Evaluation of Left Ventricle Function by Regional Fractional Area Change (RFAC) in a Mouse Model of Myocardial Infarction Secondary to Valsartan Treatment.
OBJECTIVE
Left ventricle (LV) regional fractional area change (RFAC) measured by cardiac magnetic resonance (CMR) allows the non-invasive localization and quantification of the degree of myocardial infarction (MI), and could be applied to assess the effectiveness of pharmacological or regenerative therapies. Here we investigate the ability of RFAC to identify regional dysfunction and discriminate the effect of pharmacological treatment with valsartan, a selective antagonist of angiotensin II type 1 receptor, in a model of MI.


RESULTS
C57BL/6N mice, undergoing coronary artery ligation, were divided into two groups: untreated (MI) or treated with valsartan (MI+Val). Sham-operated mice were used as a control. Cardiac dimensions and function were assessed at baseline, 24 hours, 1 and 4 weeks post surgery by CMR and echocardiography. At sacrifice histology and whole-genome gene expression profiling were performed. RFAC was able to detect significant differences between treatment groups whereas the global ejection fraction was not. RFAC showed greater loss of regional contraction in remote non-infarcted myocardium in MI group than in MI+Val group. Consistently, in the same region MI+Val mice showed reduced myocyte hypertrophy, fibroblast proliferation, and fibrosis and modulation of target genes; in addition, left atrium volumes, appendage length and duct contraction were preserved.


CONCLUSIONS
In this study, RFAC effectively estimated the degree of systolic dysfunction and discriminated the regions preserved by pharmacological treatment. RFAC index is a promising tool to monitor changes in LV contraction and to assess the effectiveness of therapeutic regimens in clinical settings.
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Laura
L
Castiglioni
Centro Cardiologico Monzino IRCCS, Milan, Italy.
Francesca
F
Colazzo
Centro Cardiologico Monzino IRCCS, Milan, Italy.
Lucia
L
Fontana
Centro Cardiologico Monzino IRCCS, Milan, Italy.
Gualtiero I
GI
Colombo
Centro Cardiologico Monzino IRCCS, Milan, Italy.
Luca
L
Piacentini
Centro Cardiologico Monzino IRCCS, Milan, Italy.
Elisa
E
Bono
Centro Cardiologico Monzino IRCCS, Milan, Italy.
Giuseppina
G
Milano
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Serena
S
Paleari
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Annamaria
A
Palermo
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Uliano
U
Guerrini
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Centro Cardiologico Monzino IRCCS, Milan, Italy.
Elena
E
Tremoli
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; Centro Cardiologico Monzino IRCCS, Milan, Italy.
Luigi
L
Sironi
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D020869:Gene Expression Profiling; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D000068756:Valsartan / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D000068756:Valsartan