = 0.003, LV anterior wall diameter in systole (LVAWDs): rs = 0.718, P < 0.0001). Conclusion Our results indicate that EAM leads to an initial dilatation of the LV that is followed by ventricular “hypertrophy.” On day 21, there was no significant difference in LV systolic function between immunized animals and controls. Furthermore, the ageing of the animals had a major impact on the echocardiographic parameters; therefore, the use of healthy age‐matched controls seems warranted when echocardiography is performed in rodents.

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“…Additional reagents and equipment for assessing titer of bacteria (Elbing and Brent, 2002), isoflurane anesthesia of mice (Phoon and Turnbull, 2016), injection of mice (Donovan and Brown, 2006a), and euthanasia of mice by CO 2 asphyxiation (Donovan and Brown, 2006b) Preparation of mouse NTHi inoculum 1. Grow NTHi overnight at 37°C in a 5% CO 2 atmosphere on sBHI agar.…”

Section: Methodsmentioning

confidence: 99%

“…2. Anesthetize mice aged 8 weeks with isoflurane (Phoon and Turnbull, 2016) and inoculate intranasally by applying 10 µl of bacterial suspension to each nostril (10 8 cfu in 20-µl total volume; see Basic Protocol 1, step 5).…”

Section: Methodsmentioning

confidence: 99%

Non‐Typeable Haemophilus influenzae Infection of the Junbo Mouse

Cheeseman

Hood

2017

CP Mouse Biology

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Acute otitis media, inflammation of the middle ear bulla, is the most common bacterial infection in children. For one of the principal otopathogens, non-typeable Haemophilus influenzae (NTHi), animal models allow us to investigate host-microbial interactions relevant to the onset and progression of infection and to study treatment of middle ear disease. We have established a robust model of NTHi middle ear infection in the Junbo mouse. Intranasal inoculation with NTHi produces high rates of bulla infection and high bacterial titers in bulla fluids; bacteria can also spread down the respiratory tract to the mouse lung. An innate immune response is detected in the bulla of Junbo mice following NTHi infection, and bacteria are maintained in some ears at least up to day 56 post-inoculation. The Junbo/NTHi infection model facilitates studies on bacterial pathogenesis and antimicrobial intervention regimens and vaccines for better treatment and prevention of NTHi middle ear infection. © 2017 by John Wiley & Sons, Inc.

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Cardiovascular Imaging in Mice

Cited by 24 publications

References 113 publications

Reperfused hemorrhagic myocardial infarction in rats

Reperfused hemorrhagic myocardial infarction in rats

Autoimmune myocarditis is not associated with left ventricular systolic dysfunction

Non‐Typeable Haemophilus influenzae Infection of the Junbo Mouse

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