title: Effect of diltiazem on norepinephrine-induced acute left ventricular dysfunction.
abstract: The present study has examined the role of diltiazem as a protective agent in a canine model of norepinephrine cardiotoxicity. Effects of diltiazem, 20 micrograms/kg/min x 5 min pretreatment followed by 10 micrograms/kg/min x 90 min, or saline infusion were examined at baseline and 1 h after infusion of norepinephrine, 4 micrograms/kg/min for 90 min, in closed-chest anesthetized dogs. Left ventricular function was assessed by equilibrium radionuclide angiogram and two-dimensional echocardiogram. In 7 saline experiments, hypotension and increased heart rate were observed at 1 h post infusion. In the diltiazem-treated group (n = 7), mean arterial pressure and heart rate were unchanged. In the saline group, left ventricular ejection fraction fell from 0.50 +/- 0.04 to 0.28 +/- 0.04. Left ventricular ejection fraction was unchanged in the diltiazem-treated group: 0.52 +/- 0.03 to 0.55 +/- 0.07. Left ventricular end-diastolic volume was increased at 1 h post infusion in saline controls but not in the diltiazem-treated group. Measurement of fractional shortening from two-dimensional echocardiograms also indicated left ventricular dysfunction in the saline but not diltiazem-treated groups. Left ventricular end-systolic wall stress following norepinephrine infusion was significantly increased in the saline but not diltiazem-treated groups: 122.7 +/- 18.7 vs 67.6 +/- 19.7 g/cm2, respectively. In dogs receiving saline without norepinephrine infusion, no significant changes occurred over the course of the experiment. Histologic examination showed mild contraction band necrosis in saline controls but not in sham saline dogs. Diltiazem showed intermediate histologic evidence of injury, which was not further quantified. This study suggests that effects of norepinephrine on left ventricular function in the canine model of norepinephrine cardiotoxicity may be largely due to increased wall stress following a prolonged increase in afterload. Diltiazem pretreatment afforded significant protection of left ventricular function.
authors.affiliation: Department of Internal Medicine, East Carolina University School of Medicine, Greenville, NC 27858-4354.
authors.forename: S R
authors.initials: SR
authors.lastname: Jolly
authors.forename: W C
authors.initials: WC
authors.lastname: Reeves
authors.forename: S
authors.initials: S
authors.lastname: Mozingo
authors.forename: P
authors.initials: P
authors.lastname: Mehta
authors.forename: M G
authors.initials: MG
authors.lastname: Gilliland
authors.forename: E
authors.initials: E
authors.lastname: Wilson
authors.forename: A
authors.initials: A
authors.lastname: Movahed
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000473:pathology; D009638:Norepinephrine / Q000633:toxicity; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D004110:Diltiazem; D009638:Norepinephrine