| Autor: |
Roy, Shreyas K., Kubiak, Brian D., Albert, Scott P., Vieau, Christopher J., Gatto, Louis, Golub, Lorne, Lee, Hsi-Ming, Sookhu, Suraj, Vodovotz, Yoram, Nieman, Gary F. |
| Zdroj: |
Shock; April 2012, Vol. 37 Issue: 4 p424-432, 9p |
| Abstrakt: |
Experimental pharmacotherapies for the acute respiratory distress syndrome (ARDS) have not met with success in the clinical realm. We hypothesized that chemically modified tetracycline 3 (CMT-3), an anti-inflammatory agent that blocks multiple proteases and cytokines, would prevent ARDS and injury in other organs in a clinically applicable, porcine model of inflammation-induced lung injury. Pigs (n = 15) were anesthetized and instrumented for monitoring. A “2-hit” injury was induced: (a) peritoneal sepsis—by placement of a fecal clot in the peritoneum, and (b) ischemiareperfusion—by clamping the superior mesenteric artery for 30 min. Animals were randomized into two groups: CMT-3 group (n = 7) received CMT-3 (200 mgkg); placebo group (n = 9) received the same dose of a CMT-3 vehicle (carboxymethylcellulose). Experiment duration was 48 h or until early mortality. Animals in both groups developed polymicrobial bacteremia. Chemically modified tetracycline 3 treatment prevented ARDS as indicated by PaO2FIO2ratio, static compliance, and plateau airway pressure (P< 0.05 vs. placebo). It improved all histological lesions of ARDS (P< 0.05 vs. placebo). The placebo group developed severe ARDS, coagulopathy, and histological injury to the bowel. Chemically modified tetracycline 3 treatment prevented coagulopathy and protected against bowel injury. It significantly lowered plasma concentrations of interleukin 1 (IL-1), tumor necrosis factor , IL-6, IL-8, and IL-10. This study presents a clinically relevant model of lung injury in which CMT-3 treatment prevented the development of ARDS due in part to reduction of multiple plasma cytokines. Treatment of sepsis patients with CMT-3 could significantly reduce progression from sepsis into ARDS. |
| Databáze: |
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