HYPERPOLARIZED ARREST ATTENUATES MYOCARDIAL STUNNING FOLLOWING GLOBALSURGICAL ISCHEMIA - AN ALTERNATIVE TO TRADITIONAL HYPERKALEMIC CARDIOPLEGIA

There is clinical evidence that myocardial stunning is a frequent sequ ela of surgical global ischemia, despite our modern techniques of myoc ardial protection. The ubiquitous usage of hyperkalemic depolarizing s olutions in all forms of cardioplegia may be partly responsible for th is phenomenon because of the known ongoing metabolic requirements and damaging transmembrane ionic fluxes that occur at depolarized membrane potentials. Cardiac arrest at hyperpolarized potentials, the natural resting state of the heart, may avoid the shortcomings of depolarized arrest and provide an alternative means of myocardial protection. To t est this hypothesis, a potassium channel opener, aprikalim, was used t o induce hyperpolarized arrest in an isolated rabbit heart model. Apri kalim was able to produce sustained and reproducible electromechanical arrest that was reversible by reperfusion. When compared with depolar ized hyperkalemic arrest, hyperpolarized arrest afforded better protec tion after short 20-minute periods of global ischemia and resulted in less myocardial stunning. Moreover, aprikalim was able to significantl y prolong the time to ischemic contracture and improve functional reco very after the onset of ischemic contracture when compared with either traditional hyperkalemic cardioplegia or no cardioplegia at all. Ther e was a dose dependence to the protective effect of aprikalim. Prelimi nary studies in the intact porcine cardiopulmonary bypass model also h ave revealed that hyperpolarized arrest can effectively protect the he art during surgical global ischemia.