Impaired sarcoplasmic calcium release inhibits myocardial contraction in experimental sepsis.

Abstract

PURPOSE:

In septic shock, myocardial dysfunction develops over the course of illness, but the mechanism of this depression is not clear. In this study, mechanisms of myocardial dysfunction were examined in a porcine model of Escherichia coli sepsis.

MATERIALS AND METHODS:

Animals were subjected to 4 hours of bacteria infusion (n = 5) (septic group) or saline infusion (n = 5) (nonseptic group), after which trabeculae were removed from the right ventricle and placed into a recirculating water bath. Measurements of steady-state contraction (SSC) were obtained at 0.5, 1, and 2 Hz. Indirect indices were used to assess abnormalities in myocardial calcium metabolism in sepsis. Extrasystoles (ES) were used to assess transsarcolemmal (TSL) calcium flux and were measured at 300 milliseconds, 400 milliseconds, and 500 milliseconds after the preceding stimulus. Postrest contraction (PRC) is an indicator of SR recirculation from the uptake to the release site and was obtained after interposing intervals of rest between steady-state beats at 0.5 Hz. Rapid-cooling contracture (RCC) is an indicator of sarcoplasmic reticulum (SR) content and was obtained at 0.5, 1, and 2 Hz and after interposing intervals of rest at 0.5 Hz.

RESULTS:

SSC was not different between groups at 0.5 Hz, but compared with the nonseptic group, SSC decreased at 1 and 2 Hz in the septic group (P < .05). PRC and TSL were not different between groups. During rest intervals, calcium leaks out of SR through the ryanodine channel (ie, SR calcium release channel). In the septic group, as assessed by RCC, SR calcium leak was less than that found in the nonseptic group.

CONCLUSION:

These results indicate that myocardial dysfunction in sepsis is frequency dependent, and that the mechanism is most likely caused by inhibition of SR calcium release owing to blockade of the ryanodine channel.

• Authors: D Patel, K Duke, R B Light, H Jacobs, S N Mink, D Bose
• Journal: Journal of critical care (J Crit Care) Vol. 15 Issue 2 Pg. 64-72 (Jun 2000) ISSN: 0883-9441 [Print] United States
• PMID: 10877367 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ryanodine Receptor Calcium Release Channel
• Calcium

Topics

• Analysis of Variance
• Animals
• Calcium (metabolism)
• Cardiac Complexes, Premature (metabolism, physiopathology)
• Disease Models, Animal
• Escherichia coli Infections (metabolism, physiopathology)
• Female
• Heart Rate
• Heart Ventricles
• Humans
• In Vitro Techniques
• Linear Models
• Male
• Myocardial Contraction (physiology)
• Random Allocation
• Ryanodine Receptor Calcium Release Channel (metabolism)
• Sarcoplasmic Reticulum (metabolism)
• Shock, Septic (metabolism, physiopathology)
• Swine