In vivodecontamination of the nerve agent VX using the domestic swine model

Background: The identification of serum biomarkers of ischemic injury could provide a means of assessing interventions designed to limit reperfusion injury after return of spontaneous circulation (ROSC). We sought to characterize the early post-ROSC timecourse of two candidate biomarkers of ischemic injury (cytochrome- c and IL-6) in a swine model of ventricular fibrillation (VF). We hypothesized that these two biomarkers would be elevated immediately after ROSC. Methods: Twenty-five mixed breed domestic swine were anesthetized and instrumented with ECG, temperature probe, and aortic and right atrial pressure transducers. VF was induced with a transthoracic shock and untreated for 8 minutes. Then mechanical CPR was done for 2 minutes, before drugs were given (epinephrine, vasopressin, and propranolol) with 3 additional minutes of CPR (first defibrillation attempt at 13 minutes of VF). Blood samples were drawn at the end of instrumentation (i.e. just prior to VF), and at 20, 40, and 60 minutes after ROSC. Samples were centrifuged and serum extracted. Cytochrome- c was analyzed via Western immunoblotting. IL-6 was analyzed with ELISA. Results: No cytochrome- c was detected in any animal, at any timepoint through 60 min. IL-6 was similar to baseline levels through 40 min, but was 121% of baseline at 60. Conclusions: Neither biomarker was elevated immediately after ROSC. Mitochondrial damage (as indicated by the absence of cytochrome- c ) may be delayed by as much as an hour after ROSC, hinting at a possible therapeutic window for interventions like hypothermia. Likewise, inflammatory cascades (as indicated by IL-6) may not begin immediately post-ROSC, but might by one hour.

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Development of a common peroneal nerve injury model in domestic swine for the study of translational neuropathic pain treatments

Journal of Neurosurgery ◽

10.3171/2020.9.jns202961 ◽

2021 ◽

pp. 1-8

Author(s):

Abigail Hellman ◽

Teresa Maietta ◽

Alicia Clum ◽

Kanakaharini Byraju ◽

Nataly Raviv ◽

...

Keyword(s):

Neuropathic Pain ◽

Nerve Injury ◽

Peroneal Nerve ◽

Common Peroneal Nerve ◽

Pain Behavior ◽

Swine Model ◽

Pain Model ◽

Neuropathic Pain Model ◽

Peroneal Nerve Injury ◽

Domestic Swine

OBJECTIVE To date, muscular and bone pain have been studied in domestic swine models, but the only neuropathic pain model described in swine is a mixed neuritis model. Common peroneal nerve injury (CPNI) neuropathic pain models have been utilized in both mice and rats. METHODS The authors developed a swine surgical CPNI model of neuropathic pain. Behavioral outcomes were validated with von Frey filament testing, thermal sensitivity assessments, and social and motor scoring. Demyelination of the nerve was confirmed through standard histological assessment. The contralateral nerve served as the control. RESULTS CPNI induced mechanical and thermal allodynia (p < 0.001 [n = 10] and p < 0.05 [n = 4], respectively) and increased pain behavior, i.e., guarding of the painful leg (n = 12). Myelin protein zero (P0) staining revealed demyelination of the ligated nerve upstream of the ligation site. CONCLUSIONS In a neuropathic pain model in domestic swine, the authors demonstrated that CPNI induces demyelination of the common peroneal nerve, which the authors hypothesize is responsible for the resulting allodynic pain behavior. As the anatomical features of domestic swine resemble those of humans more closely than previously used rat and mouse models, utilizing this swine model, which is to the authors’ knowledge the first of its kind, will aid in the translation of experimental treatments to clinical trials.

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Comparison of selected skin decontaminant products and regimens against VX in domestic swine

Human & Experimental Toxicology ◽

10.1177/0960327108090269 ◽

2008 ◽

Vol 27 (3) ◽

pp. 253-261 ◽

Cited By ~ 42

Author(s):

S Bjarnason ◽

J Mikler ◽

I Hill ◽

C Tenn ◽

M Garrett ◽

...

Keyword(s):

Aqueous Suspension ◽

Significant Proportion ◽

Chemical Warfare Agent ◽

Skin Wound ◽

Organophosphate Poisoning ◽

Swine Model ◽

Liquid Environment ◽

Fuller’S Earth ◽

Skin Decontamination ◽

Domestic Swine

An anesthetized domestic swine model was used to compare the efficacy and cross-contamination potential of selected skin decontaminant products and regimens against the chemical warfare agent, VX. Animals topically exposed to 2×, 3× or 5× LD50 VX showed typical signs of organophosphate nerve agent poisoning, including miosis, salivation, mastication, dysrhythmias, and respiratory distress prior to death. Animals were exposed to 5× LD50 VX and then decontaminated 45 min later with the reactive skin decontamination lotion (RSDL®), Fuller’s earth (FE), 0.5% hypochlorite, or soapy water. Survival was 100% when the reactive skin decontamination lotion or FE was utilized, although 50% of Fuller’s earth-decontaminated animals exhibited serious signs of VX poisoning. Decontamination of VX-treated animals with 0.5% hypochlorite was less effective but also increased survival. Soapy water was ineffective in preventing lethality. Blood cholinesterase levels were not predictive of clinical outcome in decontaminated animals. The potential of “decontaminated” VX in open wounds to cause poisoning was assessed by vigorously mixing 5× LD50 VX with the test decontaminants for 5 min and then placing the mixture onto a full-thickness skin wound. Soapy water was ineffective in preventing lethality. Although treatment with dry Fuller’s earth prevented death and all signs of organophosphate poisoning, a significant proportion of treated animals decontaminated with Fuller’s earth in aqueous suspension exhibited serious signs of organophosphate poisoning, suggesting that live agent may be desorbed from Fuller’s earth when it is exposed to a liquid environment. Animals treated with reactive skin decontamination lotion or 0.5% hypochlorite-VX mixtures showed no signs of organophosphate poisoning during the 6- h test period.

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