title: Myocardial cyclic AMP augmentation with high-dose PDEIII inhibitor in terminal warm blood cardioplegia.
abstract: OBJECTIVE
  Phosphodiesterase (PDE) III inhibitors have been reported in various cellular protective activities via the cyclic adenosine monophosphate (cAMP) pathway. We investigated the effects of amrinone on ischemia/reperfusion injury and intracellular calcium (Ca2+) handling if utilized as a component of terminal warm blood cardioplegia (TWBCP).
  
  
  METHODS
  Anesthetized pig hearts were subjected to 90-min global ischemia with single-dose crystalloid cardioplegia, followed by 30-min reperfusion under cardiopulmonary bypass. The animals were divided into three groups according to the contents of TWBCP (n = 5 each): Control, no TWBCP; TWBCP, no additive; Amrinone, TWBCP with amrinone. The time course of cardiac function and biochemical samples were measured. Further, coronary perfusion and ventricular arrhythmia were evaluated during reperfusion.
  
  
  RESULTS
  Cardiac function improved with amrinone. Specifically, the amrinone group showed an increase of myocardial cAMP (p <0.05) and a suppression of creatine kinase, troponin-T, and lipid peroxide after reperfusion (p <0.05); many cases also showed much improvement of coronary perfusion and spontaneous resuscitation after global ischemia.
  
  
  CONCLUSIONS
  Ischemia and/or reperfusion deplete myocardial cAMP, leading to impaired Ca2+ handling and further to cardiac dysfunction. High-dose PDEIII inhibitor in TWBCP may replenish myocardial cAMP and promote rapid and sustained cardiac functional recovery with various cellular protective effects after open-heart surgery.
authors.affiliation: Department of Cardiovascular Surgery, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ko
authors.forename: Kiyozo
authors.initials: K
authors.lastname: Morita
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nagahori
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kinouchi
authors.forename: Gen
authors.initials: G
authors.lastname: Shinohara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kagawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000676:Amrinone / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism*; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism; D004195:Disease Models, Animal; D006324:Heart Arrest, Induced; D015227:Lipid Peroxidation / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology*; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000494:pharmacology*; D017680:Potassium Compounds / Q000494:pharmacology; D013552:Swine; D013997:Time Factors; D020107:Troponin T / Q000097:blood; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D058987:Phosphodiesterase 3 Inhibitors; D010726:Phosphodiesterase Inhibitors; D017680:Potassium Compounds; D020107:Troponin T; C018369:potassium cardioplegic solution; D000242:Cyclic AMP; D003402:Creatine Kinase; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000676:Amrinone