Beneficial Effect of Calcium Treatment for Hyperkalemia Is Not Due to "Membrane Stabilization"

• Published in: Critical care medicine Vol. 52; no. 10; p. 1499
• Main Authors: Piktel, Joseph S, Wan, Xiaoping, Kouk, Shalen, Laurita, Kenneth R, Wilson, Lance D
• Format: Journal Article
• Language: English
• Published: United States 01.10.2024
• Subjects: Action Potentials - drug effects; Animals; Calcium - metabolism; Cell Membrane - drug effects; Dogs; Electrocardiography; Hyperkalemia - drug therapy; Membrane Potentials - drug effects; Myocytes, Cardiac - drug effects
• ISSN: 1530-0293
• DOI: 10.1097/CCM.0000000000006376

Hyperkalemia is a common life-threatening condition causing severe electrophysiologic derangements and arrhythmias. The beneficial effects of calcium (Ca 2+ ) treatment for hyperkalemia have been attributed to "membrane stabilization," by restoration of resting membrane potential (RMP). However, the underlying mechanisms remain poorly understood. Our objective was to investigate the mechanisms underlying adverse electrophysiologic effects of hyperkalemia and the therapeutic effects of Ca 2+ treatment. Controlled experimental trial. Laboratory investigation. Canine myocytes and tissue preparations. Optical action potentials and volume averaged electrocardiograms were recorded from the transmural wall of ventricular wedge preparations ( n = 7) at baseline (4 mM potassium), hyperkalemia (8-12 mM), and hyperkalemia + Ca 2+ (3.6 mM). Isolated myocytes were studied during hyperkalemia (8 mM) and after Ca 2+ treatment (6 mM) to determine cellular RMP. Hyperkalemia markedly slowed conduction velocity (CV, by 67% ± 7%; p < 0.001) and homogeneously shortened action potential duration (APD, by 20% ± 10%; p < 0.002). In all preparations, this resulted in QRS widening and the "sine wave" pattern observed in severe hyperkalemia. Ca 2+ treatment restored CV (increase by 44% ± 18%; p < 0.02), resulting in narrowing of the QRS and normalization of the electrocardiogram, but did not restore APD. RMP was significantly elevated by hyperkalemia; however, it was not restored with Ca 2+ treatment suggesting a mechanism unrelated to "membrane stabilization." In addition, the effect of Ca 2+ was attenuated during L-type Ca 2+ channel blockade, suggesting a mechanism related to Ca 2+ -dependent (rather than normally sodium-dependent) conduction. These data suggest that Ca 2+ treatment for hyperkalemia restores conduction through Ca 2+ -dependent propagation, rather than restoration of membrane potential or "membrane stabilization." Our findings provide a mechanistic rationale for Ca 2+ treatment when hyperkalemia produces abnormalities of conduction (i.e., QRS prolongation).