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1.
ASAIO J ; 70(7): 565-569, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949771

ABSTRACT

National trends show rapid increases in the use of mechanical circulatory support devices (MCSD) over the last 20 years. While current literature has not proven a mortality benefit in cardiogenic shock as a complication of acute myocardial infarction (AMI-CS) with percutaneous MCSD, these devices are vital to maximizing cardiopulmonary parameters for definitive therapy. To minimize complications, many different techniques have been described including a novel off-pump direct apical cannulation for venoarterial-extracorporeal membrane oxygenation (VA-ECMO). This technique allows early ambulation and avoids peripheral artery access complications but has only been described in small case series. Our case series represents the largest summary of patients (50) using this technique and contains the only comparison data to date. Fifty-four percentage of our patients were Society for Cardiovascular Angiography and Interventions (SCAI) stage D and 22% were arrested before cannulation. We achieved flows on average >5 L/min and most patients required biventricular drainage (86%) and an oxygenator (92%). Thirty day survival was 56% and most survivors were bridged to heart transplant (30%). Our most common complication was bleeding (16%). This technique showed significant improvement in ejection fraction (EF), cardiac output/index (CO/CI), and pulmonary artery pressures. This case series demonstrates the safety and efficacy of this novel technique for central cannulation in cardiogenic shock at large scale within a single institution.


Subject(s)
Cannula , Extracorporeal Membrane Oxygenation , Shock, Cardiogenic , Humans , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/instrumentation , Middle Aged , Male , Female , Shock, Cardiogenic/therapy , Shock, Cardiogenic/surgery , Aged , Thoracotomy/methods , Thoracotomy/adverse effects , Catheterization/methods , Catheterization/adverse effects , Catheterization/instrumentation , Adult , Myocardial Infarction , Heart-Assist Devices/adverse effects
2.
J Card Surg ; 35(8): 2067-2069, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32652695

ABSTRACT

A 43-year-old gentleman was transferred for management of acute on chronic cardiogenic shock (left ventricular ejection fraction < 10%). Upon arrival, we inserted a left axillary intra-aortic balloon pump for hemodynamic support. He underwent an emergent left and right-heart catheterization which showed patent stents and coronaries, in the setting of severely elevated pulmonary artery and pulmonary capillary wedge pressure. On hospital day 35, we escalated support to Centrimag in conjunction with a 31 French Protek Duo Rapid Deployment cannula. A centrimag cannula apical sewing cuff was sewn in continuous fashion along the left ventricular apex. Via modified seldinger technique, we tunneled the Protek Duo Rapid Deployment cannula through the silastic sewing cuff and the ventricular apex, traversing the aortic valve. On hospital day 50, he underwent left anterior thoracotomy and mini-sternotomy for implantation of durable Heartware left ventricular assist device. He was discharged home off inotropes and had resumed his normal activities. He is currently listed as status four for heart transplantation.


Subject(s)
Cardiac Catheterization/methods , Heart-Assist Devices , Prosthesis Implantation/methods , Shock, Cardiogenic/therapy , Acute Disease , Adult , Chronic Disease , Heart Transplantation , Hemodynamics , Humans , Intra-Aortic Balloon Pumping , Male , Pulmonary Wedge Pressure , Shock, Cardiogenic/physiopathology , Sternotomy/methods , Thoracotomy/methods , Waiting Lists
3.
N Engl J Med ; 380(17): 1618-1627, 2019 04 25.
Article in English | MEDLINE | ID: mdl-30883052

ABSTRACT

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).


Subject(s)
Heart Failure/therapy , Heart-Assist Devices , Prosthesis Design , Adolescent , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Heart-Assist Devices/adverse effects , Humans , Intention to Treat Analysis , Kaplan-Meier Estimate , Male , Middle Aged , Prosthesis Failure , Reoperation/statistics & numerical data , Stroke/etiology
4.
J Card Surg ; 33(1): 50-52, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29314296

ABSTRACT

A 24-year-old female presented with sepsis and cardiogenic shock 4 days after vaginal delivery. Veno-arterial extracorporeal membrane oxygenation (VA ECMO) therapy was used for cardiovascular support as a bridge for recovery. The use of VA ECMO in patients with cardiogenic shock secondary to sepsis is reviewed.


Subject(s)
Cardiomyopathies/etiology , Cardiomyopathies/therapy , Extracorporeal Membrane Oxygenation/methods , Obstetric Labor Complications , Postpartum Period , Sepsis/complications , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Acute Disease , Female , Humans , Pregnancy , Severity of Illness Index , Treatment Outcome , Young Adult
5.
Indian J Radiol Imaging ; 28(4): 395-400, 2018.
Article in English | MEDLINE | ID: mdl-30662198

ABSTRACT

BACKGROUND: Olfactory fossa (OF) is a depression in anterior cranial cavity whose floor is formed by cribriform plate of ethmoid. Lateral lamella, which forms its lateral boundary, is a thin plate of bone and is at risk of injury during functional endoscopic sinus surgery, especially when fossa is deep/asymmetric. AIMS: To measure the variations in the depth of OF and categorize Kerala population as per Keros classification using computed tomography (CT). SETTINGS AND DESIGN: This study was conducted in our institution from January 2016 to August 2017. Patients >16 years of age undergoing CT scan of paranasal sinuses (PNS) were included. MATERIALS AND METHODS: Coronal PNS CT scan studies of 1200 patients were reviewed. The depth of OF was measured from vertical height of lateral lamella. STATISTICAL METHODS: Results were analyzed according to gender and laterality using independent sample t-test and Chi-square test. RESULTS: The mean depth of OF was 5.26 ± 1.69 mm. Statistically significant difference was seen in the mean depth of OF between males and females but not between right and left sides. Keros type I was found on 420 sides (17.5%), type II in 1790 (74.6%), and type III on 190 sides (7.9%). Type III Keros was more on the right (9%) than left (6.8%) side, more in males (9.5%) than females (5.9%), and more among males on the right side (11.4%). Asymmetry in OF depth between two sides was seen in 75% of subjects. CONCLUSION: Prevalence of the dangerous type III OF, even though low, is significant especially among males and on the right side. Therefore, preoperative assessment of OF depth must be done to reduce iatrogenic complications.

6.
Clin Case Rep ; 5(2): 130-133, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28174637

ABSTRACT

Endovascular venous stenting is increasingly performed for a variety of conditions. Inferior vena cava stent migration has been reported up to 6 months after placement; stent migration 6 months after implantation is uncommon. To our knowledge, this is only the second reported case of late stent migration with valve entrapment 1.

7.
J Cardiothorac Surg ; 11(1): 53, 2016 Apr 11.
Article in English | MEDLINE | ID: mdl-27067868

ABSTRACT

BACKGROUND: Ventricular tachycardia (VT) can persist following placement of a left ventricular assist device (LVAD). The optimal management strategy for VT during the peri-LVAD period is unknown. CASE PRESENTATIONS: Two case reports are presented that describe epicardial and endocardial VT ablation performed during LVAD placement. Subsequently, both patients developed LVAD thrombosis, a known and dreaded complication of LVADs, requiring re-operation. CONCLUSIONS: While LVAD thrombosis is likely multifactorial and remains an area of active research, these two cases should increase awareness of the possible risks of VT ablation-especially endocardial ablation-during LVAD placement. Further research is needed to understand the effects of VT ablation during the peri-LVAD period.


Subject(s)
Cryosurgery/adverse effects , Heart-Assist Devices/adverse effects , Tachycardia, Ventricular/surgery , Thrombosis/etiology , Aged , Cryosurgery/methods , Female , Heart Failure/therapy , Humans , Male , Middle Aged , Treatment Outcome
8.
Ann Thorac Surg ; 101(5): 1980-2, 2016 May.
Article in English | MEDLINE | ID: mdl-27106435

ABSTRACT

Anomalous origin of the coronary arteries may limit the applicability of aortic valve sparing techniques during root replacement. We report a case of a right coronary artery that originated from the left sinus and coursed intramurally in a patient with an aortic root aneurysm. Attention to the anatomic relation between the anomalous coronary and aortic root structures and right coronary safety button reconstruction allowed safe aortic root replacement while preserving the native aortic valve.


Subject(s)
Aorta/surgery , Aortic Aneurysm/surgery , Aortic Valve , Blood Vessel Prosthesis Implantation/methods , Coronary Vessel Anomalies/surgery , Organ Sparing Treatments/methods , Sinus of Valsalva/surgery , Aortic Aneurysm/etiology , Aortic Valve Insufficiency/etiology , Aortic Valve Insufficiency/surgery , Bioprosthesis , Blood Vessel Prosthesis , Brachiocephalic Trunk/surgery , Humans , Male , Marfan Syndrome/complications , Middle Aged , Replantation , Sinus of Valsalva/abnormalities , Suture Techniques
9.
Dimens Crit Care Nurs ; 34(6): 348-55, 2015.
Article in English | MEDLINE | ID: mdl-26436301

ABSTRACT

BACKGROUND: Progressive mobility (PM) is a clinical intervention that influences complications experienced throughout critical illness. Early PM is a relevant topic in critical care practice literature and was principle to introducing a PM care guideline in an acute cardiothoracic/cardiovascular intensive care unit. PURPOSE: A noted challenge in the cardiothoracic/cardiovascular intensive care unit is caring for acute cardiac and pulmonary failure. Often, these patients require prolonged mechanical circulatory support via extracorporeal mechanical oxygenation or a ventricular assist device. This article describes safe and effective progressive mobilization for patients experiencing MCS in a case study format. This article also highlights how a multidisciplinary clinical team supports mobility practice in specific critical care roles. CONCLUSIONS: Post-intensive care syndrome is composed of various health implications that occur following critical illness. Recent data suggest improved care outcomes when critically ill patients are awake and participate in active physical rehabilitation as early as clinically possible. The case studies presented indicate that mobility, to the point of ambulation, is a feasible clinical expectation when patients present with substantial acute respiratory and cardiac failure and are managed with MCS. CLINICAL IMPLICATIONS: Development of a PM guideline uses a critical appraisal of practice evidence, highlights multidisciplinary collaboration, and increases progression to ambulation. Mobility for complex patients is attainable, as demonstrated in the postguideline outcomes. The PM guideline provides structure to primary caregivers and promotes safe practices. The PM guideline facilitates an advanced level of care, promotes safe practices, champions holistic recovery, and encourages active patient involvement, goals satisfying to both patients and staff.


Subject(s)
Cardiopulmonary Resuscitation/methods , Critical Care , Extracorporeal Membrane Oxygenation/rehabilitation , Heart Failure/therapy , Heart-Assist Devices , Intensive Care Units , Respiratory Insufficiency/therapy , Adult , Humans , Male , Middle Aged , Physical Therapy Modalities , Treatment Outcome
10.
Am J Med ; 128(12): 1364-6, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26239095

ABSTRACT

BACKGROUND: Whipple endocarditis is caused by Tropheryma whipplei and is a well-described complication of Whipple's disease. Limited and small case series have been published regarding the presentation, diagnosis, and clinical course of this disease. METHODS/RESULTS: We describe 2 cases of patients with T. whipplei endocarditis, one of which underwent a successful heart transplant. CONCLUSION: In both cases of Whipple's endocarditis, there was a subacute prodromal phase followed by an acute rapid decompensation with severe destruction of the aortic valve, heart failure, and embolism. Because the diagnosis of T. whipplei endocarditis is typically not made until pathological examination of tissue, clinicians must have a high suspicion for it in the absence of other offending organisms, especially among middle-aged white males with sub-acute symptoms and embolic complications.


Subject(s)
Endocarditis, Bacterial/diagnosis , Tropheryma , Whipple Disease/diagnosis , Echocardiography , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/pathology , Endocarditis, Bacterial/surgery , Fatal Outcome , Heart Transplantation , Humans , Male , Middle Aged , Whipple Disease/pathology
11.
Ann Thorac Surg ; 100(2): 437-42, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26141775

ABSTRACT

BACKGROUND: The use of single lung transplantation (SLTx) for chronic obstructive pulmonary disease is often viewed as inferior therapy compared with bilateral lung transplantation (BLTx). We hypothesized from our experience that subpopulations of recipients with emphysema exist in which SLTx represents therapy that is equivalent to BLTx, therefore allowing more patients access to transplantation. METHODS: Consecutive patients undergoing LTx for emphysema between 1992 and 2012 at a single institution were identified and analyzed retrospectively. A similar cohort from the United Network of Organ Sharing (UNOS) national database was identified for comparison. Five-year survival in patients receiving SLTx and those receiving BLTx were compared using Kaplan-Meier survival curves and log-rank tests. RESULTS: Two hundred thirty-six patients meeting criteria were identified from our institution. Two hundred six underwent SLTx, and 30 underwent BLTx. Five-year survival for single-center SLTx (53.2% ± 3.6%) and BLTx (56.7% ± 10.2%) was not significantly different (p = 0.753). The national database included 7,256 patients meeting selection criteria, with 4,408 undergoing SLTx and 2,848 undergoing BLTx. Five-year survival among the national cohorts was lower for SLTx (46.4% ± 0.8%) compared with BLTx (55.9% ± 1.1%) (p < 0.0001). However, 5-year survival for our single-center SLTx experience (53.2% ± 3.6%) was comparable to the national BLTx cohort (55.9% ± 1.1%) (p = 0.539). CONCLUSIONS: Five-year survival after SLTx for emphysema was comparable to that for BLTx in cohorts from our institution and from the UNOS national database. Further study should focus on the mechanism behind these improved outcomes. Given the potential for a larger number of life-years saved, SLTx should continue to be considered a therapeutic option in appropriately selected patients with chronic obstructive pulmonary disease (COPD).


Subject(s)
Lung Transplantation , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/surgery , Pulmonary Emphysema/mortality , Pulmonary Emphysema/surgery , Female , Humans , Lung Transplantation/methods , Male , Middle Aged , Patient Selection , Retrospective Studies , Survival Rate , Time Factors
12.
Circ Heart Fail ; 8(5): 944-52, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26136459

ABSTRACT

BACKGROUND: The effects of nonpulsatile flow on the aorta are unknown. Our aim was to examine the structure of the aorta from patients with continuous-flow left ventricular assist devices (LVADs) and directly measure aortic wall composition and stiffness. METHODS AND RESULTS: Age-matched aortic wall samples were collected from consecutive patients with heart failure (HF) at the time of transplantation and compared with nonfailing donor hearts. An unbiased stereological approach was used to quantify aortic morphometry and composition, and biomechanical testing was performed to determine the stress-strain relationship of the vessel. Data were obtained from 4 patients without a left ventricular assist device (HF group: mean age, 58.3±8.0 years), 7 patients with a continuous-flow LVAD (HF+LVAD group: mean, 57.7±5.6 years), and 3 nonfailing donors (mean, 53.3±12.9 years). Compared with HF, the aortic walls from HF+LVAD had an increase in wall thickness, collagen, and smooth muscle content accompanied by a reduction in elastin and mucinous ground-substance content. Stress-strain curves from the aortas revealed increased vessel stiffness in HF+LVAD compared with HF and nonfailing. The physiological modulus of the aorta progressively stiffened from 74.3±5.5 kPa in the nonfailing to 134.4±35.0 kPa in the HF to 201.7±36.4kPa in the HF+LVAD groups (P<0.001). CONCLUSIONS: Among continuous-flow LVAD patients without aortic valve opening, there are changes in the structure and composition of the aorta as well as an increase in aortic wall stiffness compared with age-matched HF patients and nonfailing donors. Further studies examining the role of nonpulsatile blood flow on aortic function and the potential resultant systemic sequelae are needed.


Subject(s)
Aorta, Thoracic/physiopathology , Heart Failure/physiopathology , Heart-Assist Devices , Vascular Stiffness/physiology , Aorta, Thoracic/pathology , Disease Progression , Female , Follow-Up Studies , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Male , Middle Aged , Pilot Projects , Retrospective Studies , Ventricular Function, Left
15.
Ann Vasc Surg ; 28(6): 1420-5, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24704047

ABSTRACT

BACKGROUND: Endoluminal revascularization has supplanted open techniques for most aortoiliac occlusive disease with open surgery reserved for endovascular failure or long-segment aortoiliac occlusions. A number of clinical and anatomic issues can preclude the use of the infrarenal aorta for inflow. Our approach in these select patients is minimal thoracotomy thoracic bifemoral (mini-TBF) bypass. METHODS: Mini-TBF bypass used a 2-team approach. The cardiac surgery team focused on arterial inflow from the distal descending aorta via a ≤8-cm thoracotomy at ninth interspace. The vascular surgery team focused on groin reconstruction and graft tunneling. The body of the graft was tunneled through the posterior left hemidiaphragm. The left limb was tunneled retroperitoneal over the psoas and the right limb anterior to the abdominal fascia below the umbilicus to the groin. RESULTS: Thirteen patients (mean age, 64; 82% male) underwent mini-TBF bypass between 2009 and 2012 for claudication in 9 (69%) and critical limb ischemia in 4 (31%). Five patients had prior failed iliac endovascular revascularizations and 2 patients had failed prior infrarenal aortobifemoral bypass. The indication for use of thoracic aortic inflow was prior abdominal operations in 4 (31%), pelvic anatomy with a critical inferior mesenteric artery (IMA) in 5 (38%), and the condition of the infrarenal/juxtarenal aorta in 4 (31%). Median operative time was 240 min (range 181-513 min). Median length of stay was 8 days. There was no perioperative mortality. Postoperative complications occurred in 5 patients, stroke 1, pulmonary 2 (both contralateral lung issues), and 2 limb occlusion secondary to outflow disease. At median follow-up of 18 months, 2 patients required amputations, both from preexisting tissue loss despite secondary patent grafts. CONCLUSIONS: Mini-TBF bypass provides another alternative to successfully revascularize Trans-Atlantic Inter-Society Consensus II type D lesions in patients with prior abdominal revascularization, pelvic anatomy with a critical IMA, or calcification/thrombus of the infrarenal/juxtarenal aorta precludes control.


Subject(s)
Aorta, Thoracic/surgery , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures/methods , Femoral Artery/surgery , Intermittent Claudication/surgery , Ischemia/surgery , Lower Extremity/blood supply , Peripheral Arterial Disease/surgery , Thoracotomy/methods , Aged , Amputation, Surgical , Aorta, Thoracic/physiopathology , Blood Vessel Prosthesis Implantation/adverse effects , Critical Illness , Endovascular Procedures/adverse effects , Female , Femoral Artery/physiopathology , Humans , Intermittent Claudication/diagnosis , Intermittent Claudication/physiopathology , Ischemia/diagnosis , Ischemia/physiopathology , Length of Stay , Limb Salvage , Male , Middle Aged , Operative Time , Patient Selection , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/physiopathology , Postoperative Complications/etiology , Postoperative Complications/surgery , Reoperation , Retrospective Studies , Risk Factors , Thoracotomy/adverse effects , Time Factors , Treatment Outcome , Vascular Patency
17.
J Thorac Cardiovasc Surg ; 139(4): 1019-25, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20304146

ABSTRACT

OBJECTIVE: Acid exposure to esophageal epithelium leads to hyperplasia and mucosal thickening. This is associated with upregulation of antiapoptotic genes. Recently, heat shock proteins have been implicated in esophageal mucosal response to stress. We sought to determine the influence of gastroduodenal reflux on esophageal mucosal heat shock protein 27 gene (murine analog Hspb1, human HSPB1) expression in vivo and the effect of HSPB1 overexpression on proliferation of esophageal mucosal cells in vitro. METHODS: Balb/c mice underwent either anastomosis of gastroesophageal junction and first portion of duodenum to induce continuous gastroduodenal reflux (n = 14) or sham procedure (n = 12). Quantitative reverse transcriptase polymerase chain reaction was used to determine the influence of gastroduodenal reflux on Hspb1 expression. Immunofluorescent microscopy and immunoblotting were used to quantify changes in heat shock protein 27 protein expression. Lentiviral infection techniques were used to overexpress HSPB1 in human esophageal epithelial cells. Both 3-(4,5-dimethylthiazole-2-yl) 2,5,-diphenyl tetrazolium bromide and 5-bromo-2-deoxyuridine incorporation assays were used to assess cell proliferation. RESULTS: Expressions of Hspb1 and its protein product were increased in esophageal tissue after 12 weeks' reflux relative to sham control group. Expression was located mainly in hyperplastic epithelial cells. Overexpression of HSPB1 in human esophageal epithelial cells resulted in increased proliferation. CONCLUSIONS: Heat shock protein 27 is upregulated in response to gastroduodenal reflux and is a mediator of human esophageal epithelial cell proliferation and growth. This novel finding illustrates the importance of its expression in the development of inflammation and mucosal thickening associated with esophageal reflux.


Subject(s)
Duodenogastric Reflux/physiopathology , Esophagus/metabolism , HSP27 Heat-Shock Proteins/biosynthesis , Heat-Shock Proteins/biosynthesis , Mucous Membrane/metabolism , Neoplasm Proteins/biosynthesis , Animals , Cell Proliferation , Cells, Cultured , Disease Models, Animal , Epithelial Cells/metabolism , Esophagus/physiopathology , Humans , Male , Mice , Mice, Inbred BALB C , Molecular Chaperones , Mucous Membrane/physiopathology , Up-Regulation
18.
Dis Esophagus ; 23(5): 430-6, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20095996

ABSTRACT

Exposure of esophageal epithelium to gastric and duodenal contents results in the histologic changes of hyperproliferation and mucosal thickening. We have previously shown that presence of secretory phospholipase A(2) (sPLA(2)) is necessary to produce these histologic changes in a murine model of gastroduodenal reflux. We sought to determine the influence of gastroduodenal reflux (GDR) on sPLA(2) protein and mRNA levels as well as enzyme activity in esophageal tissue. BALB/c (sPLA(2)(+/+)) mice (n= 28) underwent side-to-side surgical anastomosis of the first portion of the duodenum and GE junction (DGEA) resulting in continuous exposure of esophageal mucosa to mixed gastric and duodenal contents. Sham control mice (n= 14) underwent laparotomy, esophagotomy and closure. Real-time RT PCR was used to quantitate the influence of GDR on group IIa sPLA(2) expression. Immunofluorescent staining was quantitated by digital microscopy using a specific antibody to identify and locate sPLA(2) protein. A colorimetric assay was used to quantify total sPLA(2) activity after standardization of protein levels. Statistical analysis was conducted using Student's t-test. Group IIa sPLA(2) mRNA and protein levels were increased at 4 and 8 weeks compared with sham controls. This increase occurred in a time-dependent manner and correlated with esophageal mucosal thickness. Furthermore, sPLA(2) enzyme activity was increased significantly at 4 and 8 weeks compared with untreated controls. The expression of group IIa sPLA(2) as well as sPLA(2) activity is induced by GDR. This novel finding indicates that sPLA(2) may play a role in the development of the histologic changes produced by GDR in esophageal mucosa.


Subject(s)
Esophagitis, Peptic/enzymology , Esophagus/enzymology , Gastroesophageal Reflux/enzymology , Group II Phospholipases A2/metabolism , Animals , Disease Models, Animal , Esophagitis, Peptic/pathology , Esophagus/pathology , Fluorescent Antibody Technique , Gastroesophageal Reflux/pathology , Group II Phospholipases A2/genetics , Hyperplasia/pathology , Male , Mice , Mice, Inbred BALB C , Mucous Membrane/enzymology , Mucous Membrane/pathology , RNA, Messenger , Reverse Transcriptase Polymerase Chain Reaction
19.
J Gastrointest Surg ; 13(12): 2212-8, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19672667

ABSTRACT

BACKGROUND: The initial response of esophageal mucosa to gastroduodenal reflux is inflammation and hyperplasia. Secretory phospholipase A(2) (sPLA(2)) is a known mediator of gut inflammation, and its levels are increased in Barrett's esophagus. We hypothesized that the sPLA(2) gene is required to produce esophageal mucosal hyperplasia in response to gastroduodenal reflux. METHODS: C57BL/6 (n = 5) sPLA(2) (-/-) mice and C57BL/6( Cg-Tg(PLA2G2A)703N16 ) mice (n = 4) sPLA(2) (-/+) underwent a side-to-side surgical anastomosis between the duodenum and gastroesophageal junction (DGEA). Control animals [sPLA(2) (-/-) (n = 5), sPLA(2) (-/+) (n = 4)] underwent laparotomy with incision and repair of the esophagus. Tissue was harvested after 4 weeks, and H&E staining was performed to quantify esophageal mucosal thickness. Ki67 and sPLA(2) immunostaining were performed to quantitate differences in cell division and sPLA(2) expression. RESULTS: Mice expressing human sPLA(2) had a 2.5-fold increase in thickness of the esophageal mucosa as compared to controls (p = 0.01). A 6.5-fold increase in proliferation (p = 0.02) and a twofold increase in sPLA(2) expression (p = 0.04) were demonstrated in animals exposed to gastroduodenal reflux. CONCLUSIONS: The presence of sPLA(2) is necessary for early mucosal hyperplasia produced by exposure of the esophagus to gastroduodenal contents. sPLA(2) expression is upregulated by gastroduodenal reflux, strengthening its role as a critical mediator of early mucosal hyperplasia.


Subject(s)
Esophagus/pathology , Gastroesophageal Reflux/pathology , Phospholipases A2, Secretory/genetics , Animals , Cell Division , Duodenogastric Reflux/metabolism , Duodenogastric Reflux/pathology , Fluorescent Antibody Technique , Gene Expression , Mice , Mice, Inbred C57BL , Mucous Membrane/pathology , Phospholipases A2, Secretory/analysis
20.
J Am Coll Surg ; 208(4): 592-8, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19476795

ABSTRACT

BACKGROUND: The clinical sequel of ischemia and reperfusion remains a challenge in several clinical areas. Overexpression of heme oxygenase-1 (HO-1), using viral vectors, endotoxemia, and hypoxia, provides protection against ischemia and reperfusion injury. To date, however, no clinically viable therapy exists to safely induce HO-1. We have recently observed that administration of a hemoglobin-based oxygen carrier (HBOC) attenuates postinjury systemic inflammation. We have further demonstrated that an HBOC can induce HO-1 in vitro. We now explore the tissue-specific induction of heme oxygenase-1 after administration of an HBOC. STUDY DESIGN: Rats were infused with doses of HBOC or saline through femoral vein injection (n=5 per group). Animals were sacrificed and organs were flushed. Heart, lung, and brain samples were taken for evaluation of total organ levels of HO-1 induction and for histologic localization of the cellular expression of the HO-1. Heat shock protein 72 levels were also analyzed to determine whether HO-1 induction was a generalized stress response. RESULTS: Both the heart and lung demonstrated a dose-dependent induction of total organ HO-1. Interestingly, brain tissue did not have any significant amount of HO-1, either at baseline or after HBOC therapy. The cellular localization of HO-1 between organs was also specific, predominantly occurring in the cardiac myocyte and alveolar macrophages. Heat shock protein 72 levels were not significantly changed in any group examined, suggesting the induction of HO-1 is specific. CONCLUSIONS: This study demonstrates that a clinically accessible product, HBOC, can specifically and selectively induce the expression of the protective enzyme HO-1 in vivo. These findings begin to characterize which organ systems may benefit by preischemic treatments with HBOC and further expand potential clinical applications of HBOCs.


Subject(s)
Brain/metabolism , Heme Oxygenase-1/metabolism , Hemoglobins/pharmacology , Lung/metabolism , Myocardium/metabolism , Animals , Dose-Response Relationship, Drug , Hemoglobins/administration & dosage , Immunohistochemistry , Infusions, Intravenous , Organ Specificity , Rats , Rats, Sprague-Dawley
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