title: Mechanisms involved in the effect of M6434 on experimental hemorrhagic shock: I. Effects on myocardial contractility and venous return.
abstract: To elucidate the mechanisms of protective effect of M6434 on experimental shock, the authors examined the effects of this compound on the survival time and hemodynamic changes in severely hemorrhagic-shocked dogs. We also examined the effects of M6434 on contractile tension of isolated canine ventricular strips and on venous return in dogs with cardiopulmonary bypass in normal and shock state. Intravenous infusion of M6434 at 10 micrograms/kg/min prolonged survival and maintained mean arterial pressure, cardiac output, and first derivative of left ventricular pressure at higher levels than those in the control group, whereas dopamine (10 micrograms/kg/min) did not significantly affect survival time and hemodynamic parameters. M6434 did not change contractile tension in electrically stimulated canine ventricular strips. M6434 (20 micrograms/kg/min) increased the venous return of dogs with cardiopulmonary bypass in both shock and normal state. Phenylephrine (20 micrograms/kg/min) slightly increased venous return in normal state, but not during shock. Dopamine had no effect at 20 micrograms/kg/min, but it increased venous return in both states at 50 micrograms/kg/min. These results suggest that M6434 may improve the hemodynamic derangement in severe hemorrhagic shock through decreasing venous blood pooling.
authors.affiliation: Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Uemura
authors.forename: T
authors.initials: T
authors.lastname: Dabasaki
authors.forename: T
authors.initials: T
authors.lastname: Notsu
authors.forename: F
authors.initials: F
authors.lastname: Yamasaki
authors.forename: M
authors.initials: M
authors.lastname: Nakakuki
authors.forename: T
authors.initials: T
authors.lastname: Shinkawa
authors.forename: H
authors.initials: H
authors.lastname: Kosuzume
authors.forename: K
authors.initials: K
authors.lastname: Okada
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D014690:Venous Pressure / Q000187:drug effects*
chemical_list: D007093:Imidazoles; C032482:2-((5-chloro-2-methoxyphenyl)azo)-1H-imidazole; D004298:Dopamine