title: Amrinone increases ventricular contractility and diastolic compliance in endotoxemia.
abstract: Systolic and diastolic dysfunction occur during human septic shock, and sensitivity to beta-adrenergic agents is reduced. We sought to determine whether amrinone, an inotropic agent independent of beta-receptors, increases left-ventricular contractility or diastolic compliance after endotoxin infusion. We measured left-ventricular volume (using a conductance catheter) and pressure (using a Millar catheter) before and after administering amrinone (4.5 mg/kg i.v., then 10 micrograms/kg/min) to six endotoxemic and seven control pigs. The slope of the end-systolic pressure-volume relationship, Ees, was used as the primary measure of contractility. Diastolic stiffness was characterized using stiffness parameters taken from pressure-volume relationships (k) and from pressure-volume strain relationships. Amrinone increased Ees from a median of 10.4 mm Hg/ml (interquartile range, 7.2 to 12.3) to 16.4 (13.7 to 18.6) (p < 0.05) in the endotoxin group (p < 0.05). Amrinone decreased diastolic stiffness (k) in the endotoxin group by 35 +/- 18% (p < 0.05). Amrinone did not significantly change Ees or k in the control group. Mean arterial pressure decreased after endotoxin infusion from 117 +/- 23 mm Hg to 76.5 +/- 14.9 mm Hg (p < 0.05), and decreased further after amrinone to 62.0 +/- 14.8 mm Hg (p < 0.05). We conclude that in this model of sepsis, amrinone may beneficially increase systolic contractility and diastolic compliance, but may dangerously decrease an already low mean arterial pressure.
authors.affiliation: Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: H A
authors.initials: HA
authors.lastname: Werner
authors.forename: M J
authors.initials: MJ
authors.lastname: Herbertson
authors.forename: K R
authors.initials: KR
authors.lastname: Walley
mesh_terms: D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D016280:Atrial Function, Right / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D002302:Cardiac Output / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003971:Diastole; D004548:Elasticity; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D010100:Oxygen / Q000097:blood; D012772:Shock, Septic / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D004731:Endotoxins; D000676:Amrinone; D010100:Oxygen