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Ann Thorac Surg 2002;73:1259-1260
© 2002 The Society of Thoracic Surgeons

Invited commentary

^a Director of Cardiac Surgery, Austin & Repatriation Medical Centre, Level 5, Studley Rd, Heidelberg, Victoria 3084, Australia

e-mail: Brian.Buxton{at}armc.org.au

Potassium channel openers (KCOs) have been used to treat ischemic heart disease and hypertension by reducing the oxygen demand and promoting vasodilation and bradycardia KCOs hyperpolarize the cell and mitochondrial membranes, operating through the potassium (K⁺) ATP-sensitive channels. Because some of these actions mimic those following hyperkalemic-induced cardioplegic arrest during open-heart surgery, it has been suggested that KCOs may have a role as cardioplegic agents. KCO induced cardiac arrest has been followed by improved myocardial contractile function and a reduction of the extracellular matrix damage compared with conventional K⁺ cardioplegia.

Potassium channel openers (KCOs) may also play a role with cerebral protection after hypothermic cardiac arrest. The heart and brain are very dependent on oxidative phosphorylation and are particularly sensitive to ischemic injury. Both are rich in mitochondrial potassium ATP-sensitive channels. KCOs decrease membrane potential and the Na⁺-Ca²⁺calcium exchange. They lower oxygen free radical production, and may alter glycolytic pathways during ischemia. The mitrochondrial K⁺ ATP-sensitive opener diazoxide has been found to reduce brain injury following deep hypothermic circulatory arrest in the dog [1].

Doctor Hong-Yu Li and colleagues hypothesized that the benefit of KCOs is a result of limiting the increase of intracellular calcium, oxygen demand and attenuation of the Na⁺-Ca²⁺ exchange during reperfusion. They investigated the outward current, a measure of Na⁺-Ca²⁺ exchange activity in a single rat myocyte following aprikalim (APK) induced hyperkalemia and correlated the exchange activity with myocyte function. They confirmed amelioration of the Na⁺-Ca²⁺ exchange current and improved myocyte function. They suggested the beneficial effects of APK was not due solely to K⁺ efflux through the K ATP-sensitive channels but to inhibition of the Na⁺-Ca²⁺ exchange which limited the adverse effects of hyperkalemic elevated levels of intracellular calcium. The authors have provided insight into the complex mechanism surrounding KCO cardioplegia. Their research raises three additional questions. Are there any other factors affecting intracellular calcium? How does hyperkalemia activate the Na⁺-Ca²⁺ exchange? And how does opening the K⁺ ATP-sensitive channel attenuate the Na⁺-Ca²⁺ exchange?

Potassium channel openers (KCOs) are potentially valuable agents which could improve the outcome after cardiac surgery. Before KCOs are recommended for use as cardioplegic agents or to protect the brain, safety and efficacy studies are required to define the balance between the beneficial effects of reducing postischemic myocardial and cerebral dysfunction, and the potentially lethal effects of these agents such as arrhythmias.

References

1. Shake J.G., Peck E.A., Marban E., et al. Pharmacologically induced preconditioning with diazoxide: a novel approach to brain protection. Ann Thorac Surg 2001;72:1849-1854.[Abstract/Free Full Text]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Brian F. Buxton Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Buxton, B. F. Search for Related Content PubMed Articles by Buxton, B. F. Related Collections Myocardial protection Related Article