title: Blood pool contrast-enhanced MRI detects suppression of microvascular permeability in early postinfarction reperfusion after nicorandil therapy.
abstract: Nicorandil is an adenosine triphosphate-sensitive potassium channel opener with a nitrate-like effect. It is approved for clinical use in Europe and Japan as an antianginal drug. The purpose of this investigation was to assess the acute effects of nicorandil therapy on microvascular injury using the blood pool MR contrast medium, NC100150 injection (Clariscan). Microvascular injury was produced in 24 rats using 45 min of coronary occlusion / 3 hr reperfusion. Nicorandil was infused at 15 min of occlusion and during reperfusion. Control animals received a saline solution. MR imaging was used to characterize microvascular permeability, quantify the extent of microvascular injury, LV volume, and wall thickness. Hyperenhancement at 30 min after administration of 0.05 mmol/kg Clariscan mapped the extent of ischemia-induced loss of microvascular integrity. The accumulation of Clariscan in the injured region was significantly suppressed in nicorandil compared to control rats. Nicorandil reduced the extent of microvascular injury from 44 +/- 2% to 18 +/- 2% (P < 0.01) and true infarction size from 29 +/- 2% to 12 +/- 1%. The extent of the hyperenhanced region correlated with the true size of area at risk at autopsy. On spin-echo MRI during end-diastole, nicorandil reduced LV end-diastolic volume and preserved wall thickness in remote myocardium; both parameters are markers of LV dilatation caused by acute infarction (remodeling). In conclusion, blood pool contrast-enhanced MRI has the potential to depict and quantify the extent of microvascular permeability and injury. Nicorandil suppressed microvascular permeability, reduced infarction size, and improved LV function in early postinfarction reperfusion.
authors.affiliation: Department of Radiology, University of California, San Francisco 94143-0628, USA.
authors.forename: Gabriele A
authors.initials: GA
authors.lastname: Krombach
authors.forename: Charles B
authors.initials: CB
authors.lastname: Higgins
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Chujo
authors.forename: Maythem
authors.initials: M
authors.lastname: Saeed
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D007089:Image Enhancement / Q000379:methods; D007501:Iron; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008833:Microcirculation / Q000187:drug effects*; D009203:Myocardial Infarction / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D010087:Oxides; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; D014665:Vasodilator Agents; C097921:ferumoxtran-10; D020108:Nicorandil; D007501:Iron; D052203:Ferrosoferric Oxide