Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response.

OBJECTIVE: Both donor pulmonary macrophages and recipient circulating leukocytes may be involved in reperfusion injury after lung transplantation. By using the macrophage inhibitor gadolinium chloride and leukocyte filters, we attempted to identify the roles of these two populations of cells in lung transplant reperfusion injury. METHODS: With our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour cold storage and 2-hour blood reperfusion. Measurements of pulmonary artery pressure, lung compliance, and arterial oxygenation were obtained. Group I (n = 8) served as a control. Group II (n = 8) received gadolinium chloride at 14 mg/kg 24 hours before lung harvest. Group III (n = 8) received leukocyte-depleted blood reperfusion by means of a leukocyte filter. RESULTS: The gadolinium chloride group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with control subjects and an improved arterial oxygenation compared with the filter group after 30 minutes of reperfusion. After 120 minutes of reperfusion, however, the filter group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with the control group and an improved arterial oxygenation compared with the gadolinium chloride group. CONCLUSIONS: Lung transplant reperfusion injury occurs in two phases. The early phase is mediated by donor pulmonary macrophages and is followed by a late injury induced by recipient circulating leukocytes.

Epidermal growth factor augments postpneumonectomy lung growth.

OBJECTIVE: Epidermal growth factor has been shown to play an important role in prenatal and postnatal lung development, but little is known about its effects on adult lung growth. We hypothesized that postpneumonectomy compensatory lung growth can be augmented by the administration of epidermal growth factor. METHODS: Adult Sprague-Dawley rats were divided into 3 groups. Sham left thoracotomy was performed in the first group (group C), left pneumonectomy in the second group (group P), and left pneumonectomy with administration of epidermal growth factor (0.2 microgram/g body weight intraperitoneally, at 72-hour intervals) in the third group (group E). The right lung growth was studied in each group 1, 3, 5, 10, and 21 days after the operation. Lung weights (in grams) and volumes (in milliliters) were expressed as a ratio to the total body weight (in kilograms) (lung weight and volume indices). Epidermal growth factor receptor was quantitated by using Western blotting. RESULTS: Using analysis of variance and contrast analysis, we noted a significant increase in lung weight index in group E versus group P rats at 3 days (3.08 vs 2.75; P =.034) and 21 days (4.62 vs 3.61; P =.006). Lung volume index was significantly increased in group E versus group P rats at 5 (16.98 vs 15.09), 10 (24.48 vs 18.81), and 21 (28.54 vs 21.01) days (P <.001). Epidermal growth factor receptor was noted to be up-regulated in the lungs of animals that received exogenous epidermal growth factor. CONCLUSIONS: This study demonstrates that administration of exogenous epidermal growth factor has a significant effect on postpneumonectomy lung growth. This process may be mediated by an up-regulation of growth factor receptor expression in the contralateral lung.

Influence of graft ischemic time on outcomes following lung transplantation.

BACKGROUND: Reperfusion injury is the most common cause of early mortality following lung transplantation. Although cold graft ischemic time has been reported to influence this injury, some lung grafts with short ischemic times develop significant reperfusion injury, whereas other grafts with more prolonged ischemic times do not develop injury. Our hypothesis was that ischemic time did not significantly influence reperfusion injury or other outcomes following lung transplantation. METHODS: Data on 136 patients who had lung transplantation over a 10 year period was used for analysis. RESULTS: Cold graft ischemic time > or = 6 hours did not increase the risk of reperfusion injury, acute rejection, cytomegalovirus infection, bacterial or fungal pneumonia, bronchiolitis obliterans syndrome, 1-month mortality, 1-year mortality, or 5-year mortality compared with ischemic times of either < 4 hours or 4 to 6 hours. The incidence of reperfusion injury was at least 20% for each time group. CONCLUSIONS: At least 20% of all patients will develop reperfusion injury regardless of cold graft ischemic time. Prolonged ischemic times up to 8 hours do not result in a significant increase in adverse short-term, intermediate, or long-term outcomes. Cautious extension of ischemic time beyond the current target of 4 to 6 hours may be warranted for geographic expansion of the donor lung pool.

Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion.

BACKGROUND: We hypothesized that inflammation during spinal cord reperfusion worsens ischemic injury. ATL-146e, an adenosine A(2A) agonist with known anti-inflammatory properties, was used to test this hypothesis at varied intervals to determine the time course of reperfusion injury. METHODS: Forty rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group (n = 14 animals) received 0.06 microg/kg/min systemic ATL-146e over 3 hours, beginning after 30 minutes of ischemic time. A second group (n = 6 animals) received ATL-146e over 1.5 hours. A third group (n = 3 animals) received ATL-146e over 1 hour, and a fourth group (n = 17 animals) received saline solution. All animals were assessed at 48 hours for hind limb motor function (Tarlov scale, 0-5). RESULTS: Animals that received ATL-146e for 3 hours (Tarlov score, 4.3 +/- 0.22; P <.001) or 1.5 hours (Tarlov score, 2.7 +/- 0.6; P <.05) had improved neurologic outcomes compared with rabbits that received saline solution (Tarlov score, 0.6 +/- 0.29). Animals that received ATL-146e for 1 hour (Tarlov score, 0.7 +/- 0.8) were not significantly different from those animals that received saline solution. CONCLUSIONS: Systemic ATL-146e, given during reperfusion, results in time-dependent improvement in spinal cord function after ischemia. This implies that the mechanism of spinal reperfusion injury includes leukocyte-mediated inflammation at a critical post-ischemic time interval.

Management of innominate artery injury in the setting of bovine arch anomaly.

Blunt injury to the aortic arch vessels is rare and can be life-threatening. Historically urgent repair of these injuries is emphasized. We describe the initial nonoperative management of a blunt injury to the brachiocephalic trunk in the setting of bovine arch anomaly, followed by delayed surgical management.

Pulmonary macrophages are involved in reperfusion injury after lung transplantation.

BACKGROUND: Reperfusion injury is a perplexing cause of early graft failure after lung transplantation. Although recipient neutrophils are thought to have a role in the development of reperfusion injury, some researchers have shown that neutrophils are not involved in its earliest phase. Intrinsic donor pulmonary macrophages may be responsible for this early phase of injury. Using the macrophage inhibitor gadolinium chloride, we attempted to investigate the role of pulmonary macrophages in reperfusion injury after lung transplantation. METHODS: Using our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour storage (4 degrees C) and blood reperfusion for 30 minutes. Group I served as a control. Group II received gadolinium chloride at 7 mg/kg 24 hours before harvest. Group III received gadolinium chloride at 14 mg/kg 24 hours before harvest. RESULTS: Group III had significantly improved arterial oxygenation and pulmonary artery pressures compared with groups I and II after 30 minutes of reperfusion. CONCLUSIONS: The earliest phase of reperfusion injury after lung transplantation involves donor pulmonary macrophages.

When to discontinue extracorporeal membrane oxygenation for postcardiotomy support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has demonstrated limited success in adult postcardiotomy shock. The goal of this study was to determine when to discontinue ECMO for postcardiotomy support. METHODS: During a 7-year period ECMO was used in 51 postcardiotomy patients, of whom 16 (31%) weaned and 8 (16%) survived. RESULTS: Patients in the heart transplant group were more likely to wean compared with patients in the non-heart transplant group (p = 0.03). Patients aged greater than 65 years (p = 0.04) or with ejection fractions of less than 30% after 48 hours of ECMO (p < 0.001) were less likely to wean. Time on ECMO was significantly longer for survivors in the heart transplant group (101.3 +/- 7.5 hours) compared with survivors in the non-heart transplant group (28.3 +/- 11.9 hours, p < 0.001). CONCLUSIONS: After 48 to 72 hours, consideration should be given to discontinuing ECMO, either by moving to an implantable ventricular assist device or by withdrawal of support, except in those patients with heart transplants. In the latter, both severe postoperative pulmonary hypertension and reperfusion injury may take as long as 120 hours to reverse.

Retinoic acid enhances lung growth after pneumonectomy.

BACKGROUND: We sought to identify the role of retinoic acid (RA) upon lung growth. RA has a role in perinatal lung development, and we hypothesized that exogenous RA would enhance postpneumonectomy compensatory lung growth. METHODS: Utilizing the postpneumonectomy rat model, we studied the impact of RA upon contralateral lung growth. Adult Sprague-Dawley rats were divided into three groups. Group S underwent a sham left thoracotomy, group P underwent left pneumonectomy, and group R underwent left pneumonectomy with administration of exogenous RA (0.5 microg/g/day intraperitoneally). We then quantitated right lung growth after 10 and 21 days. Lung weight and volume were expressed as a ratio to the final body weight (lung weight and volume indices, LWI and LVI). Epidermal growth factor receptor (EGFR) expression was quantitated using Western blot analysis. Cellular proliferation index (CPI) was determined using BrdU immunostaining. RESULTS: LWI, LVI, CPI, and EGFR expression at 21 days were significantly higher in group R versus S and P. At the 10-day interval, both LWI and LVI were significantly higher in group R versus S and P. CONCLUSIONS: RA administration markedly enhances lung growth after pneumonectomy, as evidenced by increases in LWI, LVI, and CPI. Upregulation of EGFR expression was associated with these effects.

Cardiac reoperation in the intensive care unit.

BACKGROUND: At our institution, cardiac reoperations are routinely performed in the cardiac intensive care unit, as opposed to taking these patients back to the operating room. Our hypothesis was that reoperation in a cardiac intensive care unit does not increase sternal infection rate. METHODS: A retrospective analysis was performed on 6,908 adult patients undergoing cardiac operation over a 9-year period. Excluding those in cardiac arrest, 340 (4.9%) patients underwent reoperation in the cardiac intensive care unit, of which 289 survived (85%). RESULTS: Of the 289 patients who survived reoperation in the intensive care unit, 6 developed wound infections that required operative debridement (2.1%), which was not significantly different from those patients not requiring reoperation (1.9%, 121 of 6,497, p = 0.70). Hospital charges for a 2-hour reoperation in the intensive care unit and operating room are approximately $1,972/patient and $5,832/patient, respectively. CONCLUSIONS: Reoperation in the intensive care unit does not increase wound infection rate compared to those without reoperation. Decreased charges, avoiding transport of potentially unstable patients, quicker time to intervention, and convenience are advantages of reoperation in an intensive care unit.

Epidermal growth factor receptor up-regulation is associated with lung growth after lobectomy.

BACKGROUND: We hypothesized that compensatory lung growth after lobectomy is characterized by a combination of cellular hyperplasia and hypertrophy and that up-regulation of epidermal growth factor receptor (EGFR) is involved in these processes. METHODS: Age-matched mature pigs were divided into four groups. The control group (group C) did not have operation. Two groups underwent left upper lobectomy and were studied 2 weeks (group L2) or 3 months (group L3) later. The last group underwent a sham left thoracotomy, and the left lower lobe was harvested 2 weeks later for EGFR analysis. Left lower lobes were studied using wet weight, cell proliferation index through immunostaining for 5-bromo-2'-deoxyuridine, morphometry, and Western blot analysis for EGFR. Content of protein and DNA (deoxyribonucleic acid) in the lung tissue was also determined. RESULTS: Left lower lobe weights were elevated in both groups L2 and L3 compared with group C. We noted a significant rise in the proliferation index, with a concomitant increase in EGFR expression, in group L2 compared with group C. In group L3, there was an increase in the protein to DNA ratio compared with group C. CONCLUSIONS: We conclude that compensatory lung growth after lobectomy comprises an early increase in the cell proliferation index (ie, cellular hyperplasia) and a late increase in the protein to DNA ratio (ie, cellular hypertrophy). The early proliferative phase is associated with EGFR up-regulation.

Systemic adenosine A2A agonist ameliorates ischemic reperfusion injury in the rabbit spinal cord.

BACKGROUND: The adenosine A2A agonist ATL-146e (4-[3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxytetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester) has been shown to prevent reperfusion injury in multiple organ systems through inhibition of activated leukocyte-endothelial interaction. We hypothesized that systemic ATL-146e could reduce spinal cord reperfusion injury after aortic clamping. METHODS: Twenty-six rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group received intravenous ATL-146e for 3 hours during reperfusion. A second cohort received only vehicle and served as controls. Animals were assessed at 24 and 48 hours using the Tarlov (0 to 5) scoring system for hind limb function. To evaluate neuronal attrition, immunostaining of lumbar spinal cord sections was performed using anti-SMI 33 antibody against neurofilament. RESULTS: Systemic ATL-146e was tolerated without hemodynamic lability. Animals that received ATL-146e had significantly improved neurologic outcomes 24 and 48 hours after spinal cord ischemia (p < 0.001). There was preservation of neuronal architecture in the ventral horn of spinal cord sections from animals receiving ATL-146e compared with control animals. CONCLUSIONS: Intravenous ATL-146e given during reperfusion is tolerated without hemodynamic lability, and results in substantially improved spinal cord function after ischemia by preservation of ventral horn neurons.

Toxicological and biochemical responses of the earthworm Lumbricus rubellus to pyrene, a non-carcinogenic polycyclic aromatic hydrocarbon.

The effects of the polycyclic aromatic hydrocarbon (PAH) pyrene on earthworms were investigated in contact and soil tests. In addition to measuring toxic effects on survival and reproduction, Ethoxyresorufin-o-deethylase (EROD) activity and catalase activity were also studied as possible biomarkers of toxic stress. The survival data indicated that LC50 values were 0.0068 mg/ml for the contact test, and 283 mg/kg in the soil test. Cocoon production rate was significantly reduced compared to controls at 160, 640 and 2560 mg/kg in the soil test. No EROD activity could be detected in preliminary studies using control and exposed animals from the contact test, so this assay was not used to the soil test. Catalase activity was shown to be significantly lower at 640 mg/kg in the soil test compared to all other treatments and the control. When compared to toxicological data for other soil invertebrates, Lumbricus rubellus has an intermediate sensitivity in respects of survival and a lower sensitivity for reproductive effects, although the soil used in this study had a higher organic content than previous studies, meaning that the sensitivity of this species may be underestimated in comparison to previous published data for other soil invertebrates.

Polyarteritis nodosa presenting as acute blindness.

Polyarteritis nodosa is a vasculitic disease commonly involving coronary arteries, mesenteric arteries, kidneys, muscles, and vasa nervorum. Central nervous system involvement in polyarteritis nodosa is unusual and tends to occur later in the course of disease. We report the case of a 23-year-old woman who presented to our emergency department with acute loss of vision. Her evaluation led to a diagnosis of polyarteritis nodosa. We present what may be the first published case report of polyarteritis nodosa presenting as acute bilateral visual loss.

Trends in indigenous foodborne disease and deaths, England and Wales: 1992 to 2000.

BACKGROUND: Commitment to food safety is evidenced by high profile governmental initiatives around the globe. To measure progress towards targets, policy makers need to know the baseline from which they started. AIM: To describe the burden (mortality, morbidity, new presentations to general practice, hospital admissions, and hospital occupancy) and trends of indigenous foodborne disease (IFD) in England and Wales between 1992 and 2000. METHODS: Routinely available surveillance data, special survey data, and hospital episode statistics were collated and arithmetic employed to estimate the burden and trends of IFD in England and Wales. Adjustments were made for underascertainment of disease through national surveillance and for foreign travel. The final estimates were compared with those from the USA. RESULTS: In 1995 there were an estimated 2,365,909 cases, 21,138 hospital admissions, and 718 deaths in England and Wales due to IFD. By 2000 this had fallen to 1,338,772 cases, 20,759 hospital admissions, and 480 deaths. In terms of disease burden the most important pathogens were campylobacters, salmonellas, Clostridium perfringens, verocytotoxin producing Escherichia coli (VTEC) O157, and Listeria monocytogenes. The ratio of food related illness in the USA to IFD in England and Wales in 2000 was 57:1. Taking into account population rates, this ratio fell to 11:1 and converged when aetiology and disease severity were considered. CONCLUSION: Reducing IFD in England and Wales means tackling campylobacter. Lowering mortality rates however also requires better control and prevention of salmonellas, Cl perfringens, L monocytogenes, and VTEC O157.

General outbreaks of infectious intestinal disease linked with salad vegetables and fruit, England and Wales, 1992-2000.

Between 1992 and 2000, 1,518 foodborne general outbreaks of infectious intestinal disease (IID) were reported to the Public Health Laboratory Service (PHLS) Communicable Disease Surveillance Centre (CDSC), of which 83 (5.5%) were associated with the consumption of salad vegetables or fruit (SVF). The pathogens most frequently reported were salmonellas (41.0%) and Norwalk-like virus (NLV) (15.7%). In total 3,438 people were affected; 69 were admitted to hospital and one person died. Most outbreaks were linked to commercial catering premises (67.5%). Three community outbreaks, of Salmonella enterica serovar Typhimurium Definitive Phage Type (DT) 104, S. Typhimurium DT 204b and Shigella sonnei infection, were found to be associated with lettuce contaminated at source, and these accounted for 501 (14.6%) cases. The latter two outbreaks were international, involving several European countries. This demonstrates how contamination of SVF during production/processing can result in major, geographically widespread, outbreaks of infection with serious public health consequences.

Role of thyroid hormones in hepatic effects of peroxisome proliferators.

Peroxisome proliferators are endocrine disrupting chemicals that cause liver tumors in rodents but not humans. Although the receptor that mediates key hepatic effects, the peroxisome proliferator-activated receptor alpha (PPAR-alpha), and its endogenous ligands have been identified, the mechanism whereby these commonly used chemicals cause liver tumors in rodents has yet to be elucidated. Species differences in PPAR-alpha and DNA response elements may explain some of the variability in response upon exposure to peroxisome proliferators. The possibility that thyroid-modulating effects of peroxisome proliferators may contribute to the hepatic effects of peroxisome proliferators has yet to be fully explored. When the potent peroxisome proliferator, WY-14,643, was given to hypothyroid rats, there was a blunting of the hepatomegaly and hepatocyte proliferative responses seen in thyroid-intact animals. Acyl-CoA oxidase activity was unaltered by changes in thyroid hormone status. In addition, preliminary evidence indicates that peroxisome proliferators increased hepatic thyroid receptor (TRalpha1) expression, but TRalpha1 levels in liver tumors were similar to those in unexposed animals. Significant differences between humans and rodents with respect to thyroid hormone physiology and metabolism, in conjunction with the results of these studies, may be indicative of yet another mechanism to explain differential sensitivity to hepatic effects of peroxisome proliferators.

A technique for the treatment of sternal infections using the Vacuum Assisted Closure device.

BACKGROUND: Sternal infections after median sternotomy remain a serious cause of postoperative morbidity and mortality. The treatment of sternal infections has evolved over the past few decades, and now aggressive surgical debridement with rotational muscle flap closure has provided an acceptable means of managing this complication. However, there are several disadvantages with this approach, mainly related to the morbidity associated with serial debridements with dressing changes and open packing until the wound is closed. Other disadvantages include potential morbidity and mortality associated with the shearing forces between the beating heart and the debrided sternal edges, and the need to paralyze the patient during the period after debridement. METHODS: Our method of managing sternal infections is based on the triad of prompt surgical debridement, serial quantitative wound cultures, and the use of the Vacuum Assisted Closure (VAC) device (KCI International, San Antonio, TX). Following debridement and irrigation, a biopsy of the healthy appearing bone is sent for quantitative culture. If culture results are favorable, the wound is then fitted with the VAC device, which consists of a non-collapsible, open-cell, polyurethane sponge with embedded vacuum tubing, a vacuum pump, and transparent adhesive dressing. When systemic signs of infection and quantitative cultures indicate the resolution of the local infection, regional muscle flap or primary wound closure is performed. CONCLUSIONS: The VAC serves as a bridge to sternal wound closure and is a safe and effective therapeutic strategy for patients with impaired physiologic reserve and/or highly contaminated wounds. We feel that it is also reasonable to consider the VAC as a preventive strategy against right ventricular rupture. Furthermore, because the firmness of the vacuum sponge apparatus acts as an impressive sternal stabilizer, post-debridement extubation is possible, reducing the need for prolonged paralysis and mechanical ventilation. This stabilization also allows early postoperative ambulation with the VAC in place. In summary, we believe that the VAC device offers an effective means of managing patients with sternal infections.

A technique for adequate coverage of the proximal suture line during abdominal aortic aneurysm repair.

The proximal suture line is a vulnerable area after abdominal aortic aneurysm repairs. This area has been implicated in various postoperative complications, such as pseudoaneurysm formation, graft-enteric fistula, and suture line disruption. We present a technique that provides safe and adequate coverage of this suture line by using the aneurysm sac. This technique is derived from the z-plasty technique used for scar revision. The technique is illustrated with detailed line drawings. None of the patients in whom we used this technique have had any complications related to the proximal suture line.