Login to view PhD Thesis

Enter your username and password here in order to log in on the website:


Forgot your password?

Cardiac electrophysiological effects in atrial fibrillation and exercise, and potassium regulation in hypokalemia

Cao Thach Tran

Summary

Plasma K concentration is under long-term regulation by the kidneys and short-termregulation through K uptake and release from skeletal muscle. The Na,K-ATPase is animportant mediator of the short-term regulation through the pumping of Na out of the cells inexchange of K. Plasma K concentration abnormalities have previously been associated withincreased risk of cardiac arrhythmias. The thesis is based on 3 manuscripts. In these, Khomeostasis in the setting of hypokalemia and hyperkalemia was investigated in a series ofstudies based on both human subjects and laboratory animals. In addition, it was assessedwhether plasma K concentration fluctuations may affect cardiac repolarisation and risk ofatrial fibrillation.Na, K-ATPase quantification in human atrial myocardium with vanadatefacilitated 3H-ouabain binding assay showed a concentration of 275 pmol/g wet weight. Highatrial Na,K-ATPase concentration and sudden plasma K concentration increase wereassociated with increased risk of the development of atrial fibrillation.In severe hypokalemia, plasma K concentration was resistant to the plasma Kconcentration lowering effect of terbutalin. Acute K loading through intravenous K infusionreversed the resistance. Concomitant administration of insulin was not associated with asynergistic effect.In patients with end-stage renal failure, exercise-induced plasma Kconcentration fluctuations were accentuated by hemodialysis. The decreased peak Kconcentration after hemodialysis was not associated with increased exercise performance.QT hysteresis during recovery was related to the plasma K concentration variations.

In conclusion, the present studies show that perturbation of the K homeostasisis associated with altered plasma K concentration response to sympathomimetic stimulus andexercise. Plasma K concentration variations were associated with the risk of atrial fibrillationand cardiac repolarisation changes. Abnormal plasma K concentration response to intrinsicand extrinsic stress may be important for the development of cardiac arrhythmias.