title: Obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.
abstract: The present study was designed to determine modulation of the direct inotropic effect of an anticholinesterase organophosphorus compound, phosphamidon, by the reactivator obidoxime. We investigated the effects of phosphamidon (n = 9), obidoxime (n = 5), and their combination (n = 5) on the mechanical and energetic indices of left ventricular function, in the isolated working rat heart model. Phosphamidon at a concentration range of 10(-6)-10(-3) M had a positive inotropic effect. Obidoxime at a concentration range of 10(-6)-10(-3) M had no significant effect on heart rate, but did have a statistically significant positive inotropic effect on end-systolic pressure, cardiac output, mean left ventricular pressure, and maximal time derivative of left ventricular pressure (dP/dtmax) (P less than 0.01). Perfusion with 10(-3) M obidoxime caused a 19% increase in left ventricular stroke work and a 31% increase in total pressure-volume area. Perfusion with phosphamidon and obidoxime at concentrations ranging from 10(-6) to 10(-3) M resulted in a more intense inotropic response than the separate drug effects. At the highest combined concentrations tested, cardiac output increased by 60%, left ventricular stroke work increased by 100%, and left ventricular total pressure volume area increased by 111% of their control values (P less than 0.001). We conclude that obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart.
authors.affiliation: Cardiovascular Research Group, Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa.
authors.forename: S A
authors.initials: SA
authors.lastname: Ben-Haim
authors.forename: H
authors.initials: H
authors.lastname: Ben-Ami
authors.forename: G
authors.initials: G
authors.lastname: Hayam
authors.forename: U
authors.initials: U
authors.lastname: Taitelman
authors.forename: Y
authors.initials: Y
authors.lastname: Edoute
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009768:Obidoxime Chloride / Q000494:pharmacology*; D010707:Phosphamidon / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D010707:Phosphamidon; D009768:Obidoxime Chloride