POTASSIUM CHANNEL OPENER-AUGMENTED CARDIOPLEGIA - PROTECTION OF MYOCYTE CONTRACTILITY WITH CHRONIC LEFT-VENTRICULAR DYSFUNCTION

Background An increased number of patients with preexisting left ventr icular (LV) dysfunction and congestive heart failure (CHF) are undergo ing cardiac surgery with a higher risk for decreased LV contractility after hyperkalemic cardioplegic arrest. Activation of adenosine tripho sphate-sensitive potassium channels by potassium channel openers (PCO) within the myocyte appears to confer a protective effect in the setti ng of ischemia. Accordingly, the present study was designed to determi ne whether PCO supplementation during hyperkalemic cardioplegic arrest would provide protective effects on myocyte contractile function, par ticularly in the setting of CHF. Methods and 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 gr oups: normothermia (cell culture media, 2 hours, 37 degrees C); cardio plegia (24 mEq/L K+, 2 hours, 4 degrees C; then 10 minutes of reperfus ion); or PCO/cardioplegia (cardioplegia supplemented with 100 mu mol/L of the PCO aprikalim). Myocyte velocity of shortening was reduced in both control (66+/-2 versus 33+/-1 mu m/s) and CHF myocytes (32+/-1 ve rsus 22+/-1 mu m/s) after hyperkalemic cardioplegic arrest (P<.05). Co ntractility after PCO cardioplegia was similar to normothermic values in control (57+/-2 mu m/s) and CHF (33+/-1 mu m/s) myocytes (P<.05). I ntracellular 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 i n control (110+/-6 nmol/L) and CHF (383+/-22 nmol/L) myocytes (P<.05). Conclusions PCO-augmented cardioplegic arrest preserved myocyte contr actility and reduced the intracellular free Ca2+ release, which theref ore may be of particular benefit in the setting of preexisting LV dysf unction.