title: Local inotropic stimulation by methylene blue does not improve mechanical dysfunction due to myocardial stunning.
abstract: We tested the hypothesis that reduction of intramyocardial cyclic guanosine monophosphate (GMP) by methylene blue (MB) would improve mechanical dysfunction in stunned myocardium. Regional stunning was produced in nine open-chest anesthetized dogs by a 12-min left anterior descending coronary artery (LAD) occlusion. MB was infused into the LAD during reperfusion (1 mg/kg per min). Stunning reduced LAD force development, introduced a significant time delay between the onset of force and shortening (delay) and caused significant systolic bulging to occur. Stunning reduced systolic regional work (the integrated product of force and segment shortening during systole), but did not significantly alter regional oxygen consumption or cyclic GMP levels. MB decreased cyclic GMP (1.8 +/- 0.2 to 0.9 +/- 0.1 pmol/g) and increased peak force (36 +/- 5 to 55 +/- 10 g). However, MB increased delay (93.9 +/- 18.4 to 233 +/- 19 ms) and systolic bulging (5.9 +/- 2.1% to 9.3 +/- 2.8%) and further reduced systolic regional work (control; 4204 +/- 933 g x mm/min; stunned: 2191 +/- 542 g x mm/min; MB: 1153 +/- 516 g x mm/min). MB increased regional myocardial oxygen consumption (7.4 +/- 1.0 to 15.6 +/- 2.7 ml O2/min per 100 g). These results suggest that depressed contractility, while present in myocardial stunning, is not the primary cause of mechanical dysfunction.
authors.affiliation: Department of Physiology & Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Naim
authors.forename: H R
authors.initials: HR
authors.lastname: Weiss
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Sadoff
authors.forename: P
authors.initials: P
authors.lastname: Scholz
authors.forename: J
authors.initials: J
authors.lastname: Kedem
mesh_terms: D000818:Animals; D004396:Coloring Agents / Q000494:pharmacology*; D003331:Coronary Vessels / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D003971:Diastole / Q000502:physiology; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D017682:Myocardial Stunning / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology
chemical_list: D004396:Coloring Agents; D006152:Cyclic GMP; D008751:Methylene Blue