title: Hemodynamic effects of a new inotropic compound, PST-2744, in dogs with chronic ischemic heart failure.
abstract: Inotropic agents for acute decompensated heart failure are associated with a lack of efficacy or increased mortality. New compounds are needed to support patients with acute exacerbations of heart failure. This study examined the hemodynamic effects of a new inotropic agent (PST-2744) in dogs with chronic ischemic heart failure. Eight mongrel dogs at low risk for postmyocardial infarction (MI) sudden death entered the protocol. Dogs were studied after ischemic left ventricular dysfunction was induced by repeated injections of latex microspheres into the circumflex artery until the ejection fraction reached 35%. Hemodynamic parameters were measured at baseline and peak drug effect (PST-2744 5 microg.kg-1.min-1). In 5 animals, PST-2744 effects were compared with dobutamine. Heart rates, PR intervals and QT intervals were unchanged following PST-2744 administration. PST-2744 increased contractility (+dP/dt) by 56% from 1881 +/- 282 mm Hg/s to 2939 +/- 734 mm Hg/s (P < 0.01). The inotropic effect of PST-2744 was equal to that produced by 5-microg.kg-1.min-1 dobutamine (56% increase in +dP/dt), but peak heart rates were significantly higher with dobutamine (129 +/- 24 bpm PST-2744 versus 160 +/- 6 bpm 5-microg.kg-1.min-1 dobutamine, P < 0.002). No arrhythmias or conduction delays were seen with either compound. PST-2744 is an effective inotropic agent without positive chronotropic effect in subjects with stable moderate left ventricular dysfunction.
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, 920 S.L. Young Boulevard, WP 3120, Oklahoma City, OK 73104, USA. Philip-adamson@ouhsc.edu
authors.forename: Philip B
authors.initials: PB
authors.lastname: Adamson
authors.forename: Emilio
authors.initials: E
authors.lastname: Vanoli
authors.forename: Giovan G
authors.initials: GG
authors.lastname: Mattera
authors.forename: Robin
authors.initials: R
authors.lastname: Germany
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gagnol
authors.forename: Paolo
authors.initials: P
authors.lastname: Carminati
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D005043:Etiocholanolone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
chemical_list: D002316:Cardiotonic Agents; D004280:Dobutamine; D005043:Etiocholanolone; C468128:Istaroxime