Stimulation of myocardium during reperfusion injury by a new inotrope-vasodilator agent, MCI-154.
The systemic and coronary hemodynamic actions of a newly synthesized inotropic agent structurally related to milrinone and amrinone, MCI-154 (0.5-4.0 micrograms/kg/min IV), were studied in 2 groups of conscious, chronically instrumented dogs with normal or depressed postischemic, reperfused myocardium after a 15-min coronary artery occlusion. In an additional group of control experiments, the time course of recovery of postischemic, reperfused myocardium was studied to verify the constancy of regional segment shortening in the previously ischemic zone during the time corresponding to drug infusion. Similar inotropic actions of MCI-154 were observed in both normal and postischemic, reperfused hearts, indicating significant contractile reserve to be present in 'stunned' myocardium. Global contractility as measured by peak positive dP/dt was significantly increased in both groups. In postischemic, reperfused myocardium 90 min after initiation of reflow, regional segment function remained depressed at 44% of control but improved to 93% of control after administration of MCI-154. In addition, MCI-154 produced significant dose-related decreases in mean arterial pressure, left ventricular end-diastolic pressure, end-diastolic segment length, and diastolic coronary vascular resistance. The data demonstrate that in addition to producing beneficial hemodynamic changes, MCI-154, a new non-sympathomimetic inotropic agent, markedly enhances regional contractility of postischemic, reperfused myocardium.
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
J C
JC
Wynsen
T M
TM
Shimshak
K C
KC
Preuss
G J
GJ
Gross
H L
HL
Brooks
D C
DC
Warltier
D000818:Animals; D003327:Coronary Disease / Q000503:physiopathology; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D011724:Pyridazines; D014665:Vasodilator Agents; C052228:MCI 154