Preservation of myocyte contractile function after hyperthermic cardioplegic arrest by activation of ATP-sensitive potassium channels.
BACKGROUND
Left ventricular (LV) dysfunction can occur after hyperkalemic cardioplegic arrest and subsequent reperfusion and rewarming. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels within the myocyte sarcolemma has been shown to be cardioprotective for myocardial reperfusion injury and ischemia and may play a contributory role in preconditioning for cardioplegic arrest. Accordingly, the present study tested the hypothesis that cardioplegic arrest and activation of KATP channels by a potassium channel opener (PCO) would attenuate alterations in ionic homeostasis and improve myocyte contractile function.


RESULTS
Porcine LV myocytes were isolated and randomly assigned to the following treatment groups: normothermic control, incubation in cell culture media for 2 hours at 37 degrees C (n=60); hyperkalemic cardioplegia, incubation for 2 hours in hypothermic hyperkalemic cardioplegic solution (n=60); or PCO/cardioplegia, incubation in cardioplegic solution containing 100 micromol/L of the PCO aprikalim (n=60). Hyperkalemic cardioplegia and rewarming caused a significant reduction in myocyte velocity of shortening compared with normothermic control values (33+/-2 versus 66+/-2 microm/s, P<.05). Cardioplegic arrest with PCO supplementation significantly improved indices of myocyte contractile function when compared with hyperkalemic cardioplegia (58+/-4 microm/s, P<.05). Myocyte intracellular calcium increased during hyperkalemic cardioplegic arrest compared with baseline values (147+/-2 versus 85+/-2 nmol/L, P<.05). The increase in intracellular calcium was significantly reduced in myocytes exposed to the PCO-supplemented cardioplegic solution (109+/-4 nmol/L, P<.05).


CONCLUSIONS
Cardioplegic arrest with simultaneous activation of KATP channels preserves myocyte contractile processes and attenuates the accumulation of intracellular calcium. These findings suggest that changes in intracellular calcium play a role in myocyte contractile dysfunction associated with cardioplegic arrest. Moreover, alternative strategies may exist for preservation of myocyte contractile function during cardioplegic arrest.
Dorman
B H
BH
Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston 29425, USA.
Hebbar
L
L
Hinton
R B
RB
Roy
R C
RC
Spinale
F G
FG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002314:Cardioplegic Solutions; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D006358:Hot Temperature; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009206:Myocardium / Q000166:cytology; D010847:Picolines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011714:Pyrans / Q000494:pharmacology*; D013552:Swine; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D002314:Cardioplegic Solutions; D010847:Picolines; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011714:Pyrans; D014665:Vasodilator Agents; C061043:aprikalim; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium