RESUMO
OBJECTIVES: We attempted to evaluate the efficacy and tissue reaction of a new miniature interventional ductal occlusion device in neonatal pigs. BACKGROUND: A variety of devices are used to close persistent ductus arteriosus (PDA) by interventional measures. Because of the size of these devices, they have not been applied to term or preterm neonates. Newborn piglets are comparable in size and fragility to human term and preterm neonates. METHODS: Memory-shaped double-cone stainless steel coils were mounted on a titanium-nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 3F Teflon catheter. Two piglet models of PDA were used: 1) ductal patency maintained by stents (n = 6), and 2) ductal patency produced by angioplasty (n = 7) to avoid stent-coil interaction. RESULTS: Placement of the coils within the PDA was possible in all piglets. Before final detachment, the coils were retrieved or repositioned, or both, up to eight times. In all but two piglets the ductus was closed within 1 h of the procedure. The coils were never dislocated and caused no infections or relevant aortic and pulmonary artery obstruction (95% confidence interval for missing complications [0 of 13] extends to 23%). Histologic and electron microscopic studies revealed endothelial coverage of the implants and histiocytic reaction but no local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device was effective in experimental models of PDA. The information obtained warrants initial trials of the device in neonates.
Assuntos
Permeabilidade do Canal Arterial/terapia , Embolização Terapêutica/instrumentação , Animais , Animais Recém-Nascidos , Materiais Biocompatíveis , Cateterismo Cardíaco , Modelos Animais de Doenças , Desenho de Equipamento , Estudos de Avaliação como Assunto , Feminino , Masculino , Stents , SuínosRESUMO
OBJECTIVES: We sought to evaluate the efficacy and tissue reaction of a new miniature interventional device for occlusion of large patent ductus arteriosus (PDA) in a neonatal lamb model. BACKGROUND: A variety of devices are used to close PDAs by interventional measures. Spring coils found to have a high cumulative occlusion rate have thus far been limited to smaller PDAs because of the physical limitation of grip forces. METHODS: Memory-shaped double-cone stainless steel coils with enhanced stiffness of the outer rings by a double-helix configuration were mounted on a titanium/nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 4F or 5F Teflon catheter. A chronic lamb model (n = 8) of PDA (>5 mm) was used in which ductus patency was secured by a protocol of repetitive angioplasty procedures. The animals were killed after 1 to 181 days, and the ductal region was examined by inspection as well as by light and electron microscopy. RESULTS: Placement of the coils within the PDA was possible in all lambs. Before final detachment, the coils were retrieved or repositioned, or both, up to 12 times. In all but one animal the ductus was closed within 6 days after the procedure. The coils caused no infections or aortic and pulmonary artery obstruction. Histologic and electron microscopic studies revealed endothelial coverage of the implants but no foreign body reaction or local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device effectively closed large PDAs in our model and may overcome the previous limitations of coils. Clinical trials are indicated.
Assuntos
Permeabilidade do Canal Arterial/terapia , Embolização Terapêutica/instrumentação , Angiografia , Animais , Animais Recém-Nascidos , Procedimentos Cirúrgicos Cardíacos/métodos , Modelos Animais de Doenças , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/patologia , OvinosRESUMO
OBJECTIVES: The goal of this study was to test the hypothesis that moderate hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND: Moderate hypothermia during experimental CPB stimulates production of interleukin-10 (IL10) and blunts release of tumor necrosis factor-alpha (TNFalpha). METHODS: Twelve young pigs were assigned to a temperature (T degrees ) regimen during CPB: moderate hypothermia (T degrees : 28 degrees C; n = 6) and normothermia (T degrees : 37 degrees C; n = 6). Intra-myocardial TNFalpha- and IL10-messenger RNA were detected by competitive reverse transcriptase polymerase chain reaction and quantification of cytokine synthesis by Western blot. Levels of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined during and after CPB. Myocardial cell damage was assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h after CPB. RESULTS: Synthesis of IL10 was significantly higher, while that of TNFalpha was significantly lower, in pigs that were in moderate hypothermia during surgery than in the others. In contrast with normothermia, moderate hypothermia was also associated with significantly lower cumulative cardiac lymphatic flow during and after CPB, significantly lower lymphatic cTnI concentrations after CPB, significantly lower percentages of myocardial cell necrosis and a significantly lower score of ultrastructural anomalies of myocardial cells. While the percentage of apoptotic cells was not different between groups, the apoptosis/necrosis ratio tended to be higher in animals that were in moderate hypothermia during surgery. In all animals, TNFalpha synthesis correlated positively while IL10 production correlated negatively with necrosis and total cell death, respectively. CONCLUSIONS: Our results suggest that moderate hypothermia during CPB provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.
Assuntos
Ponte Cardiopulmonar , Hipotermia Induzida , Miocárdio/patologia , Animais , Apoptose , Morte Celular , Feminino , Hemodinâmica , Marcação In Situ das Extremidades Cortadas , Interleucina-10/biossíntese , Miocárdio/metabolismo , Suínos , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Serum concentrations and half-life times of digoxin were determined in ten mature and nine premature newborns. Median serum digoxin concentration was 2.3 ng/ml (1.2 to 3.5 ng/ml) in mature newborns and 2.4 ng/ml (1.5 to 4.5 ng/ml) in premature newborns. Median serum digoxin half-life was 35 hours (17 to 52 hours) in mature newborns and 57 hours (38 to 88 hours) in premature newborns. The difference in serum digoxin half-life between the two groups is statistically significant. The relatively long serum digoxin half-life in premature newborns is probably due to immature renal function in this group. The data emphasize the need for cautious digoxin administration, especially in premature infants.
Assuntos
Digoxina/sangue , Doenças do Recém-Nascido/sangue , Doenças do Prematuro/sangue , Digoxina/administração & dosagem , Digoxina/uso terapêutico , Meia-Vida , Humanos , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Doenças do Prematuro/tratamento farmacológicoRESUMO
Part 1 of the study measured the end-systolic and end-diastolic left atrial (LA) areas and volumes in 30 children through sector echocardiography, and compared these values with those obtained with biplane angiocardiography. A strong correlation exists between the LA area in the frontal plane as determined by apical (r greater than 0.91) and subcostal (r greater than 0.98) echocardiography on the one hand and by angiocardiography on the other. However, there is a slight underestimation of the LA area by the apical 4-chamber view. LA volume as determined by subcostal sector echocardiography in the frontal and sagittal plane also correlated well with LA volume calculated with biplane angiocardiography (r greater than 0.97). Part 2 of the study determined LA areas and volumes in 74 healthy newborns and infants by echocardiography and related them to body weight and body surface area, thus obtaining normal values for this age group. The relation of the LA area and volume measurements in newborns and infants to body weight or surface area was best described by a linear function. The mean of the percentage of systolic-diastolic area diminution was 53 +/- 6% for the apical 4-chamber view and 50 +/- 4% for the subcostal 4-chamber view. LA ejection fraction determined by the subcostal biplane volume measurements was 62 +/- 7% (mean +/- standard deviation). These values were independent of body weight or surface area.
Assuntos
Volume Cardíaco , Ecocardiografia , Átrios do Coração/anatomia & histologia , Angiocardiografia , Superfície Corporal , Peso Corporal , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Valores de ReferênciaRESUMO
Children who underwent arterial switch operation for simple transposition of the great arteries in the neonatal period are now reaching an age when exercise testing becomes feasible. This study was conducted to assess exercise tolerance and electrocardiographic response to exercise stress in 50 asymptomatic children, aged 4 to 9 years, using the Bruce walking treadmill protocol to voluntary exhaustion. Heart rate and blood pressure response to exercise stress, endurance time, and electrocardiographic changes were analyzed and compared with those of age-matched normal children. Forty-seven patients had normal exercise capacity and parameters. One patient, whose coronary angiogram showed occlusion of the left main coronary artery, developed electrocardiographic signs of myocardial ischemia during exercise. In 1 patient with a single right coronary artery ostium and in another, who underwent a neonatal internal mammary bypass graft for obstruction of the right coronary artery, the resting electrocardiogram showed ventricular premature complexes and exercise stress-induced salvos of ventricular tachycardia. We conclude that most of the children who underwent the neonatal arterial switch operation for simple transposition of the great arteries have a normal exercise capacity. Exercise testing appears to be useful in detecting ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve.
Assuntos
Teste de Esforço , Tolerância ao Exercício , Transposição dos Grandes Vasos/fisiopatologia , Transposição dos Grandes Vasos/cirurgia , Fatores Etários , Pressão Sanguínea , Estudos de Casos e Controles , Criança , Pré-Escolar , Angiografia Coronária , Feminino , Frequência Cardíaca , Humanos , Masculino , Transposição dos Grandes Vasos/complicaçõesRESUMO
This study examined the hypothesis that core temperature (T(o)) during cardiopulmonary bypass (CPB) influences the perioperative systemic inflammatory response and post-operative organ damage. Twenty-four pigs were assigned to a T(o) regimen during CPB: normothermia (T(o) 37 degrees C; n = 8), moderate hypothermia (T(o) 28 degrees C; n = 8), or deep hypothermia (T(o) 20 degrees C; n = 8). Perioperative leukocyte activation, endotoxin release, and production of tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL10) were examined with regard to post-operative organ damage, which was scored at histological examination of tissue probes of heart, lungs, liver, kidney, and ileum, taken 6 h after CPB. Total blood leukocyte count and TNFalpha plasma levels during CPB were significantly lower and IL10 levels were significantly higher in the moderate hypothermic group than in both other groups. Elastase activity, leukotriene B4-, and endotoxin levels were not affected by T(o) regimen. Moderate hypothermia was associated with the lowest histological organ damage score and normothermia with the highest. In all animals organ damage score for heart, lungs, and kidneys correlated significantly with TNFalpha levels at the end of CPB. Our data demonstrate a clear relationship between TNFalpha production during cardiac operations and post-operative multiple-organ damage. Moderate hypothermia, by stimulating IL10 synthesis and suppressing TNFalpha production during CPB, might provide organ protection.
Assuntos
Ponte Cardiopulmonar , Animais , Ponte Cardiopulmonar/efeitos adversos , Citocinas/imunologia , Feminino , Leucócitos/imunologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/patologia , Suínos , TemperaturaRESUMO
OBJECTIVE: The developmental status of children beyond 3 years of age after the neonatal arterial switch operation has not yet been systematically evaluated and is the topic of the present work. METHODS: Seventy-seven unselected children operated on as neonates with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass were examined at an age of 3.2 to 9.4 years (5.4 +/- 1.6 years, mean +/- standard deviation). Clinical neurologic status, standard scores of intelligence, acquired abilities and vocabulary, and standardized tests on gross motor and fine motor functions were carried out, and the results were related to preoperative, perioperative, and postoperative status and management. RESULTS: Neurologic impairment was more frequent (9.1%) than in the normal population. Intelligence was not different in these patients compared with normal children (p = 0.11), but motor function, vocabulary, and acquired abilities were poorer. Reduced intelligence was found in 9.1%, fine motor dysfunction in 22.1%, and gross motor dysfunction in 23.4% of the children. Intelligence was weakly but significantly inversely related to the duration of bypass (Spearman correlation coefficient -0.25, p = 0.03) and tended to be inversely related to the duration of circulatory arrest (-0.21, p = 0.07), but not to core cooling time on bypass or degree of hypothermia. Gross motor function, vocabulary, and acquired abilities were not significantly related to any of the perioperative parameters considered. No correlation was found between the test results and the variables perinatal asphyxia, perioperative and postoperative cardiocirculatory insufficiency, resuscitation events, and plexal or intraventricular cerebral hemorrhage. CONCLUSIONS: The neonatal arterial switch operation with combined circulatory arrest and low-flow bypass in our experience is associated with neurologic as well as fine and gross motor impairment but appears to be well tolerated concerning cognitive functions as based on formal intelligence testing.
Assuntos
Deficiências do Desenvolvimento/etiologia , Complicações Pós-Operatórias/epidemiologia , Transposição dos Grandes Vasos/cirurgia , Ponte Cardiopulmonar , Estudos de Casos e Controles , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Seguimentos , Parada Cardíaca Induzida , Humanos , Recém-Nascido , Testes de Inteligência , Exame Neurológico , Complicações Pós-Operatórias/diagnóstico , Valores de Referência , Fatores de TempoRESUMO
Twenty-nine children 3 months to 17 years of age undergoing operations for congenital heart disease were included in this prospective study. Complement activation, activation of the plasma contact system, leukocytes, leukocyte elastase release, and C-reactive protein were studied during and after cardiopulmonary bypass for the first postoperative week and related to multiple system organ failure occurring in eight (27.5%) of the 29 children. During cardiopulmonary bypass complement activation via the alternative pathway as indicated by significant conversion of C3 (expressed by C3d/C3) and abnormally high C5a values at the end of cardiopulmonary bypass without consumption of C4 was shown in all children. At the end of cardiopulmonary bypass, C3 conversion was significantly higher in the eight patients with multiple system organ failure than in the others (p < 0.05), whereas no difference in C5a level was shown. All children had a significant increase in leukocyte count directly after protamine administration (p < 0.0001) and elastase release during cardiopulmonary bypass that was significantly higher in patients with multiple system organ failure than in those without (p < 0.05). Consumption of prekallikrein as an indicator of activation of the Hageman system was not detectable during cardiopulmonary bypass in any child. After cardiopulmonary bypass, in patients without multiple system organ failure, C3d/C3 decreased and reached preoperative values within the first postoperative week, whereas, in patients with multiple system organ failure, C3d/C3 increased further, reaching a maximal value on the third postoperative day. In comparison with patients without multiple system organ failure, patients with multiple system organ failure showed a severe decrease of C4 (with minimal values on the third postoperative day), suggesting consumption by activation of the classic pathway of the complement system or a hepatic synthesis deficiency. Prekallikrein values were also significantly lower in patients with multiple system organ failure than in the others, with a maximal difference on the third postoperative day (p < 0.005). C-reactive protein was significantly lower in patients with multiple system organ failure than in the others for the first 2 postoperative days (p < 0.05), probably because of severe hepatic failure in patients with multiple system organ failure. This study demonstrates that, in children, cardiopulmonary bypass induces complement activation principally via the alternative pathway. It suggests a relationship between complement activation and multiple system organ failure observed in the postoperative period. Furthermore, it points out the role of multiple system organ failure itself on the C3 conversion and on the synthesis of the markers of the inflammatory response in children after heart operations.
Assuntos
Ponte Cardiopulmonar/efeitos adversos , Ativação do Complemento , Insuficiência de Múltiplos Órgãos/fisiopatologia , Adolescente , Proteína C-Reativa/análise , Criança , Pré-Escolar , Complemento C3/análise , Complemento C4/análise , Complemento C5a/análise , Feminino , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Hematócrito , Humanos , Lactente , Contagem de Leucócitos , Masculino , Insuficiência de Múltiplos Órgãos/sangue , Elastase Pancreática/sangue , Pré-Calicreína/análise , Estudos ProspectivosRESUMO
In 13 neonates undergoing cardiac operations for congenital cardiac defects, complement, leukocytes, and leukocyte elastase were studied during and after cardiopulmonary bypass. All but two neonates received prostaglandin E1 before the operation. The C3d/C3 ratio rose significantly during cardiopulmonary bypass from 0.86 +/- 0.55 to 1.40 +/- 0.56 (mean +/- standard deviation; p < 0.0001). Abnormally elevated C5a levels (18.6 +/- 7.3 micrograms/L) were measured at the end of cardiopulmonary bypass. C4 was not overtly consumed during the procedure. Leukocytes fell from a preoperative value of 10.06 +/- 3.15 x 10(9)/L to 3.21 +/- 0.64 x 10(9)/L after beginning of cardiopulmonary bypass (p < 0.0001) and rose at the end of the procedure from 2.33 +/- 0.67 x 10(9)/L to 7.19 +/- 1.84 x 10(9)/L, after protamine administration (p < 0.0001). Neutrophils fell from a preoperative value of 5.14 +/- 1.18 x 10(9)/L to 1.46 +/- 0.35 x 10(9)/L after beginning of cardiopulmonary bypass and rose at the end of extracorporeal circulation from 1.00 +/- 0.31 x 10(9)/L to 4.10 +/- 1.18 x 10(9)/L, after protamine administration (p < 0.005). Elastase release occurred in all neonates during cardiopulmonary bypass and averaged 331.5 +/- 175.7 micrograms/L. Complement activation and leukocyte stimulation did not correlate with postoperative complications or outcome. This study demonstrates complement activation and leukocyte stimulation in neonates undergoing cardiac operation.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Proteínas do Sistema Complemento/análise , Cardiopatias Congênitas/cirurgia , Contagem de Leucócitos , Elastase Pancreática/sangue , Alprostadil/uso terapêutico , Ponte Cardiopulmonar , Ativação do Complemento , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/imunologia , Humanos , Recém-Nascido , Elastase de Leucócito , MasculinoRESUMO
We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.
Assuntos
Reação de Fase Aguda/etiologia , Permeabilidade Capilar , Ponte Cardiopulmonar/efeitos adversos , Transposição dos Grandes Vasos/cirurgia , Proteínas Sanguíneas/análise , Proteínas Inativadoras do Complemento 1/análise , Complemento C3/análise , Complemento C3d/análise , Complemento C4/análise , Complemento C5a/análise , Proteínas do Sistema Complemento/análise , Hematócrito , Antagonistas de Heparina/administração & dosagem , Histamina/sangue , Liberação de Histamina , Humanos , Imunoglobulina G/sangue , Recém-Nascido , Contagem de Leucócitos , Peso Molecular , Complicações Pós-Operatórias , Protaminas/administração & dosagem , Albumina Sérica/análise , Síndrome , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise , alfa-Macroglobulinas/análiseRESUMO
Tumor necrosis factor-alpha production and products of mast cell, basophil, and eosinophil degranulation (prostaglandin D2, histamine, and eosinophil cationic protein) were prospectively studied in 26 children undergoing cardiac operations. The relationship between inflammatory response to cardiopulmonary bypass and transient postoperative arrhythmias was analyzed. Cardiopulmonary bypass was conducted with circulatory arrest and deep hypothermia in 10 patients and with continuous low-flow and moderate hypothermia in 16 patients. Transient postoperative arrhythmias diagnosed on standard or atrial electrocardiograms (or both) were seen in eight of the 26 examined children: accelerated junctional rhythm (n = 3), junctional ectopic tachycardia (n = 3), second-degree atrioventricular block (n = 1), and third-degree atrioventricular block (n = 1). Children with transient postoperative arrhythmias were younger than those without (p < 0.05). Compared with baseline values, there was in all patients a significant release of histamine and eosinophil cationic protein (p < 0.05) related to cardiopulmonary bypass, reaching peak values 4 hours after the operation. In contrast, tumor necrosis factor-alpha production and prostaglandin D2 release were not significant. This suggests that activated basophils but not mast cells are the major sources of histamine liberated during and after cardiopulmonary bypass. Histamine release but not eosinophil cationic protein release correlated with circulatory arrest and deep hypothermia (p < 0.05), suggesting the participation of physicochemical alterations of circulating basophils leading to histamine liberation. Four hours after the operation, patients with transient postoperative arrhythmias had significantly higher blood concentrations of histamine (p < 0.02) and eosinophil cationic protein (p < 0.05) than did those without transient postoperative arrhythmias. On the first postoperative day, four of the eight patients with transient postoperative arrhythmias had persisting elevated histamine levels, whereas in patients without transient postoperative arrhythmias histamine reached baseline values. The multivariate analysis retained histamine release and eosinophil cationic protein variations related to cardiopulmonary bypass for the emerging model to predict transient postoperative arrhythmias. The results of this study show significant histamine release related to cardiopulmonary bypass. Furthermore, they document a possible relationship between circulating histamine and transient postoperative arrhythmias. The latter may therefore be suspected among the consequences of the inflammatory response to cardiopulmonary bypass.
Assuntos
Arritmias Cardíacas/etiologia , Ponte Cardiopulmonar/efeitos adversos , Liberação de Histamina , Ribonucleases , Adolescente , Proteínas Sanguíneas/análise , Criança , Pré-Escolar , Proteínas Granulares de Eosinófilos , Feminino , Histamina/sangue , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Prostaglandina D2/sangue , Fator de Necrose Tumoral alfa/análiseRESUMO
Complement activation and leukocyte stimulation were prospectively studied during and after cardiopulmonary bypass in 16 children receiving sodium nitroprusside--a nitrovasodilator releasing nitric oxide--for vasodilation during the cooling and rewarming periods of extracorporeal circulation. Results were compared with those in 29 patients who were not treated with sodium nitroprusside during the operation. Patients treated with sodium nitroprusside had significantly less C3 conversion during cardiopulmonary bypass as measured by the ratio C3d/C3 (p <0.05) and significantly less C5a liberation immediately after cardiopulmonary bypass (p < 0.005) than patients not treated with sodium nitroprusside. C4 was not overtly consumed in our series. Leukocyte count during the rewarming period of cardiopulmonary bypass, but not leukocyte elastase release during cardiopulmonary bypass, was significantly reduced in patients treated with sodium nitroprusside (p <0.05). In vitro experiments were conducted to analyze the effect of sodium nitroprusside on complement hemolytic activity initiated by the classic and the alternate pathways and on zymosan-induced C3 conversion by the activation of the alternate pathway. The in vitro experiments clearly demonstrate inhibition of complement hemolytic activity by sodium nitroprusside in the sera tested. The 50% inhibitory concentration of sodium nitroprusside on the available complement hemolytic activity was less through the alternate pathway than through the classic one (4.2 +/- 0.8 mmol/L and 14.0 +/- 2.88 mmol/L, respectively). The decrease of complement hemolytic activity measured was dose-dependent and was enhanced by the sodium nitroprusside preincubation of the sera tested. This effect was related to the duration of preincubation. Sodium nitroprusside photodegradation (enhancing nitric oxide release) increased the anticomplementary effect of the drug, reducing the 50% inhibitory concentration on complement hemolytic activity to 0.24 to 0.02 mmol/L for the alternate pathway and 2.74 o 0.3 mmol/L for the classic pathway. the zymosan-induced C3 conversion was inhibited by sodium nitroprusside. Nitroglycerin and isosorbide dinitrate (other nitric oxide donors) had in vitro effects on complement hemolytic activity similar to those of nonphotodegraded sodium nitroprusside at similar concentrations (1 mmol/L). Our results suggest that sodium nitroprusside, both in vitro and in vivo, has an inhibiting effect on complement activation initiated by both classic and alternate pathways and that this effect is mediated by nitric oxide release from sodium nitroprusside. This is the first report on the anticomplementary effect of sodium nitroprusside by nitric oxide release.
Assuntos
Ponte Cardiopulmonar , Ativação do Complemento/efeitos dos fármacos , Nitroprussiato/farmacologia , Vasodilatadores/farmacologia , Criança , Pré-Escolar , Complemento C3/análise , Complemento C4/análise , Via Alternativa do Complemento/efeitos dos fármacos , Via Clássica do Complemento/efeitos dos fármacos , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Contagem de Leucócitos , Elastase de Leucócito , Elastase Pancreática/metabolismo , Estudos ProspectivosRESUMO
RATIONALE AND OBJECTIVES: Several devices have been suggested and tested for interventional closure of the persistent ductus arteriosus. Coils were found effective only in small ducts due to their lack of maneuverability and physical limitation of grip forces leading to risk of embolization. The authors evaluated the feasibility to place single coils with selectively enhanced stiffness into high shunting ductus arteriosus, the coils being deployed and controlled through a veno-arterial loop in a bovine model. METHODS: "Double-cone" shaped, stainless steel coils with enhanced stiffness of the outer rings were mounted on either end on a nitinol core wire. A snap-in mechanism attaches the coil to this delivery wire and is freed by a pusher system of coiled steel wire that is advanced over the core wire. Forming a veno-arterial loop across the patent ductus allows for repositioning into the pulmonary artery or aortic catheter. A chronic lamb model of large patent ductus arteriosus (PDAs) (> or = 9 mm) was used in which ductus patency was secured by a protocol of repetitive angioplasties. Different systems (n = 10) were placed having retrieved the previous coil by a snare after definitive release. RESULTS: Placement of coils was possible in all 10 attempts. The coils were pulled back into the catheters between five and eight times before definitive release. CONCLUSIONS: The device allows controlled placement of single coils in our model of large PDAs and may lead the way to overcome previous limitations of coils. Clinical trials are warranted.
Assuntos
Cardiologia/instrumentação , Permeabilidade do Canal Arterial/terapia , Animais , Animais Recém-Nascidos , Desenho de Equipamento , OvinosRESUMO
RATIONALE AND OBJECTIVES: The authors evaluate the feasibility to accelerate occlusion of high-velocity flow vessels by a combination of transcutaneous coil placement and application of radiofrequency current. METHODS: Piglets (n = 8) were anesthetized and acutely instrumented via cutdowns in both carotid and one brachial arteries. Two identical cylindrically shaped coils (length, 3 mm; outer diameter, 2.4 mm; inner diameter, 1.4 mm) were mounted on titanium-nickel core wire and placed via 3-French Nylon catheters in both iliac arteries. The coils were kept connected to the delivery wire, which is isolated from the surrounding tissue by the catheter. The first-placed system served as control, the contralateral coil was connected to a radiofrequency generator closing electrical circuit via an external indifferent electrode. Angiograms via the brachial artery demonstrated the adequate placement of the coils and the status of the iliac arteries without and with current application. In 6 of the 8 cases, 25 watts of radiofrequency current were applied repeatedly over 10 seconds to the coil on one side at 4-minute intervals until occlusion was demonstrated. In 2 of 8 cases. 25 watts were applied continuously over 30 seconds. The coils were detached from the wire the catheters removed. Additional angiograms were performed after 5, 15, 45, and 60 minutes to show the patency of the control setting. RESULTS: Complete occlusion was achieved in all cases after a maximum of three consecutive applications of current for 10 seconds. The control remained patent for a minimum of 45 minutes. On gross and histologic examination the arteries on both sides remained intact. Disruption and charring occurred only after continuous application of current over 30 seconds. CONCLUSIONS: It is feasible to use detachable coils in conjunction with high-frequency electrocoagulation to promote coil fixation and accelerate occlusion of vessels with high blood flow.
Assuntos
Ablação por Cateter/métodos , Artéria Ilíaca/cirurgia , Angiografia , Animais , Animais Recém-Nascidos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/patologia , SuínosRESUMO
RATIONALE AND OBJECTIVES: The clinically most widely used devices (Porstmann-plug, Rashkind-umbrella, Botallooccluder) have inherent specific limitations (eg, transarterial approach, residual shunts, limited retrieval). The authors assess practicability, efficacy, and tissue reaction of the new retrievable transvenous plug device for the occlusion of the persistent patent ductus arteriosus (PDA). METHODS: A foam plug (polyvinyl alcohol) is mounted on a titanium core pin where, at both ends, small legs (titanium nickel alloy) with titanium heads are anchored, to ensure safe fixation in the ductus. The device is introduced transvenously through a long sheath (Mullins sheath) and held by a modified biopsy forceps allowing complete retrieval until final release. A common lamb model of large PDAs (n = 11) was used to test for practicability and the histomorphologic outcome. Clinical results were obtained from a consecutive series of 16 patients (aged 13 to 71 years). RESULTS: In all lambs, placement of the plug within the PDA was possible. Histopathology (follow-up 10 to 215 days; mean 112 days) revealed an adequate ingrowing of the device and no pathologic foreign body reaction. The diameter of the human PDAs ranged from 3 to 7 mm (mean 5 mm). The size of the sheath used for introducing the plug (diameter 8 to 16 mm) ranged from 8 to 16 French. Fourteen of 16 PDAs were closed immediately after or on day 1 after implantation, 1 was closed after the 12-month follow-up, and 1 needed an additional plug after 30 months for definitive closure. CONCLUSIONS: The device demonstrated practicability and biocompatibility in our experimental lamb model and effectively closed the PDA in a consecutive series of 16 patients. A greater number of patients and a longer follow-up period are necessary for the definitive clinical assessment of the new device.
Assuntos
Permeabilidade do Canal Arterial/terapia , Embolização Terapêutica/métodos , Polivinil/uso terapêutico , Adolescente , Adulto , Idoso , Animais , Animais Recém-Nascidos , Aortografia , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/patologia , Embolização Terapêutica/instrumentação , Feminino , Seguimentos , Humanos , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Ovinos , Resultado do TratamentoRESUMO
RATIONALE AND OBJECTIVES: The authors evaluate the use of a new device for interventional creation of atrial septal defects (ASD) working with high-frequency alternating current in an in vitro study with porcine atria. METHODS: The device consists of a symmetrical cage of six superelastic monofile wires, including a microthermistor that is placed via a catheter into a punctured hole in the porcine foramen ovale. The device is used as a differential electrode for monopolar, temperature-controlled application of high-frequency alternating current for thermal modelling of ASD. RESULTS: Application of current for 60 seconds caused temperature-dependent, sized ASDs. CONCLUSION: In vivo animal studies to evaluate possible side effects and long term patency of the ASDs are justified and warranted.
Assuntos
Ablação por Cateter/métodos , Átrios do Coração/cirurgia , Defeitos dos Septos Cardíacos/cirurgia , Animais , Átrios do Coração/patologia , Defeitos dos Septos Cardíacos/patologia , Septos Cardíacos , Técnicas In Vitro , SuínosRESUMO
Anti-thrombogenicity and rapid endothelialisation are prerequisites for the use of closure devices of intra-atrial communications in order to reduce the risk of cerebral embolism. The purpose of this study was therefore to assess the effect of bioactive coatings on biocompatibility of Nitinol coils designed for the closure of intra-atrial communications. Nitinol coils (n = 10, each) and flat Nitinol bands (n = 3, each) were treated by basic coating with poly(amino-p-xylylene-co-p-xylylene) and then coated with either heparin, r-hirudin or fibronectin. Anti-thrombogenicity was studied in vitro in a dynamic model with whole blood by partial thromboplastin time (PTT), platelet binding and thrombin generation, respectively, and cytotoxicity by hemolysis. Endothelialisation was studied on Nitinol bands with human umbilical venous endothelial cells (HUVEC) by 3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium (MTT) assay and immnuofluorescence analysis of Ki67, vinculin, fibronectin and von Willebrand Factor. Uncoated or coated devices did not influence hemolysis and PTT. r-Hirudin (but not heparin) and fibronectin coating showed lower platelet binding than uncoated Nitinol (p < 0.005, respectively). Heparin and r-hirudin coating reduced thrombin formation (p < 0.05 versus Nitinol, respectively). HUVEC adhesion, proliferation, and matrix formation decreased in the order: fibronectin coating > uncoated Nitinol > r-hirudin coating > heparin coating > basic coating. MTT assay corroborated these findings. In conclusion, r-hirudin and fibronectin coating, by causing no acute cytotoxicity, decreasing thrombogenicity and increasing endothelialisation improve in vitro biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.
Assuntos
Ligas/química , Materiais Biocompatíveis , Fibronectinas/química , Heparina/química , Hirudinas/química , Animais , Plaquetas/metabolismo , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Hemólise , Humanos , Imuno-Histoquímica , Microscopia Confocal , Microscopia Eletrônica de Varredura , Tempo de Tromboplastina Parcial , Ovinos , Sais de Tetrazólio/farmacologia , Tiazóis/farmacologia , Veias Umbilicais/metabolismoRESUMO
Between 1979 and 1988, a total of 53 infants less than 1 year of age underwent repair of coarctation. Thirty-seven patients (70%) were younger than 3 months. Median age was 0.9 month. Four different surgical techniques were used: resection with end-to-end anastomosis, patch enlargement, subclavian flap aortoplasty, and subclavian displacement aortoplasty (Meier-Mendonca technique). Hospital mortality was 7.5% and was limited to patients with additional complex intracardiac defects. Neither age nor surgical technique had an influence on the operative risk. Follow-up averaged 15 to 43 months for the four different groups. Restenosis developed in 9 (19%) of 47 patients regularly followed up, 5 (11%) of whom have had reoperation. Age at operation was not a predictor for restenosis, which occurred in 17.4% of patients less than 1 month and 20.8% of those greater than 1 month of age at operation. Patch enlargement and the subclavian displacement technique demonstrated the highest restenosis rates (42% and 43%, respectively). However, patients who underwent patch enlargement had less favorable pathological conditions. It is concluded that results of coarctation repair in early infancy do not depend as much on the operative method itself as on the specific pathological aspect, which largely determines the method of treatment. Some reservation must be made in regard to the subclavian displacement technique.
Assuntos
Aorta/cirurgia , Coartação Aórtica/cirurgia , Artéria Subclávia/cirurgia , Anastomose Cirúrgica/métodos , Estudos de Avaliação como Assunto , Seguimentos , Humanos , Lactente , Recém-Nascido , Recidiva , ReoperaçãoRESUMO
BACKGROUND: The arterial switch operation (ASO) is the treatment of choice for transposition of the great arteries. METHODS: Anatomical risk factors on mortality and morbidity were analyzed retrospectively in 312 patients who underwent ASO between 1982 and 1997. RESULTS: Survival was 95%, 92%, and 92% after 30 days, 5, and 10 years, respectively. Operative survival improved after 1990 to 97% (p < 0.001). Risk factors for operative mortality were complex anatomy (p = 0.018), coronary anomalies (p = 0.008), and prolonged bypass time (p < 0.001). Determinants of late mortality were coronary distribution (p = 0.03), position of the great arteries (p = 0.0095), bypass time (p = 0.047), and aortic coarctation (p = 0.046). After a follow-up of 3.6 +/- 2.7 years (0.1 to 14.9 years), 98% had good left ventricle function, 94% were in sinus rhythm, 2.4% had moderate to severe pulmonary stenosis, 0.3% had significant aortic regurgitation, and 1% had coronary stenosis. Freedom from reoperation was 100%, 96%, and 94% after 1, 5, and 10 years, respectively. No preoperative anatomic parameter correlated with long-term morbidity. CONCLUSIONS: ASO can be performed with low operative mortality (< 5%) and long-term morbidity. Malformations associated with complex transposition of the great arteries influence early and late mortality.