title: Nitric oxide synthase inhibition partially prevents decreased LV contractility during endotoxemia.
abstract: Decreased contractility of myocytes after cytokine exposure can be prevented by nitric oxide synthase inhibition. Whether this is true in an intact animal model of sepsis is unknown. Anesthetized pigs were pretreated with saline or a nitric oxide synthase inhibitor, N omega-nitro-L-arginine, and then treated with saline or endotoxin. We measured hemodynamics and left ventricular pressures (Millar catheter) and volumes (conductance catheter). Left ventricular contractility was assessed using the slope (E(max)) of the end-systolic pressure-volume relationship. Four hours after endotoxin infusion, E(max) had decreased by 44 +/- 5% (P < 0.05) and mean arterial pressure had decreased by 30 +/- 10% (P < 0.05). Pretreatment with N omega-nitro-L-arginine significantly reduced the decrease in E(max) to 28 +/- 3% (P < 0.05) and prevented the decrease in mean arterial pressure. However, it also raised pulmonary arterial pressure. We conclude that nitric oxide contributes to the early decrease in left ventricular contractility after endotoxin in the intact animal. However, the vascular effects of nitric oxide synthase inhibition increase right and left ventricular afterloads, which were detrimental to cardiac function.
authors.affiliation: Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Herbertson
authors.forename: H A
authors.initials: HA
authors.lastname: Werner
authors.forename: K R
authors.initials: KR
authors.lastname: Walley
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004731:Endotoxins / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D012772:Shock, Septic / Q000503:physiopathology; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D016277:Ventricular Function, Left
chemical_list: D004731:Endotoxins; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D012965:Sodium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase