Effect of a calcium-sensitizing agent, levosimendan, on the postcardioplegic inotropic response of the myocardium.
Myocardial contractile function after coronary artery bypass graft surgery is often depressed and may require inotropic support, particularly in patients on treatment with beta-adrenergic and Ca2+ blockers. In view of the increase in cytosolic Ca2+ during early reperfusion, use of Ca2+ sensitizing agents may be preferable to adrenergic agonists for enhancement of contractile function after cardioplegic arrest. The aim of this study was to assess the efficacy of the Ca2+ sensitizer, levosimendan, as an inotrope on the mechanical recovery of hearts after normothermic and hypothermic cardioplegic arrest in the absence and presence of Ca2+ and beta-blockers. Isolated perfused working guinea pig hearts were perfused in the absence or presence of propranolol (10(-6) M) and/or nifedipine (10(-8) M), subjected to 45 minutes of normothermic or 180 minutes of hypothermic cardioplegic arrest, reperfused, and exposed to increasing concentrations of levosimendan (10(-9) to 10(-6) M). Levosimendan (10(-7) to 10(-6) M) has positive inotropic, chronotropic, and vasodilatory effects on normoxic perfused control hearts, as well as during reperfusion after 45 minutes of normothermic cardioplegic arrest. Similar effects were elicited in the presence of the blockers. Levosimendan had no stimulatory effect during reperfusion of hearts subjected to prior hypothermic arrest. Except for the increase in heart rate, the effects of levosimendan on functional performance during reperfusion were comparable with those of adrenaline. Levosimendan elicits a positive inotropic and chronotropic response during reperfusion of hearts after normothermic cardioplegic arrest, both in the absence and presence of Ca2+ and beta-adrenergic blockers.
Department of Medical Physiology and Biochemistry, University of Stellenbosch, Faculty of Medicine, Tygerberg, Republic of South Africa. alo@gerga.sun.ac.za
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Lochner
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Colesky
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Genade
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D006835:Hydrazones / Q000494:pharmacology*; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011217:Practolol / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D000077464:Simendan
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D006835:Hydrazones; D011724:Pyridazines; D011943:Receptors, Adrenergic, beta; D000077464:Simendan; D011217:Practolol