Hyperkalemic depolarized
cardiac arrest has been the cornerstone of myocardial protection during cardiac surgery for more than 30 years. Many of the advances in myocardial protection seek to minimize the cellular damage and to reduce the ongoing metabolic processes occurring as a direct consequence of the depolarized state. Ideally,
cardiac arrest at hyperpolarized cellular membrane potentials--the natural resting state of the heart--will meet all the requirements of modern
cardioplegia, namely, electromechanical
asystole and cardiac relaxation, while preserving the vital integrity of the heart itself.
METHODS AND RESULTS: To determine whether activation of
adenosine triphosphate-sensitive
potassium channels by pharmacologic agents could produce hyperpolarized
cardiac arrest, we tested the ability of
aprikalim, a known
adenosine triphosphate-sensitive
potassium channel opener, to arrest the intact beating heart. In a normothermic (37 degrees C) isolated rabbit heart preparation,
aprikalim was found to rapidly shorten the action potential duration and produce cardiac
asystole that was maintained during 20 minutes of "no-flow" global
ischemia without a rise in end-diastolic pressure. Cardiac rhythm and function were fully restored by reperfusion alone (developed pressure was 100.6% +/- 7.9% of prearrest value after 30 minutes of reperfusion). In contrast, 20 minutes of unprotected normothermic global
ischemia resulted in a 2.7 +/- 0.55 mmHg rise in end-diastolic pressure and only 58.2% +/- 3.8% recovery of developed pressure after 30 minutes of reperfusion. By way of comparison, 20 minutes of standard hyperkalemic depolarized normothermic rest was accompanied by a 1.2 +/- 0.6 mmHg rise in end-diastolic pressure and only 80.8% +/- 2.6% recovery of developed pressure after 30 minutes of reperfusion. To directly compare hyperkalemic depolarized
cardiac arrest to hyperpolarized
cardiac arrest induced by
potassium channel openers and to better define the characteristics of such hyperpolarized arrest, we studied a fixed (4 mmHg rise in end-diastolic pressure--
contracture) ischemic injury model. The time to development of the
contracture was prolonged by hyperkalemic arrest (35.8 +/- 1.7 minutes) and significantly more so by hyperpolarized arrest (47.0 +/- 3.3 minutes) when compared with that of unprotected hearts (24.0 +/- 1.2 minutes). Moreover,
aprikalim resulted in significantly better postischemic recovery of function (developed pressure was 69.0% +/- 6.7% of prearrest value after 30 minutes of reperfusion) than after no
cardioplegia (45.4% +/- 7.5%) or standard hyperkalemic
cardioplegia (44.3% +/- 5.7%).
CONCLUSIONS: Pharmacologic activation of
adenosine triphosphate-sensitive
potassium channels can result in predictable and sustainable hyperpolarized
cardiac arrest that is reversible by reperfusion. This method of myocardial protection was found to fully preserve cardiac electromechanical function after a 20-minute period of global normothermic
ischemia. Furthermore, hyperpolarized arrest induced by
potassium channel openers significantly prolonged the period to the development of
contracture and afforded a significantly better postischemic recovery of function than obtained in either hearts protected with hyperkalemic depolarized arrest or those not protected by any form of
cardioplegia.