Potassium channel opener-augmented cardioplegia: protection of myocyte contractility with chronic left ventricular dysfunction.
BACKGROUND
An increased number of patients with preexisting left ventricular (LV) dysfunction and congestive heart failure (CHF) are undergoing cardiac surgery with a higher risk for decreased LV contractility after hyperkalemic cardioplegic arrest. Activation of adenosine triphosphate-sensitive potassium channels by potassium channel openers (PCO) within the myocyte appears to confer a protective effect in the setting of ischemia. Accordingly, the present study was designed to determine whether PCO supplementation during hyperkalemic cardioplegic arrest would provide protective effects on myocyte contractile function, particularly in the setting of CHF.


RESULTS
LV myocytes were isolated from control pigs (n=7) and pigs with CHF (rapid pacing, 240 beats per minute; n=7) and then assigned to the following treatment groups: normothermia (cell culture media, 2 hours, 37 degrees C); cardioplegia (24 mEq/L K+, 2 hours, 4 degrees C; then 10 minutes of reperfusion); or PCO/cardioplegia (cardioplegia supplemented with 100 micromol/L of the PCO aprikalim). Myocyte velocity of shortening was reduced in both control (66+/-2 versus 33+/-1 microm/s) and CHFmyocytes (32+/-1 versus 22+/-1 microm/s) after hyperkalemic cardioplegic arrest (P<.05). Contractility after PCO cardioplegia was similar to normothermic values in control (57+/-2 microm/s) and CHF (33+/-1 microm/s) myocytes (P<.05). Intracellular free Ca2+ increased from normothermia during hyperkalemic cardioplegia in control (81+/-4 to 145+/-7 nmol/L) and CHF (262+/-30 to 823+/-55 nmol/L) myocytes (P<.05). PCO cardioplegia attenuated the intracellular increase in free Ca2+ during the cardioplegic interval in control (110+/-6 nmol/L) and CHF (383+22 nmol/L) myocytes (P<.05).


CONCLUSIONS
PCO-augmented cardioplegic arrest preserved myocyte contractility and reduced the intracellular free Ca2+ release, which therefore may be of particular benefit in the setting of preexisting LV dysfunction.
Dorman
B H
BH
Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston 29425-2207, USA.
Hebbar
L
L
Clair
M J
MJ
Hinton
R B
RB
Roy
R C
RC
Spinale
F G
FG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002908:Chronic Disease; D006324:Heart Arrest, Induced; D006333:Heart Failure / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects*; D015425:Myocardial Reperfusion; D010847:Picolines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*; D013552:Swine; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
D010847:Picolines; D015221:Potassium Channels; D011714:Pyrans; C061043:aprikalim; D002118:Calcium