Increased cardiomyocyte intracellular calcium during endotoxin-induced cardiac dysfunction in guinea pigs

Marita Thompson, Allis Kliewer, David Maass, Lisa Becker, D. Jean White, Debora Bryant, Grace Arteaga, Jureta Horton, Brett P. Giroir

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41 Scopus citations

Abstract

Septic shock is a complex pathophysiologic state characterized by circulatory insufficiency, multiple system organ dysfunction, and frequent mortality. Although profound cardiac dysfunction occurs during sepsis, the pathogenesis of this dysfunction remains poorly understood. To determine whether abnormalities in intramyocyte calcium accumulation might contribute to the development of cardiac dysfunction, we measured myocyte intracellular calcium during peak cardiac dysfunction after an endotoxin challenge. Intraperitoneal administration of Escherichia coli lipopolysaccharide 4 mg/kg to adult guinea pigs resulted in significantly impaired cardiac performance (Langendorff preparation) 18 h after challenge compared with control. This included diminished left ventricular pressure development (56 ± 7 versus 95 ± 4 mm Hg, p < 0.05), maximal rate of left ventricular pressure rise (998 ± 171 versus 1784 ± 94 mm Hg/s, p < 0.05) and left ventricular pressure fall (1014 ± 189 versus 1621 ± 138 mm Hg/s, p < 0.05). Assay of intracellular calcium in fura-2AM-loaded cardiac myocytes demonstrated increased intracellular calcium concentration in myocytes obtained from lipopolysaccharide-challenged animals compared with controls (234 ± 18 versus 151 ± 6 nM, p < 0.05). Inhibition of calcium-release channel (ryanodine receptor) opening by administration of dantrolene prevented the increase in intracytoplasmic calcium (159 ± 8 versus 234 ± 18 nM, p < 0.05) and partially ameliorated systolic and diastolic ventricular dysfunction. These data indicate that abnormalities of intracellular calcium contribute to the development of endotoxin-induced myocardial dysfunction.

Original languageEnglish (US)
Pages (from-to)669-676
Number of pages8
JournalPediatric Research
Volume47
Issue number5
DOIs
StatePublished - May 2000

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Thompson, M., Kliewer, A., Maass, D., Becker, L., White, D. J., Bryant, D., Arteaga, G., Horton, J., & Giroir, B. P. (2000). Increased cardiomyocyte intracellular calcium during endotoxin-induced cardiac dysfunction in guinea pigs. Pediatric Research, 47(5), 669-676. https://doi.org/10.1203/00006450-200005000-00019