title: Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics.
abstract: A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK(-/-)) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (V(max)) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK(-/-) mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK(-/-) mice, but ejection fraction (EF) remained normal. V(max), however, was significantly reduced in the CK(-/-) mice [wild-type, 2.32 +/- 0.09 vs. CK(-/-), 1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK(-/-) MI, 1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK(-/-) mice (wild-type, 6.68 +/- 0.27 vs. CK(-/-), 4.12 +/- 0.63 ml/g.min, P < 0.05; and wild-type MI, 3.97 +/- 0.65 vs. CK(-/-) MI, 3.71 +/- 0.57 ml/g.min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK(-/-) phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system.
authors.affiliation: Medizinische Klinik und Poliklinik 1, Universität Würzburg, Josef Schneider-Strasse 2, 97080 Würzburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Jörg U
authors.initials: JU
authors.lastname: Streif
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Hiller
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Peter
authors.initials: P
authors.lastname: Nordbeck
authors.forename: Oliver
authors.initials: O
authors.lastname: Ritter
authors.forename: David
authors.initials: D
authors.lastname: Sosnovik
authors.forename: Lisa
authors.initials: L
authors.lastname: Bauer
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jakob
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Matthias
authors.initials: M
authors.lastname: Spindler
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Bauer
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology; D003326:Coronary Circulation / Q000235:genetics* / Q000502:physiology*; D003402:Creatine Kinase / Q000172:deficiency* / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008858:Microscopy, Phase-Contrast; D009200:Myocardial Contraction / Q000235:genetics* / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D010641:Phenotype; D013113:Spin Labels; D020257:Ventricular Remodeling
chemical_list: D013113:Spin Labels; D003402:Creatine Kinase