title: Aminoguanidine inhibits inducible NOS and reverses cardiac dysfunction late after ischemia and reperfusion--implications for iNOS-mediated myocardial stunning.
abstract: BACKGROUND
  The functional significance of inducible nitric oxide synthase (iNOS) activation in response to myocardial ischemia and reperfusion (I/R) was investigated.
  
  
  METHODS
  New Zealand rabbits were randomly treated with either placebo, aminoguanidine (AMG; selective iNOS inhibitor), or L-arginine. Left-ventricular hemodynamics and myocardial blood flow were measured before coronary occlusion and 30 minutes and 48 h after initiation of reperfusion.
  
  
  RESULTS
  I/R resulted in left-ventricular dysfunction and increased myocardial iNOS activity. Placebo treatment had no effects on myocardial function. However, AMG significantly inhibited iNOS activity, significantly improved left-ventricular maximum + dP/dt and decreased LVEDP, whereas administration of L-arginine reduced + dP/dt and slightly increased LVEDP, compared to AMG-treated animals. Myocardial blood flow in the affected myocardium significantly increased after both AMG and L-arginine.
  
  
  CONCLUSIONS
  The present data indicate that induction of myocardial iNOS after 48 h I/R contributes to the development of reversible left-ventricular dysfunction, suggesting the involvement of iNOS in myocardial stunning. Whereas L-arginine is associated with further reduction of left-ventricular contractility, continuous inhibition of iNOS activation by AMG improves left-ventricular performance; this may be a novel and clinically important therapeutic modality in certain disease states associated with I/R, including cardiac operations using extracorporeal circulation and coronary angioplastic procedures.
authors.affiliation: Department of Cardiac Surgery, Ludwig-Maximilians University, Munich, Germany. wildhirt@hch.med.uni-muenchen.de
authors.forename: S M
authors.initials: SM
authors.lastname: Wildhirt
authors.forename: C
authors.initials: C
authors.lastname: Schulze
authors.forename: N
authors.initials: N
authors.lastname: Conrad
authors.forename: A
authors.initials: A
authors.lastname: Kornberg
authors.forename: D
authors.initials: D
authors.lastname: Horstman
authors.forename: B
authors.initials: B
authors.lastname: Reichart
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D011817:Rabbits; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D001120:Arginine; D019001:Nitric Oxide Synthase; C004479:pimagedine