title: Inotropic reserve and histological appearance of hibernating myocardium in conscious pigs with ameroid-induced coronary stenosis.
abstract: Inotropic reserve, demonstrated with administration of sympathomimetic amines, is characteristic of hibernating myocardium. The goal of this study was to determine whether inotropic reserve was present following chronic coronary artery constriction in the pig, which is one potential model of hibernating myocardium. The effects of isoproterenol were examined in five conscious pigs 21 +/- 2.1 days after ameroid implantation on the left circumflex coronary artery on measurements of left ventricular (LV) pressure, LV dP/dt, and regional wall thickening in the ameroid-dependent zone (posterior wall) and contralateral non-ischemic zone (anterior wall). Isoproterenol, 0.1 microgram/kg/min, increased LV dP/dt by 96 +/- 11%, heart rate by 43 +/- 13 beats/min, and normalized systolic wall thickening, slightly, but not significantly more in the ameroid-dependent zone (+1.57 +/- 0.31 mm) than in the contralateral non-ischemic zone (+1.04 +/- 0.31 mm), although the baseline wall thickening was reduced significantly in the ameroid-dependent zone. This occurred at a time when baseline myocardial blood flow was preserved and myocardial perfusion in the ameroid-dependent zone was derived in part from the native coronary circulation and also through collateral channels. Two weeks later histological evidence of lesions characteristic of hibernating myocardium, i.e., myofibrolysis and increased glycogen deposition, were observed. Thus, these histological changes and the confluence of chronically depressed regional function and residual inotropic reserve in the conscious pig with chronic ameroid-induced coronary constriction support this model for further study of hibernating myocardium.
authors.affiliation: Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772, USA.
authors.forename: Y T
authors.initials: YT
authors.lastname: Shen
authors.forename: R K
authors.initials: RK
authors.lastname: Kudej
authors.forename: S P
authors.initials: SP
authors.lastname: Bishop
authors.forename: S F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000633:toxicity; D001783:Blood Flow Velocity; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002364:Caseins; D002908:Chronic Disease; D003327:Coronary Disease / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology*; D020100:Hydrogels; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology*; D013552:Swine; D013556:Swine, Miniature; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D017725:Ventricular Pressure
chemical_list: D001672:Biocompatible Materials; D002316:Cardiotonic Agents; D002364:Caseins; D020100:Hydrogels; C009719:ameroid; D007545:Isoproterenol