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Potassium-channel opener in cardioplegia may restore coronary endothelial function
1Department of Surgery, University of Hong Kong, Grantham Hospital, Aberdeen. gwhe@hkucc.hku.hk
Insights
Potassium-channel openers can preserve coronary vasorelaxation impaired by hyperkalemic solutions. This effect is significant at 20 mmol/L potassium but diminished at 50 mmol/L, offering insights into cardioprotection.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Cardiac Surgery
Background:
- Hyperkalemic solutions used in cardioplegia can impair coronary endothelial function.
- This impairment involves the endothelium-derived hyperpolarizing factor (EDHF) mechanism.
Purpose of the Study:
- To investigate if potassium-channel openers can restore EDHF-mediated coronary vasorelaxation when combined with hyperkalemic cardioplegia.
- To assess the efficacy of aprikalim in preserving endothelial function under varying hyperkalemic conditions.
Main Methods:
- Porcine coronary arteries were exposed to hyperkalemia (20 or 50 mmol/L) with or without aprikalim (0.1 mmol/L).
- EDHF-mediated relaxation was induced by calcium ionophore A23187 and bradykinin.
- Experiments were conducted in the presence of indomethacin and Nomega-nitro-L-arginine to isolate EDHF pathways.
Main Results:
- Hyperkalemia significantly impaired EDHF-mediated relaxation at both 20 mmol/L and 50 mmol/L potassium concentrations.
- Aprikalim significantly recovered relaxation in the presence of 20 mmol/L hyperkalemia.
- A lesser recovery of relaxation was observed with aprikalim at 50 mmol/L hyperkalemia.
Conclusions:
- Potassium-channel openers show potential in preserving EDHF-mediated coronary relaxation during hyperkalemic cardioplegia.
- The protective effect is concentration-dependent, being more pronounced at 20 mmol/L potassium than at 50 mmol/L.
- Findings may inform strategies for enhanced cardioprotection in open-heart surgery.
Background:
Depolarizing (hyperkalemic) solutions impair the coronary endothelial function through an endothelium-derived hyperpolarizing factor mechanism. I examined the hypothesis that potassium-channel openers may restore the impaired endothelium-derived hyperpolarizing factor-mediated coronary vasorelaxation when added to hyperkalemic cardioplegia.
Methods:
The porcine coronary arteries were exposed to hyperkalemia (potassium, 20 or 50 mmol/L) or hyperkalemia plus the potassium-channel opener aprikalim at 0.1 mmol/L for 1 hour. Endothelium-derived hyperpolarizing factor-mediated relaxation (percentage of 30 nmol/L U46619 precontraction) was induced by calcium ionophore A23187 and bradykinin in the presence of indomethacin (7 micromol/L) and Nomega-nitro-L-arginine (300 micromol/L).
Results:
The endothelium-derived hyperpolarizing factor-mediated relaxation was significantly impaired by exposure to hyperkalemia (20 mmol/L: 24.9%+/-14.1% versus 88.0%+/-3.3% in control, p = 0.002 for A23187; 50 mmol/L: 40.5%+/-12.3% versus 76.5%+/-3.8%, p = 0.003 for bradykinin). This reduced relaxation was significantly recovered by addition of aprikalim into the hyperkalemic (20 mmol/L) solution in A23187 experiments (81.2%+/-4.8%, p = 0.002) but only slightly recovered when added into the higher concentration of potassium (50 mmol/L) in bradykinin experiments (56.1%+/-4.7%, p = 0.2).
Conclusions:
Potassium-channel openers may preserve endothelium-derived hyperpolarizing factor-mediated coronary relaxation when added to traditional hyperkalemic cardioplegia. This effect is significant when the potassium concentration is 20 mmol/L but partially lost when it reaches 50 mmol/L. This study may provide new insights into cardioprotection during open heart operations.