Hypertonic Saline Resuscitation After Mesenteric Ischemia/Reperfusion Induces Ileal Apoptosis
ABSTRACT We have previously demonstrated that hypertonic saline (HS) resuscitation decreased inflammation and mucosal injury after mesenteric ischemia/reperfusion (I/R). In contrast to I/R cell necrosis, apoptosis provides controlled cell death that minimizes inflammation. We therefore hypothesized that HS resuscitation after mesenteric I/R would induce apoptosis and decrease mucosal injury.
Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then received no resuscitation or resuscitation with 4 mL/kg of HS, 4 mL/kg of lactated Ringer's (LR) solution (equal volume), or 32 mL/kg of LR solution (equal salt load). Rats were killed at 6 hours of reperfusion, and ileum was harvested for analysis. DNA fragmentation (apoptosis) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and mucosal injury by histology (Chiu score 0-5). Caspase-3 (proapoptotic mediator) and Bcl-xL (antiapoptotic mediator) protein expression were analyzed by Western immunoblot.
SMAO with no resuscitation, SMAO with 4 mL/kg of LR, and SMAO with 32 mL/kg of LR increased apoptosis (quantitated by TUNEL) and I/R-induced mucosal injury (quantitated by Chiu score). This was associated with an increase to similar levels in both proapoptotic caspase-3 and antiapoptotic Bcl-xL protein expression. Moreover, SMAO with 4 mL/kg of HS further increased apoptosis but decreased mucosal injury. This was associated with a differential expression of proapoptotic caspase-3 over antiapoptotic Bcl-xL.
HS resuscitation after mesenteric I/R significantly increased ileal mucosal apoptosis while decreasing mucosal injury and may represent a novel mechanism by which HS resuscitation after mesenteric I/R reduces inflammation and imparts protection to the gut.
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ABSTRACT: Исследованы реакции подбородочноязычной мышцы спонтанно дышащих трахеостомированных кроликов на увеличение сопротивления дыханию. У вагально интактных животных активность подбородочноязычной мышцы повышалась в первом же нагруженном вдохе. У билатерально ваготомированных – лишь с третьего дыхательного цикла, когда в действие вступал хеморецепторный механизм активации. Полученные результаты позволяют рассматривать рефлекс Геринга-Брейера в качестве основного механизма быстрого вовлечения фарингеальных мышц в компенсаторные реакции на увеличение сопротивления дыханию.
Article: CURRICULUM VITAE AND BIBLIOGRAPHY
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ABSTRACT: Conventional resuscitation (CR) from hemorrhagic shock (HS) often restores and maintains hemodynamics but fails to restore intestinal perfusion. Post-CR intestinal ischemia has been implicated in the initiation of a gut-derived exaggerated systemic inflammatory response and in the progressive organ failure following HS. We propose that intestinal ischemia can be prevented with hypertonic saline resuscitation (HTSR). Anesthetized male Sprague-Dawley rats (200 to 215 g) were hemorrhaged to 50% of mean arterial pressure (MAP) for 60 minutes and randomly assigned to 1 of the resuscitation groups (n = 7 each): Group I: sham operation and no HS; Group II: HS + CR with the return of the shed blood + 2 volumes of normal saline (NS); Group III: HS + return of the shed blood + hypertonic saline (HTS); (7.5 % NaCl, 4 ml/kg); Group IV: HS + HTS, then return of the shed blood after 60 minutes; Group V: HS + HTS, then 1 volume of NS after 60 minutes. Microvascular diameters of inflow (A1) and proximal and distal premucosal arterioles (A3) in terminal ileum and flow in A1 were measured using in vivo videomicroscopy and optical Doppler velocimetry. Hematocrit, plasma osmolarity, and electrolytes were measured in Groups II and III. HS caused a selective vasoconstriction in A1 arterioles that was not seen in the premucosal arterioles. CR restored and maintained MAP and caused generalized, progressive vasoconstriction at all intestinal arteriolar levels that is associated with hypoperfusion. HTSR failed to restore or maintain MAP or intestinal A1 arteriolar blood flow until the shed blood was returned. However, HTSR prevented the post-resuscitation, premucosal vasoconstriction and produced an insidious selective vasodilation in the A3 arterioles, which was most significant with early blood return (Group III). This selective arteriolar vasoactivity was associated with a significant improvement of endothelial cell function. Plasma hyperosmolality and hypernatremia persisted during the entire 2 hours post-resuscitation with HTS. Small-volume HTSR can be used as a resuscitation regimen at the trauma scene and for selective clinical conditions where hypotensive resuscitation is indicated. HTSR improves intestinal perfusion by selective vasodilation of the precapillary arterioles even at MAP close to shock levels.Surgery 11/2006; 140(4):579-87; discussion 587-8. DOI:10.1016/j.surg.2006.05.015 · 3.11 Impact Factor