Recurrent prosthetic valve endocarditis with aortic-ventricular disruption: a surgical challenge.

BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE) after aortic valve replacement occurs infrequently but carries a high mortality rate, particularly with previous valved conduit root replacement or aortic root reconstruction (ARR). Infection can lead to paravalvular aortic root abscess, aorto-left ventricular disruption, and left ventricular pseudoaneurysm formation. Herein is presented a case series of aortic-left ventricular disruption and ventricular psuedoaneurysm secondary to PVE after previous aortic root replacement; the surgical approach and outcomes are discussed. METHODS: All patients who underwent cardiac valve surgery at The Methodist DeBakey Heart and Vascular Center between October 2008 and May 2011 were reviewed for cases of PVE with previous ARR with valved conduit and aortic root replacement. Five cases were identified, for whom the record review and follow up by clinic visit or telephone call after discharge was complete. RESULTS: All patients survived surgical repair after complete redo aortic root excision and reconstruction with valved-conduit and coronary reimplantation. All patients underwent delayed sternal closure with mediastinal packing and, in four cases, definitive closure with omental flap. All patients were discharged and remain recurrence-free with the current management scheme. CONCLUSION: Aortic left ventricular disruption from PVE after aortic root replacement with valved conduit can be managed successfully. The authors' strategy includes careful sternal entry with preparations for emergency bypass, complete excision of all infected material, redo total aortic root replacement and coronary reimplantation, initial open sternal management to control coagulopathy, and definitive closure with an omental transposition flap in a delayed fashion.

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.

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.

Alterations in content and localization of defensins in rat ileum and jejunum following ischemia-reperfusion. Specific peptides, in specific places, for specific jobs?

OBJECTIVE: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. METHODS: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular location of antimicrobials. RESULTS: Ischemia-reperfusion increased neutrophil defensin alpha (RNP-1) in jejunum; rat beta defensin 1 was increased 2-fold in ileal mucosa and slightly reduced in jejunal mucosa; rat beta defensin 2 was reduced by ischemia-reperfusion in ileum, but slightly increased in jejunum; rat beta defensin 3 was concentrated in the muscularis externa and myenteric plexus of the jejunum; ischemia-reperfusion did not alter cathelicidin LL-37 content in the small intestine, although a greater concentration was seen in jejunum compared with ileum. CONCLUSION: Ischemia-reperfusion injury caused changes in antimicrobial content in defined areas, and these different regulations might reflect the specific roles of jejunum versus ileum.

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.

Monitoring trauma and intensive care unit resuscitation with tissue hemoglobin oxygen saturation.

INTRODUCTION: The purpose of the present review is to review our experience with near-infrared spectroscopy (NIRS) monitoring in shock resuscitation and predicting clinical outcomes. METHODS: The management of critically ill patients with goal-oriented intensive care unit (ICU) resuscitation continues to evolve as our understanding of the appropriate physiologic targets improves. It is now recognized that resuscitation to achieve supranormal indices is not beneficial in all patients and may precipitate abdominal compartment syndrome. RESULTS: Over the years, ICU technology has provided physicians with specific physiologic parameters to guide shock resuscitation. Throughout this time, the tissue hemoglobin oxygen saturation (StO2) monitor has emerged as a non-invasive means to obtain reliable physiologic parameters to guide clinicians' resuscitative efforts. StO2 monitors have been shown to aid in early identification of nonresponders and to predict outcomes in hemorrhagic shock and ICU resuscitation. These data have also been used to better understand and refine existing resuscitation protocols. More recently, use of NIRS technology to guide resuscitation in septic shock has been shown to predict outcomes in high-risk patients. CONCLUSIONS: StO2 is an important tool in identifying high-risk patients in septic and hemorrhagic shock. It is a non-invasive means of obtaining vital information regarding outcome and adequacy of resuscitation.

Computerized clinical decision support for traumatic shock resuscitation.

PURPOSE OF REVIEW: To review what we learned through implementation of computerized decision support for ICU resuscitation of major torso trauma patients who arrive in shock. RECENT FINDINGS: Overall, these patients respond well to preload-directed goal-orientated ICU resuscitation; however, the subset of patients destined to develop abdominal compartment syndrome do not respond well. In fact, this strategy precipitates the full-blown syndrome that is a new iatrogenic variant of multiple organ failure. The clinical trajectory of abdominal compartment syndrome starts early after emergency department admission and its course is fairly well defined by the time patients reach the ICU. It occurs in patients who arrive with severe bleeding that is not readily controlled. These patients require a very different emergency department management strategy. Hemorrhage control is paramount. Alternative massive transfusion protocols should be used with an emphasis on hemostasis and avoidance of excessive isotonic crystalloids. Finally, near-infrared spectroscopy that measures tissue hemoglobin saturation in skeletal muscle (StO2) is good at identifying high-risk patients. A falling StO2 in the setting of ongoing resuscitation is a harbinger of death from early exsanguination and multiple organ failure. SUMMARY: Fundamental changes are needed in the care of trauma patients who arrive in shock and require a massive transfusion.