title: Norepinephrine-induced left ventricular dysfunction in anesthetized and conscious, sedated dogs.
abstract: These studies were conducted to evaluate effects of high dose norepinephrine infusion on left ventricular function in anesthetized and conscious dogs. Separate groups of pentobarbital anesthetized closed-chest dogs received norepinephrine infusion for 90 min followed by 1 h of recovery. Arterial pressure, electrocardiogram, two-dimensional echocardiogram and an equilibrium radionuclide angiogram were monitored. One hour following infusion of norepinephrine, left ventricular ejection fraction was reduced in a dose-dependent fashion. Fractional shortening was similarly reduced, with increased left ventricular systolic and diastolic dimensions also observed. Left ventricular end-systolic wall stress was increased at 60 min following infusion of norepinephrine but not saline: saline, 68 +/- 8, norepinephrine, 4 micrograms/kg/min, 113 +/- 8 g/cm2. The left ventricular end-systolic wall stress/fractional shortening relationship showed reduction of contractility. In 10 conscious dogs pretreated with morphine, norepinephrine at 5 micrograms/kg/min x 90 min produced similar changes to those seen in anesthetized animals. Ejection fraction was reduced from 0.69 +/- 0.3 to 0.36 +/- 0.04 at 60 min post infusion. Fractional shortening was also reduced. Left ventricular end-diastolic dimension was increased. However, when animals were followed for 1 week, complete recovery occurred within 48 h. Histology showed mild contraction band necrosis in acute experiments and mild perivascular fibrosis in chronic experiments. Therefore, norepinephrine cardiotoxicity produced significant left ventricular dilation and reduction of ejection phase indices of left ventricular function associated with reduced contractility. In chronic dogs, histologic changes were mild, and left ventricular dysfunction was reversible.
authors.affiliation: Department of Internal Medicine, East Carolina University School of Medicine, Greenville, NC 27838-4354.
authors.forename: A
authors.initials: A
authors.lastname: Movahed
authors.forename: W C
authors.initials: WC
authors.lastname: Reeves
authors.forename: P M
authors.initials: PM
authors.lastname: Mehta
authors.forename: M G
authors.initials: MG
authors.lastname: Gilliland
authors.forename: S L
authors.initials: SL
authors.lastname: Mozingo
authors.forename: S R
authors.initials: SR
authors.lastname: Jolly
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016292:Procedural Sedation; D004108:Dilatation, Pathologic / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000009:adverse effects* / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D009638:Norepinephrine