Myocardial cyclic AMP augmentation with high-dose PDEIII inhibitor in terminal warm blood cardioplegia

Yoshihiro Ko, Kiyozo Morita, Ryuichi Nagahori, Katsushi Kinouchi, Gen Shinohara, Hiroshi Kagawa, Kazuhiro Hashimoto

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Purpose: 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)311-317
Number of pages7
JournalAnnals of Thoracic and Cardiovascular Surgery
Volume15
Issue number5
Publication statusPublished - Oct 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Gastroenterology

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