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Combined Peroxynitrite Decomposition Catalyst and Vasopressin therapy in Methicilin Resistant Staphylococcus aureus (MRSA) Sepsis
Author(s) -
Jonkam Collette Changie,
Enkhbaatar Perenlei,
Traber Lillian,
Bansal Kamna,
Esechie Aimalohi,
Traber Daniel
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1154.17
Subject(s) - peroxynitrite , vasopressin , chemistry , sepsis , vasopressin receptor , staphylococcus aureus , medicine , anesthesia , endocrinology , arginine , biochemistry , amino acid , enzyme , bacteria , biology , genetics , superoxide
Sepsis is associated with excessive production of reactive nitrogen species such as peroxynitrite, a potent inducer of cellular damage. Currently we tested the effects of peroxynitrite decomposition catalyst (INO‐4885) on MRSA sepsis. METHODS: Eves were surgically prepared for study: Control (injured, non‐treated, n=6), INO‐4885 (injured, treated with INO‐4885, n=5) and INO + Vasopressin (injured, treated with INO‐4885 and Vasopressin, n=3). Injured animals were given 48 breaths of cotton smoke and ~2.5 x 1011 CFU of live MRSA into the lungs. INO‐4885 bolus was given at 1h post injury followed by continuous infusion. 3 sheep also received Vasopressin when the mean arterial pressure (MAP) decreased by 10mmHg below baseline value. RESULTS: The severe hypotension and fall in systemic vascular resistance seen in control animals was partially alleviated by INO, and totally reversed by combined INO and AVP. AVP alone failed to attenuate these variables. The control group also developed severe signs of vascular leakage (fluid retention, decreased plasma protein and oncotic pressure), which was partially improved by INO alone and reversed by combined therapy. AVP alone had no effect. CONCLUSION: Peroxynitrite may decrease the sensitivity of AVP receptors. Inhibition of peroxynitrite restores the AVP receptor sensitivity and reduces the requirement of AVP.