title: Proof for piroximone's inotropic influence; can it safely be used in coronary artery disease? Analysis of end-systolic pressure-volume relations (conductance technique).
abstract: Improved contractility after applying piroximone (PIR) a new phosphodiesterase III inhibitor drug, is difficult to prove clinically. However, augmented contractility could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). Analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular (LV) function allows for differentiation of PIR's effects: contractility vs. unloading. We therefore analyzed ESPVR and LV function in 16 CAD patients before and after PIR, 0.75 mg/kg intravenously. Emax increased by 39% (9/16 patients) and loops of the ESPVR (16 patients) moved leftward, indicating improved contractility. The difference in percent change PIR versus control (16 patients) demonstrated augmentation of LV function via unloading: LV volumes decreased (ESV by 37%, EDV by 19%), LV-filling pressure by 34%, and systemic vascular resistance by 19%; dP/dtmax increased by 28%, LV efficiency by 24%, cardiac index by 21%, and ejection fraction by 13%. Pacing-induced anginal threshold increased by 47% after PIR while the ischemic postpacing LV-filling pressure and ST-segment changes tended to normalize under the drug's influence. Thus, PIR improved LV function both by unloading and by positive inotropy. Lack of PIR-induced angina and an increased anginal threshold indicate that the drug can be used safely in CAD patients as well. The analysis of ESPVR proved to be safe and reliable in identifying contractility during the diagnostic cardiac catheterization routine.
authors.affiliation: Kerckhoff-Klinik der Max-Planck-Gesellschaft, Bad Nauheim, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Thormann
authors.forename: A
authors.initials: A
authors.lastname: Liebrich
authors.forename: V
authors.initials: V
authors.lastname: Mitrovic
authors.forename: R
authors.initials: R
authors.lastname: Strasser
authors.forename: H A
authors.initials: HA
authors.lastname: Dieterich
authors.forename: M
authors.initials: M
authors.lastname: Schlepper
mesh_terms: D000368:Aged; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006334:Heart Function Tests; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011312:Pressure; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; C039686:piroximone