title: Dopamine and lipophilic derivates protect cardiomyocytes against cold preservation injury.
abstract: Donor heart allografts are extremely susceptible to prolonged static cold storage. Because donor treatment with low-dose dopamine improves clinical outcome after heart transplantation, we tested the hypothesis that dopamine and its lipophilic derivate, N-octanoyl dopamine (NOD), protect cardiomyocytes from cold storage injury. Neonatal rat cardiomyocytes were treated with dopamine or NOD or left untreated and subsequently subjected to static cold storage (8-12 hours). Dopamine- and NOD-treated cardiomyocytes displayed a better viability compared with untreated cells after hypothermia. In untreated cardiomyocytes, cell damage was reflected by lactate dehydrogenase (LDH) release and a decrease in intracellular ATP. NOD was approximately 20-fold more potent than dopamine. Similarly to cardiomyocytes in vitro, rat hearts perfused with NOD before explantation showed significantly lower LDH release after static cold storage. ATP regeneration and spontaneous contractions after cold storage and rewarming only occurred in treated cardiomyocytes. Hypothermia severely attenuated isoprenaline-induced cAMP formation in control but not in dopamine- or NOD-treated cells. Esterified derivates of NOD with redox potential and lipophilic side chains reduced cell damage during cold storage similarly to NOD. In contrast to dopamine, neither NOD nor its derivates induced a significant β-adrenoceptor-mediated elevation of cellular cAMP levels. The β1-adrenoceptor antagonist atenolol and D1/D2 receptor antagonist fluphenazine had no impact on the protective effect of NOD or dopamine. We conclude that dopamine as well as NOD treatment mitigates cold preservation injury to cardiomyocytes. The beneficial effects are independent of β-adrenoceptor or dopaminergic receptor stimulation but correlate with redox potential and lipophilic properties.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology (C.V., T.W.), Fifth Medical Clinic (M.C.H., R.S., U.B., P.S., B.K.K., S.H., B.A.Y.), and Department of Anesthesiology (C.T.), University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany; and Institute of Pharmacology, University Medical Center Göttingen, Heart Center, Georg-August-University Medical School Göttingen, Göttingen, Germany (C.V., A.E.-A.).
authors.forename: Christiane
authors.initials: C
authors.lastname: Vettel
authors.forename: Maximilia C
authors.initials: MC
authors.lastname: Hottenrott
authors.forename: Rahel
authors.initials: R
authors.lastname: Spindler
authors.forename: Urs
authors.initials: U
authors.lastname: Benck
authors.forename: Peter
authors.initials: P
authors.lastname: Schnuelle
authors.forename: Charalambos
authors.initials: C
authors.lastname: Tsagogiorgas
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Krämer
authors.forename: Simone
authors.initials: S
authors.lastname: Hoeger
authors.forename: Ali
authors.initials: A
authors.lastname: El-Armouche
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieland
authors.forename: Benito A
authors.initials: BA
authors.lastname: Yard
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003080:Cold Temperature / Q000009:adverse effects; D015925:Cryopreservation / Q000379:methods; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D009926:Organ Preservation / Q000009:adverse effects* / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; C554838:N-octanoyldopamine; D004298:Dopamine