Background: Cardiovascular collapses, syncopes, and sudden deaths have been observed following the rapid administration of intravenous vitamin K. Our objectives were to characterize the effects of vitamin K on cardiac action potentials and to evaluate effects of vitamin K on sodium and potassium currents, namely INa, IKr, and IKs.Methods and Results: Guinea pig hearts (n = 21) were paced at a cycle length of 250 msec and exposed to vitamin K at 1.15-4.6 μmol/L (2.5-10 mg/L). Monophasic action potential duration measured at 90% repolarization (MAPD90) was not significantly reduced (-1.6 ± 0.3 msec; P > .05; N.S.) at 1.15 μmol/L, but increased by 6.5 ± 0.4 msec ( P < .05) at 2.3 μmol/L. MAPD90was not measurable at 4.6 μmol/L, as a result of inexcitability. Patch-clamp experiments in ventricular myocytes demonstrated a' ~50% reduction in INaby 10 μmol/L vitamin K and a concentration-dependent reduction of the K+current elicited by short depolarizations (250 msec; IK250). Estimated IC50for IK250, mostly representing IKr, was 2.3 μmol/L. Vitamin K was less potent to block the K+current elicited by long depolarizations (5,000 msec; IK5000), mostly representing IKs, with an estimated IC50over 100 μmol/L. Conclusions: Therapeutic concentrations (~1.5 μmol/L) of intravenous vitamin K modulate cardiac action potential by blocking ionic currents involved in cardiac depolarization and repolarization.