Comparison of the cardiovascular effects of two novel superoxide dismutase mimetics, SC-55858 and SC-54417, in conscious dogs. Eur J Pharmacol 1996 May 23;304(1-3):81-6
Date
05/23/1996Pubmed ID
8813587DOI
10.1016/0014-2999(96)00120-3Scopus ID
2-s2.0-0030598627 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
The hemodynamic actions and left ventricular mechanical effects of two new superoxide dismutase mimetics, SC-55858 [Manganese (II) dichloro (2R,3R,8R,9R-bis-cyclohexano-1,4,7,10,13-pentaazacyclopentadeca ne)] (n = 10) and SC-55417 [Manganese (II) dichloro (trans-2,3-cyclohexano-1,4,7,10,13-pentaazacyclopentadecane) ] (n = 8), were studied in chronically instrumented dogs in the conscious state and after 30 min equilibration at 0.033, 0.067, 0.233, and 0.667 microM.kg-1.min-1 SC-55858 or SC-54417 (total doses of 1, 2, 7, and 20 microM.kg-1). SC-55858 and SC-54417 increased heart rate and decreased mean arterial pressure and left ventricular systolic and end-diastolic pressures. SC-55858 decreased preload recruitable stroke work slope and +dP/dtmax and increased the time constant of isovolumic relaxation, consistent with a direct negative inotropic and lusitropic effect. In contrast, SC-54417 did not depress left ventricular systolic and diastolic function. Decreases in mean arterial pressure caused by SC-55858 may be secondary to negative inotropic effects and reduction in cardiac preload. In contrast, SC-54417 does not depress myocardial contractility but also reduces arterial pressure via venodilation.
Author List
Lowe D, Pagel PS, McGough MF, Hettrick DA, Warltier DCMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Cardiac Output
Depression, Chemical
Dogs
Free Radical Scavengers
Heart Rate
Hemodynamics
Myocardial Contraction
Organometallic Compounds
Stroke Volume
Superoxide Dismutase
Vascular Resistance
Ventricular Function, Left
