title: Chronic coronary artery stenosis induces impaired function of remote myocardium: MRI and spectroscopy study in rat.
abstract: Our purpose was to study morphological, functional, and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Cine-MRI was performed 2 wk after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared with 7 control rats. Two weeks after stenosis was induced, spin-labeling MRI for measurement of perfusion was performed in 14 isolated hearts. In eight isolated hearts with coronary stenosis, MR spectroscopy was performed, followed by angiography. 31P metabolite maps were fused with three-dimensional coronary angiograms. Induction of stenosis led to reduced segmental wall thickening (control: 75 +/- 9%, ischemic region: 9 +/- 3%, P < 0.05 vs. control) but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9 +/- 4.0% within ischemic segments compared with a septal control region. The phosphocreatine (PCr)/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09 +/- 0.09) compared with remote (1.27 +/- 0.08) and control hearts (1.43 +/- 0.08; P < 0.05). The histological fraction of fibrosis within the ischemic region (12.8 +/- 1.4%) correlated to ATP signal reduction from remote to the ischemic region (r = 0.71, P < 0.05), but not to reduced wall thickening. Coronary narrowing caused declining function accompanied by diminished PCr/ATP, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased PCr. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.
authors.affiliation: Physikalisches Institut, Universität Würzburg, Josef Schneider-Str. 2, 97080 Würzburg, Germany. M.Nahrendorf@medizin.uni-wuerzburg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Hiller
authors.forename: Andreas
authors.initials: A
authors.lastname: Greiser
authors.forename: Sascha
authors.initials: S
authors.lastname: Kohler
authors.forename: Thomas
authors.initials: T
authors.lastname: Neuberger
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.forename: Christiane
authors.initials: C
authors.lastname: Waller
authors.forename: Matthias
authors.initials: M
authors.lastname: Albrecht
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.forename: Axel
authors.initials: A
authors.lastname: Haase
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Wolfgang R
authors.initials: WR
authors.lastname: Bauer
mesh_terms: D000818:Animals; D023921:Coronary Stenosis / Q000473:pathology* / Q000503:physiopathology*; D004280:Dobutamine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D018810:Magnetic Resonance Angiography; D009682:Magnetic Resonance Spectroscopy; D010759:Phosphorus Isotopes; D051381:Rats; D017208:Rats, Wistar; D013566:Sympathomimetics / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D010759:Phosphorus Isotopes; D013566:Sympathomimetics; D004280:Dobutamine