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A Novel Rat Model to Test Intra-Abdominal Anti-adhesive Therapy.

ABSTRACT: Background: Adhesion formation after abdominal surgery is considered almost inevitable and a major cause of morbidity. Novel treatments have been proposed, however there is a lack of suitable small animal models for pre-clinical evaluation, mainly due to inconsistency in adhesion formation in positive control animals. Here, we propose a new rat model of abdominal adhesions using Kaolin as the adhesion-inducing agent at an optimized dosage for testing newer agents in respect to their anti-adhesive property. Materials and Methods: Twenty-five adult (8-10 week old) male Wistar albino rats underwent midline laparotomy and caecal abrasion and were randomized to receive topical applications of normal saline or different concentrations and volumes of a Kaolin-based formulation. At day 14 rats were humanely killed, and adhesions graded macroscopically by an investigator blinded to the treatment groups, using pre-determined adhesion scores and microscopically using histopathology. Results: Kaolin at 0.005 g/mL caused consistent adhesions without compromising rat viability. At higher doses significant morbidity and mortality was observed in the animals treated. Conclusions: Kaolin induced adhesion in a rat abdominal surgery model is reliable and can be safely used to test the efficacy of novel anti-adhesive formulations to prevent intra-abdominal adhesions.

SUBMITTER: Vediappan RS

PROVIDER: S-EPMC7158702 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Novel Rat Model to Test Intra-Abdominal Anti-adhesive Therapy.

Vediappan Rajan Sundaresan RS Bennett Catherine C Bassiouni Ahmed A Smith Matthew M Finnie John J Trochsler Markus M Psaltis Alkis J AJ Vreugde Sarah S Wormald Peter J PJ

Frontiers in surgery 20200408

<b>Background:</b> Adhesion formation after abdominal surgery is considered almost inevitable and a major cause of morbidity. Novel treatments have been proposed, however there is a lack of suitable small animal models for pre-clinical evaluation, mainly due to inconsistency in adhesion formation in positive control animals. Here, we propose a new rat model of abdominal adhesions using Kaolin as the adhesion-inducing agent at an optimized dosage for testing newer agents in respect to their anti- ...[more]

PMID: 32322586

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Project description:BackgroundAmong all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model.Materials and methodsForty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair's scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β). The collagen deposition was assessed by Sirius red staining and α-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H2O2 and DHI, and NF-κB phosphorylation was detected to illustrate the effect of DHI on oxidative stress.ResultsThe intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-α, TGF-β1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-κB phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs.ConclusionDHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.

Project description:BackgroundThe intra-abdominal pressure (IAP) is an important clinical parameter that can significantly change during respiration. Currently, IAP is recorded at end-expiration (IAPee), while continuous IAP changes during respiration (?IAP) are ignored. Herein, a novel concept of considering continuous IAP changes during respiration is presented.MethodsBased on the geometric mean of the IAP waveform (MIAP), a mathematical model was developed for calculating respiratory-integrated MIAP (i.e. MIAPri=IAPee+i??IAP), where 'i' is the decimal fraction of the inspiratory time, and where ?IAP can be calculated as the difference between the IAP at end-inspiration (IAPei) minus IAPee. The effect of various parameters on IAPee and MIAPri was evaluated with a mathematical model and validated afterwards in six mechanically ventilated patients. The MIAP of the patients was also calculated using a CiMON monitor (Pulsion Medical Systems, Munich, Germany). Several other parameters were recorded and used for comparison.ResultsThe human study confirmed the mathematical modelling, showing that MIAPri correlates well with MIAP (R2 = 0.99); MIAPri was significantly higher than IAPee under all conditions that were used to examine the effects of changes in IAPee, the inspiratory/expiratory (I:E) ratio, and ?IAP (P <0.001). Univariate Pearson regression analysis showed significant correlations between MIAPri and IAPei (R = 0.99), IAPee (R = 0.99), and ?IAP (R = 0.78) (P <0.001); multivariate regression analysis confirmed that IAPee (mainly affected by the level of positive end-expiratory pressure, PEEP), ?IAP, and the I:E ratio are independent variables (P <0.001) determining MIAP. According to the results of a regression analysis, MIAP can also be calculated asMIAP=-0.3+IAPee+0.4??IAP+0.5?IE.ConclusionsWe believe that the novel concept of MIAP is a better representation of IAP (especially in mechanically ventilated patients) because MIAP takes into account the IAP changes during respiration. The MIAP can be estimated by the MIAPri equation. Since MIAPri is almost always greater than the classic IAP, this may have implications on end-organ function during intra-abdominal hypertension. Further clinical studies are necessary to evaluate the physiological effects of MIAP.

Project description:IntroductionIntra-abdominal hypertension (IAH) causes atelectasis, reduces lung volumes and increases respiratory system elastance. Positive end-expiratory pressure (PEEP) in the setting of IAH and healthy lungs improves lung volumes but not oxygenation. However, critically ill patients with IAH often suffer from acute lung injury (ALI). This study, therefore, examined the respiratory and cardiac effects of positive end-expiratory pressure in an animal model of IAH, with sick lungs.MethodsNine pigs were anesthetized and ventilated (48 +/- 6 kg). Lung injury was induced with oleic acid. Three levels of intra-abdominal pressure (baseline, 18, and 22 mmHg) were randomly generated. At each level of intra-abdominal pressure, three levels of PEEP were randomly applied: baseline (5 cmH2O), moderate (0.5 × intra-abdominal pressure), and high (1.0 × intra-abdominal pressure). We measured end-expiratory lung volumes, arterial oxygen levels, respiratory mechanics, and cardiac output 10 minutes after each new IAP and PEEP setting.ResultsAt baseline PEEP, IAH (22 mmHg) decreased oxygen levels (-55%, P <0.001) and end-expiratory lung volumes (-45%, P = 0.007). At IAP of 22 mmHg, moderate and high PEEP increased oxygen levels (+60%, P = 0.04 and +162%, P <0.001) and end-expiratory lung volume (+44%, P = 0.02 and +279%, P <0.001) and high PEEP reduced cardiac output (-30%, P = 0.04). Shunt and dead-space fraction inversely correlated with oxygen levels and end-expiratory lung volumes. In the presence of IAH, lung, chest wall and respiratory system elastance increased. Subsequently, PEEP decreased respiratory system elastance by decreasing chest wall elastance.ConclusionsIn a porcine sick lung model of IAH, PEEP matched to intra-abdominal pressure led to increased lung volumes and oxygenation and decreased chest wall elastance shunt and dead-space fraction. High PEEP decreased cardiac output. The study shows that lung injury influences the effects of IAH and PEEP on oxygenation and respiratory mechanics. Our findings support the application of PEEP in the setting of acute lung injury and IAH.

Project description:BackgroundThe prognostic role of what a surgeon observes in the abdomen of patients with complicated intra-abdominal infection (cIAI) is largely unknown. The aim of this prospective study was to systemically analyze components of the intra-abdominal view (IAV) and their association to severe complicated intra-abdominal sepsis (SCIAS) or mortality.MethodsThe study cohort consisted of adult patients with cIAI. The operating surgeon filled a paper form describing the intra-abdominal view. Demographics, operative details, and preoperative physiological status were collected. Descriptive, univariate, and multivariate statistical analyses were performed, and a new score was developed based on regression coefficients. The primary outcome was a composite outcome of SCIAS or 30-day mortality, in which SCIAS was defined as organ dysfunctions requiring intensive care unit admission.ResultsA total of 283 patients were analyzed. The primary outcome was encountered in 71 (25%) patients. In the IAV, independent risk factors for the primary outcome were fecal or bile as exudate (odds ratio (OR) 1.98, 95% confidence interval 1.05-3.73), diffuse peritonitis (OR 2.15, 1.02-4.55), diffuse substantial redness of the peritoneum (OR 5.73, 2.12-15.44), and a non-appendiceal source of cIAI (OR 11.20, 4.11-30.54). Based on these factors, an IAV score was developed and its performance analyzed. The area under the receiver operating characteristic for the IAV score was 0.81. The IAV score also correlated significantly with several outcomes and organ dysfunctions.ConclusionsThe extent of peritonitis, diffuse substantial redness of the peritoneum, type of exudate, and source of infection associate independently with SCIAS or mortality. A high IAV score associates with mortality and organ dysfunctions, yet it needs further external validation. Combining components of IAV into comprehensive scoring systems for cIAI patients may provide additional value compared to the current scoring systems.Trial registrationThe study protocol was retrospectively registered on April 4, 2016, right after the first enrolled patient at Clinicaltrials.gov database (NCT02726932).

Project description:Desmoid fibromatosis is a rare but locally aggressive tumor comprised of myofibroblasts. Desmoids do not have the ability to metastasize but can cause significant morbidity and mortality by local invasion. These tumors may occur throughout the body, but are commonly found on the abdominal wall and within the intestinal mesentery. Desmoids in these areas may cause unique clinical problems for physicians and patients. Mutations in either the β-catenin or the APC genes are usually the cause for the development of these tumors with the former comprising the sporadic development of tumors and the latter being associated with familial adenomatous polyposis syndrome. Surgical resection with histologically negative margins has been the cornerstone of therapy for this disease, but this paradigm has begun to shift. It is now common to accept a microscopically positive margin after resection as recurrence rates may not be significantly affected. An even more radical evolution in management has been the recent movement towards "watchful waiting" when new desmoids are diagnosed. As the natural history of desmoids has become better understood, it is evident that some tumors will not grow and may even spontaneously regress sparing patients the morbidity of more aggressive therapy. Other modalities of treatment for desmoids include radiation and systemic therapy which both can be used adjuvantly or as definitive therapy and have shown durable response rates as single therapy regimens. The decision to use radiation and/or systemic therapies is often based on tumor biology, tumor location, surgical morbidity, and patient preference. Systemic therapy options have increased to include hormonal therapies, non-steroidal anti-inflammatory drugs and chemotherapy, as well as targeted therapies. Unfortunately, the rarity of this disease has resulted in a scarcity of randomized trials to evaluate any of these therapies emphasizing the need for this disease to be treated at high volume multidisciplinary institutions.

Project description:The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted.

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A Novel Rat Model to Test Intra-Abdominal Anti-adhesive Therapy.

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A Novel Rat Model to Test Intra-Abdominal Anti-adhesive Therapy.

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