title: Recruitment of inotropic reserve in "stunned" myocardium by the cardiotonic agent AR-L 57.
abstract: Contractile dysfunction of reversibly injured, reperfused myocardium can be enhanced by inotropic interventions. A decrease in the Ca-sensitivity of contractile proteins with slow recovery during reperfusion has been suggested as a potential mechanism underlying this postischemic dysfunction. We therefore tested the effects of the cardiotonic agent AR-L 57 (1 mg/kg i.v.) in six anesthetized, vagotomized dogs during constant atrial pacing at 192 +/- 6 beats/min. Before ischemia, AR-L 57 increased left ventricular pressure from 131 +/- 22 to 138 +/- 21 mm Hg and maximum dP/dt from 3,022 +/- 1,427 to 4,337 +/- 2,608 mm Hg/s. Mean systolic thickening velocity of the posterior myocardium was increased from 8.9 +/- 1.1 to 11.7 +/- 1.1 mm/s. After release of a 15 min LCX-occlusion which caused complete regional akinesia, baseline function in the posterior myocardium was severely depressed and only gradually returned towards control values over 8 h of reperfusion. AR-L 57 increased systolic thickening velocity at 10 min, 4 and 8 h reperfusion to a similar extent as before ischemia. With reference to a purported Ca-sensitizing mechanism underlying the positive inotropic action of AR-L 57, our data suggest no change in the Ca-sensitivity of reperfused myocardium.
authors.affiliation: Abt. Herz- und Kreislaufphysiologie, Universität Düsseldorf.
authors.forename: G
authors.initials: G
authors.lastname: Heusch
authors.forename: S
authors.initials: S
authors.lastname: Schäfer
authors.forename: K
authors.initials: K
authors.lastname: Kröger
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis
chemical_list: D002316:Cardiotonic Agents; D007093:Imidazoles; C012633:AR-L 57 CL