Ann Thorac Surg 2001;71:1288-1289
© 2001 The Society of Thoracic Surgeons
Invited commentary
Michael E. Jessen, MDa
a Department of Thoracic and Cardiovascular Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390–8879, USA
e-mail: jessen{at}email.swmed.edu
Potassium-based cardioplegic solutions have long been used by surgeons to reduce the damaging effects of ischemia. The basic premise has been that depolarized arrest reduces cardiac work and myocardial energy demands, thereby increasing ischemic tolerance. This manuscript by Toyoda and colleagues provides new data that suggests that other mechanisms may be involved. In a carefully controlled series of experiments they suggest a role for ATP-sensitive potassium (KATP) channels in the cardioprotection afforded by cardioplegia consisting of K+ and Mg++. This work builds on studies from other investigators that have suggested that KATP channels serve an important role in modulating the effects of myocardial ischemia. Two KATP subtypes have been identified—sarcolemmal and mitochondrial—but it is the latter that appears to be most important to myocardial protection. Some recent experiments have demonstrated that KATP activation may be an important mechanism behind the endogenous cardioprotective phenomenon known as preconditioning. These results have led to attempts to manipulate KATP channels as a therapy for acute myocardial ischemia. In general, administration of potassium channel openers in pharmacologic doses prior to the onset of ischemia has led to a reduction in ischemic damage.
In present study, manipulations of KATP channels had dramatic effects on the degree of infarct reduction induced by K/Mg cardioplegia. In particular, the addition of diazoxide (a potent mitochondrial KATP channel opener) effectively reduced infarct size beyond that observed with cardioplegia alone, while 5-hydroxydecanoate (a channel blocker) reduced the effectiveness of cardioplegia. The effects of cardioplegia were not altered by blockade of sarcolemmal KATP channels. Thus potassium-based cardioplegia may do much more than reduce cardiac energy demands. It may exert an effect on ion channels within the mitochondria, an effect which may influence mitochondrial depolarization, calcium accumulation, matrix volume, or ATP production. These effects may be very important in the overall picture of ischemic tolerance. More work needs to be done to determine the molecular mechanisms of cardioprotection provided by KATP activation and by potassium cardioplegia. However, this line of investigation appears promising and may suggest strategies to extend our ability to protect the heart during cardiac surgery.
Related Article
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Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic protection
- Yoshiya Toyoda, Sidney Levitsky, and James D. McCully
Ann. Thorac. Surg. 2001 71: 1281-1288.
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