Reduced L-type calcium current in ventricular myocytes from pigs with hyperdynamic septic shock

Area of Science:

• Cardiovascular Physiology
• Sepsis Pathophysiology
• Molecular Cardiology

Background:

• Myocardial depression is a known complication of sepsis and septic shock.
• Reduced L-type calcium current contributes to myocardial depression in rodent models of endotoxemia.

Purpose of the Study:

• To investigate L-type calcium current and cardiac repolarization in a porcine model of hyperdynamic septic shock.
• To determine if reduced L-type calcium current is a feature of septic shock in a clinically relevant animal model.

Main Methods:

• Sepsis was induced in domestic pigs via bacteremia for 22 hours.
• Electrocardiograms and cardiac action potentials were recorded.
• L-type calcium current was measured in isolated ventricular myocytes.

Main Results:

• Sepsis significantly shortened RR, QT, and QTc intervals, indicating altered cardiac repolarization.
• Action potential durations were shortened in septic pig hearts.
• Peak L-type calcium current density was reduced in myocytes from septic animals, with altered voltage dependence.

Conclusions:

• Hyperdynamic septic shock in pigs leads to shortened ventricular repolarization and reduced L-type calcium current.
• The contribution of L-type calcium current to the action potential was diminished in septic ventricular myocytes.
• Tumor necrosis factor-alpha did not appear to mediate these observed effects.