Using MRI to predict future adverse cardiac remodelling in a male mouse model of myocardial infarction

Abstract

BackgroundMice are frequently used in research to examine outcomes of myocardial infarction (MI) and to investigate therapeutic interventions at an early pre-clinical stage. The MI model is generated by surgically occluding a major coronary artery, but natural variation in murine coronary anatomy can generate variable outcomes that will inevitably affect the accuracy of such investigations. The aim of this study was to use MRI to derive the most sensitive early variable that could be used to predict subsequent adverse cardiac remodelling in a male mouse model of MI.MethodsUsing a longitudinal study design, heart structure and function were evaluated using cardiac MRI at one week following surgical MI to generate the early measurements and again at four weeks, when the scar had matured. The primary variables measured at week one were left ventricular volumes at end systole (LV-ESV) and at end diastole (LV-EDV), infarct size, LV-cardiac mass, and ejection fraction (EF).ResultsUnivariate and multiple regression analyses showed that LV-ESV at one week following MI could be used to accurately predict various parameters of adverse LV remodelling at four weeks post-MI. However, the highest correlation was between LV-ESV at one week following MI and LV-EDV at four weeks (r = 0.99; p < 0.0001), making LV-ESV at one week a valuable predictor variable of future adverse ventricular remodelling after MI.ConclusionUsing MRI to determine LV-ESV at an early stage following MI enables a more robust analysis of potential therapeutic interventions to ameliorate adverse cardiac remodelling.

Exogenous TGFβ1 and its mimic HpTGM attenuate the heart’s inflammatory response to ischaemic injury and improve long term cardiac outcomes

“…Masson's trichrome staining discriminates viable muscle from collagenous scar and was used to measure mature scar size at 4 weeks post infarction. This intramural scar contrasts with the transmural scars that result from permanent LAD occlusion used in many other mouse studies in the literature, including our own 32 . The mean scar size is significantly reduced by 21% in the TGFβ1 treated mice compared with untreated mice (p=0.015; Figure 4B).…”

Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis

“…Thus increased angiogenesis alone is insufficient to improve cardiac function in a large permanent infarct, where almost all the left ventricular free wall is affected and ultimately replaced by scar tissue. In this study great care was taken to minimize variation in infarct size, due to its major impact on outcomes ( Redgrave et al., 2016 ). Furthermore, cardiac MRI was used to provide a robust readout of cardiac function, and investigators were blinded to treatments during the analysis.…”

“…Acute MI was created in adult male C57BL/6 mice (12–14 weeks) as previously described ( Redgrave et al., 2016 , van Laake et al., 2007 ). Mice were pre-medicated with fentanyl/fluanisone (Hypnorm; 0.4 mL/kg) to provide intraoperative analgesia and anesthetized using isoflurane.…”

“…Cardiac function was monitored after 7 and 28 days using MRI as previously described ( Redgrave et al., 2016 , Schneider et al., 2006 ). A horizontal bore 7.0T Varian system (Varian) equipped with a 12-cm microimaging gradient insert (40 gauss/cm) was used to acquire MR images.…”

Long-term pulmonary and cardiovascular morbidities of neonatal hyperoxia exposure in mice

“…The volume size of the space was calculated by using the known volume size of each pixel. The RV mass was determined as described previously (Redgrave et al, 2016; Urboniene et al, 2010). The observer performing the studies and measurements was masked to the experimental conditions.…”