title: Reduced L-type calcium current in ventricular myocytes from pigs with hyperdynamic septic shock.
abstract: OBJECTIVE
  To hypothesize that reduced L-type calcium current with consequent shortening of cardiac repolarization is present in a clinically relevant porcine model of hyperdynamic septic shock. Myocardial depression is a well-recognized manifestation of sepsis and septic shock. Reduction of L-type calcium current was demonstrated to contribute to the myocardial depression in endotoxemic rodents.
  
  
  METHODS
  Laboratory animal experiments.
  
  
  METHODS
  Animal research laboratory at a university.
  
  
  METHODS
  Twenty-two domestic pigs of either gender.
  
  
  METHODS
  In anesthetized, mechanically ventilated, and instrumented pigs, sepsis was induced by bacteremia (central venous infusion of live Pseudomonas aeruginosa) and continued for 22 hrs.
  
  
  RESULTS
  Electrocardiogram was recorded before and 22 hrs after induction of bacteremia. RR, QT, and QTc intervals were significantly shortened by sepsis. In vitro, action potentials were recorded in right ventricular trabeculae. Action potential durations were shortened in septic preparations. Tumor necrosis factor-alpha did not influence action potential durations. L-type calcium current was measured in isolated ventricular myocytes. Peak L-type calcium current 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 L-type calcium current activation and inactivation was shifted to more negative potentials in myocytes from septic animals. Action potential-clamp experiments revealed that the contribution of L-type calcium current to the septic action potential was significantly diminished. In cardiac myocytes incubated with tumor necrosis factor-alpha, L-type calcium current was not further affected.
  
  
  CONCLUSIONS
  In a clinically relevant porcine model, hyperdynamic septic shock induced shortening of ventricular repolarization and reduction of L-type calcium current. The contribution of L-type calcium current to the action potential in septic ventricular myocytes was significantly diminished. Tumor necrosis factor-alpha probably did not contribute to this effect.
authors.affiliation: Department of Physiology, Charles University, Prague, Czech Republic. milan.stengl@lfp.cuni.cz
authors.forename: Milan
authors.initials: M
authors.lastname: Stengl
authors.forename: Frantisek
authors.initials: F
authors.lastname: Bartak
authors.forename: Roman
authors.initials: R
authors.lastname: Sykora
authors.forename: Jiri
authors.initials: J
authors.lastname: Chvojka
authors.forename: Jan
authors.initials: J
authors.lastname: Benes
authors.forename: Ales
authors.initials: A
authors.lastname: Krouzecky
authors.forename: Ivan
authors.initials: I
authors.lastname: Novak
authors.forename: Jitka
authors.initials: J
authors.lastname: Sviglerova
authors.forename: Jitka
authors.initials: J
authors.lastname: Kuncova
authors.forename: Martin
authors.initials: M
authors.lastname: Matejovic
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology*; D012772:Shock, Septic / Q000503:physiopathology*; D034421:Sus scrofa / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium