title: Reassessment of a suggested pharmacological approach to heart failure: L-arginine is only a marginal NO donor in pigs.
abstract: OBJECTIVE
  L-Arginine has been tested in various cardiovascular diseases, mainly to improve endothelial function through NO production. However, as the results have been partly unpredictable, we assessed the hemodynamic, energetic and metabolic effects of L-arginine to clarify any potential benefits in postischemic left ventricular (LV) dysfunction.
  
  
  METHODS
  LV dysfunction was induced by repetitive brief coronary occlusions in 12 anesthetized, open chest pigs. L-Arginine was subsequently infused (bolus 400 mg·kg and continuously for 1 hour, 250 mg·kg·h). Hemodynamic parameters, metabolites of L-arginine and myocardial energetics were assessed sequentially.
  
  
  RESULTS
  L-Arginine infusions caused a substantial rise in plasma L-arginine (3474 ± 358 μmole·L) accompanied by a 2-fold increase in plasma L-citrulline. No significant alterations in vascular resistance or LV contractility were observed from L-arginine. Mean arterial pressure dropped from 78 ± 11 to 72 ± 10 mm Hg (P = 0.019) and 70 ± 8 mm Hg (P = 0.003) after bolus and infusions, respectively. Myocardial oxygen consumption was unaltered, and myocardial creatine content was not increased after 90 minutes of L-arginine infusion.
  
  
  CONCLUSIONS
  L-Arginine infusion did not influence the energetic cost of myocardial contractility, and only minor hemodynamic changes were observed despite a demonstrable turnover of L-arginine. These findings question the use of L-arginine to promote therapeutic NO formation in the acute setting.
authors.affiliation: Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. ingrid.a.andersen@uit.no
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Andersen
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Igumnova
authors.forename: Anders B
authors.initials: AB
authors.lastname: Kildal
authors.forename: Truls
authors.initials: T
authors.lastname: Myrmel
mesh_terms: D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D034421:Sus scrofa; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D020030:Nitric Oxide Donors; D001120:Arginine