title: Role of the beta 2 adrenoceptor in mediating positive inotropic activity in the failing heart and its relation to the hemodynamic actions of dopexamine hydrochloride.
abstract: In patients with severe congestive heart failure, it has been suggested that since myocardial beta 1 adrenoceptors are selectively down-regulated, activation of beta 2 receptors may be a preferable approach to augmenting contractility. Accordingly, dopexamine hydrochloride (1, 2 and 4 micrograms/kg/min) and dopamine (2 and 4 micrograms/kg/min) were administered to 8 patients with dilated cardiomyopathy. Left ventricular (LV) dimensions, thicknesses and pressures were obtained using simultaneous high-fidelity pressure measurements and echocardiographic recordings. LV contractility was assessed using the load-independent relation between LV end-systolic wall stress and rate-corrected velocity of fiber shortening. Cardiac index increased in a dose-related manner with both drugs, and was accompanied by a decline in systemic vascular resistance, a measure of peripheral arteriolar tone. LV end-diastolic pressure was unaltered except for a decrease from 29 +/- 6 to 19 +/- 5 mm Hg (p less than 0.017) at the highest dose of dopexamine hydrochloride. Heart rate was unchanged during the infusion of dopamine but increased significantly with dopexamine hydrochloride. LV end-systolic wall stress, a measure of LV internal load, decreased with both drugs. With dopamine, a dose-dependent positive inotropic effect was observed. Dopexamine hydrochloride, at the 4 micrograms/kg/min infusion dose, exerted a mild positive inotropic effect comparable to that noted with dopamine at 2 micrograms/kg/min. Thus, dopamine and dopexamine hydrochloride improved overall LV performance. With dopamine, a substantial positive inotropic effect occurred in association with a reduction in LV afterload. The increased cardiac index observed with dopexamine hydrochloride was due primarily to peripheral vasodilatation and a positive chronotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Chicago, Illinois.
authors.forename: R M
authors.initials: RM
authors.lastname: Lang
authors.forename: K M
authors.initials: KM
authors.lastname: Borow
authors.forename: A
authors.initials: A
authors.lastname: Neumann
authors.forename: J D
authors.initials: JD
authors.lastname: Carroll
authors.forename: L
authors.initials: L
authors.lastname: Weinert
authors.forename: M B
authors.initials: MB
authors.lastname: Murphy
authors.forename: J
authors.initials: J
authors.lastname: Ghali
authors.forename: S I
authors.initials: SI
authors.lastname: Rajfer
mesh_terms: D000328:Adult; D004298:Dopamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013314:Stress, Mechanical; D013599:Systole
chemical_list: D011943:Receptors, Adrenergic, beta; C046318:dopexamine; D004298:Dopamine