title: Calcium sensitizer EMD 57033, but not the beta1-adrenoreceptor agonist dobutamine, increases mechanical efficiency in stunned myocardium.
abstract: External work, efficiency of energy transfer (EET), and mechanical efficiency (defined as the ratio of external work over myocardial oxygen consumption (MVO2) are reduced in stunned myocardium. We therefore evaluated how inotropic stimulation by dobutamine and the calcium sensitizer EMD 57033 affected the regional stress-strain relationship as, from which contractility (E(es)), external work at the working point (EWwp), maximal external work (EWmax), EETwp (%), and EETmax are determined. Thirty minutes after regional stunning in 11 open chest pigs by two 10-min coronary occlusions separated by 10 min of reperfusion, dobutamine (0.5, 1, and 2 microg x kg(-1) x min(-1)) was infused, after an ample washout period followed by infusion of EMD 57033 (0.05, 0.1, 0.2 mg x kg(-1) x min(-1)). Stunning decreased E(es) (30%), EWwp (56%), EWmax (63%), EETwp (34%), EETmax (33%) and mechanical efficiency (55%), but MVO2 was unaffected. EWwp, EWmax, EETwp, and EETmax increased similarly with the two drugs, whereas MVO2 increased only after dobutamine. Consequently, mechanical efficiency increased linearly with contractility during EMD 57033 infusion but remained constant during infusion of dobutamine.
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus Medical Center Rotterdam, The Netherlands.
authors.forename: Serge A I P
authors.initials: SA
authors.lastname: Trines
authors.forename: Carlo A G
authors.initials: CA
authors.lastname: Smits
authors.forename: Joost
authors.initials: J
authors.lastname: van der Moer
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: Slager
authors.forename: Pieter D
authors.initials: PD
authors.lastname: Verdouw
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D004734:Energy Metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D017682:Myocardial Stunning / Q000378:metabolism*; D010101:Oxygen Consumption; D011804:Quinolines / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013552:Swine; D013829:Thiadiazines / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; D004280:Dobutamine; D002118:Calcium