The role of 1.5 tesla MRI and anesthetic regimen concerning cardiac analysis in mice with cardiomyopathy.

Ulrich Grabmaier,Wolfgang-M Franz,Karin Klingel,Lisa Gross,Hans D Theiss,Bruno Huber,Stefan Brunner,Christine Von Der Helm,Alexandra Keithahn,Christoph Brenner,Julia Kreiner

doi:10.1371/journal.pone.0094615

Abstract

Accurate assessment of left ventricular function in rodent models is essential for the evaluation of new therapeutic approaches for cardiac diseases. In our study, we provide new insights regarding the role of a 1.5 Tesla (T) magnetic resonance imaging (MRI) device and different anesthetic regimens on data validity. As dedicated small animal MRI and echocardiographic devices are not broadly available, we evaluated whether monitoring cardiac function in small rodents with a clinical 1.5 T MRI device is feasible. On a clinical electrocardiogram (ECG) synchronized 1.5 T MRI scanner we therefore studied cardiac function parameters of mice with chronic virus-induced cardiomyopathy. Thus, reduced left ventricular ejection fraction (LVEF) could be verified compared to healthy controls. However, our results showed a high variability. First, anesthesia with medetomidine, midazolam and fentanyl (MMF) led to depressed cardiac function parameters and more variability than isoflurane gas inhalation anesthesia, especially at high concentrations. Furthermore, calculation of an average ejection fraction value from sequenced scans significantly reduced the variance of the results. To sum up, we introduce the clinical 1.5 T MRI device as a new tool for effective analysis of left ventricular function in mice with cardiomyopathy. Besides, we suggest isoflurane gas inhalation anesthesia at high concentrations for variance reduction and recommend calculation of an average ejection fraction value from multiple sequenced MRI scans to provide valid data and a solid basis for further clinical testing.

Highlights

Myocarditis is an inflammatory disease of the heart which is frequently caused by viral pathogens
Evaluation of cardiac function using a clinical 1.5 T magnetic resonance imaging (MRI) device. In this model of cardiomyopathy, cardiac function of 22 CVB3infected mice was assessed using cine MRI and results were matched with up to 7 healthy controls in order to evaluate the grade of systolic impairment
left ventricular ejection fraction (LVEF) was significantly reduced by 11% in coxsackievirus B3 infected mice compared to healthy controls

Summary

Introduction

Myocarditis is an inflammatory disease of the heart which is frequently caused by viral pathogens. Viral infection of the heart can trigger ongoing myocardial inflammation subsequently leading to dilative cardiomyopathy and congestive heart failure [2] In these patients, optimized medication often represents the only therapeutic option, though frequent progression to end stage heart failure and death cannot be avoided [2,3,4]. Since left ventricular ejection fraction (LVEF) strongly predicts cardiovascular morbidity and mortality, it is often used for monitoring therapeutic success [5,6,7,8] Several techniques, such as pressure-volume loops [9], echocardiography [10] or dedicated small animal MRI scanners [11] have been implemented for evaluation of left ventricular function in mice. 1.5 Tesla MRI scanners have not been used routinely for cardiac function monitoring in murine models of dilative cardiomyopathy (DCM) so far

Methods

Results

Conclusion