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

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Ko Y, Morita K, Nagahori R, Kinouchi K, Shinohara G, Kagawa H, Hashimoto K

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

Ann Thorac Cardiovasc Surg. 2009 Oct;15(5):311-7.

PubMed ID

19901885 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amrinone	cGMP-inhibited 3',5'-cyclic phosphodiesterase A	Protein	Humans	Yes	Inhibitor	Details