Background: Postoperative atrial fibrillation is a common complication to cardiac surgery. Na,K-ATPase is of major importance for the resting membrane potential and action potential. The purpose of the present study was to evaluate the importance of Na,K-ATPase concentrations in human atrial biopsies and plasma potassium concentrations for the development of atrial fibrillation. Methods: Atrial myocardial biopsies were obtained from 67 patients undergoing open chest cardiac surgery. Na,K-ATPase was quantified using vanadate-facilitated 3H-ouabain binding. Plasma potassium concentration was measured with ion-selective electrode. Results: In patients with preoperative sinus rhythm, 3H-ouabain-binding site concentration was 16% higher in patients developing postoperative atrial fibrillation compared to patients maintaining sinus rhythm [302 ± 15 pmol/g wet weight (n = 20) vs. 261 ± 11 mmol/g wet weight (n = 33), p = 0.03]. Also with multivariable analysis, 3H-ouabain-binding site concentration was significantly associated with the development of atrial fibrillation. High increase in plasma potassium concentration during the perioperative period and surgery was associated with postoperative atrial fibrillation. Conclusions: The present study supports the increasing evidence of dysregulation of the potassium homeostasis as an important factor in the development of cardiac arrhythmias. High atrial Na,K-ATPase and sudden plasma potassium concentration increase may contribute to precipitate atrial fibrillation.

Keywords:
Arrhythmias, Atrial fibrillation, Na,K-ATPase, Potassium, Prediction, Diuretics, Cardiac surgery
1.
Mayson SE, Greenspon AJ, Adams S, et al: The changing face of postoperative atrial fibrillation prevention: a review of current medical therapy. Cardiol Rev 2007;15:231–241.
2.
Walsh SR, Oates JE, Anderson JA, Blair SD, Makin CA, Walsh CJ: Postoperative arrhythmias in colorectal surgical patients: incidence and clinical correlates. Colorectal Dis 2006;8:212–216.
3.
Kim MH, Deeb GM, Morady F, et al: Effect of postoperative atrial fibrillation on length of stay after cardiac surgery [the Postoperative Atrial Fibrillation in Cardiac Surgery Study (PACS2)]. Am J Cardiol 2001;87:881–885.
4.
Villareal RP, Hariharan R, Liu BC, et al: Postoperative atrial fibrillation and mortality after coronary artery bypass surgery. J Am Coll Cardiol 2004;43:742–748.
5.
Macdonald JE, Struthers AD: What is the optimal serum potassium level in cardiovascular patients? J Am Coll Cardiol 2004;43:155–161.
6.
Wahr JA, Parks R, Boisvert D, et al: Preoperative serum potassium levels and perioperative outcomes in cardiac surgery patients. Multicenter Study of Perioperative Ischemia Research Group. JAMA 1999;281:2203–2210.
7.
Kalman JM, Munawar M, Howes LG, et al: Atrial fibrillation after coronary artery bypass grafting is associated with sympathetic activation. Ann Thorac Surg 1995;60:1709–1715.
8.
Clausen T: Clinical and therapeutic significance of the Na+,K+ pump. Clin Sci (Lond) 1998;95:3–17.
9.
Sejersted OM, Sjøgaard G: Dynamics and consequences of potassium shifts in skeletal muscle and heart during exercise. Physiol Rev 2000;80:1411–1481.
10.
Crystal E, Connolly SJ, Sleik K, Ginger TJ, Yusuf S: Interventions on prevention of postoperative atrial fibrillation in patients undergoing heart surgery: a meta-analysis. Circulation 2002;106:75–80.
11.
Carmeliet E: Does the Na+,K+ pump current undergo remodeling in atrial fibrillation? Cardiovasc Res 2003;59:536–537.
12.
Glitsch HG: Electrophysiology of the sodium-potassium-ATPase in cardiac cells. Physiol Rev 2001;81:1791–1826.
13.
Rasmusson RL, Morales MJ, Wang S, et al: Inactivation of voltage-gated cardiac K+ channels. Circ Res 1998;82:739–750.
14.
Choy AM, Lang CC, Chomsky DM, Rayos GH, Wilson JR, Roden DM: Normalization of acquired QT prolongation in humans by intravenous potassium. Circulation 1997;96:2149–2154.
15.
Etheridge SP, Compton SJ, Tristani-Firouzi M, Mason JW: A new oral therapy for long QT syndrome: long-term oral potassium improves repolarization in patients with HERG mutations. J Am Coll Cardiol 2003;42:1777–1782.
16.
Nørgaard A, Bagger JP, Bjerregaard P, Baandrup U, Kjeldsen K, Thomsen PE: Relation of left ventricular function and Na,K-pump concentration in suspected idiopathic dilated cardiomyopathy. Am J Cardiol 1988;61:1312–1315.
17.
Schwinger RH, Bundgaard H, Müller-Ehmsen J, Kjeldsen K: The Na,K-ATPase in the failing human heart. Cardiovasc Res 2003;57:913–920.
18.
Schmidt TA, Allen PD, Colucci WS, Marsh JD, Kjeldsen K: No adaptation to digitalization as evaluated by digitalis receptor (Na,K-ATPase) quantification in explanted hearts from donors without heart disease and from digitalized recipients with end-stage heart failure. Am J Cardiol 1993;71:110–114.
19.
Schmidt TA, Svendsen JH, Haunsø S, Kjeldsen K: Quantification of the total Na,K-ATPase concentration in atria and ventricles from mammalian species by measuring 3H-ouabain binding to intact myocardial samples. Stability to short term ischemia reperfusion. Basic Res Cardiol 1990;85:411–427.
20.
Wang GX, Schmied R, Ebner F, Korth M: Intracellular sodium activity and its regulation in guinea-pig atrial myocardium. J Physiol 1993;465:73–84.
21.
Wang J, Schwinger RH, Frank K, et al: Regional expression of sodium pump subunits isoforms and Na+-Ca++ exchanger in the human heart. J Clin Invest 1996;98:1650–1658.
22.
Van Wagoner DR, Pond AL, Lamorgese M, Rossie SS, McCarthy PM, Nerbonne JM: Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res 1999;85:428–436.
23.
Dupont E, Ko Y, Rothery S, et al: The gap-junctional protein connexin40 is elevated in patients susceptible to postoperative atrial fibrillation. Circulation 2001;103:842–849.
24.
Maixent JM, Duran MJ, Pierre S, et al: Remodeling of Na,K-ATPase, and membrane fluidity after atrial fibrillation in sheep. J Recept Signal Transduct Res 2002;22:201–211.
25.
Workman AJ, Kane KA, Rankin AC: Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation. Cardiovasc Res 2003;59:593–602.
26.
Nørgaard A, Kjeldsen K, Hansen O: K+-dependent 3-O-methylfluorescein phosphatase activity in crude homogenate of rodent heart ventricle: effect of K+ depletion and changes in thyroid status. Eur J Pharmacol 1985;113:373–382.
27.
Bundgaard H: Potassium depletion improves myocardial potassium uptake in vivo. Am J Physiol Cell Physiol 2004;287:C135–C141.
28.
Dørup I, Skajaa K, Clausen T, Kjeldsen K: Reduced concentrations of potassium, magnesium, and sodium-potassium pumps in human skeletal muscle during treatment with diuretics. Br Med J (Clin Res Ed) 1988;296:455–458.
29.
Müller-Ehmsen J, Wang J, Schwinger RH, McDonough AA: Region specific regulation of sodium pump isoform and Na,Ca-exchanger expression in the failing human heart – right atrium versus left ventricle. Cell Mol Biol (Noisy-le-grand) 2001;47:373–381.
30.
Elmoselhi AB, Lukas A, Ostadal P, Dhalla NS: Preconditioning attenuates ischemia- reperfusion-induced remodeling of Na+-K+-ATPase in hearts. Am J Physiol Heart Circ Physiol 2003;285:H1055–H1063.
31.
Bers DM, Barry WH, Despa S: Intracellular Na+ regulation in cardiac myocytes. Cardiovasc Res 2003;57:897–912.
32.
Tieleman RG, De Langen C, Van Gelder IC, et al: Verapamil reduces tachycardia-induced electrical remodeling of the atria. Circulation 1997;95:1945–1953.
33.
Bosch RF, Nattel S: Cellular electrophysiology of atrial fibrillation. Cardiovasc Res 2002;54:259–269.
34.
Bakhtiary F, Therapidis P, Dzemali O, et al: Impact of high thoracic epidural anesthesia on incidence of perioperative atrial fibrillation in off-pump coronary bypass grafting: a prospective randomized study. J Thorac Cardiovasc Surg 2007;134:460–464.
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2009
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