Adenosine prevents K+-induced Ca2+ loading: insight into cardioprotection during cardioplegia.
In clinical practice, hyperkalemic cardioplegia induces sarcolemmic depolarization, and therefore is used to arrest the heart during open heart operations. However, the elevated concentration of K+ that is present in cardioplegic solutions promotes intracellular Ca2+ loading, which could aggravate ventricular dysfunction after cardiac operations. This review highlights recent findings that have established, at the single cell level, the protective action of adenosine against hyperkalemia-induced Ca2+ loading. When it was added to hyperkalemic cardioplegic solutions, adenosine, at millimolar concentrations and through a direct action on ventricular cardiomyocytes, prevented K+-induced Ca2+ loading. This action of adenosine required the activation of protein kinase C, and it was effective only in cardiomyocytes with low diastolic Ca2+ levels. Of importance, adenosine did not diminish the magnitude of K+-induced membrane depolarization, allowing unimpeded cardiac arrest. Taken together, these findings provide direct support for the idea that adenosine is valuable when used as an adjunct to hyperkalemic cardioplegia. This idea has emerged from previous clinical studies that have shown improvement of the clinical outcome after cardiac operations when adenosine or related substances were used to supplement cardioplegic solutions. Further studies are required to define more precisely the mechanism of action of adenosine, and the conditions that may determine the efficacy of adenosine as a cytoprotective supplement to cardioplegia.
Jovanović
A
A
Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905, USA.
Lopez
J R
JR
Alekseev
A E
AE
Shen
W K
WK
Terzic
A
A
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002314:Cardioplegic Solutions / Q000737:chemistry / Q000494:pharmacology; D006324:Heart Arrest, Induced / Q000009:adverse effects; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D018754:Ventricular Dysfunction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control
D002314:Cardioplegic Solutions; D020011:Protective Agents; D000241:Adenosine; D011188:Potassium; D002118:Calcium