Decreased Cardiac Excitability Secondary to Reduction of Sodium Current May Be a Significant Contributor to Reduced Contractility in a Rat Model of Sepsis
Introduction: Multisystem organ failure remains a poorly understood complication of sepsis. During sepsis, reduced excitability contributes to organ failure of skeletal muscle, nerves and the spinal cord. The goal of this study was to determine whether reduced excitability might also contribute to cardiac failure during sepsis.
Methods: Wistar rats were made septic by cecal ligation and puncture. One day later, action potentials were recorded from beating left ventricular papillary muscle ex vivo by impaling myocytes with sharp microelectrodes.
Results: In cardiac papillary muscle from septic rats, action potential amplitude and rate of rise were reduced, while threshold was elevated. These changes in action potential properties suggest sepsis selectively reduces sodium current. To determine the effects of selective reduction in sodium current, we applied tetrodotoxin to papillary muscle from healthy rats and found reduction in action potential amplitude and rate of rise, as well as elevation of threshold. The changes were similar to those triggered by sepsis. Blocking calcium current using nifedipine did not mimic action potential changes induced by sepsis. Contractility of healthy papillary muscle was reduced to 40% of normal following partial block of sodium current by tetrodotoxin, close to the low contractility of septic papillary muscle, which was 30% of normal.
Conclusions: Our data suggest cardiac excitability is reduced during sepsis in rats. The reduction in excitability appears to be primarily due to reduction of sodium current. The reduction in sodium current may be sufficient to explain most of the reduction in cardiac contractility during sepsis.
Koesters, A. G.,
Engisch, K. L.,
& Rich, M. M.
(2014). Decreased Cardiac Excitability Secondary to Reduction of Sodium Current May Be a Significant Contributor to Reduced Contractility in a Rat Model of Sepsis. Critical Care, 18 (2).