Angiogenic proteins in the lungs of children after cavopulmonary anastomosis.

OBJECTIVE: Pulmonary arteriovenous malformations may cause progressive cyanosis after cavopulmonary anastomosis and may develop as a result of abnormal angiogenesis. We used immunohistochemistry to determine whether angiogenic proteins are increased in the lungs of children after cavopulmonary anastomosis. METHODS: Lung specimens were obtained from 13 children after cavopulmonary anastomosis and from 6 control subjects. Specimens were stained with antibodies against vascular endothelial growth factor and its receptor (flk-1/KDR), basic fibroblast growth factor, alpha-smooth muscle actin, CD31, collagen IV, fibronectin, and proliferating cell nuclear antigen. Staining was graded on a scale of 0 to 3. Vessels positive for proliferating cell nuclear antigen were counted in 10 fields per specimen, and the results were averaged. RESULTS: After cavopulmonary anastomosis, patients demonstrated increased staining for vascular endothelial growth factor (P =.03) and its receptor (P =.03) and decreased staining for CD31 (P =.004). Proliferating cell nuclear antigen staining in patients was equivalent to that for control subjects (P =.9). CONCLUSIONS: Lung biopsy specimens from children after cavopulmonary anastomosis demonstrate increased expression of vascular endothelial growth factor and its receptor. These data confirm earlier findings that blood vessels forming after cavopulmonary anastomosis may have reduced intercellular junctions (decreased CD31 staining). Despite the increased numbers of pulmonary vessels that are present in these patients, these vessels are not highly proliferative (proliferating cell nuclear antigen staining equivalent to that of control subjects). These results suggest that vascular endothelial growth factor may be a mediator of angiogenesis in the lungs of children after cavopulmonary anastomosis; however, other factors, such as vascular dilation and remodeling, may also be important.

Is arrhythmia detection by automatic external defibrillator accurate for children?: sensitivity and specificity of an automatic external defibrillator algorithm in 696 pediatric arrhythmias.

BACKGROUND: Use of automatic external defibrillators (AEDs) in children aged <8 years is not recommended. The purpose of this study was to develop an ECG database of shockable and nonshockable rhythms from a broad age range of pediatric patients and to test the accuracy of the Agilent Heartstream FR2 Patient Analysis System for sensitivity and specificity. METHODS AND RESULTS: Children aged

First-stage palliation of complex univentricular cardiac anomalies in older infants.

BACKGROUND: Poor outcomes have been reported for children older than 30 days of age with cardiac anomalies treated with first-stage palliation. METHODS: Our institution has offered first-stage palliation for all such patients regardless of age. The results of this policy were reviewed. RESULTS: Nine patients older than 30 days (median age 67 days, range 36 to 108 days) with diagnoses of hypoplastic left heart syndrome (n = 5), double-outlet right ventricle with hypoplastic aortic arch (n = 2), unbalanced atrioventricular septal defect (n = 1), or single left ventricle with subaortic stenosis (n = 1) underwent surgical palliation. Patients underwent a Norwood (n = 7) or Damus-Kaye-Stancel (n = 2) procedure with a 4- or 5-mm modified Blalock-Taussig shunt; all patients survived the operation. Eight patients underwent a subsequent bidirectional Glenn (2 perioperative deaths, both due to pneumonia; 6 survivors). Two of the 6 surviving patients have undergone Fontan reconstruction and 4 are awaiting Fontan. CONCLUSIONS: Surgical palliation for complex univentricular cardiac malformations can be performed in older infants with results comparable to those in neonates. The use of a larger shunt may contribute to these improved outcomes.

Pulmonary microvessel density is a marker of angiogenesis in children after cavopulmonary anastomosis.

OBJECTIVE: Pulmonary arteriovenous malformations cause progressive cyanosis in children after cavopulmonary anastomosis and may be due to abnormal angiogenesis. We determined the microvessel density, a marker of angiogenesis, in the lungs of children after cavopulmonary anastomosis. METHODS: Lung biopsy specimens were obtained from 8 children after cavopulmonary anastomosis and from 4 control patients. Three of the 8 children undergoing cavopulmonary anastomosis had clinical and angiographic evidence of pulmonary arteriovenous malformations, whereas the other 5 were free of symptoms. Routine histologic and immunohistologic stains were performed with a primary antibody to von Willebrand factor. Microvessel staining for von Willebrand factor was determined for 10 fields (200x) per patient. RESULTS: Patients with and without pulmonary arteriovenous malformations after cavopulmonary anastomosis demonstrated significantly increased microvessel density compared with control subjects (32.7 +/- 2.8 vs 9.3 +/- 4.6, P =.02, and 31.5 +/- 15.7 vs 9.3 +/- 4.6, P =.01, respectively). There was no difference in microvessel density in children with and without clinically apparent pulmonary arteriovenous malformations after cavopulmonary anastomosis (P =.9). The children with pulmonary arteriovenous malformations had numerous greatly dilated vessels that were absent in the asymptomatic children after cavopulmonary anastomosis. CONCLUSIONS: After cavopulmonary anastomosis, pulmonary microvessel density is increased even in the absence of clinically apparent pulmonary arteriovenous malformations, supporting the presence of a constant angiogenic stimulus. Children with clinically apparent pulmonary arteriovenous malformations possess large numbers of greatly dilated pulmonary microvessels, which are absent in asymptomatic children after cavopulmonary anastomosis. These results suggest that the transition to clinically apparent pulmonary arteriovenous malformations may be due to mechanisms that lead to vessel dilation and remodeling.

Procollagen synthesis by fresh and cryopreserved rat pulmonary valve grafts.

OBJECTIVE: Allograft valves are frequently used in the repair of congenital cardiac anomalies. The failure rate may differ depending on the type of allograft used. Previous studies have shown that rat aortic valve grafts exhibit synthesis of procollagen, suggesting a capacity for repair and regeneration after implantation. No studies of pulmonary valve grafts in the heterotopic rat implant model have thus far been reported. This study was designed to investigate whether pulmonary valve grafts maintain in vivo viability, as demonstrated by procollagen synthesis, and whether cryopreservation, histocompatibility, or both affect this property. METHODS: Cryopreserved and fresh rat pulmonary valves were implanted into the abdominal aorta of syngeneic and allogeneic recipients. The grafts and native valves were excised 3 to 21 days after implantation. Valves were sectioned and immunohistochemically stained for procollagen. Computerized morphometry was used to calculate changes in intima, media, and adventitia as a percentage of cross-sectional area of the graft. Procollagen content was graded by semiquantitative methods. RESULTS: Pulmonary valve grafts had significantly greater collagen density in the intima and adventitia compared with native aortic and pulmonary tissues, but collagen density in the media was similar in all groups. The grafts demonstrated appreciably greater procollagen than the corresponding native valves. These findings were consistent in all grafts (ie, both fresh and cryopreserved, both syngeneic and allogeneic), irrespective of duration of implantation. CONCLUSIONS: Procollagen synthesis occurs in pulmonary valve grafts early after implantation, indicating viability of these tissues. This model of pulmonary valve implantation may have wide applicability to questions of allograft biology.

Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease.

OBJECTIVE: Cardiopulmonary bypass suppresses circulating thyroid hormone levels. Although acute triiodothyronine repletion has been evaluated in adult patients after cardiopulmonary bypass, triiodothyronine pharmacokinetics and effects have not previously been studied in infants undergoing operations for congenital heart disease. We hypothesized that triiodothyronine deficiency in the developing heart after bypass may adversely affect cardiac function reserve postoperatively. METHODS: Infants less than 1 year old undergoing ventricular septal defect or tetralogy of Fallot repair were randomized into 2 groups. Group T (n = 7) received triiodothyronine (0.4 microg/kg) immediately before the start of cardiopulmonary bypass and again with myocardial reperfusion. Control (NT, n = 7) patients received saline solution placebo or no treatment. RESULTS: These groups underwent similar ischemic and bypass times and received similar quantities of inotropic agents after the operation. The NT group demonstrated significant depression in circulating levels, compared with prebypass levels, for free triiodothyronine and total triiodothyronine at 1, 24, and 72 hours after bypass. Group T demonstrated similar low thyroxine values, but free and total triiodothyronine levels were maintained at prebypass levels for 24 hours and remained elevated over those of group NT (P <.05) at 72 hours. Heart rate was transiently elevated in group T compared with group NT (P <.05), and peak systolic pressure-rate product increased after 6 hours. CONCLUSION: These data imply that (1) triiodothyronine in the prescribed dose prevents circulating triiodothyronine deficiencies and (2) triiodothyronine repletion promotes elevation in heart rate without concomitant decrease in systemic blood pressure. Elevation of peak systolic pressure-rate product implies that triiodothyronine repletion improves myocardial oxygen consumption and may enhance cardiac function reserve after cardiopulmonary bypass in infants.

Pulmonary function after modified venovenous ultrafiltration in infants: a prospective, randomized trial.

OBJECTIVE: We sought to examine the effects of modified venovenous ultrafiltration after cardiopulmonary bypass on pulmonary compliance in infants. METHODS: We prospectively enrolled 38 infants undergoing their first operation for congenital heart disease. Infants were randomized to receive 20 minutes of modified ultrafiltration after bypass or control. Static and dynamic compliance was measured after induction of anesthesia, before and immediately after filtration in the operating theater, 1 hour after return to the pediatric intensive care unit, and 24 hours after the operation. Length of time on the ventilator, inotropic requirements, and length of stay in the intensive care unit were recorded. RESULTS: Modified ultrafiltration produced a significant immediate improvement in dynamic (pre-ultrafiltration 2.5 +/- 1.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.7 mL/cm H(2)O, P =.03) and static (pre-ultrafiltration 2.1 +/- 0.9 mL/cm H(2)O to post-ultrafiltration 2.9 +/- 2.1 mL/cm H(2)O, P =.04) compliance. However, there was no significant difference in the change in dynamic (P =.3) or static (P =.7) compliance in the ultrafiltration and control groups when compared before the operation, after the operation, and at 24 hours. There was no significant difference in the time to extubation between patients and control subjects (140 +/- 91 hours vs 90 +/- 58 hours) or the length of intensive care unit stay (10.0 +/- 9.1 days vs 7.4 +/- 5.7 days). CONCLUSIONS: Modified ultrafiltration produces an improvement in pulmonary compliance after bypass in infants. However, these improvements are not sustained past the immediate post-ultrafiltration period and do not lead to a decreased length of intubation or intensive care unit stay.

Vascular endothelial growth factor and basic fibroblast growth factor in children with cyanotic congenital heart disease.

OBJECTIVE: Vascular endothelial growth factor and basic fibroblast growth factor are potent stimulators of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor and basic fibroblast growth factor. METHODS: Serum was obtained from 22 children with cyanotic congenital heart disease and 19 children with acyanotic heart disease during cardiac catheterization. Samples were taken from the superior vena cava, inferior vena cava, and a systemic artery. Vascular endothelial growth factor and basic fibroblast growth factor levels were measured in the serum from each of these sites by enzyme-linked immunosorbent assay. RESULTS: Vascular endothelial growth factor was significantly elevated in the superior vena cava (P =.04) and systemic artery (P =.02) but not in the inferior vena cava (P =.2) of children with cyanotic congenital heart disease compared to children with acyanotic heart disease. The mean vascular endothelial growth factor level, determined by averaging the means of all 3 sites, was also significantly elevated (P =.03). Basic fibroblast growth factor was only significantly elevated in the systemic artery (P =.02). CONCLUSION: Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor. These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor.

Intermediate-term results in pediatric aortic valve replacement.

BACKGROUND: Aortic valve replacement (AVR) in children is now more commonly performed with human tissue valves. METHODS: The results of 100 consecutive pediatric AVRs (50 mechanical, 50 human) were reviewed. RESULTS: There were five perioperative deaths in the mechanical group and one in the human group (p = 0.2). Late complications in the mechanical group included 4 late deaths, 2 cases of endocarditis, 3 thromboembolic complications, and 10 reoperations on the aortic valve. In the human group, there were no late deaths, 2 reoperations for allograft aortic valve deterioration (both in Marfan's patients), and 1 reoperation for allograft pulmonary valve stenosis. Four-year actuarial survival was 83% in the mechanical group and 98% in the human group (p = 0.02). Four-year actuarial survival free of all valve-related complications was 61% in the mechanical group and 88% in the human group (p = 0.008). CONCLUSIONS: Human valves in children requiring AVR provide superior intermediate-term survival and freedom from valve-related complications compared to mechanical valves. Marfan's syndrome may represent a rare remaining contraindication for human AVR in children.

A detailed histologic analysis of pulmonary arteriovenous malformations in children with cyanotic congenital heart disease.

INTRODUCTION: Pulmonary arteriovenous malformations are a common cause of progressive cyanosis in children after cavopulmonary anastomoses. We analyzed the pulmonary histologic characteristics from children in whom pulmonary arteriovenous malformations developed after procedures that resulted in pulmonary arterial blood flow devoid of hepatic venous effluent. METHODS: We performed routine histologic studies, immunohistochemical staining, and electron microscopic analysis of peripheral lung biopsy specimens from 2 children with angiographically proven pulmonary arteriovenous malformations. Microvessel density was determined with a computer-assisted, morphometric analysis system. RESULTS: Histologic examination demonstrated large, dilated blood vessels ("lakes") and clustered, smaller vessels ("chains") in the pulmonary parenchyma. Microvessel density was significantly greater in these patients than in age-matched controls (P =.01). Immunohistochemistry demonstrated uniform staining for type IV collagen and alpha-smooth muscle actin, weak staining for the endothelial marker CD31 (cluster of differentiation, PECAM-1), and negative staining for proliferating cell nuclear antigen. Electron microscopy revealed endothelial irregularity, a disorganized basement membrane, and increased numbers of collagen and actin filaments beneath the endothelium. CONCLUSIONS: This study represents an attempt to characterize the histologic features of pulmonary arteriovenous malformations in children with congenital heart disease who have pulmonary arterial blood flow devoid of hepatic venous effluent. The histologic correlate of this condition appears to be greatly increased numbers of thin-walled vessels. Immunohistochemistry suggests that the rate of cellular proliferation is not increased in these lesions. The development of these techniques may provide a standardized histologic approach for this condition and aid in understanding its etiology.

Temperature threshold and preservation of signaling for mitochondrial membrane proteins during ischemia in rabbit heart.

Temperature modulates both myocardial energy requirements and production. We have previously demonstrated that myocardial protection induced by hypothermic adaptation preserves expression of genes regulating heat shock protein and the nuclear-encoded mitochondrial proteins, the adenine nucleotide translocator isoform 1 (ANT1), and the beta subunit of F1-ATPase (beta F1-ATPase). This preservation is associated with a reduction in ATP depletion similar to that noted in cardioplegic arrested hearts preserved at a critical temperature (30 degrees C) or below. We tested the hypothesis that expression of these genes may also be subject to this temperature threshold phenomenon. Isolated perfused rabbit hearts were subjected to ischemic cardioplegic arrest at 4, 30, or 34 degrees C for 120 min. Cardiac function indices and steady-state mRNA levels for ANT1, beta F1-ATPase, and HSP70-1 were measured prior to ischemia (B) and after 45 min of reperfusion. Cardiac function was significantly depressed in the 34 degrees C group. Ischemia at 34 degrees C reduced steady-state mRNA levels for ANT1 and beta F1-ATPase from B, but these levels were similarly preserved at 4 and 30 degrees C. HSP70-1 levels were mildly elevated (fourfold) above B to similar levels at all three temperatures. These results indicate that mRNA expression for ANT1 and beta F1-ATPase is specifically preserved in a pattern consistent with the temperature threshold phenomenon. HSP70-1 expression is not influenced by ischemic temperature. Preservation of gene expression for these mitochondrial proteins implies that signaling for mitochondrial biogenesis or resynthesis is maintained after ischemic insult.

Hypothermia preserves function and signaling for mitochondrial biogenesis during subsequent ischemia.

Hypothermia is known to protect myocardium during ischemia, but its role in induction of a protective stress response before ischemia has not been evaluated. As cold incites stress responses in other tissues, including heat shock protein induction and signaling mitochondrial biogenesis, we postulated that hypothermia in perfused hearts would produce similar phenomena while reducing injury during subsequent ischemia. Studies were performed in isolated perfused rabbit hearts (n = 77): a control group (C) and a hypothermic group (H) subjected to decreasing infusate temperature from 37 to 31 degrees C over 20 min. Subsequent ischemia during cardioplegic arrest at 34 degrees C for 120 min was followed by reperfusion. At 15 min of reperfusion, recovery of left ventricular developed pressure (LVDP), maximum first derivative of left ventricular pressure (LV dP/dtmax), LV -dP/dtmax, and the product of heart rate and LVDP was significantly increased in H (P < 0.01) compared with C hearts. Ischemic contracture started later in H (97.5 +/- 3.6 min) than in C (67.3 +/- 3.3 min) hearts. Myocardial ATP preservation and repletion during ischemia and reperfusion were higher in H than in C hearts. mRNA levels of the nuclear-encoded mitochondrial proteins adenine nucleotide translocase isoform 1 (ANT1) and beta-F1-adenosine-triphosphatase (beta-F1-ATPase) normalized to 28S RNA decreased in C hearts but were preserved in H hearts after reperfusion. Inducible heat shock protein (HSP70-1) mRNA was elevated nearly 4-fold after ischemia in C hearts and 12-fold in H hearts. These data indicate that hypothermia preserves myocardial function and ATP stores during subsequent ischemia and reperfusion. Signaling for mitochondrial biogenesis indexed by ANT1 and beta-F1-ATPase mRNA levels is also preserved during a marked increase in HSP70-1 mRNA.

Temperature threshold and modulation of energy metabolism in the cardioplegic arrested rabbit heart.

Hypothermia protects ischemic tissues by reducing ATP utilization and accumulation of harmful metabolites. However, it also reduces ATP production, which might cause deterioration in the energy supply/demand ratio. Modulation of energy supply/demand according to temperature has not been previously studied in detail. In this study, isolated, perfused rabbit hearts (n = 60) were used to determine the effects of various temperatures on myocardial energy metabolism and function during cardioplegic arrest. Ischemia was induced by crystalloid cardioplegic solution at 4, 18, 30, and 34 degrees C for 120 min, respectively. At each temperature, the hearts were divided into a glucose-treated group which contained 22 mM glucose in cardioplegic solution as the only substrate and a control group which contained 22 mM mannitol to keep same osmolarity. Following 15 min reperfusion, recovery of left ventricular developed pressure (DP), +/- dP/dtmax, and the product of heart rate and DP were significantly higher in 30, 18, and 4 degrees C groups than those in 34 degrees C control group. The functional recovery was also significantly higher in the 34 degrees C glucose-treated group than that in the 34 degrees C control group, but there was no difference between those groups at 30 degrees C and the temperature below 30 degrees C. Myocardial ATP concentration was significantly lower in 34 degrees C control group than those in other groups. There is a close relationship between myocardial ATP concentration and functional recovery (R2 = 0.90). The accumulations of lactate and CO2 were significantly higher at 34 degrees C in glucose-treated group than those in the control group. However, there was no significant difference between these two groups at 30 degrees C and the temperature below 30 degrees C. These results indicate that under these study conditions: (1) a marked decrease in energy supply/demand occurs above 30 degrees C, implying that a temperature threshold exists; and (2) this can be ameliorated by provision of glucose as substrate in cardioplegia solution.

Comparison of Ross procedures and aortic valve allografts in children.

BACKGROUND: The Ross procedure is useful, but at times an allograft valve is the only alternative to a mechanical aortic prosthesis. Since 1994 the Ross procedure or aortic allograft replacement has been used exclusively for aortic valve replacement at our institution. METHODS: Demographic, clinical, and echocardiographic data of 23 consecutive Ross and 8 allograft patients were compared. RESULTS: Groups were similar in age and weight. The Ross group had fewer prior operations. There were no deaths or major complications in either group. The Ross group had no late complications of the autograft but 1 reoperation for pulmonary allograft stenosis. In the allograft group there was one reoperation for allograft insufficiency. Echocardiography was performed 2 to 11 days (mean, 4.3 days) after operation and 1 to 28 months (mean, 10.2 months) later. In the Ross group left ventricular wall thickness (mm) decreased from 11.0 +/- 2.3 to 7.8+/-1.7 (p < 0.0001), and left ventricular outflow tract maximal systolic velocity (m/sec) decreased from 1.9 +/-0.6 to 1.4+/-0.4 (p = 0.0001). In the allograft group left ventricular wall thickness (mm) decreased from 10.5 +/-2.6 to 9.0+/-2.6 (not significant), and left ventricular outflow tract maximal systolic velocity (m/sec) increased from 1.5+/-0.9 to 1.9+/-0.7 (not significant). CONCLUSIONS: The Ross procedure results in significant improvement in left ventricular wall thickness and outflow tract velocity not seen in allograft aortic valve replacements. The Ross procedure remains the preferred operation for children requiring aortic valve replacement.

Influence of the pH of cardioplegic solutions on cellular energy metabolism and hydrogen ion flux during neonatal hypothermic circulatory arrest and reperfusion: a dynamic 31P nuclear magnetic resonance study in a pig model.

OBJECTIVES: The pH of cardioplegic solutions is postulated to affect myocardial protection during neonatal hypothermic circulatory arrest. Neither optimization of cardioplegic pH nor its influence on intracellular pH during hypothermic circulatory arrest has been previously studied in vivo. Thus we examined the effects of the pH of cardioplegic solutions on postischemic cardiac function in vivo, including two possible operative mechanisms: (1) reduction in adenosine triphosphate use and depletion of high-energy phosphate stores or (2) reduction of H+ flux during reperfusion, or both. METHODS: Dynamic 31P spectroscopy was used to measure rates of adenosine triphosphate use, high-energy phosphate depletion, cytosolic acidification during hypothermic circulatory arrest, and phosphocreatine repletion and realkalinization during reperfusion. Neonatal pigs in three groups (n = 8 each)--group A, acidic cardioplegia (pH = 6.8); group B, basic cardioplegia (pH = 7.8); and group N, no cardioplegia--underwent hypothermia at 20 degrees C with 60 minutes of hypothermic cardioplegia followed by reperfusion. RESULTS: Recoveries of peak elastance, stroke work, and diastolic stiffness were superior in group B. Indices of ischemic adenosine triphosphate use, initial phosphocreatine depletion rate, and tau, the exponential decay half-time, were not different among groups. Peak [H+] in group A (end-ischemia) was significantly elevated over that of group B. The realkalinization rate was reduced in group B compared with that in groups A (p = 0.015) and N (p = 0.035), with no difference between groups A and N (p = 0.3). Cytosolic realkalinization rate was markedly reduced and the half-time of [H+] decay was increased during reperfusion in group B. CONCLUSIONS: Superior postischemic cardiac function in group B is not related to alterations in ischemic adenosine triphosphate use or high-energy store depletion, but may be due to slowing in H+ efflux during reperfusion, which should reduce Ca++ and Na+ influx.

Effect of cryopreservation and histocompatibility on type I procollagen gene expression in aortic valve grafts.

BACKGROUND: Allograft valves are excellent substitutes for diseased or absent valves but undergo primary tissue degeneration. Fibroblast viability may determine resistance to valve deterioration. This study evaluated gene expression for procollagen by valve grafts and studied the effects of cryopreservation and histocompatibility on this property. METHODS AND RESULTS: Fresh and cryopreserved rat aortic valves were implanted heterotopically into syngeneic or allogeneic recipients. Nonviable, cryothermally injured valves were used as negative controls. The grafts and native aortic roots were excised 3 days after implantation. Northern hybridization with a human procollagen alpha 1 (I) complementary DNA probe was used to assess the expression of type I procollagen mRNA. The content of procollagen mRNA relative to 18S ribosomal RNA was evaluated by means of scanning densitometry. In situ hybridization was used to locate the areas of procollagen mRNA expression in the grafts. Both fresh and cryopreserved grafts exhibited greater expression than the native valve. This increase in expression was observed in both syngeneic and allogeneic grafts, but not in the negative control group. In situ hybridization showed a strong signal for procollagen in the aortic wall and a weak signal in the leaflet and myocardium in the viable grafts and in native tissues. CONCLUSIONS: Regardless of preservation or allogenicity, fibroblast viability in aortic valve grafts persists after implantation. Increased gene expression for procollagen suggests a capacity for repair and regeneration.

Comparison of human tissues and mechanical prostheses for aortic valve replacement in children.

BACKGROUND: Aortic valve replacement in children is problematic because of complications of mechanical valves and uncertain outcomes associated with human valves. The results of pediatric aortic valve replacements over 5 years were reviewed. METHODS AND RESULTS: Mechanical valves were used exclusively during the first part of this series (n = 26). Thereafter, 25 consecutive aortic valve replacements were performed with autografts (n = 19) or allografts (n = 6). Allografts were used for Marfan's syndrome patients or those with unusable pulmonary valves. Among autograft/allograft recipients, 16 patients underwent 27 prior operations. In the mechanical group, 18 patients underwent 19 previous operations. Three patients in each group underwent a previous mechanical aortic valve replacement. Operative complications included two mild strokes and one pacemaker in the autograft/allograft group and three deaths and two pacemakers in the mechanical group. One autograft recipient required reoperation for pulmonary allograft stenosis. In the mechanical group, late complications included six cases of nonstructural degeneration and two cases of endocarditis, with three reoperations. Reoperation-free survival was 96% at 2 years in the autograft/allograft group and 80% at 2 years and 75% at 3 years in the mechanical group. Event-free survival was 96% at 2 years in the autograft/allograft group compared with 67% at 2 years and 49% at 3 years in the mechanical group (P < .05). CONCLUSIONS: The frequency of reoperations for mechanical aortic valve replacement has been surprisingly high. Aortic valve replacement in children with only autografts or allografts achieves good early results.

Procollagen production in fresh and cryopreserved aortic valve grafts.

Long-term durability of aortic valve allografts may be enhanced by cellular capacities for regeneration and repair. To evaluate aortic valve graft production of an important structural protein, rat aortic roots were implanted heterotopically into the abdominal aorta of recipient rats. Grafts were either syngeneic or strongly allogeneic, were implanted either fresh or after cryopreservation, and were left in place 2 to 21 days after implantation. A total of 80 aortic valve grafts and the corresponding native aortic valves were examined. The grafts were retrieved and immunocytochemically stained for the presence of procollagen, a precursor to collagen. Regardless of histocompatibility or preservation, grafts exhibited consistent procollagen presence that equaled or exceeded that seen in the corresponding native valves. Positive procollagen staining was predominantly in the aortic wall. The most prominent staining was near the hinge point of the valve leaflets, with no staining in the free portion of the leaflets. Staining with alpha-actin demonstrated vascular smooth muscle in sites remote from the areas positive for procollagen, which suggests that vascular smooth muscle was not responsible for the procollagen production. These findings indicate that cryopreservation is compatible with persistent fibroblast viability and in vivo protein synthesis by both syngeneic and allogeneic aortic valve grafts.

Stent redilation in canine models of congenital heart disease: pulmonary artery stenosis and coarctation of the aorta.

In a canine puppy model, pulmonary artery stenosis was created by banding the left pulmonary artery to 30-40% of its original diameter. Animals underwent right heart catheterization and angiography 1-2 mo later, and Palmaz P308 stents were implanted. Stent redilation was performed 3-5 mo later. One mo postredilation, the animals were restudied and sacrificed. Coarctations of the aorta were created by transverse aortic incision and longitudinal repair. P308 stent implantation was performed 2-3 mo later. Stent redilation was performed after 6-10 mo, and the animals were restudied and sacrificed 1-2 mo later. Stent implantation was performed in 6 puppies with pulmonary artery stenosis, as 2 animals developed postoperative pulmonary arterial hypoplasia, precluding stenting. The stenosis diameter increased from 4.8 +/- 0.5 mm to 7.4 +/- 0.6 mm (mean +/- SE) following stenting (P = 0.005), and increased further to 9.2 +/- 0.7 mm following redilation (P < 0.001). There were no significant vessel tears or ruptures. Coarctation stenting was performed in 8 animals. The coarctation was dilated from 5.8 +/- 0.9 mm to 9.8 +/- 0.6 mm (P < 0.001), and to 13.5 +/- 0.5 mm at redilation (P = 0.002). Redilation could not be performed in 1 animal. Aortic rupture and death occurred in 2 of 7 animals at redilation. Stent implantation and redilation in experimental pulmonary artery stenosis appears safe and effective. Though stent implantation for coarctation of the aorta appears safe, there was a 28% aortic rupture rate at stent redilation in this model.