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Biomedical subjects

Carl L Backer

Publications and source records attributed to Carl L Backer.

At least 19 recordsLinked to original sources
PubMed2006

Use of partial cardiopulmonary bypass for coarctation repair through a left thoracotomy in children without collaterals.

BACKGROUND: Paraplegia is a devastating complication of coarctation of the aorta (COA) repair. Since 1990 we have used left atrium-to-descending aorta cardiopulmonary bypass (CPB) for COA repair in patients with inadequate collaterals. We reviewed the results with that strategy and compared this CPB group with COA repairs in which CPB was not used to see whether there was any increase in morbidity or delay in recovery. METHODS: From 1990 to 2006, 11 patients with COA were identified to have inadequate collaterals based on preoperative examination and intraoperative arterial monitoring and test clamp. Left thoracotomy with left atrium-to-descending aorta CPB was used in all. Age ranged from 4.2 to 17.4 years (mean, 8.7 +/- 4.6 years). Two were reoperations for recurrent COA, 3 patients had four prior transcatheter balloon dilatations. One patient had aberrant origin of the right subclavian artery. Operative techniques included resection with extended end-to-end anastomosis (n = 6), interposition graft (n = 4), and patch repair (n = 1). During the same period 71 patients older than 1 year of age had COA repair without CPB. Age ranged from 1.1 to 46.1 years (mean, 7.6 +/- 7.1 years; p = 0.6). RESULTS: Preoperative imaging of CPB patients demonstrated absence of collaterals (n = 7), possible collaterals (n = 2), small collaterals (n = 1), and anomalous origin of the right subclavian artery (n = 1). Preoperative arm leg gradient in CPB patients was 36.0 +/- 9.0 mm Hg versus 49.9 +/- 15 mm Hg in non-CPB patients (p < 0.01). Mean distal femoral artery pressure with aortic test clamp was 34.3 +/- 4.8 mm Hg in CPB patients versus 49.8 +/- 12.4 mm Hg in non-CPB patients (p < 0.01). Mean CPB flow was 53% +/- 7.3% of calculated total flow. Cardiopulmonary bypass time ranged from 17 to 46 minutes (mean, 27.5 +/- 9.7 minutes). Aortic clamp time in CPB patients ranged from 15 to 33 minutes (mean, 21.6 +/- 6.3 minutes). In the non-CPB group aortic clamp time ranged from 10 to 50 minutes (mean, 23.4 +/- 7.5 minutes; p = 0.5). In the CPB group length of stay ranged from 3 to 7 days (mean, 4.9 +/- 1.3 days), and in the non-CPB group length of stay ranged from 3 to 12 days (mean, 4.7 +/- 1.4 days; p = 0.5). No patient had a neurologic complication. There were no other major complications in the CPB group (eg, bleeding, recurrent laryngeal nerve injury, re-COA). CONCLUSIONS: Preoperative imaging and a lower arm-to-leg gradient in this series of COA patients suggested inadequate collateral circulation with the potential need for CPB. A femoral artery pressure of less than 45 mm Hg during test clamp was used as an indication for partial CPB. The use of left atrium-to-descending aorta CPB with just over 50% calculated total flow protected the spinal cord in a safe and expeditious fashion. Use of left heart bypass did not affect morbidity or recovery time as compared with COA repair in non-CPB patients.

Adolescent↗
PubMed2005

Tetralogy of Fallot: results of a pulmonary valve-sparing strategy.

BACKGROUND: Our surgical strategy for repair of tetralogy of Fallot has focused on preserving the pulmonary valve. The purpose of this review was to identify pulmonary valve characteristics that mark the limits of this strategy. METHODS: From 1997 through 2004, 102 consecutive patients underwent repair of tetralogy of Fallot at a median age of 5.9 months. Twenty-five patients had a prior shunt. Eighty-two patients (80%) had pulmonary valve-sparing procedures, predominantly through a transatrial and transpulmonary approach (n = 52). Twenty patients had a transannular patch (20%). Intraoperative measurements included the pulmonary valve annulus size and the postoperative pressure ratio between the right and left ventricles. RESULTS: Eighty of 85 (94%) patients with z-score greater than -4 had a pulmonary valve-sparing procedure compared with 2 of 17 patients (12%) with pulmonary valve annulus z-scores less than -4 (p < 0.0001). All patients with a tricuspid pulmonary valve (n = 26) had a pulmonary valve-sparing procedure compared with 56 of 76 (74%) patients with a bicuspid pulmonary valve (p = 0.0016). Five patients with initial pulmonary valve-sparing operations required reoperation for residual stenoses; 4 pulmonary valve-sparing right ventricular outflow tract resections and 1 transannular patch. The only death occurred after reoperation elsewhere. Three of 9 patients (33%) who had a postoperative pressure ratio between the right and left ventricles greater than 0.7 after their initial pulmonary valve-sparing procedure required reoperation compared with 2 of 73 with postoperative pressure ratio between the right and left ventricles less than 0.7 (3%; p = 0.008). Fifteen of 25 patients (60%) with prior shunts had pulmonary valve-sparing procedures. CONCLUSIONS: A pulmonary valve-sparing approach to the repair of tetralogy of Fallot was applied successfully in 80% of patients. Significant markers for success were a measured pulmonary annulus z-score of -4 or larger, a tricuspid pulmonary valve, and a postoperative pressure ratio between the right and left ventricles less than 0.7.

Female↗
PubMed2005

Neointimal inflammation and adventitial angiogenesis correlate with severity of cardiac allograft vasculopathy in pediatric recipients.

BACKGROUND: Chronic inflammation and angiogenesis have been implicated in the pathogenesis of both cardiac allograft vasculopathy (CAV) and age-related vasculopathy. Because concurrent atherosclerosis does not complicate assessment of CAV in children, we sought to characterize the spectrum of coronary lesions in this population and determine whether inflammatory infiltrates and angiogenesis correlate with severity of CAV. METHODS: In 18 pediatric heart specimens CAV was graded 1 to 4 (none to severe). Each case was assigned to either: Group I, no inflammation; Group II, perivascular inflammation; or Group III, perivascular and neointimal inflammation. Inflammatory infiltrates were immunophenotyped using anti-CD3, anti-CD20 and HAM 56. Angiogenesis was assessed by determining microvascular density (MVD) in 5 high-power fields (HPFs) per section. RESULTS: CAV was evident in 94% of cases, and inflammation in 61%. Cases with neointimal inflammation had significantly more severe CAV compared with cases without inflammation (2.7 +/- 0.16 vs 1.9 +/- 0.2, p = 0.002). MVD was significantly higher in both inflammation groups (Groups II and III) compared with Group I (4.1 +/- 0.5 per HPF and 5.9 +/- 0.5 vs 3.1 +/- 0.7, p = 0.018 and p = 0.002) and correlated with the degree of CAV (p = 0.007). The perivascular infiltrates (Group II, n = 5) contained lymphocytes, macrophages and plasma cells, and 67% of neointimal infiltrates (Group III, n = 6) also contained eosinophils. CONCLUSIONS: CAV in children is more common than previously reported. Our data indicate that CAV is often associated with inflammation and that adventitial angiogenesis correlated with the severity of CAV.

Adolescent↗
PubMed2005

Osteopontin expression and adventitial angiogenesis induced by local vascular endothelial growth factor 165 reduces experimental aortic calcification.

BACKGROUND: Vascular calcification is a common pathologic and precisely regulated process involving bone-associated proteins such as osteopontin. In this study, we investigated mechanisms by which recombinant human vascular endothelial growth factor 165 protects the arterial wall from severe vascular remodeling, including calcification, a newly discovered biologic action of vascular endothelial growth factor. METHODS: In a rabbit model of thoracic aortic end-to-end anastomosis that simulates cardiovascular intervention, recombinant human vascular endothelial growth factor 165 at a dose of 0.75 mug (n = 19) or albumin (control; n = 19) was delivered intraluminally and on the serosal surface. Animals were killed, and aortic tissue was evaluated by Western blotting, immunohistochemistry, and immunofluorescence at 4, 8, and 24 hours; 1 week; and 1 month after surgery. RESULTS: All controls revealed extensive aortic medial calcification at 1 month, whereas calcification was significantly reduced or absent with vascular endothelial growth factor treatment. Compared with controls, vascular endothelial growth factor treatment resulted in an earlier infiltration of macrophages in the vessel media (at 8 hours: 5.7 +/- 2.3 macrophages per high-power field in control vs 32.1 +/- 7.5 in vascular endothelial growth factor-treated aortas; P < .001), whereas controls showed an increase in macrophages starting at 1 week (24.1 +/- 6.9 vs 4.3 +/- 1.8; P < .001). Osteopontin expression was transiently increased and detected in macrophages and endothelial cells in vascular endothelial growth factor-treated vessels, and adventitial microvascular density was significantly increased by 1 week (9.5 +/- 0.43 vs 25.0 +/- 1.3; P < .001). CONCLUSIONS: Our data suggest that exogenous vascular endothelial growth factor is capable of increasing adventitial angiogenesis and shifting macrophage infiltration and osteopontin expression in the media to an earlier time point, thereby promoting prompt repair and diminishing vascular remodeling and calcification after acute vascular injury.

Animals↗
PubMed2005

Trends in vascular ring surgery.

OBJECTIVE: We sought to review our experience with infants and children with anatomically complete vascular rings (ie, double aortic arch and right aortic arch with left ligamentum) and define perioperative trends in diagnostic imaging, operative techniques, and clinical outcomes. METHODS: From 1946 through 2003, 209 patients (113 with double aortic arch and 96 with right aortic arch) underwent surgical repair. Mean and median ages at the time of the operation were as follows: double aortic arch, 1.4 +/- 2.4 years and 0.75 years, respectively; right aortic arch, 2.7 +/- 3.9 years and 0.9 years, respectively. Fourteen (14.6%) patients with right aortic arch had an associated Kommerell diverticulum. Cardiac diagnoses were present in 26 (12.4%) of 209 patients. RESULTS: There has been no operative mortality since 1959. In the past 30 years, mean hospital stay decreased from 8 to 3 days. Primary means of diagnosis has shifted from barium swallow and angiography to computed tomographic scanning or magnetic resonance imaging. In the past 10 years, 73% of patients had preoperative or intraoperative bronchoscopy. The technique of operation has shifted to a muscle-sparing left thoracotomy without routine chest drainage. In 7 recent patients with right aortic arch and a Kommerell diverticulum, the diverticulum was resected, and the left subclavian artery was transferred to the left carotid artery as a primary procedure. CONCLUSIONS: At our institution, computed tomographic scanning has replaced barium swallow as the diagnostic procedure of choice for vascular ring evaluation. We recommend both preoperative bronchoscopy and echocardiography. Use of a muscle-sparing thoracotomy without routine chest drainage has decreased mean hospital stay. For patients with a right aortic arch and associated Kommerell diverticulum, we recommend diverticulum resection with left subclavian artery transfer to the left carotid artery.

Aorta, Thoracic↗
PubMed2005

Local delivery of osteopontin attenuates vascular remodeling by altering matrix metalloproteinase-2 in a rabbit model of aortic injury.

OBJECTIVE: Vascular remodeling, often accelerated after cardiovascular procedures, may result in stenosis or aneurysm formation. The bone-associated protein osteopontin has been suggested to be involved in vascular remodeling, yet the effect of locally applied osteopontin in an acute vascular injury model of aortic calcification has not been examined. METHODS: Vascular healing of rabbit thoracic aortas treated locally with recombinant osteopontin (dose: 1 microg; n = 16) or albumin (control, n = 16) after acute injury created by end-to-end anastomosis was evaluated. Matrix metalloproteinase-2 level was quantified by gelatin zymography. Proliferation of smooth muscle cells was detected by immunostaining for proliferative cell nuclear antigen. RESULTS: Osteopontin-treated aortas showed significantly diminished vascular remodeling with less calcification (P = .001) and reduced anastomotic luminal stenosis (4% vs 28%, P = .002) compared with controls 2 months postsurgery. Moreover, osteopontin-treated aortas revealed a thickened adventitia with increased fibrosis (P = .006). Matrix metalloproteinase-2 level was up-regulated 2-fold with osteopontin treatment compared with control at 1 week, returning to baseline by 1 month. Staining for proliferation cell nuclear antigen disclosed an increase in proliferation cell nuclear antigen-positive smooth muscle cells in the media of osteopontin-treated aortas at 1 week, normalizing by 1 month. CONCLUSIONS: These data suggest a beneficial effect of locally applied osteopontin after acute injury possibly by altering matrix metalloproteinase-2 activity and smooth muscle cell proliferation. Brief application of osteopontin may effectively enhance vascular healing by reducing calcification and thus maintaining luminal integrity. The role of the osteopontin-related increase in adventitial fibrosis on vascular healing has to be explored.

Animals↗
PubMed2005

Effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children.

OBJECTIVES: We sought to determine the effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children and to assess whether such changes are associated with morbidity. METHODS: At 6 perioperative time points in 25 patients, plasma levels of atrial natriuretic peptide, brain natriuretic peptide, and guanosine 3', 5'-monophosphate were measured, and the biologic activity of the natriuretic hormone system was quantified. Relationships were sought between changes in brain natriuretic peptide levels, biologic activity, and a number of morbidity indicators. RESULTS: There was a significant change in atrial natriuretic peptide levels (P = .037), brain natriuretic peptide levels (P = .001), and biologic activity of the natriuretic hormone system (P = .009) over the first 4 time points in the study. Atrial natriuretic peptide levels transiently decreased from baseline to 12 hours after surgical intervention. Compared with baseline values, brain natriuretic peptide levels were increased at 12 hours after surgical intervention and on postoperative day 1. The increase in brain natriuretic peptide levels from baseline to 12 hours after surgical intervention was associated with cardiopulmonary bypass time (r(s) = 0.4, P = .047). The biologic activity transiently decreased from baseline to intensive care unit admission but was not associated with any morbidity indicators. CONCLUSIONS: Increased postoperative brain natriuretic peptide levels are associated with longer bypass times. The biologic activity of the natriuretic hormone system is transiently impaired. Larger studies should investigate brain natriuretic peptide as a predictor of postoperative morbidity and the potential for natriuretic hormone infusions to improve postoperative hemodynamics and urine output.

Adolescent↗
PubMed2005

The case against minimally invasive cardiac surgery.

Stellar outcomes have been achieved for patent ductus arteriosus (PDA), atrial septal defect (ASD), and ventricular septal defect (VSD) repairs by using the traditional surgical methods. Over the last decade, minimally invasive procedures have been introduced that promise excellent results with an improved cosmetic appearance, shorter rehabilitation period, less pain, and decreased hospital cost. We reviewed various minimally invasive procedures that are used in PDA, ASD, and VSD to assess their safety and efficacy. These techniques use limited approaches to the heart (partial sternotomies, transxiphoid, anterolateral thoracotomy, and mini-thoracotomy) that reduce the surgeons access and control of the cardiac structures. Cannulation sites for the establishment of cardiopulmonary bypass have been altered. Minimally invasive therapies for congenital heart surgery cannot be adopted until evidence-based data has proven them to be equal or better than the traditional procedure.

Cardiac Surgical Procedures↗
PubMed2005

Hypertensive emergency associated with thoracoabdominal aneurysm: case report and review.

OBJECTIVE: To provide a description and thorough discussion of the diagnostic considerations for a rare case of malignant hypertension and aortic aneurysm in a pediatric patient. DESIGN: Case report. SETTING: A university pediatric intensive care unit. SUBJECT: A young child with a hypertensive crisis and a thoracoabdominal false aortic aneurysm. INTERVENTIONS: The child required urgent surgical intervention to resect the aneurysm and aggressive medical therapy in the pediatric intensive care unit to treat the underlying hypertension. CONCLUSIONS: Hypertensive emergencies and aortic aneurysms are unusual but potentially lethal entities in pediatric patients, requiring a high index of suspicion, prompt initiation of medical therapy, and urgent surgical consultation.

Aneurysm, False↗
PubMed2004

Captopril suppresses post-transplantation angiogenic activity in rat allograft coronary vessels.

BACKGROUND: The development of transplant coronary artery disease is associated with neovascularization in the thickened neointima. We previously reported that captopril inhibits neointimal proliferation in a rat allograft model. We postulated that angiogenic inducers are upregulated post-transplantation and captopril ameliorates transplant coronary artery disease by suppressing the angiogenic activity of coronaries. METHODS: Animals received no treatment or captopril (50 mg/kg/day). Allograft hearts were analyzed at post-transplantation Days 0, 14, and 21 and angiogenic inducer, plasma platelet-activating factor, determined. The conditioned media from coronaries and myocardium were tested for vascular endothelial growth factor, thrombospondin-1 and angiogenic activity using an endothelial migration assay and rat corneal neovascularization assay. RESULTS: The captopril-treated group had reduced plasma platelet-activating factor and coronary media revealed earlier upregulation of thrombospondin-1 secretion, diminished vascular endothelial growth factor and no angiogenic activity. At Day 0, the coronary and myocardial conditioned medium had inhibitory activity due to thrombospondin-1, and circulating levels of platelet-activating factor were negligible. By 21 days post-transplantation, plasma platelet-activating factor was elevated and the conditioned medium from untreated coronaries had significantly higher angiogenic activity due to increased vascular endothelial growth factor whereas the myocardium remained non-angiogenic. CONCLUSIONS: After transplantation, coronary vessels switch to an angiogenic phenotype and vascular endothelial growth factor contributes to the high angiogenic activity, possibly exacerbated by high circulating levels of platelet-activating factor. The ability of captopril to modulate angiogenic mediators and maintain the allograft coronary to its normal anti-angiogenic phenotype may be one mechanism by which it suppresses transplant coronary artery disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Surgery for arrhythmias in children.

BACKGROUND: Transcatheter radiofrequency ablation to treat supraventricular and ventricular arrhythmias has supplanted routine surgical ablative therapy and redefined its role. A small population of arrhythmia patients now requires surgical ablation: those who have failed catheter ablation, patients with concomitant congenital heart disease in association with arrhythmias, those with atrial fibrillation and very young patients for whom transcatheter techniques are prohibitive because of small size, cyanosis or distorted anatomy. METHODS: From July 1992 through August 2003, 133 patients underwent arrhythmia surgery at Children's Memorial Hospital, 50% (67/133) in association with Fontan conversion (FC), 22% (28/133) with concomitant initial Fontan (IF) procedure and 28% (38/133) for various arrhythmias (MISC) in patients with (36/38, 95%) or without (2/38, 5%) associated structural heart disease. Mean age at surgery in the FC group was 20+/-7.6 years (median 19 years), and in the IF group and the MISC group, mean ages were 8.1+/-8.9 (median 4.2) years and 16.4+/-10.9 (median 11.3) years, respectively. RESULTS: There were three operative (3/133, 2.6%; 1 FC, 2 MISC) and three late deaths (2 FC, 1 MISC). Four patients in the FC group had progressive ventricular failure and underwent successful cardiac transplantation. Follow-up data are available for non-transplant, surviving patients and reveal 11 incidences of persistent arrhythmia recurrence and 2 new-onset arrhythmias. Five of the 11 recurrences occurred early in our series of FC patients, when isthmus block interruption of arrhythmia foci was performed. Four additional recurrences occurred later in the FC series, two post-maze and two post-Cox-maze III. In the MISC group, there were two recurrences. Atrial reentry tachycardia (ART) recurred in a patient with no structural heart disease and accessory connection-mediated tachycardia recurred in a child who underwent concomitant initial Fontan. Two patients had ventricular tachycardia inducible at postoperative studies (2/7, 29%), but no clinical recurrence. Two new-onset tachycardias occurred, one child developed ART post-surgical ablation of accessory connections and one patient with inducible ventricular tachycardia developed ART 5 years postoperatively. CONCLUSION: Variations in atrial and ventricular anatomy that may limit the catheter approach can be addressed surgically. Patient size or anatomic complexity should not be limiting factors in the combined surgical arrhythmia approach. Incorporation of arrhythmia therapy into planned surgical revision should be considered.

Adolescent↗
PubMed2003

Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model.

BACKGROUND: Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis. METHODS AND RESULTS: In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n=15), resection of an aortic ring (tension; n=14) or resection and topical VEGF treatment (0.75 microg VEGF165; tension+VEGF; n=14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at 1 month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group). CONCLUSIONS: In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.

Administration, Topical↗
PubMed2003

Aprotinin reduces operative closure time and blood product use after pediatric bypass.

BACKGROUND: The use of aprotinin in children undergoing cardiopulmonary bypass is controversial. We hypothesized that aprotinin would reduce blood product use and operative closure time in selected pediatric patients. METHODS: For a 6-month period starting in October 1999, consecutive cardiopulmonary bypass patients 6 months of age or less (n = 18) or having a repeat sternotomy (n = 18) received aprotinin. Similar consecutive patients from the preceding 6 months served as controls (n = 35 and 41, respectively). Data extracted from medical records included preoperative clinical characteristics, operative and postoperative procedures, and total blood product use. RESULTS: Patients in the aprotinin and control groups were well matched with regard to preoperative and intraoperative variables. Patients 6 months of age or less who received aprotinin required less operative closure time when compared with controls (median, 93 vs 127 minutes, p = 0.004), and trended toward requiring fewer red blood cell unit exposures (median, three vs five exposures, p = 0.07). Patients undergoing repeat sternotomy who received aprotinin required less operative closure time when compared with controls (mean, 126 vs 159 minutes, p = 0.007), fewer red blood cell unit exposures (median three vs four exposures, p = 0.002), and fewer fresh-frozen plasma unit exposures (median, zero vs one exposure, p = 0.007). CONCLUSIONS: Aprotinin reduced operative closure time and blood product exposure in pediatric patients undergoing cardiopulmonary bypass who were 6 months of age or less or underwent a repeat sternotomy.

Aprotinin↗