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Ann Thorac Surg 1997;63:153-161
© 1997 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Adenosine Prevents Hyperkalemia-Induced Calcium Loading in Cardiac Cells: Relevance for Cardioplegia

Aleksander Jovanovi, MD, Alexey E. Alekseev, PhD, Jóse R. López, MD, Win K. Shen, MD, Andre Terzic, MD

Division of Cardiovascular Diseases and Departments of Internal Medicine and Pharmacology, Mayo Clinic, Mayo Foundation, Rochester, Minnesota

Accepted for publication July 24, 1996.

Background. Hyperkalemic cardioplegic solutions effectively arrest the heart but also induce membrane depolarization, which could lead to intracellular Ca²⁺ loading and contribute to ventricular dysfunction associated with cardiac operations. Adenosine, which possesses cardioprotective properties, has been proposed as an adjunct to conventional cardioplegic solutions. However, it is not known whether adenosine supplementation enables cardiac cells to withstand hyperkalemia-induced Ca²⁺ loading.

Methods. Single ventricular cardiomyocytes were isolated from guinea pig hearts, loaded with a Ca²⁺-sensitive fluorescent probe, and imaged by digital epifluorescent microscopy. The emitted fluorescence of the probe, a measure of the intracellular Ca²⁺ concentration, was recorded from single myocytes during hyperkalemic challenges in the absence and the presence of adenosine to assess the protective effectiveness of this agent.

Results. Hyperkalemic solutions induced intracellular Ca²⁺ loading (estimated intracellular Ca²⁺ concentration, 88 ± 5 nmol/L before and 1,825 ± 112 nmol/L after addition of 16 mmol/L KCl). Adenosine (1 mmol/L) prevented K⁺-induced Ca²⁺ loading (intracellular Ca²⁺ concentration, 86 ± 6 nmol/L before and 85 ± 8 nmol/L after exposure to K⁺). Whereas glyburide (3 µmol/L), an antagonist of adenosine triphosphate–sensitive K⁺ channels, had no effect, staurosporine (200 nmol/L) and chelerythrine (5 µmol/L), two inhibitors of protein kinase C, did abolish the action of adenosine.

Conclusions. Adenosine prevents hyperkalemia-induced Ca²⁺ loading in cardiomyocytes. This effect is due to a direct action on ventricular cells, as the preparation employed was free from atrial, neuronal, and vascular elements, and appears to be mediated through a protein kinase C–dependent mechanism. The property of adenosine to prevent hyperkalemia-induced Ca²⁺ loading may contribute to the cytoprotective efficacy of this agent as an adjunct to conventional hyperkalemic cardioplegic solutions.

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