Escherichia coli porcine peritonitis induces histological and transcriptome evidence of cardiac injury

Introduction

Cardiac dysfunction is a feature of sepsis. In order to gain insight into the fundamental mechanisms of this phenotype, gene expression analysis (Affymetrix) was applied to serial cardiac biopsies of sham (n = 2) and E. coli infected pigs (n = 3).

Methods

Cardiac samples were taken basal and hourly after infection for gene analysis and at the end of the experiment for histopathological examination. Genes were determined to be differentially regulated at a greater than or less than twofold change and P < 0.05.

Results

Sham pigs had stable heart rate, cardiac output (CO) and core temperature for the 5-hour period; infected pigs demonstrated an early elevation in CO and ventricular shortening and/or ejection (assessed by echocardiography) followed by development of hypodynamics. In infected animals, increasing numbers of genes were upregulated or downregulated (36, 278, 514, 842 and 1,238 at 1, 2, 3, 4 and 5 hours) (Figure 1) whereas sham infection altered fewer (247, 67 and 384 genes at 2, 3 and 4 hours). Comparing sham vs infected animals at the same time, numbers of significantly altered genes increased with time (32 at basal, to 74, 189 and 601 at 2, 3 and 4 hours post infection). In hematoxylin–eosin-stained sections, histopathological assessment revealed acute inflammation in pericardium and myocardium in infected pigs.

Figure 1

(abstract P13)

Conclusion

These results will provide biomarker and mechanistic insights to pathogenesis of cardiac dysfunction of septic peritonitis and may also help identify some altered novel gene transcription pathways that can serve as new targets for diagnostic tools and therapeutic strategies. All candidate genes will be validated by quantitative PCR.