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ABSTRACT: There are several adult studies using computed tomography (CT-scan) to examine lung aeration changes during or after a recruitment maneuver (RM) in ventilated patients with acute lung injury (ALI). However, there are no published data on the lung aeration changes during or after a RM in ventilated pediatric patients with ALI.
To describe CT-scan lung aeration changes and gas exchange after lung recruitment in pediatric ALI and assess the safety of transporting patients in the acute phase of ALI to the CT-scanner.
We present a case series completed in a subset of six patients enrolled in our previously published study of efficacy and safety of lung recruitment in pediatric patients with ALI. Intervention: RM using incremental positive end-expiratory pressure.
There was a variable increase in aerated and poorly aerated lung after the RM ranging from 3% to 72% (median 20%; interquartile range 6, 47; P = 0.03). All patients had improvement in the ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (PaO(2) /FiO(2)) after the RM (median 14%; interquartile range: 8, 72; P = 0.03). There was a decrease in the partial pressure of arterial carbon dioxide (PaCO(2)) in four of six subjects after the RM (median -5%; interquartile range: -9, 2; P = 0.5). One subject had transient hypercapnia (41% increase in PaCO(2)) during the RM and this correlated with the smallest increase (3%) in aerated and poorly aerated lung. All patients tolerated the RM without hemodynamic compromise, barotrauma, hypoxemia, or dysrhythmias.
Lung recruitment results in improved lung aeration as detected by lung tomography. This is accompanied by improvements in oxygenation and ventilation. However, the clinical significance of these findings is uncertain. Transporting patients in early ALI to the CT-scanner seems safe and feasible.
Pediatric Pulmonology 02/2012; 47(8):771-9. · 2.53 Impact Factor
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Kirsten Neudoerffer Kangelaris, Anil Sapru,
Carolyn S Calfee,
Kathleen D Liu,
Ludmila Pawlikowska,
John S Witte,
Eric Vittinghoff,
Hanjing Zhuo,
Andrew D Auerbach,
Elad Ziv,
Michael A Matthay
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ABSTRACT: Acute lung injury (ALI) mortality is increased among African Americans compared with Americans of European descent, and genetic factors may be involved. A functional T-46C polymorphism (rs2814778) in the promoter region of Duffy antigen/receptor for chemokines (Darc) gene, present almost exclusively in people of African descent, results in isolated erythrocyte DARC deficiency and has been implicated in ALI pathogenesis in preclinical and murine models, possibly because of an increase in circulating Duffy-binding, proinflammatory chemokines like IL-8. We sought to determine the effect of the functional rs2814778 polymorphism, C/C genotype (Duffy null state), on clinical outcomes in African Americans with acute lung injury.
Clinical data and biologic specimens from African American patients with ALI who enrolled in three randomized controlled trials were analyzed. Multivariate analysis accounted for proportion of African ancestry, sex, cirrhosis, and severity of illness on presentation.
Among 132 subjects, 88 (67%) were Duffy null (C/C genotype). The Duffy null state was associated with a 17% absolute risk increase (95% CI, 1.4%-33%) in mortality at 60 days, a median of 8 fewer ventilator-free days (95% CI, 1-18.5), and 4.5 fewer organ failure-free days (95% CI, 0-18) compared with individuals with the C/T or T/T genotypes (all P values < .05). Estimates were similar on multivariate analysis. In African Americans without the null variant, clinical outcomes were similar to those in patients of European descent. A subgroup analysis suggested that plasma IL-8 levels are increased in Duffy null individuals.
Our results provide evidence that the functional rs2814778 polymorphism in the gene encoding DARC is associated with worse clinical outcomes among African Americans with ALI, possibly via an increase in circulating IL-8.
Chest 12/2011; 141(5):1160-9. · 5.25 Impact Factor
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ABSTRACT: Left ventricular outflow tract obstruction (LVOTO) is caused by a spectrum of lesions. This study was performed to determine the outcomes of surgical management of LVOTO.
All patients who had surgery of the LVOT between 2002 and 2010 were retrospectively reviewed.
There were 103 consecutive patients with median age 6.8 years (range 8 days to 62 years). Fourteen patients had simple subaortic membrane. Eighty-nine patients had complex LVOTO including fibromuscular obstruction (n = 53), tunnel obstruction (n = 22), hypertrophic cardiomyopathy/muscular obstruction (n = 15), and anomalies of the mitral subvalvar apparatus (n = 13). There were no early deaths. Mean LVOT gradient decreased from 33 mmHg (range 1 to 108 mmHg) to 6 mmHg (range 0 to 45 mmHg) (p < 0.001). Median follow-up was 3.8 years (range 0.9 to 8.5 years). There were three late deaths. Cumulative survival at one, three, and five years was 96% (95% CI 89% to 99%). All patients are in New York Heart Association classes I-II. Ten patients required reoperation (three for recurrent/residual LVOTO). Freedom from reoperation was 94%, 90%, and 78% at one, three, and five years (95% CI 86% to 98%, 80% to 95%, and 59% to 89%, respectively). No patient with complex LVOTO who had release of the fibrous trigones required reoperation [0% (0/26) vs. 16% (10/63) (p = 0.031)]. Factors associated with increased reoperation risk were interrupted aortic arch (OR 6.4, p = 0.22), atrioventricular septal defect (OR 15.4, p = 0.008), and higher mean LVOT gradient at discharge (OR 1.08, p = 0.023).
Utilizing a multitude of operative strategies for surgery of the LVOT results in favorable early and midterm outcomes. Residual LVOTO and original cardiac diagnosis are associated with increased reoperation risk. Release of the fibrous trigones decreases reoperation risk in patients with complex LVOTO.
Journal of Cardiac Surgery 12/2011; 27(1):103-11. · 0.87 Impact Factor
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ABSTRACT: The "sutureless" repair technique has improved outcomes for post-repair pulmonary vein (PV) stenosis. The purpose of this study is to determine the early outcomes of primary sutureless repair of pulmonary venoocclusive disease in infants with congenital PV stenosis-hypoplasia or PVs at high risk for progressive stenosis.
This is a retrospective review of infants who had primary sutureless repair of the PVs from October 2002 to April 2010.
Twenty-five infants had primary sutureless repair of the PVs. Eighteen infants had total anomalous pulmonary venous return; 14 with obstruction, 10 with heterotaxy syndrome, and 9 with univentricular anatomy. Seven infants had congenital PV stenosis. There were 24 perioperative survivors (96%; 95% confidence interval [CI], 75% to 99%) and 2 late deaths from extracardiac causes. Follow-up was available on 21 out of 22 survivors at a median duration of 34 months (range, 9 to 100 months). Persistence-recurrence of PV stenosis occurred in 3 veins (3%) of 2 infants (8%). On follow-up echocardiography, right ventricular systolic pressure was normal in 13 out of 14 infants with a biventricular heart and 60% of systemic blood pressure in 1 infant. Kaplan-Meier 1-year cumulative survival was 88% (95% CI, 66% to 96%). Kaplan-Meier cumulative disease-free survival was 96% (95% CI, 75% to 99%) at 30 days and 84% (95% CI, 58% to 95%) at 1 year. By Cox proportional hazards, age, univentricular anatomy, and atrial isomerism-heterotaxy syndrome were not associated with an increased risk of death or persistence-recurrence. One-year disease-free survival was lower in infants with prematurity (p=0.0055) and low birth weight (p=0.0011).
Primary sutureless repair is a feasible, safe, and relatively effective method of addressing congenital PV stenosis and (or) high-risk PVs, particularly in infants with single ventricle anatomy and (or) heterotaxy syndrome.
The Annals of thoracic surgery 06/2011; 92(2):666-71; discussion 671-2. · 3.74 Impact Factor
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ABSTRACT: A modification of the Fontan operation was recently applied, which includes anastomoses of the extracardiac conduit to the right pulmonary artery and inferior vena cava using simple clamping with no additional circulatory support, venous shunting, pulmonary artery preparation, or prior maintenance of azygos vein patency. The objective of this study is to assess the outcomes of this novel off-pump "clamp and sew" Fontan procedure.
This is a retrospective review of all patients having a Fontan procedure between January 2009 and October 2010 at a single institution.
Twelve patients had a Fontan procedure with the use of cardiopulmonary bypass (CPB group), and 12 had an off-pump Fontan procedure (off-pump group). Preoperative demographic and hemodynamic data were similar except for higher mean pulmonary artery pressure in the CPB group (12.2±1.6 mm Hg versus 9.9±2.4 mm Hg; p=0.02). No patients in the off-pump group required conversion to CPB. The mean inferior vena cava clamp time in the off-pump group patients was 10±3 minutes. There were no early or midterm deaths. No patients exhibited postoperative hepatic or renal dysfunction. Postoperative maximal serum creatinine and aspartate transaminase were significantly lower in the off-pump group compared with the CPB group (0.59±0.12 versus 0.77±0.22 mg/dL; p=0.03 and 35.5±8.3 versus 53.1±19.0 U/L; p=0.02, respectively). At median follow-up of 13 months (range, 1 to 20 months), all but 1 patient in the CPB group are in New York Heart Association class I with unobstructed Fontan circulation.
The clamp and sew technique for completion of an extracardiac conduit Fontan procedure appears safe and feasible for selected patients.
The Annals of thoracic surgery 05/2011; 91(5):1453-9. · 3.74 Impact Factor
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Anil Sapru,
Ludmila Pawlikowska,
Kathleen D Liu,
Kiran K Khush,
Lee Ann-Baxter-Lowe,
Vanessa Hayden,
Rebecca L Menza,
Maureen Convery,
Annie Poon,
Megan Landeck,
Jonathan G Zaroff,
Michael A Matthay
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ABSTRACT: Pulmonary edema and associated impaired oxygenation are a major reason for rejection of donor lung allografts offered for transplantation. Clearance of pulmonary edema can be upregulated by stimulation of β-adrenergic receptors (βARs). Single-nucleotide polymorphisms (SNPs) in βAR genes have functional effects in vitro and in vivo. We hypothesized that SNPs in βAR genes would be associated with rates of utilization of donor lung allografts offered for transplantation.
Nine hundred fifty-one organ donors were genotyped for 4 amino-acid-coding SNPs in the βAR genes. Lung allograft utilization was compared among donors stratified by genotypes.
Utilization of donor lung allografts was 55% vs 35% (p = 0.02) among donors with GG vs AA/AG genotypes of the Ser49Gly SNP, 39% vs 32% (p = 0.04) with GG vs AA/AG genotype of Gly16Arg SNP and 37% vs 32% (p = 0.1) with CC vs GC/GG genotype of the Arg389Gly SNP. In the combined analysis, donors carrying 0 or 1 associated genotype had a utilization rate of 33%, whereas donors carrying 2 or 3 associated genotypes had utilization rates of 44% and 58%, respectively (p = 0.008). There was a stepwise decrease in chest radiograph infiltrates and an increase in partial pressure of oxygen/fraction of inspired oxygen (PaO(2)/FIO(2)) with an increasing number of these associated genotypes.
Genetic variants in the βAR genes among organ donors are associated with higher rates of lung allograft utilization. The increased utilization may be related to increased clearance of pulmonary edema and improved oxygenation in donors with favorable genotypes and suggests that βAR agonists may have a role in donor management.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 02/2011; 30(2):211-7. · 3.54 Impact Factor
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ABSTRACT: Bidirectional cavopulmonary anastomosis has been performed without cardiopulmonary bypass for some single-ventricle heart defects. Limited data are available for the outcomes of off-pump bidirectional cavopulmonary anastomosis in infants with hypoplastic left heart syndrome. The purpose of this study is to determine the early outcomes for stage II palliation of hypoplastic left heart syndrome without cardiopulmonary bypass.
This is a retrospective review of infants having surgical palliation of hypoplastic left heart syndrome from April 2003 to March 2010 at a single institution.
Seventy-five infants had a modified Norwood procedure, 65 with a right ventricle-pulmonary artery conduit, 10 with an aortopulmonary shunt, 2 with atrioventricular valve repair, and 3 with extracorporeal life support. Sixty-eight patients had hypoplastic left heart syndrome or one of its variants, and 7 had other single-ventricle lesions. There were 2 stage I deaths. Stage I survival was 97% (95% confidence interval, 88%-99%). Another 5 infants succumbed in the interstage period. Of the 68 stage I and interstage survivors, 61 had bidirectional cavopulmonary anastomoses, 20 without cardiopulmonary bypass. Median age was 6 months (range, 4-13 months), and median weight was 6.1 kg (range, 5.2-9.0 kg). There were no conversions to cardiopulmonary bypass when off-pump bidirectional cavopulmonary anastomosis was attempted. There were no hospital deaths. Median ventilation duration was 10 hours (range, 6-18 hours), and length of stay was 5 days (range, 4-9 days). Follow-up was available on all infants at a median duration of 17 months (range, 3-43 months), with no unplanned reinterventions.
Bidirectional cavopulmonary anastomosis without the use of cardiopulmonary bypass can be performed safely and with low mortality for selected infants with hypoplastic left heart syndrome. Midterm to long-term outcomes remain to be determined.
The Journal of thoracic and cardiovascular surgery 02/2011; 141(2):400-6. · 3.41 Impact Factor
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ABSTRACT: Low birth weight (LBW) is a risk factor for mortality in neonatal and infant heart surgery. The purpose of this study was to determine the contemporary outcomes and risk factors of cardiac surgery in low weight babies. The records of 75 consecutive infants weighing <2.5 kg having heart surgery were reviewed. The median weight was 2100 g (range 800-2500 g) and median age was 11 days (range 2-86 days). Half (n=38) of the infants were premature. Diagnoses included: arch obstruction (n=14), hypoplastic left heart syndrome (HLHS) (n=12), tetralogy of Fallot (ToF) or pulmonary atresia (PA)/ventricular septal defect (VSD) (n=11), transposition of the great arteries (TGA) (n=7), total anomalous pulmonary venous return (TAPVR) (n=5), and other (n=20). There were two early deaths. Follow-up was available on all infants with a median duration of 1320 days (range 6-3055 days). Cumulative Kaplan-Meier survival at one year was 90% [95% confidence interval (CI), 80-95%] and at five years was 88% (95% CI, 77-94%). Overall mortality amongst patients with genetic/chromosomal abnormalities was higher, 28% vs. 5.4% amongst patients without such abnormalities (P=0.008). Age, prematurity, preoperative mechanical ventilation, prostaglandins, non-cardiac organ dysfunction, extra-cardiac malformations, perioperative extracorporeal membrane oxygenation (ECMO), and type of procedure were not associated with significant differences in mortality. Cardiac surgery in LBW infants can be performed with low early and mid-term mortality. LBW infants with chromosomal/genetic anomalies have a higher risk.
Interactive cardiovascular and thoracic surgery 11/2010; 12(3):409-13, discussion 414.
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ABSTRACT: To assess the safety and efficacy of a recruitment maneuver, the Open Lung Tool, in pediatric patients with acute lung injury and acute respiratory distress syndrome.
Prospective cohort study using a repeated-measures design.
Pediatric intensive care unit at an urban tertiary children's hospital.
Twenty-one ventilated pediatric patients with acute lung injury.
Recruitment maneuver using incremental positive end-expiratory pressure.
The ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (Pao2/Fio2 ratio) increased 53% immediately after the recruitment maneuver. The median Pao2/Fio2 ratio increased from 111 (interquartile range, 73-266) prerecruitment maneuver to 170 (interquartile range, 102-341) immediately postrecruitment maneuver (p < .01). Improvement in Pao2/Fio2 ratio persisted with an increase of 80% over the baseline at 4 hrs and 40% at 12 hrs after the recruitment maneuver. The median Pao2/Fio2 ratio was 200 (interquartile range, 116-257) 4 hrs postrecruitment maneuver (p < .05) and 156 (interquartile range, 127-236) 12 hrs postrecruitment maneuver (p < .01). Compared with prerecruitment maneuver, the partial pressure of arterial carbon dioxide (Paco2) was significantly decreased at 4 hrs postrecruitment maneuver but not immediately after the recruitment maneuver. The median Paco2 was 49 torr (interquartile range, 44-60) prerecruitment maneuver compared with 48 torr (interquartile range, 43-50) immediately postrecruitment maneuver (p = .69), 45 torr (interquartile range, 41-50) at 4 hrs postrecruitment maneuver (p < .01), and 43 torr (interquartile range, 38-51) at 12 hrs postrecruitment maneuver. Recruitment maneuvers were well tolerated except for significant increase in Paco2 in three patients. There were no serious adverse events related to the recruitment maneuver.
Using the modified open lung tool recruitment maneuver, pediatric patients with acute lung injury may safely achieve improved oxygenation and ventilation with these benefits potentially lasting up to 12 hrs postrecruitment maneuver.
Pediatric Critical Care Medicine 11/2010; 12(4):431-6. · 3.13 Impact Factor
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ABSTRACT: The purpose of this study is to determine the outcome and performance of bovine pericardial valves in the pulmonary position.
This is a retrospective review of all patients with congenital heart disease who had pulmonary valve replacement using a bovine pericardial valve from 2002 to 2009 at a single institution.
There were 73 consecutive patients, with a median age of 17.3 years (range, 2.1 to 64.4). Their diagnosis was tetralogy of Fallot (n = 47), pulmonary stenosis (n = 11), or other (n = 15). Sixty-nine patients had 91 previous surgical procedures. The mean time from last surgery was 19.9 ± 11.6 years. Forty-three patients had concomitant surgical procedures. There were no perioperative deaths. Clinical follow-up was available in 68 patients (93%). There were no late deaths, and all patients were in New York Heart Association functional class I during a median follow-up period of 2.6 years (range, 0.2 to 8.0). One patient had endocarditis necessitating valve removal 2 years after surgery. Freedom from pulmonary valve reoperation was 100%, 97.7%, and 97.7% at 1, 3, and 5 years, respectively (95% confidence interval: 93.2% to 100%). Mean pulmonary valve gradient at follow-up was 19 ± 14 mm Hg. Degree of pulmonary insufficiency was less than moderate in 62 patients, moderate in 4, and more than moderate in 2. Freedom from moderate-severe or severe pulmonary insufficiency was 97.7%, 89.1%, and 89.1% at 1, 3, and 5 years, respectively (5-year 95% confidence interval: 77.0% to 100%).
Pulmonary valve replacement using a bovine pericardial valve can be accomplished with low perioperative morbidity and favorable midterm outcomes. Further follow-up is necessary to evaluate the long-term performance of bovine pericardial valves in the pulmonary position.
The Annals of thoracic surgery 10/2010; 90(4):1295-300. · 3.74 Impact Factor
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ABSTRACT: Deposition of fibrin in the alveolar space is a hallmark of acute lung injury (ALI). Plasminogen activator inhibitor-1 (PAI-1) is an antifibrinolytic agent that is activated during inflammation. Increased plasma and pulmonary edema fluid levels of PAI-1 are associated with increased mortality in adults with ALI. This relationship has not been examined in children. The objective of this study was to test whether increased plasma PAI-1 levels are associated with worse clinical outcomes in pediatric patients with ALI.
We measured plasma PAI-1 levels on the first day of ALI among 94 pediatric patients enrolled in two separate prospective, multicenter investigations and followed them for clinical outcomes. All patients met American European Consensus Conference criteria for ALI.
A total of 94 patients were included. The median age was 3.2 years (range 16 days-18 years), the PaO(2)/F(i)O(2) was 141 +/- 72 (mean +/- SD), and overall mortality was 14/94 (15%). PAI-1 levels were significantly higher in nonsurvivors compared to survivors (P < 0.01). The adjusted odds of mortality doubled for every log increase in the level of plasma PAI-1 after adjustment for age and severity of illness.
Higher PAI-1 levels are associated with increased mortality and fewer ventilator-free days among pediatric patients with ALI. These findings suggest that impaired fibrinolysis may play a role in the pathogenesis of ALI in pediatric patients and suggest that PAI-1 may serve as a useful biomarker of prognosis in patients with ALI.
European Journal of Intensive Care Medicine 10/2009; 36(1):157-63. · 5.17 Impact Factor
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ABSTRACT: Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia.
The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination.
A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype.
The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia.
Anesthesiology 06/2009; 110(5):1086-91. · 5.36 Impact Factor
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ABSTRACT: Clinical study to determine the acceptability and feasibility of acupuncture for acute postoperative pain control in hospitalized children.
Nonrandomized clinical trial.
A single, tertiary referral pediatric intensive care unit.
A total of 20 patients aged 7 months to 18 years. Eleven of the patients had posterior spinal fusion surgery and the remaining nine patients had other surgical diagnoses.
Two 10- to 15-minute sessions of acupuncture 24-48 hours apart.
The treatment was highly accepted (27 patients were approached and 4 patients refused; of the 23 patients enrolled, 20 patients completed the study). Acupuncture was well tolerated by patients without adverse events related to treatment. In follow-up interviews, 70% of both parents and patients believed acupuncture helped the child's pain. Eighty-five percent of the parents said they would pay out of pocket for acupuncture if not covered by insurance. The pain scores, vital signs, and narcotic usage were recorded before and several times after acupuncture. In posterior spinal fusion patients, the mean pain scores (0-10) immediately before and 4 and 24 hours after acupuncture were: 3.7, 1.7, and 3.1, respectively, after the first acupuncture session and 3.7, 2.2, and 3.1, respectively, after the second session. In the other surgical cohort, the mean pain scores immediately before and 4 and 24 hours after the first session of acupuncture were 2.5, 0.3, and 1.6, respectively.
Our results support that acupuncture is highly accepted and feasible in critically ill, postoperative pediatric patients with acute pain. Our findings suggest that acupuncture may be a potentially useful adjunctive tool for acute pediatric postoperative pain management. A randomized, controlled clinical trial is warranted to confirm these findings.
Pediatric Critical Care Medicine 03/2009; 10(3):291-6. · 3.13 Impact Factor
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Jan Hirsch,
Claus U Niemann,
Kirk C Hansen,
SooJinNa Choi,
Xiao Su,
James A Frank,
Xiaohui Fang,
Ryutaro Hirose,
Pierre Theodore, Anil Sapru,
Alma L Burlingame,
Michael A Matthay
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ABSTRACT: Hepatic ischemia-reperfusion can be associated with acute lung injury. Alveolar epithelial type II cells (ATII) play an important role in maintaining lung homeostasis in acute lung injury.
To study potentially new mechanisms of hepatic ischemia-reperfusion-induced lung injury, we examined how liver ischemia-reperfusion altered the proteome of ATII.
Laboratory investigation.
Spontaneously breathing male Zucker rats.
Rats were anesthetized with isoflurane. The vascular supply to the left and medial lobe of the liver was clamped for 75 mins and then reperfused. Sham-operated rats were used as controls. After 8 hrs, rats were killed.
Bronchoalveolar lavage and differential cell counts were performed, and tumor necrosis factor-alpha and cytokine-induced neutrophil chemotactic factor-1 in plasma were determined by enzyme-linked immunosorbent assay. ATII were isolated, lysed, tryptically digested, and labeled using isobaric tags (iTRAQ). The samples were fractionated by cation exchange chromatography, separated by high-performance liquid-chromatography, and identified using electrospray tandem mass spectrometry. Spectra were interrogated and quantified using ProteinProspector. Quantitative proteomics provided quantitative data for 94 and 97 proteins in the two groups. Significant changes in ATII protein content included 30% to 40% increases in adenosine triphosphate synthases, adenosine triphosphate/adenosine diphosphate translocase, and catalase (all p < .001). Following liver ischemia-reperfusion, there was also a significant increase in the percentage of neutrophils in bronchoalveolar lavage (48% +/- 26%) compared with sham-operated controls (5% +/- 3%) (p < .01), and plasma tumor necrosis factor-alpha levels were also significantly increased.
The proteins identified by quantitative proteomics indicated significant changes in moderators of cell metabolism and host defense in ATII. These findings provide new insights into possible mechanisms responsible for hepatic ischemia-reperfusion-related acute lung injury and suggest that ATII cells in the lung sense and respond to hepatic injury.
Critical care medicine 06/2008; 36(6):1846-54. · 6.37 Impact Factor
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ABSTRACT: Mechanical ventilation with high tidal volumes leads to increased permeability, generation of inflammatory mediators, and damage to alveolar epithelial cells (ATII).
To identify changes in the ATII proteome after two different ventilation strategies in rats.
Rats (n = 6) were ventilated for 5 hours with high- and low tidal volumes (VTs) (high VT: 20 ml/kg; low VT: 6 ml/kg). Pooled nonventilated rats served as control animals. ATII cells were isolated and lysed, and proteins were tryptically cleaved into peptides. Cellular protein content was evaluated by peptide labeling of the ventilated groups with (18)O. Samples were fractionated by cation exchange chromatography and identified using electrospray tandem mass spectrometry. Proteins identified by 15 or more peptides were statistically compared using t tests corrected for the false discovery rate.
High Vt resulted in a significant increase in airspace neutrophils without an increase in extravascular lung water. Compared with low-VT samples, high-VT samples showed a 32% decrease in the inositol 1,4,5-trisphosphate 3 receptor (p < 0.01), a 34% decrease in Na(+), K(+)-ATPase (p < 0.01), and a significantly decreased content in ATP synthase chains. Even low-VT samples displayed significant changes, including a 66% decrease in heat shock protein 90-beta (p < 0.01) and a 67% increase in mitochondrial pyruvate carboxylase (p < 0.01). Significant differences were found in membrane, acute phase, structural, and mitochondrial proteins.
After short-term exposure to high-VT ventilation, significant reductions in membrane receptors, ion channel proteins, enzymes of the mitochondrial energy system, and structural proteins in ATII cells were present. The data supports the two-hit concept that an unfavorable ventilatory strategy may make the lung more vulnerable to an additional insult.
American Journal of Respiratory and Critical Care Medicine 06/2007; 175(10):1006-13. · 11.08 Impact Factor
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ABSTRACT: There is evidence that dysregulation of coagulation and fibrinolysis may participate in the pathogenesis of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Altered concentrations of several proteins of the coagulation and fibrinolytic pathways in plasma and pulmonary edema fluid from patients with acute lung injury have been related to the severity of lung injury and clinical outcomes. Polymorphisms in the genes encoding for proteins of the protein C and fibrinolysis pathways are known to regulate the production of the respective proteins. It is plausible that these polymorphisms may be associated with the susceptibility to and severity of illness in ALI and ARDS. Well-designed studies that examine the association of these polymorphisms with susceptibility and severity of ALI and ARDS are needed to test the influence of both genetic and environmental factors on the clinical outcomes in patients with ALI and ARDS. There are several important considerations in the design of these genetic association studies, including selection of candidate genes with the most biological plausibility, definition of the phenotype, selection of appropriate controls, determination of the appropriate sample size and assessment of Hardy-Weinberg equilibrium among controls as a measure of internal validity.
Intensive Care Medicine 10/2006; 32(9):1293-303. · 5.40 Impact Factor
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ABSTRACT: B-type natriuretic peptide, a cardiac hormone with diuretic, natriuretic, and vasoactive properties, is used in the diagnosis, risk stratification, and management of adult cardiac patients. However, no study has yet determined the prognostic value of B-type natriuretic peptide after surgical intervention for congenital heart disease. The objectives of this study were (1) to determine alterations in B-type natriuretic peptide levels after repair of congenital heart disease with cardiopulmonary bypass and (2) to investigate potential associations between B-type natriuretic peptide levels and outcomes in this patient population.
Fifty-one infants and children undergoing repair of congenital heart disease were studied. B-type natriuretic peptide levels were measured before and after surgical intervention, and the ability of the postoperative 12-hour B-type natriuretic peptide level to predict postoperative outcomes was evaluated.
B-type natriuretic peptide levels increased after separation from cardiopulmonary bypass, with an 8-fold peak increase at 12 hours (P < .005). Postoperative 12-hour B-type natriuretic peptide levels were associated with the duration of mechanical ventilation and the presence of a low cardiac output state after surgical intervention. On multivariate analysis, the 12-hour B-type natriuretic peptide level was an independent predictor of the duration of mechanical ventilation. In fact, B-type natriuretic peptide levels of greater than 540 pg/mL predicted mechanical ventilation beyond 48 hours, with a sensitivity of 88.9% and a specificity of 82.5%. In addition, B-type natriuretic peptide levels of greater than 815 pg/mL predicted the presence of a low cardiac output state within 48 hours after surgical intervention, with a sensitivity of 87.5% and a specificity of 90.2%.
B-type natriuretic peptide determinations might be a useful tool for clinicians caring for infants and children after surgical intervention for congenital heart disease.
The Journal of thoracic and cardiovascular surgery 03/2006; 131(3):632-8. · 3.41 Impact Factor
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ABSTRACT: Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute lung injury (ALI). The low tidal volume lung-protective ventilation strategy is associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy. The primary objective of this study was to test whether the institution of lung-protective positive pressure ventilation in spontaneously ventilating patients with ALI exacerbates pre-existing lung injury by using measurements of biomarkers of lung injury before and after intubation.
A prospective observational cohort study was conducted in the intensive care unit of a tertiary care university hospital. Twenty-five intubated, mechanically ventilated patients with ALI were enrolled. Physiologic data and serum samples were collected within 6 hours before intubation and at two different time points within the first 24 hours after intubation to measure the concentration of interleukin (IL)-6, IL-8, intercellular adhesion molecule 1 (ICAM-1), and von Willebrand factor (vWF). The differences in biomarker levels before and after intubation were analysed using repeated measures analysis of variance and a paired t test with correction for multiple comparisons.
Before endotracheal intubation, all of the biological markers (IL-8, IL-6, ICAM-1, and vWF) were elevated in the spontaneously breathing patients with ALI. After intubation and the institution of positive pressure ventilation (tidal volume 7 to 8 ml/kg per ideal body weight), none of the biological markers was significantly increased at either an early (3 +/- 2 hours) or later (21 +/- 5 hours) time point. However, the levels of IL-8 were significantly decreased at the later time point (21 +/- 5 hours) after intubation. During the 24-hour period after intubation, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio significantly increased and the plateau airway pressure significantly decreased.
Levels of IL-8, IL-6, vWF, and ICAM-1 are elevated in spontaneously ventilating patients with ALI prior to endotracheal intubation. The institution of a lung-protective ventilation strategy with positive pressure ventilation does not further increase the levels of biological markers of lung injury. The results suggest that the institution of a lung-protective positive pressure ventilation strategy does not worsen the pre-existing lung injury in most patients with ALI.
Critical care (London, England) 02/2006; 10(5):R126. · 4.61 Impact Factor
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ABSTRACT: To estimate the prevalence of type 2 diabetes mellitus (DM2) in 9-18 year-old children with diabetic ketoacidosis (DKA) and to describe the presenting biochemical characteristics and response to standardized DKA treatment.
Data were collected from a consecutive sample of 9-18 year-old children presenting with DKA. DKA was defined as hyperglycemia and ketosis with an initial pH <7.3, or bicarbonate <15 mmol/l. Patients were classified as having DM2 if they had negative autoantibody status and normal or elevated fasting C-peptide.
The prevalence of DM2 in patients with DKA was 13.0% (6.1-23.3%). There was no significant difference in the presenting pH (7.14 vs 7.15), but blood glucose was higher (735 vs 587 mg/dl) in patients with DM2, than in patients with type 1 DM (DM1). The duration of insulin infusion until resolution of acidosis (17.3 vs 13.2 h) and intensive care unit stay (2.4 vs 1.6 days) were longer in patients with DM2. Seven of the nine patients with DM2 did not require insulin at 1-year follow-up.
Children with DM2 can present with DKA and constitute a significant percentage in the above 9-year age group. The need for insulin must be carefully re-evaluated as DKA resolves in these patients. Adolescents with DM2 and their families need to be educated about DKA.
Journal of pediatric endocrinology & metabolism: JPEM 10/2005; 18(9):865-72. · 0.88 Impact Factor
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ABSTRACT: To determine and compare outcome of the modified Norwood procedure using either a systemic to pulmonary artery (SPA) shunt or right ventricle to pulmonary artery (RV-PA) conduit in a consecutive series of neonates at a single institution.
The medical records were retrospectively examined for preoperative demographic and echocardiographic data, operative variables, and postoperative clinical and hemodynamic data. From November 2001 to March 2003, 21 neonates had a modified Norwood procedure (SPA shunt, n = 8; RV-PA conduit, n = 13) at a median age of 5 days (range 1 to 18 days) and a median weight of 2.9 kg (range 1.7 to 4.1 kg). Of the 21 infants, 12 were considered high risk due to presence of low birth weight (n = 4), extracardiac or genetic anomalies (n = 5) or obstruction to pulmonary venous return (n = 5). Nine "high risk" infants were in the RV-PA conduit group.
Overall Norwood operation survival was 90% (19/21) and did not differ between groups. There were 2/19 interstage deaths and Kaplan-Meier survival at 1 year is 79%. Neonates in the RV-PA conduit group had significantly higher diastolic blood pressures at 1, 6, and 24 hours postoperatively (p < 0.05). Neonates in the SPA shunt group had significantly higher heart rates at 1 hour postoperatively (p < 0.05) than those in the RV-PA group. There was a trend to higher number of ventilatory interventions to balance Qp:Qs in the SPA shunt group (p = 0.06).
In a relatively high-risk group, neonates having an RV-PA conduit as part of the Norwood procedure have favorable postoperative hemodynamics and a good likelihood of stage I survival.
The Annals of Thoracic Surgery 05/2004; 77(5):1727-33. · 3.74 Impact Factor
