C5a-blockade improves burn-induced cardiac dysfunction.

Abstract

We previously reported that generation of the anaphylatoxin C5a is linked to the development of cardiac dysfunction in sepsis due to C5a interaction with its receptor (C5aR) on cardiomyocytes. Burn injury involves inflammatory mechanisms that can lead to C5a generation as well. In this study, we investigated the effects of C5a blockade on burn-induced cardiac dysfunction. Using a standardized rat model of full thickness scald injury, left ventricular pressures were recorded in vivo followed by in vitro assessment of sarcomere contraction of single cardiomyocytes. Left ventricular pressures in vivo and cardiomyocyte sarcomere contractility in vitro were significantly reduced following burn injury. In the presence of anti-C5a Ab, these defects were greatly attenuated 1, 6, and 12 h after burn injury and completely abolished 24 h after burn. In vitro incubation of cardiomyocytes with bacterial LPS accentuated the impaired contractility, which was partially prevented in cardiomyocytes from burned rats that had received an anti-C5a Ab. Based on Western blot analyses, real-time PCR, and immunostaining of left ventricular heart tissue, there was a significant increase in cardiomyocyte expression of C5aR after burn injury. In conclusion, an in vivo blockade of C5a attenuates burn-induced cardiac dysfunction. Further deterioration of contractility due to the exposure of cardiomyocytes to LPS was partially prevented by C5a-blockade. These results suggest a linkage between C5a and burn-induced cardiac dysfunction and a possible contribution of LPS to these events.

• Authors: Laszlo M Hoesel, Andreas D Niederbichler, Julia Schaefer, Kyros R Ipaktchi, Hongwei Gao, Daniel Rittirsch, Matthew J Pianko, Peter M Vogt, J Vidya Sarma, Grace L Su, Saman Arbabi, Margaret V Westfall, Stewart C Wang, Mark R Hemmila, Peter A Ward
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 12 Pg. 7902-10 (Jun 15 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17548628 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Lipopolysaccharides
• Receptor, Anaphylatoxin C5a
• Complement C5a

Topics

• Animals
• Antibodies (pharmacology)
• Blotting, Western
• Burns (complications)
• Complement C5a (antagonists & inhibitors)
• Lipopolysaccharides (immunology)
• Male
• Myocardial Contraction (drug effects)
• Myocytes, Cardiac (chemistry, immunology)
• Polymerase Chain Reaction
• Pressure
• Rats
• Rats, Sprague-Dawley
• Receptor, Anaphylatoxin C5a (analysis, genetics, metabolism)
• Sarcomeres (physiology)
• Ventricular Dysfunction, Left (immunology, physiopathology)