PubMed Health⌕ Search

Biomedical subjects

James S Tweddell

Publications and source records attributed to James S Tweddell.

At least 19 recordsLinked to original sources
PubMed2006

Characterizing the inflammatory response to cardiopulmonary bypass in children.

Cardiopulmonary bypass is known to trigger a global inflammatory response. Age-dependent differences in the inflammatory response, the increased susceptibility to injury of immature organ systems, and the larger extracorporeal circuit to patient size ratio results in greater susceptibility of younger and smaller patients to the damaging effects of cardiopulmonary bypass. In this review the components of the inflammatory response to cardiopulmonary bypass are reviewed with special reference to the pediatric age group, including the age-specific impact on organ systems. In addition the current and evolving strategies to prevent, limit, and treat the inflammatory response to cardiopulmonary bypass in children are examined.

Age Factors↗
PubMed2006

Early cavopulmonary anastomosis after Norwood procedure results in excellent Fontan outcome.

BACKGROUND: Children with univentricular hearts and aortic arch obstruction are treated sequentially with Norwood procedure, superior cavopulmonary anastomosis (SCPA), and Fontan operation. Early SCPA results in lower initial O2 saturation and longer hospitalization, but not increased mortality. We sought to determine the impact of early SCPA on Fontan candidacy and outcomes. METHODS: Eighty-five consecutive patients undergoing Norwood operation between January 1998 and February 2003 were divided into group 1 (SCPA at less than 4 months, n = 33) and group 2 (SCPA at more than 4 months, n = 52). Of the original cohort, 69 have undergone Fontan operation, 7 await Fontan, 1 was transplanted, 3 are not Fontan candidates, and 5 died late after SCPA. Group 1 (n = 25) and group 2 (n = 44) patients who have completed Fontan operation were compared for preoperative and perioperative variables: age, size, O2 saturation, pulmonary artery pressure and size, prevalence of tricuspid regurgitation and ventricular dysfunction, extubation rate in operating room, duration of pleural drainage, hospital stay, and discharge O2 saturation. Late functional status and ventricular function were also compared. Survival was compared for original groups 1 and 2. RESULTS: There were no differences for any preoperative or perioperative variable, or late functional assessment. Actuarial survival at 6 years was also not different (88% +/- 5% for group 1 and 94% +/- 4% for group 2, p = 0.72). CONCLUSIONS: Although initially more cyanotic and hospitalized longer than older peers, younger SCPA patients achieve clinical equivalence by the time of Fontan operation and afterward. We conclude that both short- and long-term outcomes support performance of early SCPA.

Anastomosis, Surgical↗
PubMed2006

Right ventricle-to-pulmonary artery conduit versus Blalock-Taussig shunt: a hemodynamic comparison.

BACKGROUND: A comprehensive assessment of 48 hour postoperative hemodynamics in neonates randomized to the right ventricle-to-pulmonary artery (RV-PA) conduit or modified Blalock-Taussig (BT) shunt for stage 1 palliation of hypoplastic left heart syndrome was performed to determine the potential benefits of the modified technique. METHODS: Randomization to either RV-PA conduit or BT shunt was stratified by surgeon and the presence of aortic atresia. The designated procedure was performed by using hypothermic cardiopulmonary bypass with phenoxybenzamine, continuous cerebral perfusion, pH-stat blood gas management, and continuous postoperative venous oximetry. Differences between treatments were analyzed by time-series generalized least-squares regression, chi2 tests, two-way repeated measures analysis of variance, and the Levene variance ratio test for variability in parameters, as appropriate. RESULTS: All patients underwent the procedure to which they were randomized. There were no differences in age, weight, deep hypothermic circulatory arrest, or cardiopulmonary bypass times between patients receiving the BT shunt (n = 8) or the RV-PA conduit (n = 9). There was one early and one late death in the RV-PA conduit group, and one interstage death in the BT shunt group. Other than diastolic blood pressure (39 mm Hg in BT shunt versus 46 mm Hg in RV-PA conduit, p < 0.001), there were no differences in the mean values of arterial saturation, venous oximetry, mean arterial blood pressure, pulmonary-to-systemic flow ratio (Qp/Qs), or any other physiologic or inotropic support variable between groups. The variability of physiologic values related to pulmonary blood flow was greater in the RV-PA group (Qp/Qs coefficient of variation, 0.91 versus 2.50, p < 0.001). CONCLUSIONS: In this randomized prospective study, no hemodynamic benefits of the RV-PA modification for stage 1 palliation of hypoplastic left heart syndrome were found. Pulmonary blood flow was more variable, and the diastolic blood pressure was higher. These findings did not influence indicators of systemic oxygen delivery with our afterload reduction strategy.

Anastomosis, Surgical↗
PubMed2006

Ventricular septal defect and aortic valve regurgitation: pathophysiology and indications for surgery.

As the velocity of a fluid increases a low-pressure zone is created, this is the Venturi effect and it explains the pathogenesis of aortic valve prolapse (AVP) and aortic insufficiency (AI) that is observed in a subset of patients with a ventricular septal defect (VSD). The VSDs complicated by AI are restrictive with high velocity shunting through the VSD, creating a low-pressure zone that impacts the adjacent aortic valve cusp resulting in AVP and subsequent AI. AVP and AI are therefore acquired lesions. AI is absent at birth because the forces necessary to create the low-pressure zone within the restrictive VSD do not exist in utero. The risk of development of AI increases during childhood, peaking at 5 to 10 years of age. VSD closure eliminates the low-pressure zone that is the cause of ongoing aortic valve cusp deformity and, if performed early, prevents development of AI. Patients with a subarterial VSD and AVP should undergo surgery to prevent the development of AI because this complicates about half of subarterial VSDs with AVP and spontaneous closure is rare. Patients with perimembranous VSDs with AVP should be followed with serial echocardiography and undergo VSD closure if more than trivial AI develops.

Aortic Valve Insufficiency↗
PubMed2006

Near infrared spectroscopy monitoring during pediatric aortic coarctation repair.

BACKGROUND: Near infrared spectroscopy (NIRS) measures regional tissue oxygenation continuously and noninvasively and may allow assessment of changes in regional perfusion in real time. METHODS: We used NIRS monitoring to track real-time changes in regional oxygenation (rSO2) above and below the aortic cross-clamp in patients undergoing aortic coarctation repair and routinely stored these data in an operative electronic data base. This allowed us to analyze the changes in rSO2 during aortic coarctation repair for three pediatric age groups (neonates, infants <1 year, and children >1 year). Two site [cerebral (rSO2-C) and somatic thoracodorsal (rSO2-S)] rSO2 monitoring was performed in patients undergoing aortic coarctation repair. Data for rSO2 were analyzed across sites and age groups before, during and after cross-clamp. RESULTS: Twenty-six patients were available for analysis (11 neonates, 5 infants and 10 children). The regional oxygenation below the cross clamp (rSO2-S) declined significantly in all three age groups, but the decrease in neonates and infants <1 year of age was significantly greater than in the older children. CONCLUSIONS: Monitoring rSO2-S provides real-time trend information of regional oxygenation below the aortic cross-clamp. The decline in rSO2-S during aortic cross-clamp was rapid and large in most neonates and young infants <1 year which suggests impairment of regional perfusion presumably because of a lack of adequate collateral circulation to the monitored regional tissue. In contrast, the rSO2-S changed only to a minor degree in most infants and children >1 year, possibly because they had time to develop a more adequate collateral circulation around incomplete aortic obstruction.

Adolescent↗
PubMed2005

A medical strategy to reduce persistent chest tube drainage after the fontan operation.

A standardized medical regimen aimed at reducing pleural effusions after the Fontan operation was compared with a randomly selected retrospective cohort. The duration of chest tube drainage, hospital stay, and the need for pleural sclerosis were significantly reduced, indicating that postoperative management plays an important role in reducing this morbidity.

Adult↗
PubMed2005

The neonate with congenital heart disease: what the cardiac surgeon needs to know from the neonatologist and the cardiologist.

To plan and accomplish a successful operation for a neonate with congenital heart disease, the cardiac surgeon requires a complete anatomic description of the cardiovascular malformation. For optimum outcome, this information must be supplemented by a complete report of the prenatal and postnatal course of the newborn as well as by a thorough summary of any noncardiac congenital or acquired abnormalities. In the most favorable circumstance, the neonate arrives in the operating room completely diagnosed, fully resuscitated, well nourished, and with appropriate monitoring devices in place. Unique perioperative considerations attach to each cardiac anomaly and are briefly reviewed, and the importance of continuity of care for the patient and family is emphasized.

Cardiology↗
PubMed2005

Complex aortic valve repair as a durable and effective alternative to valve replacement in children with aortic valve disease.

OBJECTIVE: This study was undertaken to determine the utility of aortic valve repair in children. METHODS: A retrospective analysis was conducted on aortic valve surgery from 1973 to 2004 at Children's Hospital of Wisconsin. RESULTS: Procedures were classified as simple repairs (blunt valvotomy, commissurotomy with or without thinning, n = 147), repair of aortic insufficiency with ventricular septal defect (n = 22), complex repairs (any combination of additional procedures including suspension of prolapsed leaflets, leaflet extensions, repair of torn or perforated leaflets, annuloplasty, reduction of sinus of Valsalva plasty, and concomitant repair of supravalvular or subvalvular stenosis, n = 57), and replacements (n = 57, 20 mechanical, 2 porcine, and 35 human valves). Freedoms from reintervention for simple repairs and repair of aortic insufficiency with ventricular septal defect at 10 years were 86% +/- 5% and 93.3% +/- 6%, respectively. For complex valve repair, freedoms from reintervention at 1, 5, and 10 years were 94% +/- 3%, 85% +/- 6%, and 44% +/- 15%, versus 96% +/- 3%, 77% +/- 9%, and 77% +/- 9% for valve replacement ( P = .3). At intermediate follow-up, patients with complex valve repair had a residual gradient of 20 +/- 21 mm Hg, and 94% were free of severe aortic insufficiency. Residual aortic stenosis ( P < .05) but not the preoperative diagnosis of combined aortic stenosis and insufficiency predicted the need for reintervention. CONCLUSION: Freedom from reintervention after complex valve repairs was not different from that after valve replacement, with acceptable residual aortic stenosis and insufficiency. Simple repairs and repair of aortic insufficiency with ventricular septal defect yielded excellent long-term freedom from reintervention.

Adolescent↗
PubMed2005

Systemic venous oxygen saturation after the Norwood procedure and childhood neurodevelopmental outcome.

OBJECTIVE: Neonates with hypoplastic left heart syndrome have impaired systemic oxygen delivery and also have a high risk of hypoxic ischemic brain injury with resultant neurodevelopmental impairment. We hypothesized that decreased postoperative oxygen delivery, as measured on the basis of systemic venous oxyhemoglobin saturation, would be related to persistent neurodevelopmental abnormality assessed in childhood. METHODS: Early perioperative hemodynamic data, prospectively acquired from neonates undergoing staged palliation of hypoplastic left heart syndrome by using deep hypothermic circulatory arrest with uniform perioperative management, were tested for relationship to later neurodevelopmental outcome assessed at age 4 years. RESULTS: Complete hemodynamic and neurodevelopmental data were available in 13 patients aged 7 +/- 8 days at the time of the Norwood procedure and aged 4.5 +/- 0.7 years at follow-up assessment. The subjects scored significantly below the population mean for motor, visual-motor integration, and composite neurodevelopmental outcomes. The 5 (38%) patients with abnormal outcomes had significantly lower postoperative systemic venous oxygen saturation values than those with normal outcomes (46% +/- 8% vs 56% +/- 6%, P = .024). Standard hemodynamic parameters did not differentiate patient outcomes. The risk of abnormal outcome increased with increasing time at a systemic venous oxygen saturation of less than 40% (P < .001). A multivariate model of deep hypothermic circulatory arrest time, systemic venous oxygen saturation, blood pressure, and carbon dioxide tension accounted for 79% of the observed variance (P < .001). CONCLUSIONS: Decreased systemic oxygen delivery in the neonatal postoperative period is associated with hypoxic-ischemic brain injury and childhood neurodevelopmental abnormality. Measures of systemic oxygen delivery should be used to guide perioperative strategies to reduce the risk of hypoxic-ischemic brain injury.

Cardiac Surgical Procedures↗
PubMed2005

Noninvasive assessment of cardiac output.

Improved outcome from shock depends on early detection and correction of circulatory abnormalities. Global cardiac output and oxygen delivery must be adequate and distributed appropriately to meet metabolic demands to prevent the development of multiple organ system dysfunction, prolonged morbidity, and death. Circulatory assessment using standard monitors gives incomplete and sometimes misleading information. This article focuses on the available and emerging technologies that emphasize assessment of blood flow and regional tissue oxygenation.

Calorimetry, Indirect↗
PubMed2005

Aortic valve repair.

Aortic valve replacement options are limited in children, and all of them have disadvantages. Aortic valve repair techniques have evolved slowly and have not gained wide acceptance; however, large series using a variety of techniques demonstrate that valve repair is possible with excellent early hemodynamics and satisfactory intermediate durability. The results of aortic valve repair at the Children's Hospital of Wisconsin are presented. Simple repairs (blunt valvotomy, commissurotomy, or commissurotomy with leaflet thinning) directed at congenital aortic stenosis resulted in 86% +/- 5% freedom from reintervention at 10 years. Repair of aortic insufficiency with ventricular septal defect (VSD) resulted in 93.3% +/- 6% freedom from reoperation at 10 years. Complex repairs included a combination of techniques and yielded 5-year freedom from reintervention of 83% +/- 7% compared with 73% +/- 11% for patients undergoing aortic valve replacement (P = .62). Aortic valve repair provides an alternative to aortic valve replacement in selected patients. The utility of aortic valve repair and aortic valve replacement must be measured not only in freedom from reintervention but also in regression of left ventricular mass and exercise testing. Improvement in outcome depends on better patient selection and suitable bioprosthetic materials.

Adolescent↗
PubMed2004

Erythropoietin protects the infant heart against ischemia-reperfusion injury by triggering multiple signaling pathways.

The immediate protective effect of erythropoietin (EPO) against ischemia in heart suggests a role beyond hematopoiesis and the treatment of anemia. We determined the role of JAK/STAT and Ras/Rac/MAPK in the protective effect of EPO against ischemia-reperfusion injury in infant rabbit heart. EPO (1.0 U/ml) administered 15 minutes prior to 30-minutes global ischemia and 35 minutes reperfusion resulted in increased recovery of postischemic ventricular developed pressure in rabbit hearts. EPO exerted its immediate cardioprotective effect via activation of multiple signaling pathways by: 1) phosphorylation and activation of JAK1/2, STAT3 and STAT5A but not of STAT1alpha and STAT5B, 2) phosphorylation and activation of PI(3) kinase and its downstream kinases Akt and Rac, 3) activation of PKCepsilon, Raf, MEK1/2, p42/44 MAPK and p38 MAPK. Pretreatment with Wortmannin abolished EPO-induced Akt activation and phosphorylation. Pretreatment with Chelerythrine followed by EPO treatment resulted in partial inhibition of Raf activation, and abolished PKCepsilon and p38 MAPK activation without any effect on Akt, MEK1/2 and p42/44 MAPK. PD98059 abolished MEK1/2 and p42/44 MAPK activation with no effect on Akt, Raf and p38 MAPK activation. SB203580 inhibited only p38 MAPK activation by EPO. We can conclude EPO increases immediate cardioprotection through the activation of multiple signal transduction pathways.

Age Factors↗
PubMed2004

Delayed cardioprotection with isoflurane: role of reactive oxygen and nitrogen.

We determined whether isoflurane can confer delayed cardioprotection in the adult rat by triggering increased production of reactive oxygen (ROS) and nitrogen species (RNS). Our objectives were to determine 1) the concentration of isoflurane that confers delayed cardioprotection in the adult rat, 2) the role of ROS and RNS in the induction of delayed cardioprotection, and 3) the cellular sources of ROS and RNS responsible for induction of delayed cardioprotection by isoflurane. Male Sprague-Dawley rats at 8 wk of age (n = 8 rats/group) were exposed to 0.5%, 0.8%, 1%, and 2% (vol/vol) isoflurane-100% oxygen for 2 h. Isoflurane conferred delayed cardioprotection 24 h later at a concentration of 0.8% (vol/vol). Administration of manganese (III) tetrakis (4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide scavenger (15 mg/kg ip), or N(G)-nitro-L-arginine methyl ester (L-NAME), a general nitric oxide synthase inhibitor (15 mg/kg ip), 15 min before isoflurane treatment abolished the delayed cardioprotective effects of isoflurane. MnTBAP and L-NAME had no effect on delayed cardioprotection in untreated hearts. Perfusion of isolated hearts with hydroethidine, a fluorescent probe for superoxide, after isoflurane treatment resulted in a twofold increase in ethidine staining of isoflurane-treated hearts compared with untreated controls, which was attenuated by myxothiazol, an inhibitor of the mitochondrial electron transport chain (0.2 mg/kg ip) and L-NAME (15 mg/kg ip). Nitrite and nitrate content in isoflurane-treated hearts was 1.5-fold higher than in untreated hearts, whereas myocardial reduced glutathione levels were decreased by 13% in 0.8% but not in 1.0% isoflurane-treated hearts. We conclude that isoflurane confers delayed cardioprotection in the adult rat, triggered by ROS and RNS.

Anesthetics, Inhalation↗
PubMed2004

Cardioprotection in chronically hypoxic rabbits persists on exposure to normoxia: role of NOS and KATP channels.

Hypoxia from birth increases resistance to myocardial ischemia in infant rabbits. We hypothesized that increased cardioprotection in hearts chronically hypoxic from birth persists following development in a normoxic environment and involves increased activation of nitric oxide synthase (NOS) and ATP-dependent K (K(ATP)) channels. Resistance to myocardial ischemia was determined in rabbits raised from birth to 10 days of age in a normoxic (Fi(O(2)) = 0.21) or hypoxic (Fi(O(2)) = 0.12) environment and subsequently exposed to normoxia for up to 60 days of age. Isolated hearts (n = 8/group) were subjected to 30 min of global ischemia followed by 35 min of reperfusion. At 10 days of age, resistance to myocardial ischemia (percent recovery postischemic recovery left ventricular developed pressure) was higher in chronically hypoxic hearts (68 +/- 4%) than normoxic controls (43 +/- 4%). At 10 days of age, N(G)-nitro-L-arginine methyl ester (200 microM) and glibenclamide (3 microM) abolished the cardioprotective effects of chronic hypoxia (45 +/- 4% and 46 +/- 5%, respectively) but had no effect on normoxic hearts. At 30 days of age resistance to ischemia in normoxic hearts declined (36 +/- 5%). However, in hearts subjected to chronic hypoxia from birth to 10 days and then exposed to normoxia until 30 days of age, resistance to ischemia persisted (63 +/- 4%). L-NAME or glibenclamide abolished cardioprotection in previously hypoxic hearts (37 +/- 4% and 39 +/- 5%, respectively) but had no effect on normoxic hearts. Increased cardioprotection was lost by 60 days. We conclude that cardioprotection conferred by adaptation to hypoxia from birth persists on subsequent exposure to normoxia and is associated with enhanced NOS activity and activation of K(ATP) channels.

Adaptation, Physiological↗
PubMed2004

Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels.

Erythropoietin is protective against cardiac ischemia, but the underlying mechanisms are unknown. We determined whether erythropoietin (0.5 - 10.0 U/ml) confers acute cardioprotection in infant rabbit hearts and the contribution of protein kinases, nitric oxide synthase and potassium channels to the underlying mechanism. Hearts from normoxic infant New Zealand White rabbits (n=8/group) were isolated and perfused in the Langendorff mode. Biventricular function was recorded under steady-state conditions prior to 30 min global no-flow ischemia and 35 min reperfusion. Administration of erythropoietin for 15 min immediately prior to ischemia resulted in a concentration-dependent increase in recovery of left and right ventricular developed pressure in rabbit hearts following myocardial ischemia and reperfusion. The optimal concentration of erythropoietin that afforded maximum recovery of developed pressure was manifest at 1.0 U/ml. Erythropoietin (1.0 U/ml) treatment resulted in phosphorylation of PKC, p38 MAP kinase and p42/44 MAP kinase. The cardioprotective effects of erythropoietin were abolished by the protein kinase inhibitors SB203580 (p38 MAP kinase), PD98059 (p42/44 MAP kinase) and chelerythrine (PKC) as well as the potassium channel blockers glibenclamide, HMR 1098, 5-HD and Paxilline. Nitrite and nitrate release from hearts before (2.3 +/- 0.9 nmol/min/g) and after (2.4 +/- 1.9 nmol/min/g) 15 min treatment with erythropoietin (1.0 U/ml) were not different. L-NAME and L-NMA did not block the cardioprotective effect of erythropoietin. We conclude the rapid activation of potassium channels and protein kinases by erythropoietin represents an important new mechanism for increasing cardioprotection.

Animals↗
PubMed2004

Orthotopic heart transplantation in a child with histiocytoid cardiomyopathy.

We report a case of histiocytoid cardiomyopathy in a 30-month-old child. This rare disorder has been identified in <100 patients worldwide and no previous reports of cardiac transplantation with this condition have been identified. We reviewed the clinical and pathologic findings and compared them to previous studies.

Adult↗
PubMed2004

Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic left heart syndrome using continuous regional cerebral perfusion.

OBJECTIVES: Stage 1 palliation of hypoplastic left heart syndrome requires the interruption of whole-body perfusion. Delayed reflow in the cerebral circulation secondary to prolonged elevation in vascular resistance occurs in neonates after deep hypothermic circulatory arrest. We examined relative changes in cerebral and somatic oxygenation with near-infrared spectroscopy while using a modified perfusion strategy that allowed continuous cerebral perfusion. METHODS: Nine neonates undergoing stage 1 palliation for hypoplastic left heart syndrome had regional tissue oxygenation continuously measured by frontal cerebral and thoraco-lumbar (T10-L2) somatic (renal) reflectance oximetry probes (rSO(2), INVOS; Somanetics, Troy, Mich). Surgery was accomplished using cardiopulmonary bypass with whole-body cooling (18 degrees C-20 degrees C) and regional cerebral perfusion through the innominate artery at flow rates guided by estimated minimum flow requirements and measured rSO(2) during reconstruction of the aortic arch. Data were logged at 1-minute intervals and analyzed using repeated measures analysis of variance. RESULTS: A total of 3176 minutes of data were analyzed. Prebypass cerebral rSO(2) was 65.4 +/- 8.9, and somatic rSO(2) was 58.9 +/- 12.4 (P <.001, cerebral vs somatic). During regional cerebral perfusion, cerebral rSO(2) was 80.7 +/- 8.6, and somatic rSO(2) was 41.4 +/- 7.1 (P <.001). Postbypass cerebral rSO(2) was 53.2 +/- 14.9, and somatic rSO(2) was 76.4 +/- 7.7 (P <.001). The risk of cerebral desaturation was significantly increased after cardiopulmonary bypass. CONCLUSIONS: Cerebral oxygenation was maintained during regional cerebral perfusion at prebypass levels with deep hypothermia. However, after rewarming and separation from cardiopulmonary bypass, cerebral oxygenation was lower compared with prebypass or somatic values. These results indicate that cerebrovascular resistance is increased after deep hypothermic cardiopulmonary bypass, even with continuous perfusion techniques, placing the cerebral circulation at risk postoperatively.

Analysis of Variance↗