Effects of a TREM-like transcript 1-derived peptide during hypodynamic septic shock in pigs.

Abstract

The objective of this study was to determine the effects of a TREM (triggering receptor expressed on myeloid cells 1)-like transcript 1-derived peptide (LR12) administration during septic shock in pigs. Two hours after induction of a fecal peritonitis, anesthetized and mechanically ventilated adult male minipigs were randomized to receive LR12 (n = 6) or its vehicle alone (normal saline, n = 5). Two animals were operated and instrumented without the induction of peritonitis and served as controls (sham). Resuscitation was achieved using hydroxyethyl starch (up to 20 mL/kg) and norepinephrine infusion (up to 10 μg/kg per minute). Hemodynamic parameters were continuously recorded. Gas exchange, acid-base status, organ function, and plasma cytokines concentrations were evaluated at regular intervals until 24 h after the onset of peritonitis when animals were killed under anesthesia. Peritonitis induced profound hypotension, myocardial dysfunction, lactic acidosis, coagulation abnormalities, and multiple organ failure. These disorders were largely attenuated by LR12. In particular, cardiovascular failure was dampened as attested by a better mean arterial pressure, cardiac index, cardiac power index, and S(v)O(2), despite lower norepinephrine requirements. LR12, a TREM-like transcript 1-derived peptide, exhibits salutary properties during septic shock in adult minipigs.

• Authors: Marc Derive, Amir Boufenzer, Youcef Bouazza, Frédérique Groubatch, Corentine Alauzet, Damien Barraud, Alain Lozniewski, Pierre Leroy, Nguyen Tran, Sébastien Gibot
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 39 Issue 2 Pg. 176-82 (Feb 2013) ISSN: 1540-0514 [Electronic] United States
• PMID: 23324887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiovascular Agents
• Hydroxyethyl Starch Derivatives
• Receptors, Immunologic
• TREML1 protein, human

Topics

• Animals
• Blood Coagulation Disorders (prevention & control)
• Cardiovascular Agents (therapeutic use)
• Cardiovascular Diseases (prevention & control)
• Hemodynamics (drug effects)
• Hydroxyethyl Starch Derivatives (pharmacology)
• Hypotension (drug therapy)
• Male
• Multiple Organ Failure (prevention & control)
• Random Allocation
• Receptors, Immunologic (therapeutic use)
• Shock, Septic (drug therapy)
• Swine
• Swine, Miniature