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1.
Cardiol Young ; 31(10): 1644-1650, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33686934

ABSTRACT

INTRODUCTION: Systemic ventricular end-diastolic pressure is important in patients with single ventricle heart disease. Predictors of an elevated systemic ventricular end-diastolic pressure prior to bidirectional Glenn operation have been incompletely identified. METHODS: All patients who underwent bidirectional Glenn operation operation at our centre between January 2007 and March 2017 were retrospectively identified and patient variables were extracted. For patients who had undergone Fontan operation at the time of this study, post-Fontan patient variables were also extracted. RESULTS: One-hundred patients were included with a median age at pre-bidirectional Glenn operation catheterisation of 4.5 months. In total, 71 (71%) patients had a systemic right ventricle. At the pre-bidirectional Glenn operation catheterisation, the mean systemic ventricular end-diastolic pressure was higher amongst those with systemic right ventricle compared to left ventricle (9.1 mmHg ± 2.1 versus 7.7 ± 2.7 mmHg, p < 0.01). On univariate analysis, pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01), history of recoarctation (p = 0.03), history of Norwood operation (p = 0.04), and ventricular systolic pressure (p < 0.01). On multivariate analysis, systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01) and ventricular systolic pressure (p < 0.01). Amongst those who had undergone Fontan operation at the time of study (n = 49), those with a higher pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure were more likely to have experienced death, transplantation, or listed for transplantation (p = 0.02) and more likely to have had heart failure symptoms (p = 0.04) at a mean time from Fontan of 5.2 years ± 1.3. CONCLUSIONS: In patients undergoing bidirectional Glenn operation operation, the volume-loaded, pre-bidirectional Glenn operation state may expose diastolic dysfunction that has prognostic value.


Subject(s)
Fontan Procedure , Norwood Procedures , Blood Pressure , Heart Ventricles/diagnostic imaging , Heart Ventricles/surgery , Humans , Infant , Retrospective Studies , Treatment Outcome , Ventricular Pressure
2.
JTCVS Tech ; 3: 294, 2020 Sep.
Article in English | MEDLINE | ID: mdl-34317904
3.
J Thorac Cardiovasc Surg ; 157(3): 1128-1129, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30591379
4.
J Pediatr Intensive Care ; 7(3): 163-165, 2018 Sep.
Article in English | MEDLINE | ID: mdl-31073489

ABSTRACT

Post-cardiotomy mediastinitis is an especially serious complication after the implantation of prosthetic vascular grafts. Standard of care is irrigation, debridement, and removal of all prosthetic material present in the surgical field. The use of antibiotic impregnated beads at the site of infection has been reported in the salvage of vascular grafts in the adult population. We present the case of a 3-year-old child with hypoplastic left heart syndrome who developed mediastinitis following the Fontan operation. In a nontraditional approach, the Fontan conduit, which was surrounded by gross purulence, was successfully salvaged with the adjunctive use of vancomycin-impregnated beads.

6.
Congenit Heart Dis ; 8(1): E24-30, 2013.
Article in English | MEDLINE | ID: mdl-22176554

ABSTRACT

Tetralogy of Fallot is characterized by a ventricular septal defect, a large, overriding aorta, subpulmonic stenosis, and right ventricular hypertrophy. These lesions can be associated with abnormal development of the pulmonary vasculature. This can include peripheral pulmonic stenosis, discontinuous pulmonary arteries, anomalous pulmonary venous return, and the development of aortopulmonary collateral vessels. Aortopulmonary collateral vessels develop to supply underperfused areas of the pulmonary bed and pose a unique and challenging problem at the time of surgical repair, which involves closure of the ventricular septal defect, relief of right ventricular outflow tract obstruction, maintenance of pulmonary valve competency when possible, and establishment of laminar pulmonary blood flow to all segments of the pulmonary bed. We describe a 36-year-old man with unrepaired tetralogy of Fallot with distinctive aortopulmonary collaterals, who underwent complete surgical repair with good outcome. Two-dimensional echocardiogram, cardiac magnetic resonance imaging, and cardiac catheterization each provided vital details allowing a stepwise approach to defining his unique anatomy for surgical correction.


Subject(s)
Aorta/physiopathology , Cardiac Surgical Procedures/methods , Collateral Circulation , Lung/blood supply , Pulmonary Artery/physiopathology , Pulmonary Circulation/physiology , Tetralogy of Fallot/pathology , Tetralogy of Fallot/surgery , Abnormalities, Multiple/surgery , Adult , Cardiac Catheterization , Cardiac Surgical Procedures/adverse effects , Collateral Circulation/physiology , Humans , Male , Postoperative Complications/surgery , Pulmonary Artery/pathology , Pulmonary Artery/surgery , Pulmonary Infarction/surgery , Tetralogy of Fallot/diagnostic imaging , Tetralogy of Fallot/physiopathology , Ultrasonography
7.
J Cardiovasc Med (Hagerstown) ; 9(4): 363-7, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18334890

ABSTRACT

OBJECTIVES: Adenosine receptor activation at reperfusion has been shown to ameliorate ischemia-reperfusion injury of the spinal cord, but the effects of therapy given in response to ischemic injury are unknown. We hypothesized that adenosine receptor activation with ATL-146e would produce similar protection from ischemic spinal cord injury, whether given at reperfusion or in a delayed fashion. METHODS: Twenty-two New Zealand white rabbits were divided into three groups. All three groups, including the ischemia-reperfusion group (IR, n = 8), underwent 45 min of infrarenal aortic occlusion. The early treatment group (early, n = 8) received 0.06 mug/kg/min of ATL-146e for 3 h beginning 10 min prior to reperfusion. The delayed treatment group (delayed, n = 6) received ATL-146e starting 1 h after reperfusion. After 48 h, hind limb function was graded using the Tarlov score. Finally, lumbar spinal cord neuronal cytoarchitecture was evaluated. RESULTS: Hemodynamic parameters were similar among the groups. Hind limb function at 48 h was significantly better in the early group (3.5 +/- 1.0) compared to the IR group (0.625 +/- 0.5, P < or = 0.01). There was a trend towards better hind limb function in the early group compared to the delayed group (2.4 +/- 1.1, P = 0.08). Hind limb function was similar between delayed and IR groups. Hematoxylin-eosin spinal cord sections demonstrated preservation of viable motor neurons in the early group compared to the delayed and IR groups. CONCLUSIONS: Early therapy with ATL-146e provided better protection in this study; therefore, therapy should not be delayed until there is evidence of ischemic neurological deficit. This study suggests that adenosine receptor activation is most effective as a preventive strategy at reperfusion for optimal protection in spinal cord ischemia-reperfusion injury.


Subject(s)
Cyclohexanecarboxylic Acids/pharmacology , Purines/pharmacology , Reperfusion Injury/drug therapy , Spinal Cord/pathology , Analysis of Variance , Animals , Disease Models, Animal , Hemodynamics , Rabbits , Receptor, Adenosine A2A , Recovery of Function/drug effects , Reperfusion Injury/pathology , Spinal Cord/blood supply , Statistics, Nonparametric
8.
Cardiovasc Pathol ; 16(3): 179-82, 2007.
Article in English | MEDLINE | ID: mdl-17502248

ABSTRACT

The majority of primary cardiac tumors are benign; of these tumors, cardiac paragangliomas are among the rarest. We report a case of biatrial cardiac paraganglioma discovered during workup for palpitations and fatigue. The tumor involved the interatrial septum, with a lobulated portion protruding through the foramen ovale into the right atrium. The tumor was successfully excised, leading to uneventful recovery.


Subject(s)
Heart Neoplasms/pathology , Paraganglioma/pathology , Adult , Echocardiography, Transesophageal , Heart Atria/pathology , Heart Atria/surgery , Heart Neoplasms/surgery , Heart Septum/pathology , Heart Septum/surgery , Humans , Magnetic Resonance Imaging , Male , Paraganglioma/surgery , Tomography, X-Ray Computed , Treatment Outcome
9.
Surg Innov ; 14(1): 9-11, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17442873

ABSTRACT

Stentless mitral valves have found little clinical utility to date due to difficulty in insertion. A new design for a stentless mitral valve, a modification of an existing aortic stentless prosthesis, is described. The new design mimics the native mitral physiology, and its insertion is easier than with existing stentless mitral valves. Commercially available stentless aortic valves were inserted into 2 pigs. The valves were modified so that the commissural posts were restrained. The valves were partially recessed into the left ventricular cavity, secured to the annulus, and anchored to the native papillary muscles. Both pigs were weaned from bypass successfully, and both valves functioned normally with trace regurgitation noted on echocardiography. This design affords the benefit of the reapproximation of native physiology. Preservation of papillary-annular continuity should allow maximal left ventricular function. Lack of a stent should allow avoidance of long-term anticoagulation.


Subject(s)
Heart Valve Prosthesis , Animals , Mitral Valve , Prosthesis Design , Sutures , Swine
10.
Ann Thorac Surg ; 83(1): 193-6, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17184659

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate the role of a routine protocol for evaluation of oropharyngeal aspiration after thoracotomy for pulmonary resection. METHODS: Demographic, operative, and outcomes data were collected prospectively for consecutive patients undergoing thoracotomy for pulmonary resection starting in April 2005. Starting on postoperative day one, patients underwent evaluation by a licensed speech therapist before per os intake. Patients failing clinical examination were referred for radiographic evaluation. Diets were advanced on the basis of results from both clinical and radiographic evaluation. Data analysis included descriptive statistics, Student's t test, and chi2 test when appropriate. RESULTS: One hundred forty patients were prospectively evaluated during this period. Thirty-two patients (22.9%) failed initial clinical swallowing evaluation and were referred for dynamic videofluoroscopic esophagram. Twenty-five patients (17.8%) had evidence of potential oropharyngeal aspiration on videofluoroscopic esophagram. Only 1 patient (0.7%) aspirated after a negative clinical evaluation. Univariate risk factor analysis revealed that patients demonstrating aspiration were older (67.7 +/- 1.6 years versus 64.4 +/- 1.1 years; p = 0.10) and had a higher incidence of head and neck malignancy (p < 0.001). Patients without radiographic aspiration had a shorter median hospital stay when compared with those who did (6 days versus 5 days). CONCLUSIONS: Aspiration after thoracotomy for pulmonary resection may affect nearly 20% of patients and is likely underrepresented in the surgical literature. The institution of a protocol to evaluate risk of aspiration has characterized patients at high risk and led to an increased awareness of the potential for aspiration after thoracotomy.


Subject(s)
Deglutition Disorders/etiology , Pneumonectomy/adverse effects , Pneumonia, Aspiration/etiology , Thoracotomy/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Cost-Benefit Analysis , Female , Humans , Male , Middle Aged , Risk Factors , Speech-Language Pathology/economics
11.
Am Surg ; 72(7): 627-30, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16875085

ABSTRACT

The objective of this study is to demonstrate the effectiveness and feasibility in treating empyema after pulmonary resection with a modified Clagett procedure performed at the bedside (BMCP). A retrospective review of a single surgeon's experience at a single institution was undertaken. All operative, postoperative, and outcome data were analyzed. Follow-up data were obtained from subsequent clinic charts. Five patients, including four males, were identified who underwent BMCP after pulmonary resection. The original operative procedures included two lobectomies, one pneumonectomy, one bilobectomy, and one bilateral metastastectomy. Patients were diagnosed with an empyema (positive thoracostomy tube culture, fever, and radiographic abnormality) at a mean time of 31 days from their initial procedure. Culture results disclosed Gram-positive empyemas in all patients. Three patients underwent BMCP as an outpatient, whereas the other two had BMCP during their hospitalizations. All patients are free from complications or recurrence at a mean follow up of 11.2 months. No patient required a further procedure after BMCP. The bedside modified Clagett procedure is both safe and effective. It is a valuable option in the management of postoperative empyema because it avoids additional operative procedures. This procedure is cost-effective when compared with operative management of perioperative empyema.


Subject(s)
Empyema, Pleural/drug therapy , Pneumonectomy , Point-of-Care Systems , Postoperative Complications/drug therapy , Adult , Aged , Ambulatory Care , Anti-Bacterial Agents/therapeutic use , Cefazolin/therapeutic use , Chest Tubes , Clindamycin/therapeutic use , Empyema, Pleural/microbiology , Feasibility Studies , Female , Follow-Up Studies , Gram-Positive Bacterial Infections/drug therapy , Humans , Male , Middle Aged , Pneumonectomy/adverse effects , Pneumonectomy/classification , Postoperative Complications/microbiology , Retrospective Studies , Safety , Thoracostomy , Treatment Outcome , Vancomycin/therapeutic use
12.
J Vasc Surg ; 44(2): 392-7, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16890874

ABSTRACT

BACKGROUND: ATL-146e protects the spinal cord from ischemia/reperfusion injury, presumably via adenosine A(2A) receptor activation, but this relationship remains unproven. We hypothesized that spinal cord functional and cytoarchitectural preservation from ATL-146e would be lost with simultaneous administration of the specific adenosine A(2A) antagonist ZM241385 (ZM), thus proving that adenosine A(2A) receptor activation is responsible for the protective effects of this compound. METHODS: New Zealand White rabbits underwent 45 minutes of infrarenal aortic cross-clamping. Groups (n = 10) included sham, ischemia, ischemia plus ATL-146e (ATL-146E), ischemia plus ZM, or ischemia with both compounds (agonist-antagonist). Tarlov scores were recorded every 12 hours. After 48 hours, the spinal cord was fixed for histology and microtubule-associated protein 2 immunohistochemistry. RESULTS: Tarlov scores at 48 hours were significantly better in the sham and ATL-146E groups (5.0 and 3.9, respectively) compared with the other three groups (all < or =1.3; P < .001). On hematoxylin and eosin, neuronal viability was higher in the sham, ATL-146E, and agonist-antagonist groups compared with the control and ZM groups (P < .05). Microtubule-associated protein 2 expression was preserved in the sham and ATL-146E groups but was lost in the ATL + ZM, ZM241385, and control groups. CONCLUSIONS: ATL-146e preserves the spinal cord in terms of both cytoarchitecture and function after reperfusion of the ischemic spinal cord, but this preservation is not completely blocked by competitive adenosine A(2A) receptor antagonism. Although ATL-146e does seem to partially function through activation of the adenosine A(2A) receptor, the neuroprotective mechanism may not be limited to this particular receptor.


Subject(s)
Adenosine A2 Receptor Agonists , Cyclohexanecarboxylic Acids/pharmacology , Neuroprotective Agents/pharmacology , Purines/pharmacology , Reperfusion Injury/prevention & control , Spinal Cord Ischemia/drug therapy , Spinal Cord/drug effects , Adenosine A2 Receptor Antagonists , Animals , Cell Survival , Cyclohexanecarboxylic Acids/therapeutic use , Disease Models, Animal , Microtubule-Associated Proteins/metabolism , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/therapeutic use , Paraplegia/metabolism , Paraplegia/prevention & control , Purines/therapeutic use , Rabbits , Receptor, Adenosine A2A/metabolism , Reperfusion Injury/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord Ischemia/metabolism , Time Factors , Triazines/pharmacology , Triazoles/pharmacology
13.
J Card Surg ; 21(3): 261-3, 2006.
Article in English | MEDLINE | ID: mdl-16684054

ABSTRACT

Right-sided aortic arch with a concomitant coarctation is an exceedingly rare congenital cardiac anomaly. We report of a 4-year-old boy who presented with a history of a stenotic bicuspid aortic valve who upon further evaluation was found to have a coarctation of a right-sided aortic arch. The frequency with which other anomalies exist in either of the above conditions requires thorough cardiac evaluation and detailed imaging. Surgical repair of this anomaly can safely be undertaken through a right thoracotomy.


Subject(s)
Aortic Coarctation/complications , Aortic Valve Stenosis/complications , Aortic Valve/abnormalities , Cardiac Surgical Procedures/methods , Aortic Coarctation/diagnosis , Aortic Coarctation/surgery , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Aortography , Child, Preschool , Echocardiography , Follow-Up Studies , Humans , Male , Thoracotomy
14.
Ann Thorac Surg ; 81(4): 1234-8, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16564249

ABSTRACT

BACKGROUND: After pneumonectomy, the remaining lung vasculature must vasodilate to compensate for increased blood volume. We hypothesized that endothelial nitric oxide synthase (eNOS) is essential for compensatory vasodilation after pneumonectomy. METHODS: Adult, wild-type C57BL6 (WT) and eNOS knockout (eNOS-/-) mice underwent left pneumonectomy and recovered under normoxic conditions. Animals were lightly anesthetized at 1, 3, 7, or 14 days after pneumonectomy, and closed chest, systolic right ventricular pressure (RVP) was recorded using fine-needle cannulation. The right ventricle to left ventricle plus septum weight ratios were measured as an index of right ventricular hypertrophy. Two additional groups of mice (WT and eNOS-/-) were recovered after pneumonectomy in inhaled nitric oxide (iNO, 10 ppm), and RVP was measured on day 7. RESULTS: The eNOS-/- mice had significantly higher preoperative RVP than did WT (17.1 +/- 0.4 versus 14.2 +/- 0.2 cmH2O, p = 0.001). Both groups exhibited transient periods of pulmonary hypertension after pneumonectomy. On day 1, RVP was 80% above baseline in eNOS-/- mice (30.7 +/- 0.8 cmH2O) versus 42% in WT mice (20.2 +/- 0.7 cmH2O, p = 0.0001). The RVP returned to baseline in WT mice (16.3 +/- 0.2 cmH2O) but remained significantly elevated in eNOS-/- mice (28.6 +/- 0.9 cmH2O) at day 3 and at each time thereafter (p = 0.0001). The iNO significantly reduced RVP in eNOS-/- animals to 15.2 +/- 0.3 cmH2O (p = 0.0001) while having no effect in WT animals. Right ventricular hypertrophy was not observed in any group. CONCLUSIONS: Pneumonectomy results in a transient increase in RVP. Under normal circumstances, these pressures return to baseline within 3 days. The eNOS-/- mice failed to display compensatory vasodilation yet could be rescued with iNO. These results suggest that eNOS is essential for postpneumonectomy compensatory vasodilation.


Subject(s)
Endothelium, Vascular/enzymology , Nitric Oxide Synthase/physiology , Pneumonectomy , Vasodilation/physiology , Administration, Inhalation , Animals , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/prevention & control , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide Synthase/therapeutic use , Pneumonectomy/adverse effects
15.
Ann Thorac Surg ; 81(3): 902-9, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16488692

ABSTRACT

BACKGROUND: Paraplegia remains a devastating complication of thoracic aortic surgery, which has been attenuated by retrograde adenosine and systemic adenosine A2A receptor activation. We hypothesized that despite retrograde spinal perfusion of an adenosine A2A agonist (ATL-146e), systemic therapy produces superior spinal cord protection with reduced inflammation. METHODS: Forty pigs underwent 30-minute thoracic aortic cross-clamping. Pigs received: no therapy (control); retrograde saline (retrograde control); retrograde ATL-146e; systemic ATL-146e; systemic ATL-146e with retrograde saline; or systemic and retrograde ATL-146e. Retrograde therapies were given during ischemia. Systemic ATL-146e (0.06 microg.kg(-1).min(-1)) was given intravenously for 3 hours at reperfusion. At 24 hours, motor function was assessed using the Tarlov scale. Tissue was analyzed for neuronal viability, microtubule-associated protein-2 expression, and neutrophil sequestration (myeloperoxidase activity). RESULTS: Four pigs received retrograde barium showing both radiographic and histologic spinal cord perfusion. Tarlov scores at 24 hours were significantly improved versus both control groups in all ATL groups except the combined ATL-146e group (all p < 0.05). Neuronal viability by hematoxylin and eosin stain was significantly preserved in systemic ATL groups compared with both control groups (all p < 0.05). Microtubule-associated protein-2 expression was significantly preserved compared with both control groups in all systemic ATL groups. Systemic ATL significantly lowered myeloperoxidase activity versus both control groups (p < 0.01). CONCLUSIONS: Both retrograde and systemic ATL-146e therapies attenuate ischemic spinal cord injury, but combining the two routes was less effective. Given comparable results between the two routes and the simplicity of systemic delivery, peripheral venous ATL-146e at reperfusion should be preferred for spinal cord protection in thoracic aortic surgery.


Subject(s)
Adenosine A2 Receptor Agonists , Aorta, Thoracic/surgery , Cyclohexanecarboxylic Acids/therapeutic use , Purines/therapeutic use , Spinal Cord Injuries/prevention & control , Animals , Hemiplegia/prevention & control , Hindlimb/physiology , Models, Animal , Postoperative Complications/prevention & control , Radiography , Spinal Cord/diagnostic imaging , Swine
16.
J Card Fail ; 11(9): 670-6, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16360961

ABSTRACT

BACKGROUND: Congestive heart failure (CHF) is the leading cause of hospital admissions in the United States. METHODS AND RESULTS: CHF has a variety of palliative options for treatment and 1 curative one: cardiac transplantation. Palliative medical therapies are often limited in effectiveness by progression of the disease or patient intolerance. Because of limited donor availability, alternative surgical strategies are now being relied on for palliation of patients in end-stage CHF. CONCLUSION: In this manuscript, we review the principles, outcomes, and practices of some of these surgical strategies often used in the palliation of end-stage CHF.


Subject(s)
Heart Failure/surgery , Palliative Care/methods , Heart Failure/epidemiology , Heart Transplantation , Heart Ventricles/surgery , Heart-Assist Devices , Humans , Mitral Valve/surgery , Myocardial Revascularization/methods , Prospective Studies , Treatment Outcome , United States/epidemiology
17.
Ann Thorac Surg ; 80(1): 60-4; discussion 64-5, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15975341

ABSTRACT

BACKGROUND: There is an increasing trend toward work hour restrictions for doctors world wide. These reforms have been inspired, in part, by the assertion by some that the fatigued physician is more prone to making errors. Interestingly, there is very little in the way of objective data with regard to the effects of sleep deprivation on patient outcomes. We have recently studied this in attending surgeons. The present study focused on thoracic surgical residents. Our hypothesis was that acute sleep deprivation would not lead to an increase in operative times or complications. METHODS: A retrospective review of all cases performed by thoracic surgical residents at the University of Virginia from January 1994 to March of 2004 was done. Complication rates of cases performed by "sleep deprived" (SD) residents were compared with cases done when the residents were "not sleep deprived" (NSD). A resident was deemed sleep deprived if he or she performed a case the previous evening that started between 10 pm and 5 am or ended between the hours of 11 pm and 7:30 am. RESULTS: A total of 7,323 cases were recorded in the STS database over the 10-year period examined. Two hundred and twenty-nine of these cases (3%) were performed by SD residents. Mortality rates for coronary artery bypass operations showed no significant differences (2.1% [SD = 3 of 141 patients] vs 3.1% (NSD = 143 of 4452 patients), p = 0.63). A comparison of operative, neurologic, renal, infectious, and pulmonary complications as well as cardiopulmonary bypass times, cross-clamp times, the use of blood products, and length of stay also demonstrated no significant differences between groups. CONCLUSIONS: Acute sleep deprivation in thoracic surgical residents does not affect operative efficiency, morbidity, or mortality in cardiac surgical operations.


Subject(s)
Cardiac Surgical Procedures/statistics & numerical data , Internship and Residency , Sleep Deprivation , Thoracic Surgery , Clinical Competence , Fatigue , Female , Humans , Male , Middle Aged , Retrospective Studies , Work Schedule Tolerance
18.
J Thorac Cardiovasc Surg ; 129(5): 1137-43, 2005 May.
Article in English | MEDLINE | ID: mdl-15867791

ABSTRACT

BACKGROUND: Reperfusion injury continues to significantly affect patients undergoing lung transplantation. Isolated lung models have demonstrated that adenosine A 2A receptor activation preserves function while decreasing inflammation. We hypothesized that adenosine A 2A receptor activation by ATL-146e during the initial reperfusion period preserves pulmonary function and attenuates inflammation in a porcine model of lung transplantation. METHODS: Mature pig lungs preserved with Viaspan (Barr Laboratories, Pomona, NY) underwent 6 hours of cold ischemia before transplantation and 4 hours of reperfusion. Animals were treated with (ATL group, n = 7) and without (IR group, n = 7) ATL-146e (0.05 microg kg -1 . min -1 ATL-146e administered intravenously for 3 hours). With occlusion of the opposite pulmonary artery, the animal was maintained for the final 30 minutes on the allograft alone. Recipient lung physiology was monitored before tissue evaluation of pulmonary edema (wet-to-dry weight ratio), myeloperoxidase assay, and tissue tumor necrosis factor alpha by means of enzyme-linked immunosorbent assay. RESULTS: When the ATL group was compared with the IR group, the ATL group had better partial pressure of carbon dioxide (43.8 +/- 4.1 vs 68.9 +/- 6.3 mm Hg, P < .01) and partial pressure of oxygen (272.3 +/- 132.7 vs 100.1 +/- 21.4 mm Hg, P < .01). ATL-146e-treated animals exhibited lower pulmonary artery pressures (33.6 +/- 2.1 vs 47.9 +/- 3.5 mm Hg, P < .01) and mean airway pressures (16.25 +/- 0.08 vs 16.64 +/- 0.15 mm Hg, P = .04). ATL-146e-treated lungs had lower wet-to-dry ratios (5.9 +/- 0.39 vs 7.3 +/- 0.38, P < .02), lower myeloperoxidase levels (2.9 x 10 -5 +/- 1.2 x 10 -5 vs 1.3 x 10 -4 +/- 4.0 x 10 -5 DeltaOD mg -1 . min -1 , P = .03), and a trend toward decreased lung tumor necrosis factor alpha levels (57 +/- 12 vs 96 +/- 15 pg/mL, P = .06). The ATL group demonstrated significantly less inflammation on histology. CONCLUSION: Adenosine A 2A activation during early reperfusion attenuated lung inflammation and preserved pulmonary function in this model of lung transplantation. ATL-146e and similar compounds could play a significant role in improving outcomes of pulmonary transplantation.


Subject(s)
Cyclohexanecarboxylic Acids/therapeutic use , Disease Models, Animal , Lung Transplantation/adverse effects , Lung/blood supply , Purines/therapeutic use , Receptor, Adenosine A2A , Reperfusion Injury , Adenosine A2 Receptor Agonists , Animals , Blood Gas Analysis , Carbon Dioxide/blood , Cyclohexanecarboxylic Acids/immunology , Drug Evaluation, Preclinical , Enzyme-Linked Immunosorbent Assay , Female , Inflammation , Lung/chemistry , Lung/immunology , Lung/metabolism , Lung Transplantation/immunology , Male , Neutrophil Activation , Organ Size , Oxygen/blood , Peroxidase/analysis , Peroxidase/metabolism , Pulmonary Edema/diagnosis , Pulmonary Edema/etiology , Pulmonary Edema/prevention & control , Purines/immunology , Random Allocation , Receptor, Adenosine A2A/drug effects , Receptor, Adenosine A2A/physiology , Reperfusion Injury/diagnosis , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/prevention & control , Respiratory Function Tests , Severity of Illness Index , Swine , Time Factors , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/immunology
19.
J Surg Res ; 125(2): 161-7, 2005 May 15.
Article in English | MEDLINE | ID: mdl-15854669

ABSTRACT

BACKGROUND: Previous formulations of cyanoacrylate, though very effective, proved to have too high a tissue reactivity to be used internally. A novel cyanoacrylate compound with less tissue reactivity was recently developed. The objective of this study was to assess this novel cyanoacrylate compound for the use as vascular suture line sealant. MATERIALS AND METHODS: Twelve adult female sheep received a 6 mm PTFE interposition graft in each iliac artery, for a total of 24 grafts. Using oxidized cellulose (Surgicel) as a control, two formulations of a new cyanoacrylate compound (named "compound A" and "compound B") were assessed during this trial. Hemostatic efficiency was measured at the time of operation by the assessment of bleeding time and amount of blood loss. Long-term graft patency was assessed angiographically at 4, 6, and 18 months. Tissue reaction at 2 weeks, 1, 6, and 18 months was assessed grossly by vascular surgeons and microscopically by a blinded pathologist. RESULTS: Average time to hemostasis was 37.6, 50.6, and 219 s in group A, group B, and oxidized cellulose control groups, respectively (P

Subject(s)
Cyanoacrylates/pharmacology , Hemostasis, Surgical/methods , Suture Techniques , Anastomosis, Surgical , Animals , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation , Female , Iliac Artery/surgery , Polytetrafluoroethylene/pharmacology , Sheep , Time Factors , Tissue Adhesives/pharmacology , Treatment Outcome
20.
Ann Thorac Surg ; 79(4): 1189-95, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15797048

ABSTRACT

BACKGROUND: Ischemia-reperfusion (IR) injury negatively impacts patient outcome in lung transplantation. Clinically, we observed that lung transplant patients with ischemia-reperfusion injury tend to have cardiac dysfunction. Previous studies have shown that ATL-146e (4-{3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester), a selective adenosine A2A receptor agonist, reduces lung inflammation after ischemia-reperfusion. We hypothesized that pulmonary ischemia-reperfusion causes secondary heart dysfunction and ATL-146e will improve this dysfunction. METHODS: We utilized an in vivo rabbit lung ischemia-reperfusion model. The Sham group underwent 120 minutes single lung ventilation. The IR and ATL groups underwent 90 minutes right lung ischemia with 30 minutes right lung reperfusion. The ATL-146e was given intravenously to the ATL group during reperfusion. Cardiac output and arterial blood gases were monitored, and neutrophil sequestration was measured by myeloperoxidase activity. RESULTS: Upon reperfusion, cardiac output (mL/min) significantly dropped in the IR and ATL groups. By 15 minutes reperfusion, cardiac output in the ATL group improved significantly over the IR group and remained significant thereafter. Lung myeloperoxidase activity was significantly reduced by ATL-146e. Although never hypoxemic, arterial oxygenation was lower in the IR and ATL groups while central venous pressures and mean arterial pressures were similar among groups. A separate experiment demonstrated that reperfusion with the antioxidant N-(2-mercaptopropionyl)glycine prevented cardiac dysfunction. CONCLUSIONS: Pulmonary ischemia-reperfusion causes cardiac dysfunction independent of preload, afterload, and oxygenation. The ATL-146e improves this dysfunction presumably by the antiinflammatory effects of adenosine A2A receptor activation on neutrophils. One likely mechanism involves the release of oxidants from the ischemic lung upon reperfusion, which has immediate negative effects on the heart.


Subject(s)
Adenosine A2 Receptor Agonists , Cyclohexanecarboxylic Acids/pharmacology , Heart/drug effects , Lung/blood supply , Purines/pharmacology , Reperfusion Injury/physiopathology , Animals , Antioxidants/pharmacology , Blood Pressure/drug effects , Cardiac Output/drug effects , Heart/physiopathology , Neutrophil Activation , Oxygen/blood , Peroxidase/metabolism , Rabbits , Reactive Oxygen Species/metabolism
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