Krishnan Raghavendran

University of Michigan, Ann Arbor, Michigan, United States

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Publications (81)223.26 Total impact

  • Douglas L. Miller · Chunyan Dou · Zhihong Dong · Krishnan Raghavendran
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    ABSTRACT: The use of xylazine, a veterinary sedative, with ketamine for rat anesthesia has been shown to enhance the pulmonary capillary hemorrhage (PCH) effect of diagnostic ultrasound. This study was undertaken to assess whether the sedative/analgesic dexmedetomidine, commonly used in the intensive care unit, can also enhance ultrasound-induced PCH. Female Sprague Dawley rats were anesthetized with various combinations of ketamine plus xylazine or dexmedetomidine. The dosage of dexmedetomidine was reduced for some groups to doses relevant to human clinical usage. The right thorax of all rats was shaved and depilated for ultrasound transmission and the rats were scanned with diagnostic ultrasound using a 7.6-MHz linear array in a 38°C de-gassed water bath. There was no significant difference in PCH results for the recommended anesthetic dosages of ketamine plus xylazine and ketamine plus 500 μg/kg dexmedetomidine. The varied doses of dexmedetomidine enhanced the PCH, even for the lowest dose of 4 μg/kg, equivalent to a low human dose of 0.64 μg/kg. There was no significant difference in PCH for 500 μg/kg dexmedetomidine with or without ketamine. Further research is needed to identify and characterize other factors that may modify the patient risk from ultrasound-induced PCH.
    No preview · Article · Jan 2016 · Ultrasound in medicine & biology
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    Douglas L. Miller · Chunyan Dou · Krishnan Raghavendran
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    ABSTRACT: Pulsed ultrasound was found to induce pulmonary capillary hemorrhage (PCH) in mice about 25 years ago but remains a poorly understood risk factor for pulmonary diagnostic ultrasound. In early research using laboratory fixed beam ultrasound, thresholds for PCH had frequency variation from 1-4MHz similar to the Mechanical Index. In recent research, thresholds for B mode diagnostic ultrasound from 1.5-12MHz had little dependence on frequency. To compare the diagnostic ultrasound method to laboratory pulsed exposure, thresholds for fixed beam ultrasound were determined using comparable methods at 1.5 and 7.5MHz. PCH thresholds were lower for simple fixed-beam pulse modes than for B mode and in approximate agreement with early research. However, for comparable timing parameters, PCH thresholds had little dependence on ultrasonic frequency. These findings suggest that the MI may not be directly useful as a dosimetric parameter for safety guidance in pulmonary ultrasound.
    Preview · Article · Dec 2015 · Physics Procedia
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    ABSTRACT: Objective: To examine the outcomes of prolonged (≥14 days) extracorporeal membrane oxygenation (P-ECMO) for adult severe respiratory failure and to assess characteristics associated with survival. Background: The use of ECMO for treatment of severe respiratory adult patients is associated with overall survival rates of 50% to 70% with median ECMO duration of 10 days. No prior multi-institutional studies have examined outcomes of P-ECMO for severe respiratory failure. Methods: Data on all adult (≥18 years) patients who required P-ECMO for severe respiratory failure from 1989 to 2013 were extracted from the Extracorporeal Life Support Organization international multi-institutional registry. We examined outcomes over 23 years and compared the 2 more recent time periods of 1989 to 2006 versus 2007 to 2013. Results: Up to 974 patients, mean age 40.2 (18-83) years, had ECMO duration of mean 25.2 days/median 21.0 days (range: 14-208 days). Venovenous ECMO support was most common (venovenous: 79.5%, venoarterial: 9.9%). Reason for ECMO discontinuation included native lung recovery (54%), organ failure (23.7%), family request (6.7%), hemorrhage (2.7%), and diagnosis incompatible with life (5.6%). Forty patients (4.1%) underwent lung transplant with 50% postoperative in-hospital mortality. Increased prevalence of P-ECMO was noted with 72% (701/974) of all cases reported since 2008. Survival to hospital discharge was 45.4% (443/974) and did not vary with ECMO duration. Multivariate logistic regression analysis confirmed that P-ECMO patients 2007 to 2013 had a lower risk of death [odds ratio (OR): 0.650; 95% confidence interval (CI), 0.454-0.929; P = 0.010] compared with 1989 to 2006. Factors independently associated with survival were younger age (OR: 0.983; 95% CI, 0.974-0.993; P < 0.001) and lower PaCO2 (OR, 0.991; 95% CI, 0.986-0.996; P < 0.001). Conclusions: Prolonged ECMO use for adult respiratory failure was associated with a lower (45.4%) hospital survival rate, compared with prior reported survival rates of short duration ECMO. Prolonged ECMO survival significantly increased in recent years, and increasing ECMO duration did not alter the survival fraction in the 1989 to 2013 study cohort. Although P-ECMO survival rates are less than short ECMO runs, P-ECMO support is justified.
    No preview · Article · Nov 2015 · Annals of Surgery
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    ABSTRACT: Background: The Michigan Trauma Quality Improvement Program (MTQIP) is a collaborative quality initiative sponsored by Blue Cross Blue Shield of Michigan and Blue Care Network (BCBSM/BCN). The MTQIP benchmark reports identified our trauma center as a high outlier for venous thromboembolism (VTE) episodes. This study outlines the performance improvement (PI) process used to reduce the rate of VTE using MTQIP infrastructure. Study design: Trauma patients admitted for > 24 hours, with an Injury Severity Score (ISS) ≥ 5, were included in this study. We performed a preliminary analysis examining prophylaxis drug type to VTE, adjusted by patient confounders and timing of first dose, using MTQIP data abstracted for our hospital. It showed that patients receiving enoxaparin had a VTE rate that was half that of those receiving unfractionated heparin (odds ratio 0.46, 95% CI 0.25 to 0.85). Guided by these results, we produced the following plan: consolidation to single VTE prophylaxis agent and dose, focused education of providers, initiation of VTE prophylaxis for all patients-with clear exception rules-and dose withholding minimization. Results were monitored using the MTQIP platform. Results: After implementation of our focused PI plan, the VTE rate decreased from 6.2% (n = 36/year) to 2.6% (n = 14/year). Our trauma center returned to average performance status within MTQIP. Conclusions: Participation in MTQIP provided identification of trauma center outlier status for the outcome of VTE. Analysis of MTQIP data allowed creation of a local action plan. The MTQIP infrastructure supported execution and monitoring of the action plan consistent with loop-closure practices, as advocated by the American College of Surgeons Committee on Trauma, and a positive performance improvement result was achieved with VTE reduction.
    No preview · Article · Aug 2015 · Journal of the American College of Surgeons

  • No preview · Conference Paper · Jun 2015
  • Douglas L. Miller · Chunyan Dou · Krishnan Raghavendran
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    ABSTRACT: The induction of pulmonary capillary hemorrhage (PCH) by pulsed ultrasound was discovered 25 y ago, but early research used fixed-beam systems rather than actual diagnostic ultrasound machines. In this study, results of exposure of rats to fixed-beam focused ultrasound for 5 min at 1.5 and 7.5 MHz were compared with recent research on diagnostic ultrasound. One exposure condition at each frequency used 10-μs pulses delivered at 25-ms intervals. Three conditions involved Gaussian modulation of the pulse amplitudes at 25-ms intervals to simulate diagnostic scanning: 7.5 MHz with 0.3- and 1.5-μs pulses at 100- and 500-μs pulse repetition periods, respectively, and 1.5 MHz with 1.7-μs pulses at 500-μs repetition periods. Four groups were tested for each condition to assess PCH areas at different exposure levels and to determine occurrence thresholds. The conditions with identical pulse timing resulted in smaller PCH areas for the smaller 7.5-MHz beam, but both had thresholds of 0.69-0.75 MPa in situ peak rarefactional pressure amplitude. The Gaussian modulation conditions for both 7.5 MHz with 0.3-μs pulses and 1.5 MHz with 1.7-μs pulses had thresholds of 1.12-1.20 MPa peak rarefactional pressure amplitude, although the relatively long 1.5-μs pulses at 7.5 MHz yielded a threshold of 0.75 MPa. The fixed-beam pulsed ultrasound exposures produced lower thresholds than diagnostic ultrasound. There was no clear tendency for thresholds to increase with increasing ultrasonic frequency when pulse timing conditions were similar. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · Ultrasound in medicine & biology
  • Douglas L Miller · Chunyan Dou · Krishnan Raghavendran
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    ABSTRACT: Pulmonary ultrasound examination has become routine for diagnosis in many clinical and point-of-care medical settings. However, the phenomenon of pulmonary capillary hemorrhage (PCH) induction during diagnostic ultrasound imaging presents a poorly understood risk factor. PCH was observed in anesthetized rats exposed to 1.5-, 4.5- and 12.0-MHz diagnostic ultrasound to investigate the frequency dependence of PCH thresholds. PCH was detected in the ultrasound images as growing comet tail artifacts and was assessed using photographs of the surface of excised lungs. Previous photographs acquired after exposure to 7.6-MHz diagnostic ultrasound were included for analysis. In addition, at each frequency we measured dosimetric parameters, including peak rarefactional pressure amplitude and spatial peak, pulse average intensity attenuated by rat chest wall samples. Peak rarefactional pressure amplitude thresholds determined at each frequency, based on the proportion of PCH in groups of five rats, were 1.03 ± 0.02, 1.28 ± 0.14, 1.18 ± 0.12 and 1.36 ± 0.15 MPa at 1.5, 4.5, 7.6 and 12.0 MHz, respectively. Although the PCH lesions decreased in size with increasing ultrasonic frequency, owing to the smaller beam widths and scan lengths, the peak rarefactional pressure amplitude thresholds remained approximately constant. This dependence was different from that of the mechanical index, which indicates a need for a specific dosimetric parameter for safety guidance in pulmonary ultrasound. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · Ultrasound in Medicine & Biology
  • Douglas L Miller · Chunyan Dou · Krishnan Raghavendran
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    ABSTRACT: Pulmonary capillary hemorrhage can be induced by diagnostic ultrasound (US) during direct pulmonary US scanning in rats. The influence of specific anesthetic techniques on this bioeffect was examined. Ketamine plus xylazine has been used previously. In this study, the influence of intraperitoneal injections of ketamine and pentobarbital, inhalational isoflurane, and the supplemental use of xylazine with ketamine and isoflurane was tested. A diagnostic US machine with a 7.6-MHz linear array was used to image the right lung of anesthetized rats in a warmed water bath at different mechanical index (MI) settings. Pulmonary capillary hemorrhage was assessed by measuring comet tail artifacts in the image and by morphometry of the hemorrhagic areas on excised lungs. Pulmonary capillary hemorrhage was greatest for pentobarbital, lower for inhalational isoflurane, and lowest for ketamine anesthesia, with occurrence thresholds at MIs of about 0.44, 0.8, and 0.8, respectively. Addition of xylazine produced a substantial increase in hemorrhage and a significant proportion of hemorrhage occurrence for ketamine at an MI of 0.7 (P < .01) and for isoflurane at an MI of 0.52 (P < .01). Ketamine plus xylazine and pentobarbital yield lower thresholds than ketamine or isoflurane alone by nearly a factor of 2 in MI. These results suggest that the choice of the anesthetic agent substantially modifies the relative risks of pulmonary capillary hemorrhage from pulmonary US. © 2015 by the American Institute of Ultrasound in Medicine.
    No preview · Article · Feb 2015 · Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine
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    ABSTRACT: The usual duration of ECMO in patients with severe acute respiratory distress syndrome (ARDS) is 7-10 days. Prolonged duration ECMO (defined as > 14 days) is increasingly being documented with native lung recovery or as a bridge to lung transplantation. We report a case of prolonged duration ECMO (6,364 hours, 265 days) requiring no complete circuit exchange. As critical care improves, prolonged ECMO will continue to pose unique technological and ethical challenges that test our expectations of this treatment modality. There is a critical need for diagnostic modalities to provide objective assessment of native lung recovery in patients requiring prolonged duration ECMO.
    No preview · Article · Nov 2014 · ASAIO journal (American Society for Artificial Internal Organs: 1992)
  • Krishnan Raghavendran

    No preview · Article · Nov 2014 · Shock (Augusta, Ga.)
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    ABSTRACT: Objective: Lung contusion is a major risk factor for the development of acute respiratory distress syndrome. Hypoxia-inducible factor-1α is the primary transcription factor that is responsible for regulating the cellular response to changes in oxygen tension. We set to determine if hypoxia-inducible factor-1α plays a role in the pathogenesis of acute inflammatory response and injury in lung contusion. Design: Nonlethal closed-chest unilateral lung contusion was induced in a hypoxia reporter mouse model and type 2 cell-specific hypoxia-inducible factor-1α conditional knockout mice. The mice were killed at 5-, 24-, 48-, and 72-hour time points, and the extent of systemic and tissue hypoxia was assessed. In addition, injury and inflammation were assessed by measuring bronchoalveolar lavage cells (flow cytometry and cytospin), albumin (permeability injury), and cytokines (inflammation). Isolated type 2 cells from the hypoxia-inducible factor-1α conditional knockout mice were isolated and evaluated for proinflammatory cytokines following lung contusion. Finally, the role of nuclear factor-κB and interleukin-1β as intermediates in this interaction was studied. Results: Lung contusion induced profound global hypoxia rapidly. Increased expression of hypoxia-inducible factor-1α from lung samples was observed as early as 60 minutes, following the insult. The extent of lung injury following lung contusion was significantly reduced in conditional knockout mice at all the time points, when compared with the wild-type littermate mice. Release of proinflammatory cytokines, such as interleukin-1β, interleukin-6, macrophage inflammatory protein-2, and keratinocyte chemoattractant, was significantly lower in conditional knockout mice. These actions are in part mediated through nuclear factor-κB. Hypoxia-inducible factor-1α in lung epithelial cells was shown to regulate interleukin-1β promoter activity. Conclusion: Activation of hypoxia-inducible factor-1α in type 2 cell is a major driver of acute inflammation following lung contusion.
    Full-text · Article · Jul 2014 · Critical Care Medicine

  • No preview · Conference Paper · Jun 2014
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    ABSTRACT: Pulmonary aspiration is an important recognized cause of acute respiratory distress syndrome (ARDS). Better characterization of patients who aspirate may allow identification of potential risks for aspiration that could be used in future studies to mitigate the occurrence of aspiration and its devastating complications. We conducted a secondary analysis of the Lung Injury Prediction Score (LIPS) cohort to better characterize patients with aspiration, including their potential risk factors and related outcomes. Of the 5584 subjects at risk for ARDS and required hospitalization, 212 (3.8%) presented with aspiration. Subjects who aspirated were likely to be male (66% vs. 56%, p<0.007), slightly older (59 vs. 57years), Caucasian (73% vs. 61%, p=0.0004), admitted from a nursing-home (15% vs. 5.9%, p<0.0001), have a history of alcohol abuse (21% vs. 8%, p<0.0001) and have lower Glasgow Coma Scale (median 13 vs. 15, p<0.0001). Aspiration subjects were sicker (higher APACHE2), required more mechanical ventilation (54% vs. 32%, p<0.0001), developed more moderate-to-severe ARDS (12% vs. 3.8%, p<0.0001), and were two-fold more likely to die in-hospital, even after adjustment for severity of illness (OR=2.1; 95%CI: 1.2-3.6). Neither obesity nor gastroesophageal-reflux was associated with aspiration. Aspiration was more common in men, with alcohol abuse history, a lower GCS, and when admitted from a nursing home. It is independently associated with a significant increase in the risk for ARDS as well as morbidity and mortality. Findings from this study may facilitate the design of future clinical studies of aspiration-induced lung injury.
    No preview · Article · May 2014 · Chest
  • Douglas L. Miller · M.V. Suresh · Chunyan Dou · B. Yu · Krishnan Raghavendran
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    ABSTRACT: Routine pulmonary ultrasound for diagnosis of disease or injury relies on interpretation of image features, such as comet-tail artifacts, which can also be indicative of the poorly understood phenomenon of ultrasound-induced pulmonary capillary hemorrhage (PCH). Evans blue extraction and bronchoalveolar lavage (BAL) were evaluated for assessment of PCH induced by ultrasound scanning. Rats anesthetized with ketamine with or without xylazine received sham or scanning for 5 min with a 7.6 MHz linear array. Evans blue extraction and BAL albumin measurements failed to demonstrate significant increases for scanning, even though the induction of comet-tail artifacts was significant. BAL cell counts had an insignificant increase relative to shams at a near-threshold Mechanical Index (MI) of 0.52 (P = 0.07), but a highly significant increase at MI = 0.9 (P = 0.001). The possibility of xylazine-induced elevated albumin was tested, but no significant decrease was found for sham or scanned rats with ketamine-only anesthesia. Interestingly, without xylazine, the widths of comet-tail artifacts in the ultrasound images were significantly smaller (P = 0.001) and cell counts in BAL fluid also were reduced (P = 0.014). The BAL cell-count method provides a valuable additional means of PCH quantification.
    No preview · Article · May 2014 · Microvascular Research
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    ABSTRACT: Lung contusion (LC) is a common injury resulting from blunt thoracic trauma. LC is an important risk factor for the development acute lung injury, adult respiratory distress syndrome, and ventilator-associated pneumonia, all of which increase mortality from trauma. LC produces a nonspecific immune cellular response. Neutrophil recruitment is known to increase the severity of inflammation during LC. However, the exact role of macrophages in modulating the response to LC has not been well described. We used a cortical contusion impactor to induce unilateral LC in mice. Thoracic micro computed tomographic scans of these animals were obtained to document radiologic changes over time following LC. To understand the role of macrophages during LC, liposomal clodronate was used to deplete macrophage levels before traumatic insult. Acute inflammatory attributes after LC were assessed, by measuring pressure-volume mechanics; quantifying bronchial alveolar lavage levels of leukocytes, albumin, and cytokines; and finally examining lung specimen histopathology at 5, 24, 48, and 72 hours after injury. After LC, alveolar macrophage numbers were significantly reduced and exhibited slowed recovery. Simultaneously, there was a significant increase in bronchial alveolar lavage neutrophil counts. The loss of macrophages could be attributed to both cellular apoptosis and necrosis. Pretreatment with clodronate increased the severity of lung inflammation as measured by worsened pulmonary compliance, increased lung permeability, amplification of neutrophil recruitment, and increases in early proinflammatory cytokine levels. The presence of regulatory alveolar macrophages plays an important role in the pathogenesis of acute inflammation following LC.
    No preview · Article · Apr 2014
  • David Machado-Aranda · Krishnan Raghavendran
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    ABSTRACT: Several of the biological processes involved in the pathogenesis of acute lung injury and acute respiratory distress syndrome after lung contusion are regulated at a genetic and epigenetic level. Thus, strategies to manipulate gene expression in this context are highly desirable not only to elucidate the mechanisms involved but also to look for potential therapies. In the present chapter, we describe mouse and rat models of inducing blunt thoracic injury followed by electroporation-mediated gene delivery to the lung. Electroporation is a highly efficient and easily reproducible technique that allows circumvention of several of lung gene delivery challenges and safety issues present with other forms of lung gene therapy.
    No preview · Article · Feb 2014 · Methods in molecular biology (Clifton, N.J.)
  • Vladislav A Dolgachev · Bi Yu · Lei Sun · Thomas P Shanley · Krishnan Raghavendran · Mark R Hemmila
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    ABSTRACT: Lung contusion injury produces a vulnerable window within the inflammatory defenses of the lung that predisposes the patient to pneumonia. IL-10 is a known anti-inflammatory mediator produced by macrophages and capable of down-regulating acute lung inflammation. We investigated the impact of increased levels of IL-10 within the lung on survival and the host response to trauma in the setting of lung contusion and Gram-negative pneumonia. A bi-transgenic, tetracycline inducible, lung specific human IL-10 overexpression (IL-10 OE) mouse model and single transgenic (TG-) control mice were used. Mice underwent lung contusion injury (LC) or sham injury (Sham) at time -6 hrs. At time 0 animals were inoculated intratracheally with 500 CFU of Klebsiella pneumoniae (Pneu). Bronchoalveolar lavage fluid (BAL), lung tissue specimens, or purified macrophages were collected. Lung tissue and blood bacteria levels were quantified. Cytokine levels were assayed by ELISA and gene expression levels were evaluated by real time PCR. Cell type identification and quantification was done using real time PCR and flow cytometry. IL-10 OE mice demonstrated decreased 5 day survival compared to TG- mice following LC+Pneu (0 vs. 30%, p<0.0001). IL-10 OE mice had significantly higher lung bacteria counts (p=0.02) and levels of bacteremia (p=0.001) at 24 hrs. The IL-10 OE mice recruited more neutrophils into the alveoli as measured in BAL fluid compared to TG- mice. Alveolar macrophages from IL-10 OE mice displayed increased alternative activation (M2 macrophages, p=0.046) whereas macrophages from TG- mice exhibited classical activation (M1 macrophages) and much higher intracellular bacterial killing potential (p=0.03). IL-6, KC, and MIP-2 levels were significantly elevated in IL-10 OE LC+Pneu animals (p<0.05). Lung specific IL-10 over expression induces alternative activation of alveolar macrophages. This shift in macrophage phenotype decreases intracellular bacterial killing, resulting in a more pronounced bacteremia and accelerated mortality in a model of lung contusion and pneumonia.
    No preview · Article · Jan 2014 · Shock (Augusta, Ga.)
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    ABSTRACT: Cholesterol synthesis is a highly oxygen-dependent process. Paradoxically, hypoxia is correlated with an increase in cellular and systemic cholesterol levels and risk of cardiovascular diseases. The mechanism for the increase in cholesterol during hypoxia is unclear. Hypoxia signaling is mediated through hypoxia-inducible factor 1α (HIF-1α) and HIF-2α. The present study demonstrates that activation of HIF signaling in the liver increases hepatic and systemic cholesterol levels due to a decrease in the expression of cholesterol hydroxylase CYP7A1 and other enzymes involved in bile acid synthesis. Specifically, activation of hepatic HIF-2α (but not HIF-1α) led to hypercholesterolemia. HIF-2α repressed the circadian expression of Rev-erbα, resulting in increased expression of E4BP4, a negative regulator of Cyp7a1. To understand if HIF-mediated decrease in bile acid synthesis is a physiologically relevant pathway by which hypoxia maintains or increases systemic cholesterol levels, two hypoxic mouse models were assessed, an acute lung injury model and mice exposed to 10% O2 for 3 weeks. In both models, cholesterol levels increased with a concomitant decrease in expression of genes involved in bile acid synthesis. The present study demonstrates that hypoxic activation of hepatic HIF-2α leads to an adaptive increase in cholesterol levels through inhibition of bile acid synthesis.
    Full-text · Article · Jan 2014 · Molecular and Cellular Biology
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    ABSTRACT: Lung contusion (LC) is a unique direct and focal insult that is considered a major risk factor for the initiation of acute lung injury and acute respiratory distress syndrome. We have shown recently that consumption of nitric oxide (due to excess superoxide) resulting in peroxynitrite formation leads to decreased vascular reactivity after LC. In this study, we set out to determine whether the superoxide scavenger Mn (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) plays a protective role in alleviating acute inflammatory response and injury in LC. Nonlethal, closed-chest, bilateral LC was induced in a rodent model. Administration of the superoxide dismutase mimetic MnTBAP concurrently in LC in rats was performed, and bronchoalveolar lavage (BAL) and lung samples were analyzed for degree of injury and inflammation at 5 and 24 h after the insult. The extent of injury was assessed by the measurement of cells and albumin with cytokine levels in the BAL and lungs. Lung samples were subjected to H&E and superoxide staining with dihydro-ethidium. Protein-bound dityrosine and nitrotyrosine levels were quantified in lung tissue by tandem mass spectrometry. The degrees of lung injury after LC as determined by BAL albumin levels were significantly decreased in the MnTBAP-administered rats at all the time points when compared to the corresponding controls. The release of proinflammatory cytokines and BAL neutrophils was significantly less in the rats administered MnTBAP after LC. Administration of MnTBAP decreased tissue damage and decreased necrosis and neutrophil-rich exudate at the 24-h time point. Staining for superoxide anions showed significantly greater intensity in the lung samples from the LC group compared to the LC+ MnTBAP group. High-performance liquid chromatography/tandem mass spectrometry revealed that MnTBAP treatment significantly attenuated dityrosine and nitrotyrosine levels, consistent with decreased oxidant injury. Superoxide dismutase mimetic-MnTBAP reduced permeability and oxidative injury in LC and may have a therapeutic role in diminishing inflammation in LC.
    No preview · Article · Nov 2013 · Surgery
  • Jean A Nemzek-Hamlin · Haejin Hwang · Joseph A Hampel · Bi Yu · Krishnan Raghavendran
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    ABSTRACT: Despite the prevalence of blunt hepatic trauma in humans, there are few rodent models of blunt trauma that can be used to study the associated inflammatory responses. We present a mouse model of blunt hepatic trauma that was created by using a cortical contusion device. Male mice were anesthetized with ketamine-xylazine-buprenorphine and placed in left lateral recumbency. A position of 2 mm ventral to the posterior axillary line and 5 mm caudal to the costal margin on the right side was targeted for impact. An impact velocity of 6 m/s and a piston depth of 12 mm produced a consistent pattern of hepatic injury with low mortality. All mice that recovered from anesthesia survived without complication for the length of the study. Mice were euthanized at various time points (n = 5 per group) until 7 d after injury for gross examination and collection of blood and peritoneal lavage fluids. Some mice were reanesthetized for serial monitoring of hepatic lesions via MRI. At 2 h after trauma, mice consistently displayed laceration, hematoma, and discoloration of the right lateral and caudate liver lobes, with intraabdominal hemorrhage but no other gross injuries. Blood and peritoneal lavage fluid were collected from all mice for cytokine analysis. At 2 h after trauma, there were significant increases in plasma IL10 as well as peritoneal lavage fluid IL6 and CXCL1/KC; however, these levels decreased within 24 h. At 7 d after trauma, the mice had regained body weight, and the hepatic lesions, which initially had increased in size during the first 48 h, had returned to their original size. In summary, this technique produced a reliable, low mortality, murine model that recreates features of blunt abdominal liver injury in human subjects with similar acute inflammatory response.
    No preview · Article · Oct 2013 · Comparative medicine

Publication Stats

950 Citations
223.26 Total Impact Points

Institutions

  • 2009-2016
    • University of Michigan
      • Department of Surgery
      Ann Arbor, Michigan, United States
  • 2009-2015
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2013
    • Roswell Park Cancer Institute
      • Department of Medicine
      Buffalo, NY, United States
  • 2005-2012
    • University at Buffalo, The State University of New York
      • • Department of Anesthesiology
      • • Department of Oral Biology
      • • Department of Surgery
      Buffalo, New York, United States
    • University of Rochester
      • Department of Pediatrics
      Rochester, New York, United States
  • 2006-2007
    • State University of New York
      New York City, New York, United States
    • SUNY Ulster
      Кингстон, New York, United States
  • 2002-2004
    • Erie County Medical Center
      New York, New York, United States