Hyperkalemia alters endothelium-dependent relaxation through non—nitric oxide and noncyclooxygenase pathway: A mechanism for coronary dysfunction due to cardioplegia

• Published in: The Annals of thoracic surgery Vol. 61; no. 5; pp. 1394 - 1399
• Main Authors: He, Guo-Wei, Yang, Cheng-Qin
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.1996; Elsevier Science
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Cardioplegic Solutions - pharmacology; Clinical death. Palliative care. Organ gift and preservation; Coronary Vessels - drug effects; Coronary Vessels - physiology; Cyclooxygenase Inhibitors - pharmacology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiology; Heart Arrest, Induced - adverse effects; Heart Diseases - etiology; Heart Diseases - physiopathology; In Vitro Techniques; Indomethacin - pharmacology; Medical sciences; Nitric Oxide - pharmacology; Nitric Oxide - physiology; Swine; Cardioplegic solution; Hydroelectrolytic balance disorder; Cardiovascular disease; Experimental study; Coronary heart disease; Inorganic element; Endothelium; Pig; Hyperkaliemia; Metabolic disorder; Vertebrata; Relation; Mammalia; Organ preservation; Surgery; Animal; Complication; Artiodactyla; Biological effect; Mechanism of action; Ungulata; Biomedical engineering
• ISSN: 0003-4975; 1552-6259
• DOI: 10.1016/0003-4975(96)00086-0

Reported results of hyperkalemia (cardioplegia or organ preservation solutions) on endothelial function are contradictory. The endothelium-dependent relaxation is related to three major mechanisms: cyclooxygenase, nitric oxide, and endothelium-derived hyperpolarizing factor (K + channel related). The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through non—nitric oxide and noncyclooxygenase pathways. Porcine coronary artery rings (5 to 10 in each group) were studied in organ chambers under physiologic pressure. After incubation with 20 or 50 mmol/L K + for 1 hour, the response to substance P, an endothelium-dependent vasorelaxant peptide, in K + (25 mmol/L)-induced contraction was studied in the presence of the cyclooxygenase inhibitor indomethacin (7 μmol/L), the nitric oxide biosynthesis inhibitor N G-nitro- l-arginine (L-NNA) (300 μmol/L), or the adenosine triphosphate—sensitive K +-channel blocker glybenclamide (3 μmol/L) in comparison with control arteries (69.8 ± 4.6% of K + contraction). Without exposure to hyperkalemia, indomethacin (with or without glybenclamide) did not alter but L-NNA significantly reduced the relaxation (39.7% ± 3.7%, p < 0.001). After exposure to K +, the indomethacin- and L-NNA-resistant relaxation was further reduced (7.4% ± 3.2% for 20 mmol/L K +, p < 0.0001; or 13.5% ± 8.4% for 50 mmol/L K +, p < 0.05, compared with rings without exposure), whereas the indomethacin- and glybenclamide-resistant relaxation was not altered. Incubation with hyperkalemia (50 mmol/L) also significantly reduced the sensitivity (increased EC 50) of the indomethacin- and L-NNA-resistant relaxation (−9.75 ± 0.06 versus −9.33 ± 0.04 log M, p < 0.01). Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endothelium-dependent (endothelium-derived hyperpolarizing factor-related) relaxation. Our study may suggest a new mechanism of coronary dysfunction after exposure to hyperkalemia and open a new area for protection of coronary endothelium in cardiac surgery and for organ preservation in transplantation surgery.