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Abstract PD-017: RECOMBINANT VON WILLEBRAND FACTOR A2 POLYPEPTIDE ATTENUATES ORGAN INJURIES IN A PORCINE MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS (MRSA) SEPSIS-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

Nguyen, T.1; Marini, J.1; Guillory, B.2; Valladolid, C.2; Cirlos, S.2; Martinez-Vargas, M.2; Da, Q.2; Cohen, D.3; Stoll, B.1; Lam, F.1; Desai, M.1; Tcharmtchi, M.1; Navaei, A.1; Bashir, D.1; Vijayan, V.2; Cruz, M.2

Pediatric Critical Care Medicine: June 2018 - Volume 19 - Issue 6S - p 34–35
doi: 10.1097/01.pcc.0000537419.28665.ed
Poster Discussion Abstracts
Free

1Texas Children’s Hospital/Baylor College of Medicine, Pediatrics, Houston, USA

2Baylor College of Medicine, Medicine, Houston, USA

3Baylor College of Medicine, Pathology, Houston, USA

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Aims & Objectives:

Sepsis-induced DIC is associated with a high mortality. Currently, no therapy exists for sepsis and/or DIC other than supportive care. Worldwide incidence of MRSA sepsis is increasing and SA sepsis is associated with DIC and mortality. We previously demonstrate that our A2 polypeptide improves survival and reverses DIC in a murine model of endotoxemia-induced DIC. We hypothesize that our A2 polypeptide will attenuate organ injuries in a porcine model of MRSA sepsis-induced DIC.

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Methods

Eight 4-week old piglets (8kg), implanted with telemetry device for continuous hemodynamic monitoring as previously described, were injected intravenously (i.v.) with MRSA (USA300, TCH 1516 strain) dose of 1x10x9 CFU/kg. Fluid resuscitation was performed for predefined tachycardia and hypotension. 24h after MRSA injection, A2 was injected i.v. in 6 pigs with 2 pigs (male, female) receiving escalating doses of 1mg/kg, 2mg/kg, or 3.5mg/kg. 2 pigs received buffer. Pigs were euthanized 70h post-MRSA injection. Histological evaluation of kidney and liver were done.

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Results

All 8 pigs survived to 70h. Fig 1 showed heterogeneous dark discoloration on gross examination of kidney and liver which under microscopic examination of these areas revealed abnormalities including necrosis, microthrombi, micro-hemorrhages, congestion and lymphocytic infiltration.

Table 1 showed histological organ injury scores were lower in septic pigs that received A2 compared to those that did not receive A2

Table

Table

Figure

Figure

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Conclusions

A2 polypeptide injected 24h after MRSA injection seems to attenuate MRSA sepsis-induced organ abnormalities in the kidney and liver of septic piglets. Further studies are on-going to confirm the findings of this novel A2 polypeptide.

©2018The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies