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Biomedical subjects

Yun-Ching Fu

Publications and source records attributed to Yun-Ching Fu.

At least 19 recordsLinked to original sources

Using multidetector-row CT in neonates with complex congenital heart disease to replace diagnostic cardiac catheterization for anatomical investigation: initial experiences in technical and clinical feasibility.

BACKGROUND: Echocardiography is the first-line modality for the investigation of neonatal congenital heart disease. Diagnostic cardiac catheterization, which has a small but recognized risk, is usually performed if echocardiography fails to provide a confident evaluation of the lesions. OBJECTIVE: To verify the technical and clinical feasibilities of replacing diagnostic cardiac catheterization with multidetector-row CT (MDCT) in neonatal complex congenital heart disease. MATERIALS AND METHODS: Over a 1-year period we prospectively enrolled all neonates with complex congenital heart disease referred for diagnostic cardiac catheterization after initial assessment by echocardiography. MDCT was performed using a 40-detector-row CT scanner with dual syringe injection. A multidisciplinary congenital heart disease team evaluated the MDCT images and decided if further diagnostic cardiac catheterization was necessary. The accuracy of MDCT in detecting separate cardiovascular anomalies and bolus geometry of contrast enhancement were calculated. RESULTS: A total of 14 neonates were included in the study. No further diagnostic cardiac catheterization was needed in any neonate. The accuracy of MDCT in diagnosing separate cardiovascular anomalies was 98% (53/54) with only one atrial septal defect missed in a patient with coarctation syndrome. The average cardiovascular enhancement in evaluated chambers was 471 HU. No obvious beam-hardening artefact was observed. CONCLUSION: The technical and clinical feasibility of MDCT in complex congenital heart disease in neonates is confirmed. After initial assessment with echocardiography, MDCT could probably replace diagnostic cardiac catheterization for further anatomical clarification in neonates.

Cardiac Catheterization↗

Intra-cardiac echocardiography guided trans-septal puncture in patients with dilated left atrium undergoing percutaneous transvenous mitral commissurotomy.

Percutaneous transvenous mitral commissurotomy (PTMC) is an effective treatment for mitral stenosis, but trans-septal puncture carries a certain risk of complications. There have been few reports on phase-array intra-cardiac echocardiography (ICE) guidance in trans-septal puncture for PTMC, especially in patients with dilated left atrium or distorted anatomy. Herein, we report our preliminary experience with ICE-guided trans-septal puncture in patients with dilated left atrium (>or=5.5 cm) who underwent PTMC. From June 2005 to March 2006, there were nine consecutive patients with symptomatic mitral stenosis and left atrium size larger than 5.5 cm who underwent trans-septal puncture for PTMC with the ICE guidance in this institution by a same operator. The procedural and catheterization results were analyzed. Using ICE guidance, the success rate for trans-septal puncture was 100% for all patients with dilated left atrium (>or=5.5 cm). The trans-septal procedures were free of major and minor complications and the patients were not exposed to contrast medium. Mitral valve area increased significantly from 1.0+/-0.2 cm(2) to 1.9+/-0.2 cm(2). Our preliminary result showed that ICE safely and effectively guided trans-septal puncture for PTMC in patients with dilated left atrium (>or=5.5 cm), thus eliminating contrast medium usage and avoiding unnecessary longer X-ray exposure.

Cardiac Surgical Procedures↗

Transcatheter closure of perimembranous ventricular septal defects using the new Amplatzer membranous VSD occluder: results of the U.S. phase I trial.

OBJECTIVES: This phase I study attempted to report the initial safety and efficacy results of transcatheter closure of perimembranous ventricular septal defects (PmVSDs) using the new Amplatzer Membranous VSD Occluder (AGA Medical Corp., Golden Valley, Minnesota) in the U.S. BACKGROUND: The most common congenital heart disease is PmVSD. Surgical repair is widely accepted, but still carries a small but definite risk of morbidity and mortality. METHODS: Between October 2003 and August 2004, a total of 35 patients with PmVSD underwent an attempt of transcatheter closure under transesophageal and/or intracardiac echocardiographic guidance. The median age was 7.7 years (range, 1.2 to 54.4 years) and median weight was 25 kg (range, 8.3 to 110 kg). The median Qp/Qs ratio was 1.8 (range, 1 to 4), and the median VSD size as assessed by echocardiography was 7 mm (range, 4 to 15 mm). RESULTS: The attempt to place a device was successful in 32 patients (91%). The median device size used was 10 mm (range, 6 to 16 mm). The complete closure rates by echocardiography at 10 min (transesophageal/intracardiac), 24 h, 1 month, and 6 months (transthoracic) were 47% (15/32), 63% (20/32), 78% (25/32), and 96% (27/28), respectively. The median fluoroscopy time was 36 min (range, 14 to 191 min), and the median total procedure time was 121 min (range, 67 to 276 min). Three patients (8.6%) had serious adverse events of complete heart block, peri-hepatic bleeding, and rupture of tricuspid valve chordae tendineae. No other patient encountered serious adverse events during the follow-up. CONCLUSIONS: Transcatheter closure of a PmVSD is technically feasible and seems safe enough in children over 8 kg in weight to warrant continuation of clinical trials to assess the long-term safety and efficacy.

Adolescent↗

Norepinephrine induces apoptosis in neonatal rat endothelial cells via a ROS-dependent JNK activation pathway.

Our previous study demonstrated that norepinephrine (NE) induces endothelial apoptosis mainly through down-regulation of Bcl-2 protein and activation of the beta-adrenergic and caspase-2 pathways. However, whether reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) are involved in this signal transduction remains unknown. Endothelial cells cultured from neonatal rat heart were treated with 100 microM NE. Proteins of MAPKs and Bcl-2 family were assayed by Western blotting. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated nick end-labeling assay. ROS was analyzed with flow cytometry. Caspase activity was measured using specific fluorogenic substrates. Treatment with NE increased intracellular ROS level and extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 phosphorylation. Whereas the phosphorylated form of Akt was decreased. The NE-induced apoptosis was abrogated by SP600125 (a specific inhibitor of JNK). Antioxidants such as vitamin C and N-acetyl cysteine inhibited NE-induced ROS production, JNK phosphorylation, caspase activation and apoptosis. Exogenously added superoxide dismutase or catalase markedly diminished NE-induced ROS production and cell death. In conclusions, our study is the first report documenting that NE induces apoptosis in neonatal rat endothelial cells via a ROS-dependent JNK activation pathway. Antioxidants may be useful in the prevention and management of NE-mediated endothelial apoptosis during heart failure.

Acetylcysteine↗

High-dose norepinephrine induces disruption of myocardial extracellular matrix and left ventricular dilatation and dysfunction in a novel feline model.

BACKGROUND: Intravenous norepinephrine (NE) at a dose of 1-6 microg/kg/minute can induce increased extracellular matrix (ECM) and hypertrophic cardiomyopathy. This study aimed to investigate the effects of a higher dose of NE on cardiac remodeling. METHODS: After intraperitoneal urethane-chloralose anesthesia, 7 cats (3.03 +/- 0.58 kg) received intravenous infusion of NE 30 microg/kg/minute for 3 hours. Aortic blood pressure and heart rate (HR) were measured by polygraphy at 0, 5, 15, 30, 60, 90, 120, and 180 minutes. Left ventricular size and ejection fraction (EF) were measured by M-mode echocardiography before and after NE administration. Histopathology was performed by hematoxylin-eosin, silver impregnation, and Sirius red staining. Activity of matrix metalloproteinases (MMP) in the left ventricle was measured by zymography. RESULTS: Mean blood pressure (mmHg) increased from 139 +/- 20 to 198 +/- 19, 187 +/- 23, and 166 +/- 16 at 15, 30, and 60 minutes, respectively, during NE infusion. HR (beats/minute) decreased from 214 +/- 10 to 158 +/- 28 at 15 minutes and then recovered gradually. The left ventricles showed significant dilatation (end-diastolic diameter: from 1.20 +/- 0.18 to 1.58 +/- 0.23cm, p=0.003; end-systolic diameter: from 0.62 +/- 0.23 to 1.35 +/- 0.29cm, p=0.002) and hypokinesia (EF: from 86.2 +/- 5.2 to 33.1 +/- 16.5%, p < 0.001). Histopathology revealed that left ventricular myocytes were elongated, wavy, and fragmented, while collagen fibers were overstretched, straightened, and disrupted. MMP-9 activity was significantly elevated (p = 0.003 vs. control), while MMP-2 activity was unchanged. CONCLUSION: High-dose NE increases MMP-9 activity and causes ECM disruption, left ventricular dilatation and dysfunction.

Animals↗

Initial clinical experience of real-time three-dimensional echocardiography in neonates with isolated congenital ductus arteriosus aneurysm.

BACKGROUND: Congenital ductus arteriosus aneurysm (DAA) was considered rare but potentially fatal abnormality, often followed by surgical intervention after careful evaluation. This prospective study used real-time three-dimensional echocardiography (RT3DE) to assist in evaluation of neonatal DAA. METHODS: A total of 1390 full-term neonates were enrolled in this study between 2002 and 2003. They received two-dimensional echocardiographic (2DE) screening and periodic follow-up. RT3DE was performed selectively for newborns with DAA. RESULTS: DAA were detected in 116 (8.34%) newborns using 2DE. Maximum diameter of the DAAs ranged from 6.8 to 14.0 mm (8.2+/-1.1 mm). None of the cases were symptomatic or had complications related to DAA. There were no significant differences in sex and gestational age between the newborns with and without DAA. Neonates with DAA had a higher birth body weight and a higher incidence of large-for-gestational-age (P<0.05). RT3DE provided instant, consistent and reliable 3D images of DAA and its related structures and allowed for more rapid examination times and reduction of baby wait times. CONCLUSIONS: Congenital DAA is as common as has been previously reported. RT3DE is useful in assisting evaluation of DAA. Preferred images of DAA were typically visualized in the high parasternal short-axis view before the third day of life. Routine use of RT3DE is suggested to enhance assessment of neonates with DAA detected by 2DE.

Ductus Arteriosus↗

A rare vascular ring caused by an aberrant right subclavian artery concomitant with the common carotid trunk: a report of two cases.

In this report, we describe two rare cases with aortic branching anomalies. One was a 7-year-old girl who had an incomplete vascular ring caused by the presence of left aortic arch and aberrant, retroesophageal right subclavian artery associated with the common carotid trunk. The other was a 6-year-old boy who had a right aortic arch and mirror image branches of the former case. Both were asymptomatic and discovered incidentally. Three-dimensional surface rendering magnetic resonance angiography was used to confirm the diagnosis. Surgical intervention was not performed in either case because of lack of vascular ring-related symptoms. The incidence, clinical symptoms, pathogenesis and management of this rare vascular ring are discussed below.

Aortic Arch Syndromes↗

Sympathetic activity and myocardial damage after stimulation of dorsal medulla and vagotomy in a novel animal model.

Many kinds of brain lesions cause sympathetic hyperexcitation and myocardial damage. A novel animal model was developed for the correlation of sympathetic excitation with ventricular dysfunction and myocardial damage. Six cats (3.23+/-0.26 kg) under intraperitoneal urethane-chloralose anesthesia were artificially ventilated and bilaterally vagotomized. They underwent an electrical stimulation of unilateral dorsal medulla for 180 min (monopolar square-wave pulses, 10 Hz, 10 V, 0.5 ms). Mean blood pressure, heart rate plasma concentration of norepinephrine and left ventricular size and ejection fraction were measured at 0, 5, 15, 30, 60, 90, 120 and 180 min. Mean blood pressure (mm Hg), heart rate (beats/min) and norepinephrine (pg/ml) increased abruptly from 128+/-15, 203+/-22 and 353+/-123 to 234+/-26, 240+/-13 and 4727+/-2159 at 5 min after electrical stimulation (all p<0.01). The left ventricles showed significant dilatation (end-diastolic diameter: from 1.35+/-0.13 to 1.84+/-0.21 cm, p=0.006; end-systolic diameter: from 0.65+/-0.20 to 1.54+/-0.24 cm, p=0.002) and hypokinesia (ejection fraction: from 88.9+/-6.4% to 37.3+/-8.7%, p<0.001). Cardiac pathology revealed myocardial hemorrhage, cardiomyocyte apoptosis and coagulative myocytolysis (contraction band necrosis), characterized by sarcoplasmic coagulation, granulation and disruption. In conclusions, the present experiment develops a novel animal model in which stimulation of the pressor area in the dorsal medulla in vagotomized cats produces sympathetic hyperexcitation accompanied with myocardial dysfunction and damage. This model may be applicable for studying protective effect of drugs on myocardial dysfunction and damage caused by sympathetic hyperexcitation occurring in brain diseases.

Animals↗

Patent foramen ovale.

Patent foramen ovale is incriminated in patients with cryptogenic stroke; however, concrete evidence that closure of patent foramen ovale using various devices is superior to continued medical therapy is not yet available. Controlled randomized trials are well underway to address this issue.

Adult↗

Norepinephrine induces apoptosis in neonatal rat cardiomyocytes through a reactive oxygen species-TNF alpha-caspase signaling pathway.

OBJECTIVE: Norepinephrine (NE)-induced apoptosis in cardiomyocytes is an important cause of heart failure. Previous studies revealed that reactive oxygen species (ROS) are involved in apoptosis. Tumor necrosis factor-alpha (TNF), a well-known mediator that stimulates apoptosis, is not only produced by macrophages but also by cardiomyocytes. Until now, the role of TNF and its relationship to ROS in NE-induced apoptosis of cardiomyocytes have never been investigated. METHODS: Neonatal rat cardiomyocytes were treated with various concentrations of NE. Apoptosis of cardiomyocytes was determined using the TUNEL assay. The level of secreted TNF was measured by ELISA and TNF mRNA expression was determined by semiquantitative reverse transcriptional polymerase chain reaction. Caspase activity was measured by a fluorogenic protease assay kit. Anti-TNF antibodies, caspase inhibitors and antioxidants (N-acetyl-L-cysteine or vitamin C) were added to determine if they could inhibit the apoptotic effect of NE. RESULTS: NE induced apoptosis of cardiomyocytes in a dose- and time-dependent manner. NE up-regulated TNF mRNA expression and increased TNF secretion and caspase-2,-3,-6, and -9 activities. A neutralizing anti-TNF antibody and caspase-2 and -3 inhibitors significantly attenuated NE-induced apoptosis. Antioxidants completely abrogated NE-induced TNF secretion, caspase activation, and apoptotic death. CONCLUSION: NE induced apoptosis in neonatal rat cardiomyocytes through a ROS-TNF-caspase signaling pathway.

Animals↗

Norepinephrine induces apoptosis in neonatal rat endothelial cells via down-regulation of Bcl-2 and activation of beta-adrenergic and caspase-2 pathways.

OBJECTIVES: Heart failure is associated with increased plasma norepinephrine (NE) and endothelial apoptosis. Recent reports have suggested that endothelial dysfunction is an important target for future therapies of heart failure. However, whether NE can induce endothelial apoptosis and its mechanism remains unknown. METHODS: Endothelial cells from neonatal rat heart were treated with various concentrations of NE for different durations. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) and DNA fragmentation assays. Caspase activity was measured using specific fluorogenic substrates. Proteins of Bcl-2 family and cytochrome c were assayed by Western blotting. RESULTS: NE induced endothelial apoptosis in a dose- and time-dependent manner. After treatment for 48 h, increasing NE concentration from 5, 10, 50, 100 to 200 microM resulted in 6+/-3%, 14+/-5%, 43+/-4%, 66+/-5%, and 89+/-6% apoptotic cells, respectively. The apoptosis was accompanied by down-regulation of Bcl-2 protein synthesis but not by cytosolic cytochrome c translocation. Caspase-2, -3, -6 and -9 were activated during apoptosis and caspase-2 inhibitor (Z-VDVAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) significantly attenuated the apoptosis. Overexpression of Bcl-2 inhibited caspase activity and decreased the apoptosis. Moreover, the NE-mediated apoptotic effect was attenuated by beta- (beta2>beta>beta1) adrenergic antagonists (ICI-118,551>propranolol>atenolol) but was not affected by alpha1- or alpha2-adrenergic antagonists (prazosin or yohimbine). CONCLUSION: Our study is the first report documenting that NE induces apoptosis in neonatal rat endothelial cells mainly through down-regulation of Bcl-2 protein and activation of the beta-adrenergic (beta2>beta1) and caspase-2 pathways. beta-Adrenergic antagonists and caspases inhibitors may be useful in the prevention and management of NE-mediated endothelial apoptosis during heart failure.

Adrenergic beta-Antagonists↗

Prediction of ductus arteriosus closure by neonatal screening echocardiography.

AIMS: We reported the incidence, clinical manifestations and outcome of patent ductus arteriosus (PDA) in full-term infants by screening echocardiography. METHODS AND RESULTS: Total 1230 infants received echocardiographic screening and periodic follow-up. On the third day of life, there were 109 infants with isolated ductus arteriosus aneurysm (DAA), those with persistent patency of the ductus arteriosus (DA) in 26. The DA closed within 48 h in 828 infants, and persisted beyond 48 h in 180. The incidence of PDA in full-term infants was 0.91, 0.83 and 0.66% at 1, 4 and 6 months follow-up, and 0.82, 0.73 and 0.64% if infants with DAA were excluded. Infants with PDA had lower birth body weight (BBW) than those with closed DA (p = 0.02). The DA width on the third day of life ranged from 0.23 to 0.43 cm (0.32+/-0.08 cm) and 0.08 to 0.44 cm (0.16+/-0.06 cm) in infants with or without PDA, respectively, which was significantly different (p < 0.05). The sensitivity, specificity, predictive positive and negative values were 87.5, 92.5, 36.8 and 99% respectively for the cuff-off point at 0.25 cm of DA width. CONCLUSIONS: Risk factors in infants with PDA included lower BBW and larger measured DA width at the third day of life. We predicted the arterial duct would close if DA width <0.25 cm, and suggested follow up earlier if >0.25 cm on the third day of life.

Cardiac Surgical Procedures↗

Prediction of ductus arteriosus closure by neonatal screening echocardiography.

AIMS: We reported the incidence, clinical manifestations and outcome of patent ductus arteriosus (PDA) in full-term infants by screening echocardiography. METHODS AND RESULTS: Total 1230 infants received echocardiographic screening and periodic follow-up. On the third day of life, there were 109 infants with isolated ductus arteriosus aneurysm (DAA), those with persistent patency of the ductus arteriosus (DA) in 26. The DA closed within 48 h in 828 infants, and persisted beyond 48 h in 180. The incidence of PDA in full-term infants was 0.91, 0.83 and 0.66% at 1, 4 and 6 months follow-up, and 0.82, 0.73 and 0.64% if infants with DAA were excluded. Infants with PDA had lower birth body weight (BBW) than those with closed DA (p = 0.02). The DA width on the third day of life ranged from 0.23 to 0.43 cm (0.32 +/- 0.08 cm) and 0.08 to 0.44 cm (0.16 +/- 0.06 cm) in infants with or without PDA, respectively, which was significantly different (p < 0.05). The sensitivity, specificity, predictive positive and negative values were 87.5, 92.5, 36.8 and 99% respectively for the cuff-off point at 0.25 cm of DA width. CONCLUSIONS: Risk factors in infants with PDA included lower BBW and larger measured DA width at the third day of life. We predicted the arterial duct would close if DA width <0.25 cm, and suggested follow up earlier if >0.25 cm on the third day of life.

Aneurysm↗

Pulmonary edema of enterovirus 71 encephalomyelitis is associated with left ventricular failure: implications for treatment.

Epidemics of enterovirus 71 infections caused the rapid death of many children in Malaysia in 1997 and in Taiwan in 1998. Pulmonary edema occurred in most of the fatal cases and was considered to be neurogenic. The role of the heart was rarely investigated before. Between January 1998-January 2001, 34 consecutive patients who were admitted to the intensive care unit due to enterovirus infection were studied prospectively. Patients were divided into two groups: group I with pulmonary edema, and group II without pulmonary edema. Comparisons were made between the two groups based upon demographic, neurological, and cardiovascular manifestations. Group I consisted of 11 patients (5 boys, 6 girls; mean age, 22.8 months), and group II of 23 patients (12 boys, 11 girls; mean age, 28.8 months). There were no significant differences between the two groups in comparing sex, age, body weight, neurological severity, intracranial pressure, cell count, protein and glucose levels in cerebral spinal fluid, and blood pressure. All group I patients had left ventricular dysfunction, and their ejection fractions were significantly lower than those of patients in group II (37 +/- 11% vs. 75 +/- 6%, P < 0.001). Group I heart rates were higher than those of group II (175 +/- 24 vs. 137 +/- 25, P < 0.001). In group I, 9 patients who received conventional treatment died, and the only two survivors received left ventricular assist devices. In conclusion, the pulmonary edema of fulminant enterovirus 71 infection is associated with left ventricular failure. Left ventricular function is the major determinant of outcome. Early recognition of heart failure and aggressive cardiac intervention are life-saving. Pediatr Pulmonol. 2003; 35:263-268.

Child, Preschool↗

Usefulness of Tc-99m HMPAO-labeled WBC heart scan to predict impaired ventricular function and coronary artery dilation in children with Kawasaki disease.

Forty-nine children with Kawasaki disease were included in this study. Based on the severity of carditis as determined by Tc-99m HMPAO-labeled WBC heart scan, the children were separated into two groups. Group A (n=24) had significant carditis and group B (n=25) did not have significant carditis. The left and right ventricular ejection fractions (LVEF and RVEF) were evaluated by equilibrium multigated blood pooling ventriculography. Diameters of the left and right coronary arteries (LCA and RCA) were measured by two-dimensional echocardiography. The results showed that group A had lower LVEF and RVEF, but larger diameters of the LCA and RCA than those of group B patients. The sensitivity of significant carditis to predict left ventricular dysfunction, right ventricular dysfunction, LCA dilation and RCA dilation was 88.9, 70.6, 75, and 71.4%, respectively; the specificities were 100, 100, 100, and 67.9%, respectively. Our findings suggest that significant carditis determined by Tc-99m HMPAO-labeled WBC heart scan can accurately predict impaired ventricular function and coronary artery dilation.

Child, Preschool↗

Influence of ductal size on the results of transcatheter closure of patent ductus arteriosus with coils.

To assess the influence of ductal size on the results of transcatheter closure of patent ductus arteriosus (PDA) with coils, 154 consecutive patients were studied prospectively. Ductal size was defined as the narrowest diameter of ductus measured on aortography. All patients were divided into 5 groups according to ductal size: < 1 mm, 1-1.9 mm, 2-2.9 mm, 3-3.9 mm, and > or = 4 mm. The occlusion of PDA with coils was performed through a transarterial approach. The results were evaluated by angiography at 10 minutes and by color Doppler echocardiography at 1 day, 2 days, 1 week, 1 month, 3 months, 6 months, and 12 months after the procedure. The immediate occlusion rates for ductal sizes < 1 mm, 1-1.9 mm, 2-2.9 mm, 3-3.9 mm, and > or = 4 mm were 89.7%. 75.4%, 51.4%, 30.8%, and 40%, respectively; whereas the occlusion rates at 12-months follow-up were 100%, 98.5%, 97.3%, 69.2%, and 80%, respectively. There were no significant differences in occlusion rate at 12-months follow-up among the groups with ductal sizes < 3 mm or among the groups with ductal sizes > or = 3 mm. The occlusion rate for ductal size < 3 mm at each follow-up time was significantly higher than that for ductal size > or = 3 mm (10 minutes: 71.8% vs 34.8%. P = 0.001; 12-months: 98.5% vs 73.9%, P < 0.001). The occlusion rate of residual shuntings at 12-months follow-up for ductal size < 3 mm was also significantly higher than that for ductal size > or = 3 mm (94.6% vs 60%, P = 0.007). The results of the present study demonstrate that ductal size < 3 mm had a higher occlusion rate than that for a size > or = 3 mm. PDA with a size > or = 3 mm may need other treatment strategies or other devices to achieve better results.

Cardiac Catheterization↗