Related Experiment Videos
Potassium channel opener-augmented cardioplegia: protection of myocyte contractility with chronic left ventricular
B H Dorman1, L Hebbar, M J Clair
1Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston 29425-2207, USA.
Insights
Potassium channel openers (PCO) protect heart cells during surgery. PCO supplementation during cardioplegic arrest preserves myocyte contractility, especially in patients with heart failure.
Area of Science:
- Cardiology
- Cellular Physiology
- Cardiac Surgery
Background:
- Patients with left ventricular (LV) dysfunction and congestive heart failure (CHF) face increased risk during cardiac surgery.
- Hyperkalemic cardioplegic arrest can decrease LV contractility.
- Adenosine triphosphate-sensitive potassium channels (KATP) activation by potassium channel openers (PCO) may offer protection against ischemia.
Purpose of the Study:
- To investigate if PCO supplementation during hyperkalemic cardioplegic arrest protects myocyte contractile function.
- To assess the protective effects of PCO in the context of pre-existing congestive heart failure (CHF).
Main Methods:
- Isolated LV myocytes from control and CHF pigs were used.
- Treatment groups included normothermia, cardioplegia, and PCO-supplemented cardioplegia (using aprikalim).
- Myocyte contractility and intracellular free Ca2+ levels were measured.
Main Results:
- Hyperkalemic cardioplegic arrest reduced myocyte shortening velocity in both control and CHF groups.
- PCO-supplemented cardioplegia preserved myocyte contractility, restoring it to near normothermic levels.
- PCO cardioplegia attenuated the rise in intracellular free Ca2+ during the cardioplegic interval in both groups.
Conclusions:
- PCO-augmented cardioplegic arrest preserves myocyte contractility.
- This method reduces intracellular free Ca2+ release during arrest.
- PCO supplementation may benefit patients with pre-existing 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.
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 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.