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Adenosine prevents K+-induced Ca2+ loading: insight into cardioprotection during cardioplegia
A Jovanović1, J R Lopez, A E Alekseev
1Department of Medicine, Mayo Clinic, Mayo Foundation, Rochester, Minnesota 55905, USA.
Insights
Adenosine protects heart cells from calcium overload during heart surgery. This finding supports using adenosine as a supplement to hyperkalemic cardioplegia for improved outcomes in cardiac operations.
Area of Science:
- Cardiology
- Cellular Biology
- Pharmacology
Background:
- Hyperkalemic cardioplegia is standard for cardiac arrest during open-heart surgery.
- Elevated potassium in cardioplegia can cause intracellular calcium loading, potentially worsening post-operative ventricular function.
Purpose of the Study:
- To review evidence on adenosine's protective effects against hyperkalemia-induced calcium loading in cardiomyocytes.
- To evaluate adenosine's potential as an adjunct to hyperkalemic cardioplegia.
Main Methods:
- Review of single-cell studies examining adenosine's action on ventricular cardiomyocytes.
- Analysis of adenosine's effects on potassium-induced calcium loading and membrane depolarization.
Main Results:
- Adenosine, when added to hyperkalemic cardioplegic solutions, prevented potassium-induced calcium loading in cardiomyocytes.
- Adenosine's protective effect required protein kinase C activation and was dependent on low diastolic calcium levels.
- Adenosine did not interfere with the membrane depolarization necessary for cardiac arrest.
Conclusions:
- Adenosine demonstrates a direct cytoprotective action against hyperkalemia-induced calcium loading in cardiomyocytes.
- Findings support adenosine's value as an adjunct to hyperkalemic cardioplegia, aligning with previous clinical observations of improved outcomes.
- Further research is needed to fully elucidate adenosine's mechanism and optimize its use in cardioplegia.
Abstract:
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.