Global collaborative healthcare: assessing the resource requirements at a leading Academic Medical Center.

INTRODUCTION: Academic Medical Centers ("AMCs") have served as a hub of the United States ("US") health system and represented the state-of-the art in American health care for well over a century. Currently, the global healthcare market is both massive and expanding and is being altered by the unprecedented impact of technological advances and globalization. This provides AMCs a platform to enter into trans-national collaborative partnerships with healthcare organizations around the world, thus providing a means to deliver on its promise globally while also expanding and diversifying its resources. A number of leading US AMCs have engaged in global collaborative healthcare, employing different models based on services offered, global distribution, and inclination to assume risk. Engaging in these collaborations requires significant effort from across the health system, and an understanding of the resources required is paramount for effective delivery and to avoid overextension and diversion from the primary mission of these organizations. The goal of this paper is to discuss the role of US AMCs in this current global healthcare landscape and to also investigate our institutional faculty and staff resource requirements to support the operating model. METHODOLOGY: We extracted and retrospectively analyzed data from the JHI Global Services database for a 3-year period (Jan, 2013-Dec, 2015) to determine total utilization (hours and full time equivalent (FTE)), utilization by profession, and clinical and non-clinical areas of expertise. RESULTS: JHI utilized on average 21,940 h annually, or 10.55 FTEs of faculty and staff subject matter experts. The majority of the hours are for work performed by physician faculty members from 23 departments within the School of Medicine, representing 77% percent or on average 16,894 h annually. Clinical and allied health departments had an average annual utilization of 17,642 h or 7.8 FTEs, while non-clinical departments, schools and institutes averaged 4298 h or 1.9 FTEs, representing 80.4% and 19.6% respectively. CONCLUSION: We found that significant human resources are required within a broad range of AMC subject matter expertise across multiple disciplines, and that with adequate forecasting AMCs can successfully engage in these collaborations while continuing to fulfill their core mission.

Lung T lymphocyte trafficking and activation during ischemic acute kidney injury.

Despite advances in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely owing to extrarenal organ dysfunction. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that facilitate organ crosstalk and induce caspase-dependent lung apoptosis and injury through a TNFR1-dependent pathway. Given that T lymphocytes mediate local IRI in the kidney and are known to drive TNFR1-mediated apoptosis, we hypothesized that T lymphocytes activated during kidney IRI would traffic to the lung and mediate pulmonary apoptosis during AKI. In an established murine model of kidney IRI, we identified trafficking of CD3+ T lymphocytes to the lung during kidney IRI by flow cytometry and immunohistochemistry. T lymphocytes were primarily of the CD3+CD8+ phenotype; however, both CD3+CD4+ and CD3+CD8+ T lymphocytes expressed CD69 and CD25 activation markers during ischemic AKI. The activated lung T lymphocytes did not demonstrate an increased expression of intracellular TNF-α or surface TNFR1. Kidney IRI induced pulmonary apoptosis measured by caspase-3 activation in wild-type controls, but not in T cell-deficient (T(nu/nu)) mice. Adoptive transfer of murine wild-type T lymphocytes into T(nu/nu) mice restored the injury phenotype with increased cellular apoptosis and lung microvascular barrier dysfunction, suggesting that ischemic AKI-induced pulmonary apoptosis is T cell dependent. Kidney-lung crosstalk during AKI represents a complex biological process, and although T lymphocytes appear to serve a prominent role in the interorgan effects of AKI, further experiments are necessary to elucidate the specific role of activated T cells in modulating pulmonary apoptosis.

Single-stage repair of a complex type B aortic dissection associated with a pressurized infrarenal abdominal aortic aneurysm.

The decision-making involved in managing type 2 aortic dissections remains challenging despite the advances in endovascular technology. We report a challenging case of a patient presenting with a type 2 aortic dissection and false lumen extension into an infrarenal abdominal aortic aneurysm (AAA). Severe back pain and hypertension were the patient's initial complaints, and dynamic magnetic resonance angiography revealed 1-way pulsatile flow into the AAA sac from the false lumen. This patient underwent endovascular repair with a thoracic and infrarenal aortic endograft, successfully excluding the false lumen and decompressing the infrarenal aneursymal sac. This is a unique presentation of total endovascular repair of a symptomatic type B aortic dissection with a pressurized infrarenal AAA sac from false lumen flow into the sac.

TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury.

Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1-/- mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets.

Endovascular management of carotid artery stenosis secondary to sclerosing mediastinitis.

Sclerosing mediastinitis is a rare, progressive condition characterized by extensive fibrotic reaction. We report the first known case of symptomatic, extrinsic compression of the carotid artery by fibrotic extension of sclerosing mediastinitis. A 54-year-old woman began experiencing neurologic symptoms from extension of a known mediastinal mass resulting in 70% to 79% stenosis of the right internal carotid artery. The stenosis was treated with endovascular stenting. Completion angiogram revealed a good result with <10% residual stenosis. At 18-month follow-up, the patient was symptom free without evidence of re-stenosis. Endovascular therapy provides a novel and durable solution in the midterm to this very rare problem.

Surgical sepsis and organ crosstalk: the role of the kidney.

Acute kidney injury (AKI) is a common complication of hospitalized patients, and clinical outcomes remain poor despite advances in renal replacement therapy. The accepted pathophysiology of AKI in the setting of sepsis has evolved from one of simple decreased renal blood flow to one that involves a more complex interaction of intra-glomerular microcirculatory vasodilation combined with the local release of inflammatory mediators and apoptosis. Evidence from preclinical AKI models suggests that crosstalk occurs between kidneys and other organ systems via soluble and cellular inflammatory mediators and that this involves both the innate and adaptive immune systems. These interactions are reflected by genomic changes and abnormal rates of cellular apoptosis in distant organs including the lungs, heart, gut, liver, and central nervous system. The purpose of this article is to review the influence of AKI, particularly sepsis-associated AKI, on inter-organ crosstalk in the context of systemic inflammation and multiple organ failure (MOF).

Therapeutic distant organ effects of regional hypothermia during mesenteric ischemia-reperfusion injury.

INTRODUCTION: Mesenteric ischemia-reperfusion injury (IRI) leads to systemic inflammation and multiple organ failure in clinical and laboratory settings. We investigated the lung structural, functional, and genomic response to mesenteric IRI with and without regional intraischemic hypothermia (RIH) in rodents and hypothesized that RIH would protect the lung and preferentially modulate the distant organ transcriptome under these conditions. METHODS: Sprague-Dawley rats underwent sham laparotomy or superior mesenteric artery occlusion (SMAO) for 60 minutes with or without RIH. Gut temperature was maintained at 15°-20°C during SMAO, and systemic normothermia (37°C) was maintained throughout the study period. At 6 or 24 hours, lung tissue was collected for (1) histology, (2) myeloperoxidase activity, (3) bronchoalveolar lavage (BAL) fluid protein concentrations, (4) lung wet/dry ratios, and (5) total RNA isolation and hybridization to Illumina's Sentrix BeadChips (>22,000 probes) for gene expression profiling. Significantly affected genes (false discovery rate <5% and fold change ≥1.5) were linked to gene ontology (GO) terms using MAPPFinder, and hypothermia-suppressed genes were further analyzed with Pubmatrix. RESULTS: Mesenteric IRI-induced lung injury, as evidenced by leukocyte trafficking, alveolar hemorrhage, and increased BAL protein and wet/dry ratios, and activated a proinflammatory lung transcriptome compared with sham. In contrast, rats treated with RIH exhibited lung histology, BAL protein, and wet/dry ratios similar to sham. At 6 hours, GO analysis identified 232 hypothermia-suppressed genes related to inflammation, innate immune response, and cell adhesion, and 33 hypothermia-activated genes related to lipid and amine metabolism and defense response. Quantitative real-time polymerase chain reaction validated select array changes in top hypothermia-suppressed genes lipocalin-2 (lcn-2) and chemokine ligand 1 (CXCL-1), prominent genes associated with neutrophil activation and trafficking. CONCLUSIONS: Therapeutic hypothermia during SMAO provides distant organ protection and preferentially modulates the IRI-activated transcriptome in the rat lung. This study identifies potential novel diagnostic and therapeutic targets of mesenteric IRI and provides a platform for further mechanistic study of hypothermic protection at the cellular and subcellular level.

Academic needs in developing countries: a survey of the West African College of Surgeons.

BACKGROUND: The inaugural Fundamentals of Surgical Research Course was held in Sierra Leone in conjunction with the West African College of Surgeons (WACS). We subsequently performed a formal assessment of the academic needs of West African surgeons to plan for future courses, and hypothesized that they would differ from the goals of the U.S. course. METHODS: A survey was distributed via email to members of the WACS and returned by the same mechanism. It consisted of 6 questions addressing specific elements of the inaugural course, and potential new topics for future courses. RESULTS: Over half (53%, 25/47) of the respondents had not attended the inaugural course, while 85% (40/47) planned on attending the next course. Respondents identified least useful topics from the initial course as "Molecular Biology: Tools of the Trade" (45%, 21/47) and "Getting Promoted" (23%, 11/47). The least popular potential new topics were "Use and Abuse of Administrative Databases" (9%, 4/47), "Animal Models" (21%, 10/47), and "Genomics and Proteomics" (21%, 10/47). CONCLUSIONS: The self-reported academic needs of West African surgeons are oriented toward clinical research. Basic and translational research topics are of secondary interest to the majority of respondents. Future courses in this region must address specific local needs.

Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis.

Distant organ effects of acute kidney injury (AKI) are a leading cause of morbidity and mortality. While little is known about the underlying mechanisms, limited data suggest a role for inflammation and apoptosis. Utilizing a lung candidate gene discovery approach in a mouse model of ischemic AKI-induced lung dysfunction, we identified prominent lung activation of 66 apoptosis-related genes at 6 and/or 36 h following ischemia, of which 6 genes represent the tumor necrosis factor receptor (TNFR) superfamily, and another 23 genes are associated with the TNFR pathway. Given that pulmonary apoptosis is an important pathogenic mechanism of acute lung injury (ALI), we hypothesized that AKI leads to pulmonary proapoptotic pathways that facilitate lung injury and inflammation. Functional correlation with 1) terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and 2) active caspase-3 (aC3) activity, immunoblotting, and immunohistochemistry (IHC) identified kidney IRI-induced pulmonary apoptosis at 24 h, and colocalization studies with CD34 identified predominantly endothelial apoptosis. Mice were treated with the caspase inhibitor Z-VAD-FMK (0.25 mg ip) or vehicle 1 h before and 8 h after sham or kidney IRI, and bronchoalveolar lavage fluid protein was measured at 36 h as a surrogate for lung leak. Caspase inhibition reduced lung microvascular changes after kidney IRI. The pulmonary apoptosis seen in wild-type control mice during AKI was absent in TNFR(-/-) mice. Using an initial genomic approach to discovery followed by a mechanistic approach to disease targeting, we demonstrate that pulmonary endothelial apoptosis is a direct mediator of the distant organ dysfunction during experimental AKI.

Renal ischemia-reperfusion leads to long term infiltration of activated and effector-memory T lymphocytes.

It is well-established that significant ischemia-reperfusion injury during kidney transplantation results in increased incidence of long-term fibrosis and rejection. To test for a role of T cell infiltration and activation following ischemic injury, we induced both bilateral and unilateral renal ischemia in mice, followed by reperfusion, and then isolated mononuclear cells. Analysis of these cells by flow cytometry showed that 2 weeks after bilateral ischemia there was a significant increase of CD8(+) T cells. Furthermore, both CD4(+) and CD8(+) T cells infiltrated the injured kidney 6 weeks after unilateral ischemia. These T cells had increased expression of CD69(+) and CD44(hi)CD62L(-), markers of activation and effector-memory, respectively. CD4(+)NK1.1(+) and CD19(+) B cells were decreased in percentage both 6 and 11 weeks after bilateral or unilateral injury. There was a significant upregulation of IL-1beta, IL-6, TNF-alpha, IFN-gamma, MIP-2, and RANTES expression, measured by real-time PCR, 6 weeks after unilateral renal ischemia, further indicating T cell activation. Depletion of CD4(+) and CD8(+) T cells before ischemia caused less medullary damage and reduced kidney IFN-gamma expression, whereas their depletion following ischemia increased kidney IL-1beta; however, depletion of these cells had no effect on histological damage to the kidney. Our study demonstrates that moderate or severe kidney ischemia induces long-term T lymphocyte infiltration and cytokine/chemokine upregulation, leading to kidney structural changes.

Organ crosstalk: the role of the kidney.

PURPOSE OF REVIEW: Acute kidney injury (AKI) continues to contribute significantly to morbidity and mortality in the ICU setting, especially when associated with distant organ dysfunction. There is increasing evidence that AKI directly contributes to organ dysfunction in lung, brain, liver, heart and other organs. This review will examine our current understanding of the deleterious organ crosstalk in the critically ill, which can provide a framework for developing novel therapeutics. RECENT FINDINGS: The majority of studies correlating AKI with distant organ dysfunction have demonstrated the pathophysiological importance of proinflammatory and proapoptotic pathways as well as oxidative stress and reactive oxygen species (ROS) production. Leukocyte activation and infiltration, changes in levels of soluble factors such as cytokines and chemokines, and regulation of cell death in extra-renal organs are potentially important mechanisms by which AKI modulates multiorgan dysfunction. SUMMARY: There is increasing knowledge of AKI and deleterious interorgan crosstalk that arises, at least in part, due to the imbalance of immune, inflammatory, and soluble mediator metabolism that attends severe insults to the kidney. Further studies can build on these new mechanistic observations to develop strategies to improve outcomes in the critically ill patient.

Kidney-lung crosstalk in the critically ill patient.

Despite advances in renal replacement therapy, the mortality of acute kidney injury (AKI) has remained high, especially when associated with distant organ dysfunction such as acute lung injury (ALI). Mortality rates for combined AKI/ALI reach 80% in critically ill patients. While the clinical presentation of AKI-associated ALI is characterized by increased pulmonary edema, a defining feature of the syndrome, the AKI-induced lung effects extend beyond simple volume overload. Furthermore, ALI and associated mechanical ventilation frequently lead to a decline in renal hemodynamics, structure and function. New experimental data have emerged in recent years focusing on the interactive effects of kidney and lung dysfunction, and these studies have highlighted the pathophysiological importance of proinflammatory and proapoptotic pathways as well as the complex nature of interorgan crosstalk. This review will examine our current understanding of the deleterious kidney-lung crosstalk in the critically ill.

The local and systemic inflammatory transcriptome after acute kidney injury.

Studies in humans and animal models have demonstrated that acute kidney injury (AKI) has a significant effect on the function of extrarenal organs. The combination of AKI and lung dysfunction is associated with 80% mortality; the lung, because of its extensive capillary network, is a prime target for AKI-induced effects. The study presented here tested the hypothesis that AKI leads to a vigorous inflammatory response and produces distinct genomic signatures in the kidney and lung. In a murine model of ischemic AKI, prominent global transcriptomic changes and histologic injury in both kidney and lung tissues were identified. These changes were evident at both early (6 h) and late (36 h) timepoints after 60-min bilateral kidney ischemia and were more prominent than similar timepoints after sham surgery or 30 min of ischemia. The inflammatory transcriptome (109 genes) of both organs changed with marked similarity, including the innate immunity genes Cd14, Socs3, Saa3, Lcn2, and Il1r2. Functional genomic analysis of these genes suggested that IL-10 and IL-6 signaling was involved in the distant effects of local inflammation, and this was supported by increased serum levels of IL-10 and IL-6 after ischemia-reperfusion. In summary, this is the first comprehensive analysis of concomitant inflammation-associated transcriptional changes in the kidney and a remote organ during AKI. Functional genomic analysis identified potential mediators that connect local and systemic inflammation, suggesting that this type of analysis may be a useful discovery tool for novel biomarkers and therapeutic drug development.

Aortic arch vessel stenting: a single-center experience using cerebral protection.

HYPOTHESIS: Endovascular interventions have revolutionized the contemporary treatment of peripheral vascular occlusive disease. Traditional management of supra-aortic trunk disease has employed surgical extra-anatomic bypass via a cervical approach or median sternotomy. Endoluminal therapy may be a less morbid alternative. DESIGN AND SETTING: A retrospective review of procedures performed by vascular surgeons in an operating room angiosuite at a single university-based, tertiary referral center. PATIENTS: Eighteen consecutive patients with 20 brachiocephalic-origin stenoses. INTERVENTIONS: From December 2001 through September 2005, 20 brachiocephalic-origin stenoses were treated endoluminally with balloon-expandable stents. Treated vessels were innominate (n = 8), common carotid (n = 9), and subclavian (n = 3). The target lesion was accessed by one of the following methods: antegrade via the femoral artery (n = 5), retrograde through the brachial artery (n = 1), or via a retrograde cut-down on the common carotid artery (n = 14). Cerebral protection was achieved with either a distal embolic filter device or with open surgical occlusion of the distal common carotid artery. MAIN OUTCOME MEASURES: We report immediate and midterm outcomes of all aortic arch vessel stenting procedures with mean follow-up of 12 months. RESULTS: Mean age was 68 years (6 men and 12 women) and overall mean stenosis was 85%. Preprocedural symptoms including stroke, transient ischemic attack, arm fatigue, digital ischemia, and angina were present in 16 of 20 cases (80%). The 4 asymptomatic patients all had more than 90% stenosis on angiography. At 30-day follow-up, there were no deaths, myocardial infarctions, or strokes. During follow-up, there were no cases of restenosis. CONCLUSION: Endoluminal arterial stenting of brachiocephalic arch vessels may be a viable alternative to traditional open bypass in cases of focal stenotic disease.

The COOK TX2 thoracic stent graft: preliminary experience and trial design.

Endovascular treatment of thoracic aortic pathology (ETAP) has been under development for over a decade. Only recently has one device been approved in the United States for treatment of descending thoracic aortic aneurysms. The length of this development process is due to multiple device and deployment system modifications, as understanding has evolved of the unique challenges of reconstruction in the thoracic aorta. The TX2 system has evolved from pioneering custom-made designs into a mature system with several features designed to improve early and late results. Controlled trials are necessary to compare the outcomes of ETAP with standard open repair. This article will detail the current generation of the device, review large published single-center experiences, and describe an ongoing prospective, nonrandomized, multi-institutional, investigational device exemption (IDE) phase II pivotal clinical trial investigating the safety and effectiveness of this device in elective treatment of patients with descending thoracic aortic aneurysms.

Ischemic preconditioning protects against gut dysfunction and mucosal injury after ischemia/reperfusion injury.

Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and impairs gut function. Ischemic preconditioning (IPC) has been shown to protect organs against IR injury. We hypothesized that IPC protects the gut from IR injury. Rats were randomized to a sham group, a sham early IPC + IR group (sham IPC + SMA occlusion for 30 min and 6 h of reperfusion), an early IPC + IR group (IPC, three cycles of SMA occlusion for 4 min and reperfusion for 10 min) followed immediately by SMA occlusion for 30 min and 6 h of reperfusion), a sham 24-h group, a sham late IPC + IR group (sham IPC followed by additional reperfusion for 24 h + SMA occlusion for 30 min and 6 h of reperfusion), and a late IPC + IR group (IPC protocol followed by additional reperfusion for 24 h, and then SMA occlusion for 30 min followed by 6 h of reperfusion). At 6 h, transit was determined and expressed as the mean geometric center. Ileum was harvested for assessment of mucosal injury and myeloperoxidase (MPO) activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Early IPC + IR significantly improved transit (3.9 +/- 0.2), decreased MPO levels (3 +/- 2), and lessened mucosal injury (1.2 +/- 0.3) compared with animals subjected to sham early IPC + IR (transit, 2.9 +/- 0.2; MPO levels, 9 +/- 1; mucosal injury, 3.0 +/- 0.6). Late IPC + IR also improved transit (6.0 +/- 0.4) and decreased MPO levels (1 +/- 1) compared with sham late IPC + IR (transit, 4.4 +/- 0.2; MPO levels, 8 +/- 1), however, there was no difference in the mucosal protection between late IPC + IR (1 +/- 0.3) and sham late IPC + IR (1 +/- 1). Our results suggest that early and late IPC improves intestinal dysfunction, decreases inflammation, and provides mucosal protection in the intestine after IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both phases of IPC can potentially be useful in the clinical setting of surgical patient care.

Multi-institutional pivotal trial of the Zenith TX2 thoracic aortic stent-graft for treatment of descending thoracic aortic aneurysms: clinical study design.

Despite significant improvements in surgical techniques and perioperative management, the repair of descending thoracic aortic aneurysms remains a challenge with the potential for substantial morbidity and mortality. Over the past several years, buoyed by the technical success of endovascular repair of infrarenal abdominal aortic aneurysms, several case series reports of endovascular stent-graft placement for descending thoracic aortic aneurysms have demonstrated the potential safety and efficacy of this treatment modality. Several single-institution studies have documented promising results with these devices, but without controlled clinical trials, the data are insufficient to determine if thoracic aortic endografts provide equivalent or improved outcomes compared with standard open repair. We describe a study design of an ongoing prospective, nonrandomized, multi-institutional, investigational device exemption phase II pivotal clinical trial investigating the safety and effectiveness of the Zenith TX2 thoracic aortic endovascular graft in the elective treatment of patients with descending thoracic aortic aneurysms.

Intraischemic hypothermia differentially modulates oxidative stress proteins during mesenteric ischemia/reperfusion.

BACKGROUND: Thoracoabdominal aortic aneurysm repair requires obligatory mesenteric ischemia/reperfusion (I/R), eliciting an inflammatory response resulting in gut dysfunction and remote organ injury. Therapeutic hypothermia has been advocated for organ protection (ie, brain, spinal cord, and kidneys) during extensive aortic operation, and it has also been shown to differentially modulate proinflammatory gene transcription in the central nervous system. In other I/R models, nuclear factor Kappa-B (NF-(kappa)B) and inducible nitric oxide synthase (iNOS) worsen while heme oxygenase-1 (HO-1) protects against injury. We examined the effects of regional intraischemic hypothermia on mesenteric I/R-induced mucosal injury, NF-kappaB activation, and expression of iNOS and HO-1. METHODS: Sprague-Dawley rats underwent sham laparotomy or superior mesenteric artery occlusion for 45 minutes with or without topical hypothermia (15 degrees -20 degrees C). Intestinal epithelial permeability to (14)C inulin was assessed at 6 hours of reperfusion. In a separate set of experiments, biopsies of the ileum were obtained at 6 hours of reperfusion for: 1) mucosal histologic injury assessed by a blinded observer; 2) NF-kappaB activation by electrophoretic mobility shift assay; and 3) iNOS and HO-1 protein expression by immunoblot. RESULTS: Mesenteric I/R significantly increased intestinal permeability to (14)C inulin, histologic injury, activation of NF-kappaB, and iNOS and HO-1 expression when compared with sham control rats. In contrast, rats treated with intraischemic topical hypothermia exhibited intestinal permeability comparable with sham control rats, and reduced histologic injury. In addition, hypothermia prevented the activation of NF-kappaB and iNOS expression, but had no effect on HO-1 expression. CONCLUSIONS: On the basis of these observations, we conclude that therapeutically applied intraischemic hypothermia protects the gut during mesenteric I/R. In addition, hypothermia prevented NF-kappaB activation while differentially modulating expression of the oxidative stress proteins iNOS and HO-1 in response to mesenteric I/R.

Specific intraluminal nutrients alter mucosal blood flow during gut ischemia/reperfusion.

BACKGROUND: We have previously demonstrated in a rodent model the differential effects that specific intraluminal nutrients exert on gut ischemia/reperfusion (I/R) injury. Alanine was shown to amplify, whereas glucose protected against, gut I/R injury and associated gut dysfunction. The objective of this study was to determine whether these specific nutrients are associated with alterations in mucosal perfusion during gut I/R. METHODS: Sprague-Dawley rats had either a laser doppler probe or a tonometer inserted into a jejunal sac filled with either 10 mmol/L alanine, glucose, or mannitol (osmotic control) followed by 60 minutes of superior mesenteric artery occlusion and 60 minutes of reperfusion. Laser doppler mucosal blood flow and regional PCO2 (PrCO2) measurements were obtained. RESULTS: Mucosal blood flow was significantly increased during both ischemia and reperfusion when intraluminal glucose was present compared with intraluminal alanine. Blood flow changes were reflected by lower jejunal PrCO2 measurements with intraluminal glucose compared with intraluminal alanine. CONCLUSIONS: Intraluminal glucose can augment mucosal blood flow during gut I/R and may explain the protective effect we previously observed.