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

During cardiac surgery or cardiac transplantation, the heart is subjected t o varying periods of global ischemia. The heart must be protected during th is ischemic period to avoid additional injury, and techniques have been dev eloped that delay ischemic injury and minimize reperfusion injury. Almost u niversally, this involves using a hyperkalemic cardioplegic solution and th ese solutions have become the gold standard for myocardial protection for m ore than 20 years. Despite the extensive and continued research aimed at im proving these basic hyperkalemic cardioplegic solutions, patients undergoin g surgery almost invariably experience some degree of postoperative dysfunc tion. It is likely that this relates to the depolarizing nature of hyperkal emic solutions, which results in ionic imbalance caused by continuing trans membrane fluxes and the consequent maintenance of high energy phosphate met abolism, even during hypothermic ischemia. A potentially beneficial alterna tive to hyperkalemic cardioplegia is to arrest the heart in a "hyperpolariz ed" or "polarized" state, which maintains the membrane potential of the arr ested myocardium at or near to the resting membrane potential. At these pot entials, transmembrane fluxes will be minimized and there should be little metabolic demand, resulting in improved myocardial protection. Recent studi es 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 protect ion after normothermis or short periods of hypothermic ischemia when compar ed to hyperkalemic (depolarized) arrest. Similarly, studies from our own la boratory, in which the sodium channel blocker, tetrodotoxin, was used to in duce polarized arrest (demonstrated by direct measurement of membrane poten tial during ischemia) was also shown to provide better recovery of function after 5 hours of long-term hypothermic (7.5 degrees C) storage. These prom ising initial studies need to be consolidated before experimental promise b ecomes clinical reality. (C) 1999 by The Society of Thoracic Surgeons.