Granulocyte colony-stimulating factor but not peritoneal lavage increases survival rate after experimental abdominal contamination and infection

Abstract

In these CMRTs of intra-abdominal contamination and infection, peritoneal lavage was not beneficial, but when lavage was combined with subcutaneous administration of G-CSF mortality was reduced and the local and systemic cytokine response was downgraded. Results from these CMRTs were used directly to define the trial conditions of a randomized clinical trial with G-CSF. Peritoneal lavage is not recommended.

Beneficial effect of clopidogrel in a mouse model of polymicrobial sepsis

“…In a model of endotoxin shock in mice, it was also demonstrated that the P2Y12 receptor antagonist clopidogrel attenuates the drop in blood platelet count and fibrin deposition in lungs, as well as modulating gene expression in peripheral blood cells [5]. To obtain further evidence for a beneficial effect of antiplatelet drugs in sepsis, we studied the effects of clopidogrel on sepsis in mice induced by polymicrobial peritoneal contamination and infection (PCI) [8].…”

“…It monitors the viscoelastic properties of a clot induced in whole blood samples in vitro. Clotting time (CT), that is, the lag phase between intrinsic or extrinsic activation of coagulation and start of clot formation, is mainly dependent on plasma coagulation factors and inhibitors, whereas clot formation time (CFT), clot formation rate (CFR) and maximum clot firmness (MCF) predominantly depend on plasma fibrinogen level and blood platelet count [8,9]. As shown in Table 1, 6 h after PCI, we observed a significant prolongation of CT and CFT as well as a decrease in CFR and MCF.…”

“…Clopidogrel (kindly provided by Sanofi Aventis, Frankfurt a.M., Germany) was added at a concentration of 187.5 mg L )1 to the drinking water (corresponding to a dosage of about 5 mg kg )1 per day) for 5 days prior to PCI by intraperitoneal injection of 0.2 mL of a human feces suspension [8]. Untreated as well as clopidogrel-treated animals were used as controls.…”

Antibiotic prophylaxis influences cardiovascular stability in complicated surgery

“…the effectiveness of different combinations of H 1 + H 2 -receptor antagonists in preventing cardio-respiratory instabilities in pigs [21]. Furthermore, this concept was applied to studies in rodents investigating the effect of the immunomodulating growth factor G-CSF (granulocyte-colony stimulating factor) applied as a prophylaxis on the course and outcome of peritonitis and sepsis in rats [19,22,44]. The results of these pre-clinical experiments in rats were used for the development of a clinical study protocol which was published in three parts [45][46][47] before the prospective, randomised, clinical study was successfully conducted.…”

Individual behavioral differences in recovery from abdominal sepsis in rats

“…Laparotomy was performed through a midline incision of two-centimeter length and the inoculum was injected i.p. into the pelvic region of the rats [26]. The wound was closed in two layers using an interrupted absorbable Vicryl ® 3-0 suture technique (Ethicon, Hamburg, Germany).…”