title: Depressed function in remote myocardium after myocardial infarction: influence of orotic acid.
abstract: BACKGROUND
  We have previously shown that infarction impairs recovery of global function after subsequent cardioplegic arrest and that therapy with orotic acid improves recovery. The aim of this study was to measure the effect of infarction on regional and global left ventricular function and to determine whether orotic acid exerts a beneficial effect exclusive of the effects of cardioplegia.
  
  
  METHODS
  Acute myocardial infarction was produced in dogs. They then received either orotic acid or placebo (control) orally (n = 12 per group). Fractional radial shortening and systolic wall thickening were measured by two-dimensional echocardiography before and 1 and 3 days after infarction with and without beta-adrenergic blockade, and in 6 dogs up to 9 days after infarction. Global function was measured under anesthesia 4 days after infarction.
  
  
  RESULTS
  In control animals, fractional radial shortening in the infarct decreased from 20.6% +/- 5.1% before infarction to 3.0% +/- 2.2% at day 1 and to 1.9% at day 3 (p < 0.01). In the border zone radial shortening declined from 21.9% +/- 3.7% to 11.0% +/- 2.3% at day 1 and 9.3% +/- 2.8% at day 3 (p < 0.05). In the noninfarcted myocardium radial shortening also declined from 27.1% +/- 1.9% before infarction to 18.3% +/- 2.3% on day 1 (p < 0.05) and to 16.0% +/- 2.8% on day 3 after infarction (p < 0.05) with recovery to preinfarct levels by 9 days after infarction. These findings were confirmed by measurements of systolic thickening. Before infarction beta-receptor blockade decreased fractional shortening in all regions of the left ventricle, but this effect was absent on day 3 after infarction, implying that the myocardium had become less responsive to beta-adrenergic stimulation. Measurements of global function 4 days after infarction showed marked depression of stroke work. There was no effect of orotic acid treatment on regional or global function.
  
  
  CONCLUSIONS
  Myocardial infarction causes reversible depression of resting function and beta-adrenergic responsiveness in the remote and border zone areas, which is not prevented by metabolic therapy with orotic acid. This finding may explain the adverse response of the infarcted heart to cardioplegic arrest.
authors.affiliation: Cardiac Surgical Research Unit, Baker Medical Research Institute, Prahran, Victoria, Australia.
authors.forename: A D
authors.initials: AD
authors.lastname: Cochrane
authors.forename: S
authors.initials: S
authors.lastname: Pathik
authors.forename: J J
authors.initials: JJ
authors.lastname: Smolich
authors.forename: R A
authors.initials: RA
authors.lastname: Conyers
authors.forename: F L
authors.initials: FL
authors.lastname: Rosenfeldt
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004452:Echocardiography; D006321:Heart / Q000503:physiopathology*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D009963:Orotic Acid / Q000627:therapeutic use*; D011433:Propranolol / Q000494:pharmacology; D016277:Ventricular Function, Left
chemical_list: D000319:Adrenergic beta-Antagonists; D009963:Orotic Acid; D011433:Propranolol