Invited commentary.
Explore the source record for details and available documents.
Cardiac Surgical Procedures↗
Biomedical subjects
Glen Van Arsdell
Publications and source records attributed to Glen Van Arsdell.
Disruption of the ventricular myocardial force-frequency relationship after cardiac surgery in children: noninvasive assessment by means of tissue Doppler imaging.
OBJECTIVE: Impaired ventricular function after cardiopulmonary bypass and surgical repair remains a commonly encountered clinical problem. We hypothesized that the well-described impairment of calcium cycling after cardiac surgery would significantly affect the ventricular myocardial force-frequency relationship, which can be measured noninvasively by using the tissue Doppler echocardiography-derived index of contractility isovolumic acceleration. METHODS: Children undergoing repair of congenital heart defects were studied. Rate-related changes in contractility were measured by means of simultaneous atrial pacing and tissue Doppler echocardiography preoperatively and postoperatively. RESULTS: Although closure of atrial septal defect did not affect ventricular myocardial systolic performance, closure of ventricular septal defect lead to a marked postoperative decrease of basal contractile force (2.0 +/- 0.7 m/s2 preoperatively vs 1.0 +/- 0.7 m/s2 postoperatively, P < .02). Furthermore, the force-frequency relationship curves were significantly different (P < .001), with a reduced force-rate trajectory, and also peak force was attained. Neonates undergoing the arterial switch procedure showed the most marked postoperative decrease of isovolumic acceleration at basal heart rates and force-frequency relationship with reduced trajectory and peak force development (P < .0001). CONCLUSIONS: This is the first clinical study describing the noninvasive acquisition of ventricular force-frequency relationships in children undergoing operations for congenital heart disease. There is a marked variability in response, ranging from no effect in patients undergoing atrial septal defect closure to a profound reduction in myocardial contractile responses after neonatal arterial switch. This simple noninvasive method allows measurement of a hitherto rarely examined property of the myocardium, an understanding of which might allow refinement of myocardial protection and postoperative myocardial support.
Cardiopulmonary Bypass↗
Extracorporeal life support after staged palliation of a functional single ventricle: subsequent morbidity and survival.
OBJECTIVE: We sought to review the outcome of infants with a functional single ventricle receiving postoperative extracorporeal life support. METHODS: We reviewed all patients with a functional single ventricle receiving postoperative extracorporeal life support between January 1997 and May 2003. RESULTS: We supported 25 infants (age range, 2-139 days; median age, 15 days; weight range, 1.9-5.9 kg; median weight, 3.4 kg) with extracorporeal life support. Operative procedures were Norwood stage 1 procedure in 18 patients, modified Blalock-Taussig shunt in 4 patients, bidirectional superior cavopulmonary shunt in 2 patients, and pulmonary vein repair in 1 patient. Indications for extracorporeal life support included cardiac arrest (14/25) and low cardiac output state (11/25). Extracorporeal membrane oxygenation was initiated in 19 patients, with conversion to a ventricular assist device in 7 patients. Ventricular assist device alone was initiated in 6 patients. Survival to decannulation was 76%, with 5 late deaths from multiorgan failure and 56% intensive care unit survival. Survival to hospital discharge was 44%. On univariate analysis, the presence of arrhythmia before extracorporeal life support (P = .005), renal failure (P = .0007), Candida species-induced sepsis (P = .026), and multiorgan failure (P = .0009) were significant risk factors in the nonsurvivors. Median hospital stay was 43.5 days (range, 6-181 days) for the whole group and 93 days (range, 36-181 days) for survivors. Eight patients completed next stage palliation. CONCLUSIONS: Twenty percent of patients were supported with a ventricular assist device alone, with 50% conversion to a ventricular assist device from extracorporeal membrane oxygenation. Survival to decannulation was encouraging. Multiorgan failure and risk of invasive infection in the post-extracorporeal membrane oxygenation period mitigate against survival to hospital discharge. Use of extracorporeal life support before cardiac arrest might reduce attrition between decannulation and hospital discharge.
Advanced Cardiac Life Support↗
Outcomes and associated risk factors for aortic valve replacement in 160 children: a competing-risks analysis.
BACKGROUND: We sought to define patient characteristics, outcomes, and associated risk factors after aortic valve replacement (AVR) in children. METHODS AND RESULTS: Clinical records from children undergoing AVR from 1974 to 2004 at our institution were reviewed. Competing-risks methodology determined the time-related prevalence of 3 mutually exclusive end states: death, repeated replacement, and survival without subsequent AVR and their associated risk factors. Longitudinal echocardiographic data were analyzed by mixed linear-regression models. Children (n=160) underwent 198 AVRs, with 33 having >1. Competing-risks analysis predicted that 10 years from the initial AVR, 19% had died without subsequent AVR, 34% underwent a second AVR, and 47% remained alive without replacement. Risk factors for death without a second AVR included lower weight (P<0.001) and younger age at AVR (P=0.04), performance of aortic arch reconstruction together with AVR (P=0.03), and nonautograft use (P=0.03). Risk factors for a second AVR included earlier operation year (P=0.04) and implantation of a bioprosthetic or homograft valve (P=0.004). Analysis of serial echocardiographic measurements showed that pulmonary autograft use was associated with slower progression of peak aortic gradient (P=0.002), smaller left ventricular dimension (P=0.04), and decreased prevalence of aortic regurgitation (P=0.04). CONCLUSIONS: Mortality and repeated valve replacement are common after initial AVR in children, especially in younger patients and those with bioprosthetic or homograft valves. Pulmonary autograft use is associated with decreased mortality, slower gradient progression, and smaller left ventricular dimension.
Adolescent↗
CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro.
CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development; however, its role in development and differentiation of other organs has not been investigated. In this study, we used C2C12 myoblasts and human fetal primary myoblasts to investigate the function of Nkx2.5 in skeletal myogenesis. The expression levels of Nkx2.5 decreased as C2C12 myoblasts elongated and fused to form myotubes. The expression of human NKX2.5 in C2C12 myoblasts inhibited myocyte differentiation and myotube formation, and up-regulated Gata4 and Tbx5 expression. The expression of NKX2.5 in terminally differentiated C2C12 myotubes resulted in a change in morphology and breakdown into smaller myotubes. Furthermore, overexpression of NKX2.5 in C2C12 cells and primary cultures of human fetal myoblasts led to differentiation of myoblasts into neuron-like cells and expression of neuronal markers. This study sheds light on the previously unknown non-cardiac functions of Nkx2.5 transcription factor.
Adenoviridae↗
Transgenic expression of CECR1 adenosine deaminase in mice results in abnormal development of heart and kidney.
Cat eye syndrome is a rare developmental defect associated with duplication of chromosome 22q11. The patients demonstrate specific abnormalities of heart, kidney, and eye. Here we attempted to produce a model for this defect by expressing CECR1 adenosine deaminase, a gene duplicated in cat eye syndrome patients, in mice. The transgenic mice expressed CECR1 under the control of either beta-actin promoter for ubiquitous expression or myosin heavy chain for heart-specific expression. The transgenics expressing CECR1 in the heart demonstrated high rate of embryonic and neonatal lethality. The mice from all the lines examined showed enlargement of the heart. Abnormalities of the kidney and eye were also detected in mice expressing CECR1 under control of the actin promoter.
Actins↗
An apology for primary repair of tetralogy of Fallot.
The first repair of tetralogy of Fallot (TOF) was 50 years ago, so it would seem that the details for optimal management strategies would be clear. Timing of repair and operative repair strategy for TOF are still a source of debate. Varying institutions have published excellent outcomes with a primary repair strategy or a selective staged repair strategy. In this article, the current and historic strategy for repair of TOF at the Hospital for Sick Children in Toronto is delineated along with associated outcomes. Data from our institution indicate a clear survival advantage for primary repair of TOF.
Age Factors↗
Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis.
OBJECTIVE: We sought to assess the effects of four different CO2 tensions on systemic oxygenation, oxygen consumption, and arterial blood lactate levels early after bidirectional superior cavopulmonary anastomosis. DESIGN: Prospective study. SETTING: Quaternary pediatric cardiac critical care unit. PATIENTS: Nine children aged 2-23 months (median, 7 months). INTERVENTIONS: All patients were sedated, muscle relaxed, and mechanically ventilated. Baseline Paco2 was adjusted to 35 mm Hg by changing tidal volume. CO2 was added via the inlet port of the ventilator to maintain the Paco2 at 45 and 55 mm Hg. Measurements were repeated after discontinuing additional CO2 gas at a Paco2 of 40 mm Hg. Arterial blood gases and lactate were measured at each level of Paco2. We measured oxygen consumption continuously by respiratory mass spectrometry. MEASUREMENTS AND MAIN RESULTS: Mean (95% confidence interval) Paco2 increased from 35 (34-36) to 45 (44-46) to 55 (54-56) mm Hg (4.7 [4.5-4.9] to 6 [5.7-6.3] to 7.3 [7.2-7.4] kPa), arterial pH decreased from 7.43 (7.39-7.47) to 7.35 (7.31-7.39) to 7.28 (7.24-7.32). Pao2 increased from 36 (32-40) to 44 (40-48) to 50 (45-55) mm Hg (4.8 [4.3-5.3] to 5.9 [5.4-6.4] to 6.7 [6.2-7.2] kPa), and oxygen saturation increased from 72% (67-79%) to 77% (73-81%) to 80% (76-84%). Oxygen consumption decreased significantly, with each increase in Paco2, from 146 (125-167) to 132 (112-152) to 126 (107-145) mL.min.m (p = .0001), and lactate decreased from 1.5 (1-2.0) to 1.2 (0.8-1.6) to 0.8 (0.5-1.1) mmol/L (p < .01). These changes returned toward baseline at a Paco2 of 40 mm Hg. CONCLUSIONS: Moderate hypercapnia with respiratory acidosis improved arterial oxygenation and reduced oxygen consumption and arterial lactate levels, thus improving overall oxygen transport in children after bidirectional superior cavopulmonary anastomosis.
Carbon Dioxide↗
The effects of carbon dioxide on oxygenation and systemic, cerebral, and pulmonary vascular hemodynamics after the bidirectional superior cavopulmonary anastomosis.
OBJECTIVES: We investigated the effects of different CO(2) tensions on oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA). BACKGROUND: Hypoxemia refractory to management of a high pulmonary vascular resistance index (PVRI) may complicate recovery from the BCPA. METHODS: After BCPA, CO(2) was added to the inspired gas of mechanically ventilated patients. The Qp, Qs, PVRI, and systemic vascular resistance index (SVRI) were calculated from oxygen consumption, intravascular pressures, and oxygen saturations. Cerebral blood flow was estimated by near infrared spectroscopy and transcranial Doppler. RESULTS: In nine patients (median age 7.1, range 2 to 23 months), arterial oxygen tension increased significantly (p < 0.005) from 36 +/- 6 mm Hg to 44 +/- 6 to 50 +/- 7 mm Hg at arterial carbon dioxide tensions (PaCO(2)) of 35, 45, and 55 mm Hg, respectively and decreased to 40 +/- 8 mm Hg at PaCO(2) 40 mm Hg. At a PaCO(2) of 55 and 45 compared with 35 mm Hg, Qp, cerebral blood flow, and Qs increased significantly, PVRI, Qp/Qs, and the ratio of Qp to inferior vena caval blood flow were unchanged, but SVRI decreased. CONCLUSIONS: We have demonstrated that after the BCPA, systemic oxygenation, Qp, Qs, and cerebral blood flow increased and SVRI decreased at CO(2) tensions of 45 and 55 mm Hg compared with 35 mm Hg. We suggest that hypoxemia after the BCPA is ameliorated by a higher PaCO(2) and that low PaCO(2) or alkalosis may be detrimental. Hypercarbic management strategies may allow earlier progression to the BCPA, which may contribute to reducing the interval morbidity in patients with a functional single ventricle.
Carbon Dioxide↗
Low molecular weight heparin and unfractionated heparin are both effective at accelerating pulmonary vascular maturation in neonatal rabbits.
BACKGROUND: Creation of a bi-directional cavopulmonary shunt after the Norwood procedure for hypoplastic left heart syndrome is delayed to allow pulmonary vascular resistance to fall with maturation of the pulmonary vascular bed. We hypothesized that unfractionated heparin (UFH) and low molecular weight heparin (LMWH), which promote angiogenesis and inhibit smooth muscle cell growth, could accelerate this process. METHODS AND RESULTS: Fifty-six newborn rabbits were randomly selected to receive UFH 225U/kg (n=12), LMWH 1 mg/kg (n=14), LMWH 10 mg/kg (n=16), or saline (n=14) by subcutaneous injection every 12 hours for 14 days. Treatment with heparin reduced mean pulmonary artery (PA) pressure by 12% to 16% relative to controls [9.0+/-0.2 (UFH), 9.4+/-0.1 (LMWH 1 mg/kg), 9.2+/-0.2 (LMWH 10 mg/kg) versus 10.7+/-0.2 mm Hg (saline), P=0.0001]. Lower PA pressures were associated with reduced alveolar:arterial ratio consistent with enhanced pulmonary angiogenesis in heparin treated animals [8+/-1 (UFH), 13+/-2 (LMWH 1 mg/kg), 12+/-2 (LMWH 10 mg/kg) versus 23+/-5 (saline), P<0.03]. Reduced PA medial wall thickness and muscularization, two additional features of pulmonary vascular maturation, were also more evident in heparin treated animals. Mean PA pressures in 14-day-old rabbits treated with heparin were lower than those measured in control rabbits less than 7 weeks of age suggesting that heparin shortens the pulmonary vascular maturation process by over 60%. CONCLUSIONS: These results indicate that both UFH and LMWH are effective at accelerating pulmonary vascular maturation in newborn rabbits. This raises the possibility that administration of heparin to children after the Norwood procedure might allow for earlier conversion to a bi-directional cavopulmonary shunt.
Animals↗
Subaortic stenosis: at risk substrates and treatment strategies.
Subaortic stenosis can be a complex disease of multiple anatomic etiologies. At the core is either an elongated and narrow outflow tract as compared to normal or a fully muscle-rimmed VSD used as an intraventricular routing pathway. An array of treatment modalities is needed for an effective management strategy.
Adult↗
Levels of exhaled nitric oxide before and after surgical and transcatheter device closure of atrial septal defects in children.
OBJECTIVES: We have shown that exhaled nitric oxide levels decrease after surgical closure of congenital left-to-right cardiac shunts. It remains unclear whether the change in exhaled nitric oxide levels reflects endothelial injury caused by the use of cardiopulmonary bypass or the decrease in pulmonary blood flow attendant on shunt closure. Transcatheter atrial septal defect closure permits shunt closure without the use of cardiopulmonary bypass. Therefore we compared changes in exhaled nitric oxide levels after surgical and transcatheter device closure of atrial septal defects. METHODS: We enrolled sequentially 30 children undergoing atrial septal defect closure. Fifteen patients (age range, 0.4-16 years; median age, 6.5 years) underwent surgical atrial septal defect closure with cardiopulmonary bypass, and 15 patients (age range, 4-17 years; median age, 8.4 years) had device closure of the atrial septal defect in the catheterization laboratory. We measured nitric oxide levels in end-tidal expiratory gas with a rapid-response chemiluminescent analyzer before and after atrial septal defect closure. RESULTS: After surgical repair of the atrial septal defect, exhaled nitric oxide decreased by 21%, from 10.9 +/- 4.4 to 8.4 +/- 3.3 ppb (P <.005), whereas after transcatheter defect closure, exhaled nitric oxide increased by 23%, from 7.6 +/- 2.6 to 9.3 +/- 3.7 ppb (P <.005). Hemoglobin levels in patients undergoing surgical intervention were significantly lower (P =.0001) postoperatively. CONCLUSIONS: We confirmed that exhaled nitric oxide, despite a fall in hemoglobin, decreases after surgical closure of atrial septal defects. In contrast, exhaled nitric oxide levels increase after transcatheter closure. Exhaled nitric oxide levels may reflect bypass-induced endothelial cell injury and are independent of changes in pulmonary blood flow.
Adolescent↗