Mark K. Eskandari

Biphasic response to gut manipulation and temporal correlation of cellular infiltrates and muscle dysfunction in rat

BACKGROUND Surgical manipulation of the intestine results in the massive movement of leukocytes into the intestinal muscularis at 24 hours. This is associated with muscle inhibition. The aim of this study was to temporally associate leukocyte extravasation with ileus after surgical manipulation. METHODS Rats underwent a simple manipulation of the small bowel and were killed at various times (0, 0.25, 0.5, 1, 3, 6, 12, and 24 hours) postoperatively. Jejunal circular-muscle contractile activity was assessed in a standard organ bath. Both extravasating and resident leukocytes were immunohistochemically stained in muscularis whole mounts. RESULTS Contractile activity was significantly reduced immediately after surgery, but rapidly returned to control levels at 3 hours. After recovery, muscle function decreased at 12 and 24 hours (41% and 81%, respectively). The resident muscularis macrophage network demonstrated cellular activation 1 hour postoperatively. The number of leukocytes increased over time (neutrophils, 67.5-fold; monocytes, 98.2-fold; and mast cells, 47-fold at 24 hours). CONCLUSIONS The functional results demonstrate a biphasic response in the suppression of muscle activity after surgical manipulation. Regression analysis (r2 = 0.998) of the temporal development of leukocyte infiltration and the protracted phase of muscle inhibition provides evidence for a correlation between cellular inflammation and postoperative dysmotility.

LPS-induced muscularis macrophage nitric oxide suppresses rat jejunal circular muscle activity.

Cellular mechanisms of sepsis-induced ileus remain an enigma. The study aim was to determine the role of nitric oxide (NO) in mediating the suppression of rat jejunal circular smooth muscle activity during endotoxemia. Isolated muscularis inducible NO synthase (iNOS) mRNA was measured by RT-PCR, immunohistochemistry was employed to localize iNOS protein, and contractile activity was measured in an organ bath. The low basal expression of muscularis iNOS mRNA expression was increased in a time-dependent fashion after lipopolysaccharide (LPS), resulting in a 20-fold increase over controls 3 h after injection. Immunohistochemistry of muscularis whole mounts and dissociated muscularis cells for iNOS revealed staining only in the muscularis macrophages 12 h after LPS. LPS caused a 68% reduction in spontaneous muscle activity 12 h after injection, which improved by 53% after the in vitro application of the selective iNOS inhibitorl- N 6-(1-iminoethyl)lysine. Similar results were obtained in C57BL/6 mice but not in iNOS knockout mice. These data demonstrate that macrophage iNOS plays an important role in mediating LPS-induced intestinal circular muscle suppression.

Endovascular Repair of an Aortoduodenal Fistula

Purpose: To demonstrate the utility of endovascular stent-graft repair for the management of an unusual aortoduodenal fistula. Methods and Results: A 23-year-old man with an aortoduodenal fistula secondary to tumor necrosis was treated with a Corvita endoluminal stent-graft after several failed surgical attempts to repair the defect. At 2-year follow-up, the patient was clinically and radiographically devoid of any evidence of occult stent-graft infection. Conclusions: This case illustrates the usefulness of endovascular repair for the treatment of a primary aortoduodenal fistula. Endovascular repair should be included in the armamentarium for the management of difficult aortoduodenal fistulas.

Arterial thromboembolic events in patients with the factor V Leiden mutation

BACKGROUND The factor V Leiden mutation affects 6% of the United States population and is known to be associated with venous thrombosis. We identify, herein, 30 individuals with the Leiden mutation and known arterial thromboembolic events. METHODS The factor V mutation was assessed using polymerase chain reaction. RESULTS In the 16 patients sustaining a cerebrovascular accident, the mean age was 44.1 and 11 (69%) were younger than 50. Similarly, the 13 patients presenting with an acute myocardial infarction were relatively young with a mean age of 45.5, and 9 (65%) patients presented at less than 50 years of age. Radiographic information was available for 19 patients in this study. No significant arterial atherosclerotic disease was demonstrated in 18 (95%) of these patients. CONCLUSIONS This study demonstrates an association between the factor V Leiden mutation and the development of unexplained arterial thromboembolic events, especially in younger patients without existing atherosclerotic disease.

Oxygen-dependent chronic obstructive pulmonary disease does not prohibit aortic aneurysm repair.

BACKGROUND Severe oxygen-dependent chronic obstructive pulmonary disease (COPD) is considered by many to be a contraindication to open abdominal aortic aneurysm (AAA) repair. We reviewed our own experience with this patient population. METHODS From July 1995 to March 1999, 14 consecutive patients limited by home oxygen-dependent COPD underwent elective open infrarenal AAA repair. Their medical records were reviewed. RESULTS The mean aortic aneurysm size was 6.3 cm. The mean PaO2 = 70 mm Hg, PaCO2 = 45 mm Hg, forced expiratory volume in 1 second (FEV1) = 34% of predicted, and forced vital capacity (FVC) = 67% of predicted. All 14 patients were extubated within 24 hours, mean length of hospital stay was 5.9 days, and there were no perioperative deaths. CONCLUSIONS Severe home oxygen-dependent COPD is not a contraindication to safe elective open AAA repair.

Ruptured Abdominal Aortic Aneurysms in the 1990s: Resource Utilization, Long-Term Survival, and Quality of Life After Repair

Ruptured abdominal aortic aneurysm (RAAA) is a lethal disease. The aim of this study was to assess resource use, long-term outcome, and functional status of patients surviving repair of RAAAs. A retrospective review was made over a 42-month period. Functional status was assessed by use of the Medical Outcomes Study Short Form 36 (MOS SF-36) at a mean follow-up time of 29 months. Fifty-seven patients with an RAAA underwent surgical repair. The overall in-hospital mortality rate after surgical repair was 39%. Risk factors predictive for a poor hospital outcome were preoperative systolic blood pressure less than 90 mmHg, hematocrit less than 25%, transfusion requirements greater than 15 units, renal failure, and need for perioperative cardiopulmonary resuscitation (CPR). Total hospital costs were significantly higher for survivors compared with nonsurvivors. Hospital cost per survivor was

Autonome Regulation der zellulären Inflammation im septischen Ileus durch die Dünndarmmuskularis mittels Monocyte Chemoattractant Protein-1 (MCP-1)

86,977. Intensive Care Unit, laboratory, and blood bank costs accounted for 50% of total hospital costs. Based on the eight domains of the MOS SF-36, no significant difference was found between the functional status of those patients surviving emergent repair of RAAAs and that of the general population of a similar age.

Lipopolysaccharide activates the muscularis macrophage network and suppresses circular smooth muscle activity

Background: Endotoxemia causes a massive inflammation of the intestinal wall, which is associated with an inhibition of intestinal motility. The network of resident macrophages seems to play a major role as an initiator of this cascade. We hypothesize that these resident cells evoke the extravasation of immunocompetent leukocytes in the intestinal muscularis through the release of chemotactic cytokines (e.g. MCP-1). Methods: ACI rats were challenged with an intraperitoneal single bolus injection of lipopolysaccharide (LPS; 15 mg/kg). Observations were made over a 48 h period ( 1, 3, 6, 24, and 48 h). In a second experiment the animals were treated daily with an i.p. injection of LPS for 5 consecutive days. Cellular infiltration and MCP-1 protein expression was determined by immunohistochemistry. Semi-quantitative RT-PCR was used to measure MCP-1 mRNA expression. Spontaneous and bethanechol-stimulated circular muscle activity was assessed using a standard organ bath. Intestinal transit was measured at 24 h after LPS by evaluating the distribution of orally administered fluorescein-labeled dextran (at 90 min). Results: LPS application caused a delay in intestinal transit and a significant suppression of in vitro contractility. However, chronically injected animals showed an obvious improvement in smooth muscle activity. We observed a significant increase in leukocyte infiltration mostly attributed to extravasated monocytes. RT-PCR showed a significant increase in MCP-1 mRNA expression following LPS. LPS pretreatment resulted in a transcriptional adaption without any significant increase of the MCP-i expression. MCP-1 was immunohistochemically located in resident muscularis macrophages. Conclusions: Endotoxemia causes a distinct infiltration of leukocytes into the intestinal muscularis that was associated with a significant suppression of intestinal motility. The results suggest that locally derived MCP-1 represents a potential cause of the extravasation of immunocompetent cells. As an intestinal adaption in response to repeated LPS this mechanism disappears in chronically injected animals.