Interaction of Hemorrhagic Shock and Subsequent Polymicrobial Sepsis on Gastrointestinal Motility

Abstract

Understanding “two-hit” experimental models is crucial for the rational development of therapies for hemorrhagic shock (HS). We modeled the clinical scenario of HS followed by polymicrobial sepsis (cecal ligation and puncture [CLP]) to investigate the molecular and functional alterations that occur within the gastrointestinal tract. Control, HS, CLP, simultaneous HS + CLP, and HS + delayed CLP by 24 h groups of Sprague-Dawley rats were studied for gastrointestinal transit and in vitro colonic circular muscle contractility to bethanechol. Reverse transcription–polymerase chain reaction quantified IL-6, IL-10, and heme oxygenase 1 messenger RNA expression in the isolated colonic muscularis 6 h after insult. Myeloperoxidase-positive neutrophils were quantified in colonic muscularis whole mounts. Mortality at 24 h was significantly increased in simultaneous mild HS + CLP (88%) over control, mild HS, CLP alone, or HS + delayed CLP. Cecal ligation and puncture significantly delayed transit compared with controls and HS alone. Hemorrhagic shock + delayed CLP animals had normal transit. Colonic contractions were suppressed by 50% after CLP compared with controls and HS. In contrast, HS + delayed CLP displayed control levels of contractile responses to bethanechol. Cecal ligation and puncture and simultaneous HS + CLP caused significant inflammatory messenger RNA induction of IL-6, iNOS, IL-10, and heme oxygenase 1 compared with control and HS, and these responses were significantly suppressed in HS + delayed CLP colonic muscularis extracts. Neutrophils were significantly recruited into the colonic muscularis following CLP after 24 h compared with control and HS. This recruitment was significantly less in the HS + delayed CLP animals. These data demonstrate the ability of mild HS to precondition the animal and protect it against a delayed, but not simultaneous, polymicrobial event.

Effect of constipation on outcomes in mechanically ventilated patients

“…A possible explanation is that shock requiring vasopressors results in selective intestinal ischemia, and shock itself is associated with decreased gut motility that results in intestinal atony and functional ileus. 14 Our study showed an increased association between vasopressor use and LOS as well (mean difference, 0.8 ± 0.3 days, P < 0.001). Van der Spoel et al demonstrated that delayed defecation is associated with the administration of vasopressors; however, it cannot be distinguished whether the constipation is a consequence of the administration of vasopressors or of the severity of illness for which the medication was given in the first place.…”

The leaky gut and the gut microbiome in sepsis – targets in research and treatment

“…Reduced intestinal perfusion can be recognized in the early phase of sepsis with normal blood pressure (pre-shock stage), despite systemic vasodilatation (distributive shock) and myocardial depression (partly from hyper-cytokinaemia) [ 114 , 115 ], by a decrease in gut microcirculation as presented by sepsis-induced ileus [ 116 ]. Because ileus can be an early sign of systemic inflammation, either from infection (sepsis) or non-infection (multiple injury or multi-organ failure; MOF), but presents with normal blood pressure, the reduced gut perfusion in sepsis and MOF might occur very early in the natural course of diseases [ 117 ]. Among several factors associated with sepsis-induced intestinal disorders [ 81 ], gut hypoperfusion is an important factor that possibly results in (i) enterocyte damage (necrosis and apoptosis) with leaky gut and (ii) intestinal immunity defects (the death of immune cells) with decreased microbial control function and increased gut dysbiosis (the selection of only highly virulent bacteria).…”

WHAT'S NEW IN SHOCK, April 2009?

“…Because this response was present neither in the Bim j/j nor in the Bcl-2 +/+ mice, the authors concluded that a decreased ratio between antiapoptotic (Bcl-2) and proapoptotic (Bim) proteins assumes major importance for sepsis-induced immune cell depletion in vivo and, consequently, for the antimicrobial host defense. Overhaus et al (12) investigated the impact of a Btwo-hit[ model on gastrointestinal motility using a combination of mild hemorrhagic shock and either simultaneous or delayed CLP-induced peritonitis in rats. Gastrointestinal transit in vivo was assessed by measuring the fluorescent concentration in 15 equal bowel segment pieces after oral administration of fluorescein isothiocyanate-labeled dextran, whereas in vitro circular muscle contractility of the colon was quantified by its isometric force response to stimulation by the muscarinic agonist bethanechol.…”