Adenosine and its role in cardioplegia : experimental evaluation in the isolated rat heart and in an-vivo primate model

Doctoral Thesis

1997

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University of Cape Town

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This study was designed to investigate the role of adenosine, an endogenous cardioprotectant agent, without high potassium and as cardioplegic additive to high potassium solutions. Adenosine cardioplegia and potassium cardioplegia supplemented by adenosine (K + ADO) were investigated in terms of hemodynamic, metabolic and ultrastructural recovery in the isolated rat heart and in the in-vivo baboon model during periods of global myocardial ischemia, simulating the clinical situation during open heart surgery. The results obtained in both models show that adenosine improved postischemic hemodynamic function when used without high potassium cardioplegia. The combination of adenosine and high potassium was less effective in both models in terms of hemodynamic recovery; however, improved rhythm stability and coronary vasodilatation were still present. In addition adenosine alone was able to induce fast electromechanical arrest in the isolated rat heart. However, failure of even high concentrations of adenosine to limit ventricular fibrillation in the baboon exclude its use as cardioplegic agent on its own without additional interventions. It appears likely that adenosine without high potassium is cardioprotective via activation of A₁ receptors and opening of ATP-sensitive potassium channels, a mechanism which is probably non-functional in a high potassium environment. In view of the limited cardioprotection achieved with the combination of adenosine and high potassium further studies should aim for additional interventions to induce cardioplegia with adenosine and normokalemic solutions.
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