Search

Background: Prosthetic mesh is used frequently in abdominal wall hernia reconstruction but is prone to postoperative adhesion formation. Complications resulting from intra-abdominal adhesions represent a considerable clinical and cost burden. We, herein, investigate the antiproliferative and antiadhesiogenic properties of sirolimus and hydrogel-impregnated, drug-eluting mesh to decrease such complications in a mouse model of abdominal wall hernia repair., Methods: A 1 × 1cm(2) polypropylene mesh from 1 of 3 groups (group 1, plain control; group 2, hydrogel [2% agarose]; and group 3, hydrogel + 10 mcg sirolimus) was implanted operatively into the peritoneal cavity of BALB/c mice and followed for up to 4 weeks. Adhesions were scored by percent surface area of mesh (range, 0-100%), severity (range, 0-3), and tenacity (range, 0-4). Representative samples were assessed by scanning electron microscopy., Results: Mesh impregnated with the combination of hydrogel and sirolimus led to a significant decrease in adhesion formation. The percent surface area of adhesional attachment to mesh was decreased from 100.0 ± 0% in the plain mesh control group versus 18 ± 8% (P < .001) in the combined impregnated mesh group. Similarly, adhesion severity scores were decreased from a score of 2.9 ± 0.1 (plain mesh) versus 1.4 ± 0.1 (sirolimus/hydrogel-impregnated mesh) (P < .001). Scores for tenacity were also decreased markedly from 3.5 ± 0.2 (plain mesh) versus 1.5 ± 0.1 (sirolimus/hydrogel-impregnated mesh (P < .001)., Conclusion: Creation of a sirolimus drug-eluting and hydrogel-impregnated polypropylene mesh resulted in marked decrease of adhesion formation in this mouse model, was well tolerated without side effects, and has potential for clinical application., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: A recent study from our laboratory documented significant improvements in post-transplant viability in an experimental model of intestinal transplantation when a novel, nutrient-rich preservation solution was used during cold storage. The current study investigated the relationship between energetic/oxidative stress responses and fundamental kinase signaling events during the period of organ storage. This relationship may be a key factor contributing to improved graft viability after storage in a nutrient-rich preservation solution., Methods: Rat small intestine was harvested and flushed intraluminally with University of Wisconsin (UW) solution or an amino acid-rich (AA) solution as follows: Group 1, no luminal flush (clinical control); Group 2, luminal UW solution; Group 3, luminal AA solution. Energetics (ATP, total adenylates), oxidative stress (malondialdehyde), histology, and MAPK (P38, JNK, ERK)/AMPK/Caspase-3 were assessed throughout 12-hour cold storage., Results: P38 and JNK were upregulated strongly in Group 2 after 1- and 12-hour storage. Group 3 exhibited a delayed activation and subsequent downregulation of these pre-apoptotic signals. Between 6 to 12 hours, a strong upregulation of ERK was observed in Group 3. AMPK downregulation correlated with a reduction in AMP/ATP ratio, ERK upregulation, and P38/JNK downregulation in Group 3. After 12-hour storage, histology indicated superior preservation of mucosal architecture in Group 3 tissues., Conclusions: A nutrient-rich preservation solution abrogates pre-apoptotic signaling (JNK and P38) and upregulates cytoprotective signals (ERK). Our data support the concept of a concerted effort facilitating cellular protection in response to ischemic stress.

Background: Oxidative stress during cold small bowel (SB) storage has not been investigated because oxygen is depleted rapidly after procurement. We hypothesized that oxidative catabolism facilitated by a proven amino acid-based (AA) storage solution promotes oxidative stress; furthermore, there is an important role for antioxidant supplementation during cold storage., Methods: SB from Sprague-Dawley rats (n = 6 in each group) were procured according to standardized procedures involving vascular flush with modified University of Wisconsin solution and luminal treatment with an AA-based solution proven previously to aid preservation. SB were assigned randomly to the following antioxidant treatment groups: group 1, none; group 2, superoxide dismutase/catalase; group 3, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox, a water-soluble analogue of vitamin E). Energetics, oxidative stress, electrophysiology, and histology were assessed over 24 hours at 4 degrees C., Results: The addition of Trolox in group 3 resulted in a significant reduction in malondialdehyde levels compared with all other groups throughout 24 hours of cold storage. Tissue energetics correlated well with reduced oxidative injury; over the first 12 hours, adenosine triphosphate and total adenylates were superior in tissues treated with Trolox (group 3) versus AA solution alone (group 1). Functional assessment showed relatively normal permeability in all groups, however, Trolox-treated tissues showed significantly higher short-circuit current compared with control group (17.7 vs 5.5 microA/cm(2)). Histologic integrity was improved in group 3 after 24 hours of cold storage., Conclusions: Oxidative stress appears to be a determinant in the pathogenesis of mucosal injury during cold storage. Trolox effectively abrogates storage-related oxidative stress in SB.