Developments in cardioprotection: "polarized" arrest as an alternative to "depolarized" arrest

During cardiac surgery or cardiac transplantation, the heart is subjected to varying periods of global ischemia. The heart must be protected during this ischemic period to avoid additional injury, and techniques have been developed that delay ischemic injury and minimize reperfusion injury. Almost universally, this involves using a hyperkalemic cardioplegic solution and these solutions have become the gold standard for myocardial protection for more than 20 years. Despite the extensive and continued research aimed at improving these basic hyperkalemic cardioplegic solutions, patients undergoing surgery almost invariably experience some degree of postoperative dysfunction. It is likely that this relates to the depolarizing nature of hyperkalemic solutions, which results in ionic imbalance caused by continuing transmembrane fluxes and the consequent maintenance of high energy phosphate metabolism, even during hypothermic ischemia. A potentially beneficial alternative to hyperkalemic cardioplegia is to arrest the heart in a "hyperpolarized" or "polarized" state, which maintains the membrane potential of the arrested myocardium at or near to the resting membrane potential. At these potentials, transmembrane fluxes will be minimized and there should be little metabolic demand, resulting in improved myocardial protection. Recent studies have explored these alternative concepts for myocardial protection. The use of compounds such as adenosine or potassium channel openers, which are thought to induce hyperpolarized arrest, have demonstrated improved protection after normothermic, or short periods of hypothermic, ischemia when compared to hyperkalemic (depolarized) arrest. Similarly, studies from our own laboratory, in which the sodium channel blocker, tetrodotoxin, was used to induce polarized arrest (demonstrated by direct measurement of membrane potential during ischemia) was also shown to provide better recovery of function after 5 hours of long-term hypothermic (7.5 degrees C) storage. These promising initial studies need to be consolidated before experimental promise becomes clinical reality.