title: Release of a stable cardiodepressant mediator after myocardial ischaemia during reperfusion.
abstract: OBJECTIVE
  The aim of this study was to investigate whether cardiodepressant mediators are released after myocardial ischaemia during reperfusion.
  
  
  METHODS
  Using a double heart model, the effect of the reoxygenated coronary effluent of an isolated guinea pig heart on a sequentially perfused second heart was studied under control conditions and after 10 min ischaemia of the first heart. Investigation of the modulating role of known autacoids took place by using free radical scavengers, an NO synthase inhibitor and adenosine receptor antagonists. In order to identify the chemical nature of cardiac metabolites, the coronary effluent was also subjected to different chemical treatment modes.
  
  
  RESULTS
  No haemodynamic changes were observed during sequential perfusion under control conditions. After 10 min of global ischaemia in heart I, a marked decrease in LVP (-22%), LVdP/dtmax (-43%), LVdP/dtmin (-41%) and coronary perfusion pressure (-25%) was measured in heart II during sequential perfusion. The negative inotropic effect was rapid in onset and reversible within 5 min; free radicals, nitric oxide and adenosine were not involved. Storage of the coronary effluent of the first heart up to 24 h, heating, or protease treatment did not modify its cardiodepressant effects on the second sequentially perfused heart.
  
  
  CONCLUSIONS
  These results suggest the release--from an isolated heart after ischaemia during reperfusion--of a cardiodepressant mediator which induces a potent reversible negative inotropic effect on a sequentially perfused heart. The mediator is stable and in all probability not a protein.
authors.affiliation: Medizinische Klinik und Poliklinik I, Charité, Humboldt-Universität zu Berlin, Germany.
authors.forename: S B
authors.initials: SB
authors.lastname: Felix
authors.forename: V
authors.initials: V
authors.lastname: Stangl
authors.forename: T M
authors.initials: TM
authors.lastname: Frank
authors.forename: C
authors.initials: C
authors.lastname: Harms
authors.forename: T
authors.initials: T
authors.lastname: Berndt
authors.forename: R
authors.initials: R
authors.lastname: Kästner
authors.forename: G
authors.initials: G
authors.lastname: Baumann
mesh_terms: D000243:Adenosine Deaminase / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D012898:Autacoids / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D003864:Depression, Chemical; D005260:Female; D016166:Free Radical Scavengers; D006168:Guinea Pigs; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010477:Perfusion; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011753:Pyrones / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D012898:Autacoids; D016166:Free Radical Scavengers; D009281:Naphthalenes; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011753:Pyrones; D014970:Xanthines; D019335:Nitroarginine; C057837:3,7-dimethyl-1-propargylxanthine; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; C051360:1,3-dipropyl-8-cyclopentylxanthine; D002374:Catalase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D010741:Phospholipases A; D000243:Adenosine Deaminase; D008790:Metoprolol; D013805:Theobromine