Retrograde jejunogastric intussusception due to suture concretion.

We describe a patient who presented with acute small bowel obstruction five years after Roux-en-Y reconstruction. Computed tomography and operative exploration showed a retrograde intussusception at the gastrojejunostomy due to an intraluminal suture concretion. We describe the preoperative imaging, endoscopic and intraoperative findings, and review the literature.

A technique for visual confirmation of intrathoracic placement of tube thoracostomy using a fiberoptic laryngoscope in a cadaver.

PURPOSE: Safe intrathoracic placement of chest tubes is a continual challenge. Current techniques for determining the intrathoracic location of the thoracostomy site include blunt dissection and digital exploration, with subsequent tube placement. Using current techniques, complication rates for this procedure approach 30%. We present a novel technique using available endotracheal intubation technology for determining intrathoracic placement of tube thoracostomy. METHODS: One cadaver was used for placement of tube thoracostomy. Both sides of the thorax were prepared in the standard fashion for tube thoracostomy placement, and tube thoracostomy was performed on each hemithorax at interspaces 3 through 7. The right side of the thorax was used for standard thoracostomy placement, and the left side was used for fiberoptic visualization of thoracostomy placement using a video laryngoscope. Thoracic wall thickness was measured at all thoracostomy sites. Proper placement and any injuries were documented for each site. RESULTS: Chest wall thickness ranged from 2.4 to 3.8 cm on the right and 2.8 to 4.0 cm on the left. With use of fiberoptic thoracostomy, no injuries were generated. During the standard thoracostomy placement in the sixth intercostal space, a pulmonary laceration was caused using blunt dissection. CONCLUSIONS: Use of a fiberoptic laryngoscope offers a novel technique for direct visualization the thoracic space during tube thoracostomy. Further studies are needed to determine the safety of this technique in patients.

Surgical stabilization of flail chest: the impact on postoperative pulmonary function.

OBJECTIVES: Flail chest results in significant morbidity. Controversies continue regarding the optimal management of flail chest. No clear guidelines exist for surgical stabilization. Our aim was to examine the association of bedside spirometry values with operative stabilization of flail chest. METHODS: IRB approval was obtained to identify patients with flail chest who underwent surgical stabilization between August 2009 and May 2011. At our institution, all rib fracture patients underwent routine measurement of their forced vital capacity (FVC) using bedside spirometry. Formal pulmonary function tests were also obtained postoperatively and at three months in patients undergoing stabilization. Both the Synthes and Acute Innovations plating systems were utilized. Data is presented as median (range) or (percentage). RESULTS: Twenty patients (13 male: 65 %) with median age of 60 years (30-83) had a median of four ribs (2-9) in the flail segment. The median Injury Severity Score was 17 (9-41) and the median Trauma and Injury Severity Score was 0.96 (0.04-0.99). Preoperative pneumonia was identified in four patients (20 %) and intubation was required in seven (35 %). Median time from injury to stabilization was four days (1-33). The median number of plates inserted was five (3-11). Postoperative median FVC (1.8 L, range 1.3-4 L) improved significantly as compared to preoperative median value (1 L, range 0.5-2.1 L) (p = 0.003). This improvement continued during the follow-up period at three months (0.9 L, range 0.1-3.0) (p = 0.006). There were three deaths (15 %), none of which were related to the procedure. Subsequent tracheostomy was required in three patients (15 %). The mean hospital stay and ventilator days after stabilization were nine days and three days, respectively. Mean follow-up was 5.6 ± 4.6 months. CONCLUSION: Operative stabilization of flail chest improved pulmonary function compared with preoperative results. This improvement was sustained at three months follow-up.

Chemical components separation with botulinum toxin A: a novel technique to improve primary fascial closure rates of the open abdomen.

INTRODUCTION: Failure to definitively close the open abdomen (OA) after damage control laparotomy leads to considerable morbidity and mortality. We have developed a novel technique, the "chemical components separation," which incorporates injection of botulinum toxin A (BTX), a long-term flaccid paralytic, into the lateral abdominal wall musculature. METHODS: This is a retrospective review of all OA patients (age ≥18) from December 2009-June 2010 who underwent BTX injection. Under ultrasound guidance, a total of 300 units of BTX were injected into the external oblique, internal oblique and transversus abdominus. RESULTS: A total of 18 patients were injected with a median age of 66 years (56 % male). Indications for OA treatment included questionable bowel viability (39 %), shock (33 %), loss of abdominal domain (6 %) and feculent contamination (17 %). Median ASA score was 3 with an APACHE 3 score of 85. Patients underwent a median of 4 serial abdominal explorations. The primary fascial closure rate was 83 % with a partial fascial closure rate of 6 % and planned ventral hernia rate of 11 %. Of the 9 patients injected within 24 h of their initial OA procedure, 89 % achieved primary fascial closure. Mortality was 11 %; death was unrelated to BTX injection. The overall complication rate was 67 %; specific complications rates included fascial dehiscence (11 %), enterocutaneous fistula development (0 %), intra-abdominal abscess (44 %) and deep surgical site infection (33 %). CONCLUSION: The "chemical components separation" technique described is safe and avoids the extensive dissection necessary for mechanical components separation in critically ill patients with infected/contaminated abdominal domains. While further evaluation is required, the described technique provides potential to improve delayed primary fascial closure rates in the OA setting.

Invasive arterial BP monitoring in trauma and critical care: effect of variable transducer level, catheter access, and patient position.

OBJECTIVES: (1) To determine the validity of current recommendations for direct arterial BP measurement that suggest that the transducer (zeroed to atmosphere) be placed level with the catheter access regardless of subject positioning: and (2) to investigate the effect of transducer level, catheter access site, and subject positioning on direct arterial BP measurement. DESIGN: Prospective, controlled laboratory study. SETTING: Large animal laboratory. SUBJECTS: Five Yorkshire pigs. INTERVENTIONS: Anesthetized animals had 16F catheters placed at three access sites: aortic root, femoral artery, and distal hind limb. Animals were placed in supine, reverse Trendelenburg 35 degrees, and Trendelenburg 25 degrees positions with a transducer placed level to each access site while in every position. MEASUREMENTS AND MAIN RESULTS: For each transducer level, five systolic and diastolic pressures were measured and used to calculate five corresponding mean arterial pressures (MAPs) at each access site. When transducers were at the aortic root, MAP corresponding to aortic root pressure was obtained in all positions regardless of catheter access site. When transducers were moved to the level of catheter access, as current recommendations suggest, significant errors in aortic MAP occurred in the reverse Trendelenburg position. The same trend for error was noted in the Trendelenburg position but did not reach statistical significance. CONCLUSIONS: (1) Current recommendations that suggest placing the transducer at the level of catheter access regardless of patient position are invalid. Significant errors occur when subjects are in nonsupine positions. (2) Valid determination of direct arterial BP is dependent only on transducer placement at the level of the aortic root, and independent of catheter access site and patient position.

Nonoperative management of solid abdominal organ injuries from blunt trauma: impact of neurologic impairment.

The role of nonoperative management of solid abdominal organ injury from blunt trauma in neurologically impaired patients has been questioned. A statewide trauma registry was reviewed from January 1993 through December 1995 for all adult (age >12 years) patients with blunt trauma and an abdominal solid organ injury (kidney, liver, or spleen) of Abbreviated Injury Scale score > or =2. Patients with initial hypotension (systolic blood pressure <90 mm Hg) were excluded. Patients were stratified by Glasgow Coma Score (GCS) into normal (GCS 15), mild to moderate (GCS 8-14), and severe (GCS < or =7) impairment groups. Management was either operative or nonoperative; failure of nonoperative management was defined as requiring laparotomy for intraabdominal injury more than 24 hours after admission. In the 3-year period 2327 patients sustained solid viscus injuries; 1561 of these patients were managed nonoperatively (66 per cent). The nonoperative approach was initiated less frequently in those patients with greater impairment in mental status: GCS 15, 71 per cent; GCS 8 to 14, 62 per cent; and GCS < or =7, 50 per cent. Mortality, hospital length of stay, and intensive care unit days were greater in operatively managed GCS 15 and 8 to 14 groups but were not different on the basis of management in the GCS < or =7 group. Failure of nonoperative management occurred in 94 patients (6%). There was no difference in the nonoperative failure rate between patients with normal mental status and those with mild to moderate or severe head injuries. Nonoperative management of neurologically impaired hemodynamically stable patients with blunt injuries of liver, spleen, or kidney is commonly practiced and is successful in more than 90 per cent of cases. No differences were noted in the rates of delayed laparotomy or survival between normal, mild to moderately head-injured, and severely head-injured patients.

Metalloproteinase inhibition prevents acute respiratory distress syndrome.

BACKGROUND: The acute respiratory distress syndrome (ARDS) occurs in patients with clearly identifiable risk factors, and its treatment remains merely supportive. We postulated that patients at risk for ARDS can be protected against lung injury by a prophylactic treatment strategy that targets neutrophil-derived proteases. We hypothesized that a chemically modified tetracycline 3 (COL-3), a potent inhibitor of neutrophil matrix metalloproteinases (MMPs) and neutrophil elastase (NE) with minimal toxicity, would prevent ARDS in our porcine endotoxin-induced ARDS model. METHODS: Yorkshire pigs were anesthetized, intubated, surgically instrumented for hemodynamic monitoring, and randomized into three groups: (1) control (n = 4), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 4), infusion of Escherichia coli lipopolysaccharide at 100 microg/kg; and (3) COL-3 + LPS (n = 5), ingestion of COL-3 (100 mg/kg) 12 h before LPS infusion. All animals were monitored for 6 h following LPS or sham LPS infusion. Serial bronchoalveolar lavage (BAL) samples were analyzed for MMP concentration by gelatin zymography. Lung tissue was fixed for morphometric assessment at necropsy. RESULTS: LPS infusion was marked by significant (P < 0.05) physiological deterioration as compared with the control group, including increased plateau airway pressure (P(plat)) (control = 15.7 +/- 0.4 mm Hg, LPS = 23.0 +/- 1.5 mm Hg) and a decrement in arterial oxygen partial pressure (P(a)O(2)) (LPS = 66 +/- 15 mm Hg, Control = 263 +/- 25 mm Hg) 6 h following LPS or sham LPS infusion, respectively. Pretreatment with COL-3 reduced the above pathophysiological changes 6 h following LPS infusion (P(plat) = 18.5 +/- 1.7 mm Hg, P(a)O(2) = 199 +/- 35 mm Hg; P = NS vs control). MMP-9 and MMP-2 concentration in BAL fluid was significantly increased between 2 and 4 h post-LPS infusion; COL-3 reduced the increase in MMP-9 and MMP-2 concentration at all time periods. Morphometrically LPS caused a significant sequestration of neutrophils and monocytes into pulmonary tissue. Pretreatment with COL-3 ameliorated this response. The wet/dry lung weight ratio was significantly greater (P < 0.05) in the LPS group (10.1 +/- 1.0 ratio) than in either the control (6.4 +/- 0.5 ratio) or LPS+COL-3 (7.4 +/- 0.6 ratio) group. CONCLUSIONS: A single prophylactic treatment with COL-3 prevented lung injury in our model of endotoxin-induced ARDS. The proposed mechanism of COL-3 is a synergistic inhibition of the terminal neutrophil effectors MMPs and NE. Similar to the universal practice of prophylaxis against gastric stress ulceration and deep venous thromboses in trauma patients, chemically modified tetracyclines may likewise be administered to prevent acute lung injury in critically injured patients at risk of developing ARDS.

Visual validation of the mechanical stabilizing effects of positive end-expiratory pressure at the alveolar level.

BACKGROUND: Positive end-expiratory pressure (PEEP) reduces ventilator-induced lung injury (VILI), presumably by mechanically stabilizing alveoli and decreasing intrapulmonary shear. Although there is indirect support for this concept in the literature, direct evidence is lacking. In a surfactant depletion model of acute lung injury we observed unstable alveolar mechanics referred to as repeated alveolar collapse and expansion (RACE) as measured by changes in alveolar area from inspiration to expiration (I - E(Delta)). We tested the hypothesis that over a range of tidal volumes PEEP would prevent RACE by mechanically stabilizing alveoli. MATERIALS AND METHODS: Yorkshire pigs were randomized to three groups: control (n = 4), Tween (surfactant-deactivating detergent) (n = 4), and Tween + PEEP (7 cm H(2)O) (n = 4). Using in vivo video microscopy individual alveolar areas were measured with computer image analysis at end inspiration and expiration over consecutive increases in tidal volume (7, 10, 15, 20, and 30 cc/kg.) I - E(Delta) was calculated for each alveolus. RESULTS: Surfactant deactivation significantly increased I - E(Delta) at every tidal volume compared to controls (P < 0.05). PEEP prevented this change, returning I - E(Delta) to control levels over a spectrum of tidal volumes. CONCLUSIONS: RACE occurs in our surfactant deactivation model of acute lung injury. PEEP mechanically stabilizes alveoli and prevents RACE over a range of tidal volumes. This is the first study to visually document the existence of RACE and the mechanical stabilizing effects of PEEP at the alveolar level. The ability of PEEP to stabilize alveoli and reduce shear during mechanical ventilation has important implications for therapeutic strategies directed at VILI and acute respiratory distress syndrome.

Altered alveolar mechanics in the acutely injured lung.

OBJECTIVES: Alterations in alveolar mechanics (i.e., the dynamic change in alveolar size during tidal ventilation) are thought to play a critical role in acute lung injuries such as acute respiratory distress syndrome (ARDS). In this study, we describe and quantify the dynamic changes in alveolar mechanics of individual alveoli in a porcine ARDS model by direct visualization using in vivo microscopy. DESIGN: Prospective, observational, controlled study. SETTING: University research laboratory. SUBJECTS: Ten adult pigs. INTERVENTIONS: Pigs were anesthetized and placed on mechanical ventilation, underwent a left thoracotomy, and were separated into the following two groups post hoc: a control group of instrumented animals with no lung injury (n = 5), and a lung injury group in which lung injury was induced by tracheal Tween instillation, causing surfactant deactivation (n = 5). Pulmonary and systemic hemodynamics, blood gases, lung pressures, subpleural blood flow (laser Doppler), and alveolar mechanics (in vivo microscopy) were measured in both groups. Alveolar size was measured at peak inspiration (I) and end expiration (E) on individual subpleural alveoli by image analysis. Histologic sections of lung tissue were taken at necropsy from the injury group. MEASUREMENTS AND MAIN RESULTS: In the acutely injured lung, three distinct alveolar inflation-deflation patterns were observed and classified: type I alveoli (n = 37) changed size minimally (I - EDelta = 367 +/- 88 microm2) during tidal ventilation; type II alveoli (n = 37) changed size dramatically (I - EDelta = 9326 +/- 1010 microm2) with tidal ventilation but did not totally collapse at end expiration; and type III alveoli (n = 12) demonstrated an even greater size change than did type II alveoli (I - EDelta = 15,418 +/- 1995 microm2), and were distinguished from type II in that they totally collapsed at end expiration (atelectasis) and reinflated during inspiration. We have termed the abnormal alveolar inflation pattern of type II and III alveoli "repetitive alveolar collapse and expansion" (RACE). RACE describes all alveoli that visibly change volume with ventilation, regardless of whether these alveoli collapse totally (type III) at end expiration. Thus, the term "collapse" in RACE refers to a visibly obvious collapse of the alveolus during expiration, whether this collapse is total or partial. In the normal lung, all alveoli measured exhibited type I mechanics. Alveoli were significantly larger at peak inspiration in type II (18,266 +/- 1317 microm2, n = 37) and III (15,418 +/- 1995 microm2, n = 12) alveoli as compared with type I (8214 +/- 655 microm2, n = 37). Tween caused a heterogenous lung injury with areas of normal alveolar mechanics adjacent to areas of abnormal alveolar mechanics. Subsequent histologic sections from normal areas exhibited no pathology, whereas lung tissue from areas with RACE mechanics demonstrated alveolar collapse, atelectasis, and leukocyte infiltration. CONCLUSION: Alveolar mechanics are altered in the acutely injured lung as demonstrated by the development of alveolar instability (RACE) and the increase in alveolar size at peak inspiration. Alveolar instability varied from alveolus to alveolus in the same microscopic field and included alveoli that changed area greatly with tidal ventilation but remained patent at end expiration and those that totally collapsed and reexpanded with each breath. Thus, alterations in alveolar mechanics in the acutely injured lung are complex, and attempts to assess what may be occurring at the alveolar level from analysis of inflection points on the whole-lung pressure/volume curve are likely to be erroneous. We speculate that the mechanism of ventilator-induced lung injury may involve altered alveolar mechanics, specifically RACE and alveolar overdistension.

The mechanism of lung volume change during mechanical ventilation.

To understand ventilator-induced lung injury (VILI) during positive pressure ventilation, mechanisms of normal alveolar mechanics must first be established. Isotropic "balloonlike" alveolar volume (VA) change has been viewed as the prevailing mechanism of normal lung volume (VL) changes. We hypothesized that change in VL is predominantly caused by alveolar recruitment-derecruitment (R/D). Fifteen mongrel dogs were anesthetized and intubated with a tracheal divider. Through a thoracotomy incision, in vivo microscopy of subpleural alveoli was performed as the degassed lung was inflated to 80% TLC, and then deflated to residual volume (RV). Still photomicrographs were evaluated to determine if change in VL is due to change in VA or R/D of alveoli. We noted a steady, significant increase in alveolar recruitment as VL increased to 80% TLC (p < 0.05). However, VA increased significantly, but only to 20% TLC (p < 0.05). Once recruited, alveoli did not demonstrate any further volume change, whereas the lung as a whole maintained a normal pressure/volume relationship. In our model, changes in VL predominantly are caused by R/D.

Matrix metalloproteinase inhibitor prevents acute lung injury after cardiopulmonary bypass.

BACKGROUND: Acute lung injury (ALI) after cardiopulmonary bypass (CPB) results from sequential priming and activation of neutrophils. Activated neutrophils release neutral serine, elastase, and matrix metalloproteinases (MMPs) and oxygen radical species, which damage alveolar-capillary basement membranes and the extracellular matrix, resulting in an ALI clinically defined as adult respiratory distress syndrome (ARDS). We hypothesized that treatment with a potent MMP and elastase inhibitor, a chemically modified tetracycline (CMT-3), would prevent ALI in our sequential insult model of ALI after CPB. METHODS AND RESULTS: Anesthetized Yorkshire pigs were randomized to 1 of 5 groups: control (n=3); CPB (n=5), femoral-femoral hypothermic bypass for 1 hour; LPS (n=7), sham bypass followed by infusion of low-dose Escherichia coli lipopolysaccharide (LPS; 1 microgram/kg); CPB+LPS (n=6), both insults; and CPB+LPS+CMT-3 (n=5), both insults plus intravenous CMT-3 dosed to obtain a 25-micromol/L blood concentration. CPB+LPS caused severe lung injury, as demonstrated by a significant fall in PaO(2) and an increase in intrapulmonary shunt compared with all groups (P<0.05). These changes were associated with significant pulmonary infiltration of neutrophils and an increase in elastase and MMP-9 activity. CONCLUSIONS: All pathological changes typical of ALI after CPB were prevented by CMT-3. Prevention of lung dysfunction followed an attenuation of both elastase and MMP-2 activity. This study suggests that strategies to combat ARDS should target terminal neutrophil effectors.

Videomicroscopy provides accurate in vivo assessment of pulmonary microvascular reactivity in rabbits.

When defining the mechanism of hypoxic pulmonary vasoconstriction (HPV), investigators have employed ex vivo preparations because of the belief that accurate, quantitative assessment of pulmonary microvessels could not be obtained in vivo. We hypothesize that accurate, quantitative assessment of pulmonary microvascular reactivity can be performed using a simple, in vivo preparation. Our aim was to provide this quantitative assessment in a defined animal model, and to confirm that the chosen preparation could discriminate changes in microvascular reactivity as influenced by endogenous mediators. New Zealand rabbits were instrumented for in vivo microscopy and direct measurement of subpleural arterioles. Rabbits were first randomized to either control (n = 7) or endotoxin (n = 5), infusion of Escherichia coli lipopolysaccharide (200 Fg/kg). All rabbits were then exposed to a repeated protocol of normoxia (21% O2) for 20 min and then hypoxia (15% O2) for 10 min over 2 h. The changes in arteriole diameter were measured at the end of each interval. Normal pulmonary arterioles repeatedly constrict 15+/-3.5% during hypoxia. Altering endogenous vasoactive mediators, as with infusion of endotoxin, caused a loss of hypoxia-induced vasoconstriction. The results of our study validate this experimental preparation for the reliable quantification of pulmonary microvascular reactivity and investigation of hypoxic pulmonary vasoconstriction under both normal and pathologic conditions.

Combined blunt cardiac and pericardial rupture: review of the literature and report of a new diagnostic algorithm.

The spectrum of blunt cardiac injury varies from the asymptomatic cardiac concussion to the immediately fatal cardiac rupture. Although the majority of victims sustaining blunt cardiac rupture die before receiving medical attention, some survive to evaluation. The diagnosis of cardiac rupture, if established, typically results from the signs and symptoms of pericardial tamponade. However, some patients may have remarkably few signs and symptoms suggestive of cardiac injury and represent a significant diagnostic challenge. We provide two cases of cardiac rupture in which the diagnosis was delayed by the presence of an associated pericardial tear with decompression into the mediastinum and pleural space. In neither of the cases did existing institutional algorithms for blunt cardiac injury assist in establishing the diagnosis before the acute demise of the patient. The presence of a coexisting pericardial injury in these patients with blunt cardiac rupture obscured the diagnosis, leading to the deaths of these patients. A discussion of these two cases and review of the literature is provided with recommendations for diagnostic algorithms in patients sustaining blunt thoracic trauma with possible cardiac and pericardial injury.

Soluble tumor necrosis factor receptor prevents post-pump syndrome.

Post-pump syndrome is an acute lung injury following cardiopulmonary bypass (CPB) which is indistinguishable from the adult respiratory distress syndrome (ARDS). Tumor necrosis factor (TNF) is central to the inflammatory process and is capable of triggering the entire pathophysiologic response leading to ARDS. We hypothesized that treatment with a soluble TNF receptor-binding protein (TNFbp) would reduce the increase in serum TNF and prevent acute lung injury in our sequential insult model of ARDS following CPB. Anesthetized pigs were randomized to one of three groups: Control (n = 3), surgical preparation only; CPB + LPS (n = 6), femoral-femoral hypothermic bypass for 1 h followed by infusion of low dose Escherichia coli lipopolysaccharide (LPS; 1 microg/kg); and TNFbp + CPB + LPS (n = 4), pretreatment with intravenous TNFbp (2 mg/kg) followed immediately by both insults. CPB + LPS caused severe lung injury demonstrated by a significant fall in PaO2 and an increase in both intrapulmonary shunt and peak airway pressure as compared to all groups (P < 0.05). These changes were associated with a significant increase in plasma TNF level and pulmonary neutrophil sequestration. TNFbp significantly reduced plasma levels of TNF and prevented the lung injury typically observed with this ARDS model, but did not reduce pulmonary neutrophil sequestration. Thus, elevated serum TNF is not responsible for neutrophil sequestration but does play a role in neutrophil activation which causes lung injury. Prophylactic use of TNFbp in CPB patients may prevent neutrophil activation and reduce the incidence of post-pump ARDS.

Hyperparathyroidism and pregnancy.

BACKGROUND: Hyperparathyroidism during pregnancy can carry significant morbidity to both mother and fetus. Surgery is the definitive treatment of choice although medical management is occasionally warranted. This report looks at 6 cases of hyperparathyroidism during pregnancy and reviews the morbidity and mortality of this entity. METHODS: We retrospectively reviewed all parathyroidectomies performed over a 21-year period (May 1975 to May 1996). A total of 750 cases were performed. In 6 cases, hyperparathyroidism occurred during pregnancy. Serum calcium was measured in all patients before and after parathyroidectomy. RESULTS: A total of 6 of 750 patients (0.8%) were found to have hyperparathyroidism during pregnancy. In this review, fetal mortality rate was 17% (1 of 6). Two infants experienced neonatal tetany. Maternal morbidity included 1 woman who developed hypercalcemic crisis and acute pancreatitis. Two patients presented with hyperemesis gravidarum, 2 were asymptomatic, and 1 had recurrent urinary tract infection. CONCLUSION: Hyperparathyroidism during pregnancy, while rare, remains a preventable cause of fetal morbidity and mortality. Based on our case series and review of the literature, surgery is the definitive treatment of choice and is considered safe and effective if performed during the second trimester of pregnancy. Those involved with the care of the pregnant patient need to be diligent to diagnose and treat this entity promptly.

Matrix metalloproteinase inhibitor: differential effects on pulmonary neutrophil and monocyte sequestration following cardiopulmonary bypass.

UNLABELLED: Acute respiratory distress syndrome (ARDS) following cardiopulmonary bypass (CPB), also known as "post-pump" or "post-perfusion syndrome" (PPS), results from sequential priming and activation of neutrophils. We hypothesized that chemically modified tetracycline (CMT-3) an inhibitor of neutrophil matrix metalloproteinase (MMP) and elastase, would prevent PPS. We performed histometric analysis of lung tissue from our porcine PPS model to correlate cellular sequestration and histologic injury with CMT-3 treatment. METHODS: Yorkshire pigs were randomized into five groups: Control (n = 3); CPB (n = 5); femoral-femoral bypass 1 hour; LPS (n = 7), Escherichia coli lipopolysaccharide (1 microgram/kg); CPB + LPS (n = 6); and CPB + LPS + CMT (n = 5), sequential insults and CMT-3. Protocol histometric analysis defined cellular and tissue components of lung injury. RESULTS: CMT-3 decreased neutrophil sequestration in the CPB + LPS + CMT-3 group (p < 0.0001 vs. CPB + LPS). There were no differences in monocytes between CPB + LPS and CPB + LPS + CMT treatment groups. CONCLUSIONS: CMT-3 attenuates neutrophil sequestration but has no effect on mononuclear sequestration in our PPS model. This finding supports current research on leukocyte chemokines and has important implications regarding mechanisms of CMT-3. Despite lack of monocyte response to CMT-3, PPS was prevented by inhibiting neutrophils alone; confirming the primary role of neutrophils in PPS.

Immunoaffinity localization of the enzyme xanthine oxidase on the outside surface of the endothelial cell plasma membrane.

BACKGROUND: Reactive oxygen metabolites generated from endothelial xanthine oxidase (XO) trigger reperfusion injury in many organs. We evaluated the possibility that endothelial XO was localized on the endothelial cell surface, as well as within the cytoplasm. METHODS: Primary cultures of bovine (BAECs) and porcine (PAECs) aortic endothelial cells were grown in media documented to be free of XO. Polyclonal and monoclonal antibodies were developed against XO. These antibodies were used to evaluate BAEC and PAEC for cell surface XO through immunofluorescence staining, hybridoma cell surface labeling, and endothelial cell surface binding. RESULTS: These antibodies bound specifically to the surface of these cells when the membrane was shown to be intact and impermeable (and the cytoplasm inaccessible) to immunoglobulins Moreover, hybridoma cells expressing monoclonal antibody to XO bound specifically to the endothelial cell surface. Finally, intact endothelial cells bound specifically to the anti-XO polyclonal antibodies immobilized to the surface of a Petri dish. The integrity of these endothelial cell plasma membranes was demonstrated by the subsequent growth and replication of these cells in culture. CONCLUSIONS: These findings indicate that XO is present on the outside surface of the endothelial cell plasma membrane. This would not only explain the known in vivo efficacy of intravascularly administered large molecular weight antioxidants (such as superoxide dismutase) but could have important implications for inflammatory signaling.

Hemodynamics of pancreatic ischemia in cardiogenic shock in pigs.

BACKGROUND & AIMS: Previous studies have shown that the renin-angiotensin axis plays a pivotal role in vasoconstriction of the gastric, intestinal, and hepatic circulations during cardiogenic shock. The aim of this study was to evaluate the fundamental hemodynamic mechanism of pancreatic ischemia during cardiogenic shock induced by pericardial tamponade. METHODS: Cardiogenic shock was induced by pericardial tamponade. Cardiac output (and total peripheral vascular resistance) was determined by thermodilution. Pancreatic blood flow (and vascular resistance) was determined with radiolabeled microspheres. RESULTS: Graded increases in pericardial pressure produced corresponding decreases in cardiac output to 42% +/- 1% and arterial pressure to 67% +/- 3% of baseline and increases in total peripheral vascular resistance to 146% +/- 5% of baseline. Pancreatic blood flow decreased disproportionately to 30% +/- 3% of baseline, because of a disproportionate increase in pancreatic vascular resistance to 220% +/- 19% of baseline. Previously confirmed blockade of the renin-angiotensin axis ablated this response, whereas confirmed blockade of the alpha-adrenergic system or vasopressin system had no significant effect. Without shock, central intravenous infusions of angiotensin II closely mimicked this selective vasoconstriction. CONCLUSIONS: Angiotensin-mediated selective pancreatic vasoconstriction results in significant pancreatic ischemia during cardiogenic shock.

Conversion of xanthine dehydrogenase into xanthine oxidase in rat liver and plasma at the onset of reperfusion after ischemia.

The aim of this study was to test whether conversion of xanthine dehydrogenase into xanthine oxidase as induced by fasting, ischemia of the liver or both is an in vivo process or only occurs in vitro in homogenates. For this purpose, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied in liver homogenates obtained from rats after normal feeding or 24 hr of fasting followed or not by 2 hr of ischemia of the liver. In fed rats, the conversion rate of xanthine dehydrogenase into xanthine oxidase was studied as well in liver homogenates after different periods of reperfusion after 2 hr of ischemia. Homogenization was carried out under strictly controlled conditions, after which the supernatants were incubated at 37 degrees C in buffer for 0 to 5 hr. Enzyme activities were assayed spectrophotometrically by measuring urate production at 295 nm. Conversion started only after 2 to 3 hr of incubation of supernatants of control fed livers, whereas conversion started immediately after 24 hr of fasting. The percentage oxidase activity of total xanthine oxidoreductase activity in ischemic livers from fed animals was slightly higher (26.7% +/- 1.7%; p < 0.05) than in control livers (19.3% +/- 1.4%), whereas the percent oxidase activity in ischemic livers from fasted animals (16.7% +/- 1.0%) was not different from that in control animals (16.8% +/- 1.1%). Ischemia for 2 hr caused in vitro a substantial increase in the conversion rate in supernatants of livers of fed and fasted rats as compared with their controls.(ABSTRACT TRUNCATED AT 250 WORDS)