XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
CarDIAC L-TYPE CALCIUM CUrrENT IN SEPSIS
Milan Štengl 1 , František Barták 1 , Roman Sýkora 2 , Jiří Chvojka 2 , Jan Beneš 3 ,
Aleš Kroužecký 2 , Ivan Novák 2 , Jitka Švíglerová 1 , Jitka Kuncová 1 and Martin Matějovič 2
1
Department of Physiology, 2 First Medical Department, 3 Department of Anesthesiology
and Critical Care Medicine, Charles University in Prague, Faculty of Medicine
and Teaching Hospital in Plzen, Plzen, Czech Republic
Myocardial depression is a well recognized manifestation of sepsis and septic shock. We
hypothesize that reduced L-type calcium current (ICaL) with consequent shortening of
cardiac repolarization contributes to the myocardial depression in a clinically relevant
porcine model of hyperdynamic septic shock. In anesthetized, mechanically ventilated
and instrumented pigs (n=22), sepsis was induced by bacteremia (central venous infusion
of live P. aeruginosa) and continued for 22 hours. Electrocardiogram was recorded before
and 22 hours after induction of bacteremia. In vitro, action potentials were recorded
in right ventricular trabeculae. ICaL was measured in isolated ventricular myocytes. RR,
QT and QTc intervals were significantly shortened by sepsis. Action potential durations
(APD) were shortened in septic preparations. TNF-α did not influence APD. Peak ICaL
density was reduced in myocytes from septic animals (8.3±0.4 pA/pF vs. 11.2±0.6 pA/pF
in control). The voltage dependence of both ICaL activation and inactivation was shifted
to more negative potentials in myocytes from septic animals. Action potential-clamp
experiments revealed that the contribution of ICaL to the septic action potential was
significantly diminished. In cardiac myocytes incubated with TNF-α ICaL was not further
affected. We conclude that in a clinically relevant porcine model, hyperdynamic septic
shock induced reduction of ICaL and shortening of ventricular repolarization.
Acknowledgement: Supported by the Research Project MSM 0021620819, Replacement
of and support to some vital organs, from the Ministry of Education, Czech Republic.
XXII. Biochemistry Congress, Martin
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