Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making.

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.

An unusual manifestation of post-transplant lymphoproliferative disorder in the lip after pediatric heart transplantation.

PTLD is a serious and frequently observed complication after solid organ transplantation. We present a six-yr-old girl with a rapidly growing, solid tumor of the lip four yr after orthotopic heart transplantation, which was classified as monomorphic PTLD with the characteristics of a diffuse large B-cell lymphoma. Treatment with reduction in immunosuppression, ganciclovir, and anti B-cell monoclonal antibody (rituximab) resulted in full remission since 12 months. To the best of our knowledge, this report is the first description of PTLD in the lip in a pediatric patient after heart transplantation in the English literature.

Sonographic assessment of fetal cardiac function: indirect measurements of fetal cardiac function, newer techniques and clinical applications.

Noninvasive blood flow measurements based on Doppler ultrasound studies are the main clinical tool for studying the cardiovascular status of fetuses at risk for circulatory compromise. Usually, qualitative analysis of peripheral arteries and in particular clinical situations such as severe growth restriction or volume overload also of venous vessels close to the heart or of flow patterns in the heart is being used to gauge the level of compensation in a fetus. However, quantitative assessment of the driving force of the fetal circulation, the cardiac output remains an elusive goal in fetal medicine. This article reviews the methods for direct and indirect assessment of cardiac function and explains new clinical applications. Part 1 of this review describes the concept of cardiac function and cardiac output and the techniques that have been used to quantify output. Part 2 summarizes the use of arterial and venous Doppler studies in the fetus and gives a detailed description of indirect measurements of cardiac function (like indices derived from the duration of segments of the cardiac cycle) with current examples of their application.

Sonographic assessment of fetal cardiac function: introduction and direct measurement of cardiac function.

Noninvasive blood flow measurements based on Doppler ultrasound studies are the main clinical tool for studying the cardiovascular status in fetuses at risk for circulatory compromise. Usually, qualitative analysis of peripheral arteries and, in particular clinical situations such as severe growth restriction or volume overload, also of venous vessels close to the heart or of flow patterns in the heart are being used to gauge the level of compensation in a fetus. Quantitative assessment of the driving force of the fetal circulation, the cardiac output, however, remains an elusive goal in fetal medicine. This article reviews the methods for direct and indirect assessment of cardiac function and explains new clinical applications. Part 1 of this review describes the concept of cardiac function and cardiac output and the techniques that have been used to quantify output. Part 2 summarizes the use of arterial and venous Doppler studies in the fetus and gives a detailed description of indirect measures of cardiac function (like indices derived from the duration of segments of the cardiac cycle) with current examples of their application.

Pulsed-wave tissue Doppler echocardiography for the analysis of fetal cardiac arrhythmias.

OBJECTIVES: Rhythm analysis of the fetal heart is hampered by the inability to routinely obtain electrocardiographic recordings of the fetus. Doppler studies of fetal cardiac tissue movements, assessing cardiac movements both qualitatively and quantitatively, have recently been described. We used a conventional high-resolution ultrasound system to obtain rhythm data from pulsed-wave tissue Doppler signals of the fetal heart in normal cardiac rhythm and in a variety of fetal cardiac arrhythmias. METHODS: Fifty-five fetuses with normal (sinus) rhythm, 45 fetuses with rhythm disturbances and two neonates (one with arrhythmia and one with normal sinus rhythm) were studied. Using a conventional high-resolution ultrasound system equipped for fetal studies, but without specific tissue Doppler hardware or software, we performed pulsed-wave tissue Doppler echocardiography (PW-TDE) of atrioventricular valve ring excursions to study the atrial and ventricular mechanical actions. In the neonates, electrocardiograms were also recorded. RESULTS: PW-TDE in normal fetuses shows a typical pattern of tissue motion parallel to the long axis of the heart and in the opposite direction to the blood flow, both in systole and diastole. This pattern is easily obtained from the tricuspid valve annulus in normal sinus rhythm and shows characteristic changes in various fetal arrhythmias. CONCLUSION: PW-TDE of atrioventricular valve annulus movement patterns may prove to be a valuable additional tool for assessing fetal cardiac arrhythmias.

[Comparative investigation of treatments for evaporative dry eye]. / Vergleichende Untersuchung zur Therapie des evaporativen trockenen Auges.

BACKGROUND: Evaporative dry eye is the most common form of tear film dysfunction. The present trial aims to evaluate the efficacy of two established treatment options with different modes of action by comparison. PATIENTS/MATERIAL AND METHODS: 216 patients suffering from evaporative dry eye were included in this prospective, randomised two-centre trial. Divided into two treatment groups, patients either received treatment with hyaluronate artificial tears (Vismed light) or a phospholipid-liposome eye spray (Tears Again), each for three months. Tests (lid-parallel conjunctival folds [LIPCOF], non-invasive break-up time [NIBUT], Schirmer's test, inspection of lids and subjective assessment) were performed before as well as 4 and 12 weeks after initiation of this study. RESULTS: In the patients of the eye spray group there was a significantly greater reduction of the LIPCOF grade (p < 0.02) and the grade of inflammation of the lid margin (p < 0.002). With respect to the tear film break-up time (NIBUT) there was a significant difference between the results of both groups (p < 0.003). The improvement of the break-up time in patients of the eye spray group turned out to be more than twice as high as that in the artificial tears group. CONCLUSIONS: Both therapies improved evaporative dry eye, but patients on phospholipid-liposomal eye spray demonstrated greater clinical benefit from their therapy, particularly regarding the degree of inflammation of the lid margins as well as the grade of LIPCOF. When compared to hyaluronate artificial tears, NIBUT more than doubled in the phospholipid-liposome eye spray group. Clinical severity of dry eye is more pronounced when evaporative dry eye and aqueous tear deficiency coincide. A combination of the phospholipid-liposome eye spray and artificial tears appears to represent a considerable advancement in tear replacement therapy for severe cases of dry eye.

Two further cases supporting nonsurgical management in congenital lobar emphysema.

BACKGROUND: For decades, the well-established standard recommended treatment for patients with congenital lobar emphysema (CLE) and respiratory distress has been lobectomy of the affected lobe or lobes, whereas indications for conservative management have been controversially discussed. PATIENTS/METHODS: Description of the clinical courses including the results of diagnostic procedures and the resulting therapeutic strategies in 2 patients with congenital lobar emphysema. We review the literature on conservatively treated patients with congenital lobar emphysema. RESULTS: Considering that formerly asserted hypotheses postulating benefits of surgical treatment cannot unambiguously be corroborated from cases in literature, we could show that conservative treatment in patients with congenital lobar emphysema is appropriate in mildly to moderately symptomatic children. CONCLUSION: Conservative treatment of children with congenital lobar emphysema is an attractive option, whenever justifiable on medical grounds. Our cases may serve as paradigms in decision-making processes in similar cases and - together with the literature review - may be helpful to avoid unnecessary lobectomies in children. Patients treated conservatively will need a close follow-up, and further data on long-term follow-up courses are desirable.

Present risk of anthracycline or radiation-induced cardiac sequelae following therapy of malignancies in children and adolescents.

Anthracyclines are very potent drugs in the therapy of malignancies in childhood. The major dose limiting adverse effect of these drugs is the risk of dilated cardiomyopathy. We performed a retrospective study on 168 patients who were treated with anthracyclines for a malignant disease with or without chest radiation at the department of Pediatric Hematology and Oncology at the University of Duesseldorf between 2000 and 2004. During and after chemotherapy the patients were screened by echocardiography and ECG examinations prior to each administration of anthracyclines. Only four patients presented with adverse cardiac events, one of whom developed acute cardiac failure. This patient was additionally treated with chest radiation. Three of the four patients showed intermittent arrhythmias, mainly supraventricular tachycardia. One of them presented with atrial ectopic tachycardia and left ventricular dysfunction. We conclude that the frequency of cardiac sequelae after chemotherapy with anthracyclines is low under present guidelines. Detection of early cardiac sequelae may be more difficult than in the past. Only one patient with cardiac sequelae in our study group was diagnosed by regular performed examinations for cardiac sequelae of chemotherapy. We therefore need to modify our screening methods to increase the effectiveness of detection of cardiac dysfunction prior to clinical manifestation.

Levoatrial cardinal vein in mitral atresia and closed foramen ovale: prenatal diagnosis and perinatal management.

A levoatrial cardinal vein is a rare cardiovascular anomaly that may be present in malformed hearts with severe left heart obstruction and restrictive interatrial communication. We report the prenatal diagnosis at 23 weeks of a fetus with mitral atresia, double-outlet right ventricle, premature closure of the foramen ovale and a levoatrial cardinal vein draining into the innominate vein. In a prior examination performed elsewhere the levoatrial cardinal vein had been interpreted as an aortic arch perfused retrogradely, and hypoplastic left heart syndrome with aortic atresia had been diagnosed. Prenatal management, induction at 38 weeks and postnatal examinations and treatment are reported. To the best of our knowledge, this is the first reported prenatal diagnosis of this embryological vessel, presenting a potential pitfall for prenatal echocardiography.

Neurodegenerative diseases of the retina and potential for protection and recovery.

Recent advances in our understanding of the mechanisms in the cascade of events resulting in retinal cell death in ocular pathologies like glaucoma, diabetic retinopathy and age-related macular degeneration led to the common descriptive term of neurodegenerative diseases of the retina. The final common pathophysiologic pathway of these diseases includes a particular form of metabolic stress, resulting in an insufficient supply of nutrients to the respective target structures (optic nerve head, retina). During metabolic stress, glutamate is released initiating the death of neurones containing ionotropic glutamate (N-methyl-D-aspartat, NMDA) receptors present on ganglion cells and a specific type of amacrine cells. Experimental studies demonstrate that several drugs reduce or prevent the death of retinal neurones deficient of nutrients. These agents generally block NMDA receptors to prevent the action of glutamate or halt the subsequent pathophysiologic cycle resulting in cell death. The major causes for cell death following activation of NMDA receptors are the influx of calcium and sodium into cells, the generation of free radicals linked to the formation of advanced glycation endproducts (AGEs) and/or advanced lipoxidation endproducts (ALEs) as well as defects in the mitochondrial respiratory chain. Substances preventing these cytotoxic events are considered to be potentially neuroprotective.

Development and application of a specially designed heating system for temperature-programmed high-performance liquid chromatography using subcritical water as the mobile phase.

A specially designed heating system for temperature-programmed HPLC was developed based on experimental measurements of eluent temperature inside a stainless steel capillary using a very thin thermocouple. The heating system can be operated at temperatures up to 225 degrees C and consists of a preheating, a column heating and a cooling unit. Fast cycle times after a temperature gradient can be realized by an internal silicone oil bath which cools down the preheating and column heating unit. Long-term thermal stability of a polybutadiene-coated zirconium dioxide column has been evaluated using a tubular oven in which the column was placed. The packing material was stable after 50h of operation at 185 degrees C. A mixture containing four steroids was separated at ambient conditions using a mobile phase of 25% acetonitrile:75% deionized water and a mobile phase of pure deionized water at 185 degrees C using the specially designed heating system and the PBD column. Analysis time could be drastically reduced from 17 min at ambient conditions and a flow rate of 1 mL/min to only 1.2 min at 185 degrees C and a flow rate of 5 mL/min. At these extreme conditions, no thermal mismatch was observed and peaks were not distorted, thus underlining the performance of the developed heating system. Temperature programming was performed by separating cytostatic and antibiotic drugs with a temperature gradient using only water as the mobile phase. In contrast to an isocratic elution of this mixture at room temperature, overall analysis time could be reduced two-fold from 20 to 10 min.

Doubly committed subarterial ventricular septal defects: echocardiographic features and surgical implications.

Doubly committed subarterial (supracristal, subpulmonary) ventricular septal defects are often complicated by aortic regurgitation resulting from aortic valve herniation into the defect. The clinical, echocardiographic and catheterization findings in 48 patients aged 0.3 to 46.4 years (median 9.5) with a doubly committed subarterial ventricular septal defect were reviewed. Aortic valve herniation was present in 38 (79%) and 55% of these had aortic regurgitation. The prevalence of both findings increased gradually with advancing age. The defect was closed surgically in 41 patients. Surgery during the first 2 years of life (median 0.4 year) was performed in 13 patients (group I), mainly because of a large shunt with a pulmonary to systemic flow ratio (Qp/Qs) 3.8 +/- 1.4 (mean +/- SD). Aortic regurgitation was present preoperatively in two patients (15%), persisted postoperatively in one patient and did not develop in any after repair (median duration of follow-up 2.3 years, range 0.1 to 7.4). In the other 28 patients (group II) surgery was performed between 4.8 and 46.4 years of age (median 11.5). These patients were generally less symptomatic and had a smaller shunt (Qp/Qs 1.5 +/- 0.5, p less than 0.001). Preoperative aortic regurgitation was present in 18 (64%). It persisted in 15 postoperatively, but in 13 of these it had diminished. Two-dimensional echocardiography in multiple views identified the site of the ventricular septal defect in all patients. Serial echocardiographic examinations demonstrated the progressive nature of aortic valve herniation, the partial occlusion of the defect by the herniated sinus and the development of aortic regurgitation. These findings suggest that timely surgical closure of these defects may prevent aortic regurgitation.

Pulmonary artery origin of the left coronary artery: diagnosis by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow mapping.

Five children, aged 0.2 to 6.7 years, with pulmonary artery origin of the left coronary artery proved by angiography underwent echocardiographic examination from 1985 through 1986. Prospective identification of this condition was achieved by two-dimensional echocardiography alone in two patients. Using a parasagittal plane from the second or third intercostal space, identification of the anomalous origin from the pulmonary artery was also possible in the other children on subsequent examination. In all of these studies the right coronary artery was considerably enlarged. The ratio of the diameters of the right coronary artery and the aortic root was 0.25 to 0.33 (normal 0.12 +/- 0.02). Flow mapping by color Doppler ultrasound in three children studied most recently and peripheral arterial or aortic root contrast echocardiography identified the site of entry of the coronary flow into the pulmonary artery. The flow disturbance was detected on the aortic surface of the pulmonary artery opposite the portion from where the flow from a patent ductus is usually identified. Pulsed Doppler ultrasound identified the flow disturbance in the pulmonary artery in only three of the children. The two youngest patients did not demonstrate turbulence on pulsed Doppler ultrasound, but they were not examined by color Doppler ultrasound. The accuracy of noninvasive detection of pulmonary artery origin of the left coronary artery by ultrasound is improved by the use of a combined echocardiographic approach.

Determination of pulmonary to systemic blood flow ratio in children by a simplified Doppler echocardiographic method.

Doppler echocardiographic determination of the pulmonary to systemic blood flow (Qp/Qs) ratio requires calculation of pulmonary artery and aortic luminal areas and integrals of the Doppler systolic velocity curves. To simplify the Doppler calculation of the Qp/Qs ratio, the square of the ratio of pulmonary to aortic luminal diameters, substituted for the ratio of vessel areas, was multiplied by the ratio of pulmonary to aortic peak flow velocities, substituted for the ratio of velocity time integrals. The Qp/Qs ratios were calculated by both the conventional and the simplified Doppler method in 42 children, 1 month to 16 years of age. Fifteen children had no evidence of shunt and 27 had an intracardiac left to right shunt at the atrial or ventricular level, or both. In children with a shunt, the Qp/Qs ratio obtained at cardiac catheterization by oximetry ranged from 1.4:1 to 4.3:1. Both the conventional and the simplified Doppler Qp/Qs ratios correlated well with the oximetric Qp/Qs ratios (r = 0.94 and 0.93, respectively). Since the pulmonary to aortic luminal area ratio and velocity time integral ratio varied in each patient, neither measurement alone correlated well with the oximetric Qp/Qs ratio and, therefore, neither alone could be used as an estimate of the Qp/Qs ratio. The simplified Doppler calculation of the Qp/Qs ratio, which requires less time and no computer facilities, provides an excellent estimate of the Qp/Qs ratio in children.

Assessment of right ventricular performance by pulsed Doppler echocardiography in patients after intraatrial repair of aortopulmonary transposition in infancy or childhood.

The purpose of this study was to determine whether measurement of aortic blood flow velocity and acceleration by pulsed Doppler ultrasound can be used to assess the global performance of the systemic right ventricle noninvasively in young patients who have undergone intraatrial repair of aortopulmonary transposition. The effect of age at surgery on right ventricular performance in these patients was also studied. Pulsed Doppler velocity profiles of aortic blood flow were analyzed at a mean age of 5.5 years in 24 patients who had undergone intraatrial repair of aortopulmonary transposition either in early infancy (mean age 3.4 +/- 1.3 weeks) or later (mean age 8.5 +/- 6.5 months). Velocity and acceleration variables in these patients were compared with the same variables in 24 age-matched normal subjects and with the performance of their own right ventricle as assessed by two-dimensional echocardiographic measurement of ejection fraction. The 12 patients who underwent early repair had a higher ejection fraction than did the 12 who underwent later repair (mean +/- SD 0.60 +/- 0.07 versus 0.42 +/- 0.10; p less than 0.001). Aortic flow velocity was similar in all patients. Aortic acceleration was normal in patients after early intraatrial repair of aortopulmonary transposition (20.8 +/- 2.3 m/s2), but was abnormally slow in patients after late repair (11.1 +/- 1.8 m/s2; p less than 0.001), thus suggesting that the latter group had diminished right ventricular performance. Concomitantly, acceleration time and ratio of acceleration time to ejection time were increased in patients after late repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of right ventricular size and function in neonates after valvotomy for pulmonary atresia or critical pulmonary stenosis and intact ventricular septum.

Right ventricular end-diastolic and stroke volumes were calculated from orthogonal subcostal echocardiographic images in 24 neonates (mean weight +/- SD 3.4 +/- 0.4 kg) with pulmonary atresia (n = 18) or critical pulmonary stenosis (n = 6) and intact ventricular septum before and at an average of 5 days and then 19 days after pulmonary valvotomy. The preoperative echocardiographic volume determinations were compared with the respective angiographic determinations. In addition, the endocardial area outlines of the left and right ventricles were obtained by planimetry from an end-diastolic frame taken in the apical four-chamber view. End-diastolic and stroke volumes calculated by the echocardiographic method (y) correlated closely with those calculated by the angiographic method (x); the regression equations were y = 1.02 x -0.13 (r = 0.95, SEE +/- 0.45 ml) and y = 1.16 x -0.15 (r = 0.89, SEE +/- 0.38 ml), respectively. All except one infant had right ventricular hypoplasia before valvotomy with an end-diastolic volume of 16.6 +/- 6.4 ml/m2 (44.5 +/- 17.3% of normal). Right to left ventricular area ratio was 0.56 +/- 0.09 (normal 0.95). Five days after valvotomy, right ventricular end-diastolic volume decreased to 10.6 +/- 4.6 ml/m2 (p less than 0.05) and stroke volume decreased from 8.3 +/- 3.5 to 5.5 +/- 2.8 ml/m2 (p less than 0.05). Nineteen days after valvotomy, right ventricular end-diastolic volume and right to left ventricular area ratio had increased to their respective preoperative values; right ventricular stroke volume had increased further to 10.4 +/- 3.9 ml/m2 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of coronary artery fistula by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow imaging.

Ten consecutive patients with a coronary artery fistula, aged 1 day to 4 years, were studied by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow imaging. All patients underwent cardiac catheterization, and seven patients had surgical closure of the fistula. The origin, course and site of drainage of the coronary artery fistula were correctly identified prospectively by echocardiographic examination in all patients. Color flow imaging was particularly helpful in visualizing the site of drainage of the fistula. Diameters of the right and left coronary arteries at their origin and of the aortic root were measured from two-dimensional echocardiographic frames and compared with measurements obtained in normal children. The ratio of coronary artery diameter to aortic root diameter in normal children was 0.14 +/- 0.03 (mean +/- SD) for the right coronary artery and 0.17 +/- 0.03 for the left coronary artery. These normal ratios were greatly exceeded for coronary arteries feeding the fistula, and ranged from 0.68 to 0.84 for the right coronary artery and from 0.34 to 0.52 for the left coronary artery. All anatomic information needed for surgical treatment of coronary artery fistula was consistently obtained by echocardiography with color flow imaging. The fistula was closed from within the heart in five patients and by ligation from the epicardial surface in two patients. In these latter patients, intraoperative color flow imaging at the time of ligation proved to be extremely valuable in achieving complete closure.

Complications of pediatric cardiac catheterization: a 3-year study.

To determine the current risk of pediatric cardiac catheterization, the complications and incidents of all catheterizations performed in a pediatric laboratory between January 1986 and October 1988 were prospectively recorded and compared with results from a 1974 study from the same institution. In the current study 1,037 catheterizations, 885 diagnostic and 152 diagnostic/interventional procedures, were performed in 888 patients (aged 1 day to 27 years, median 15.6 months). There were 15 major complications (1.4%), 70 minor complications (6.8%) and 30 incidents (2.9%). Two patients died as a result of the procedure and two as a result of pericatheterization clinical deterioration caused by the cardiac abnormality. The great majority of complications were successfully treated or were self-limited and the patients had no residua. Of patients with 13 nonfatal major complications and 70 minor complications, residua were evident in 7 patients and 3 without evident residua had the potential for sequelae (0.7% and 0.3% of catheterizations). A comparison of the diagnostic and balloon atrial septostomy cases in the present study with similar cases in the 1974 study shows that the incidence of major complications has decreased from 2.9% to 0.9% (p less than 0.0001); minor complications and incidents have decreased from 11.7% to 7.9% (p less than 0.006) and pericatheterization deaths not attributable to catheterization have decreased from 2.8% to 0.2% (p less than 0.0001). Changes in pericatheterization medical management, patient selection for catheterization and catheterization techniques probably account for these improvements.

Perinatal outcome of fetal complete atrioventricular block: a multicenter experience.

The clinical course and outcome of 55 fetuses with complete atrioventricular (AV) block detected prenatally were studied to identify factors that affect the natural history of this lesion. In 29 fetuses (53%) complete AV block was associated with complex structural heart defects, usually left atrial isomerism (n = 17) or discordant AV connection (n = 7). The other 26 fetuses had normal cardiac anatomy; in 19 cases the mother had connective tissue disease or tested positive for antinuclear antibodies. Six fetuses showed progression from sinus rhythm or second degree block to complete AV block. Of the 55 pregnancies, 5 were terminated and 24 fetuses or neonates died; at the end of the neonatal period 26 fetuses were still alive. Fetal or neonatal death correlated significantly with the presence of structural heart defects (4 of 29 surviving, p less than 0.001), hydrops (0 of 22 surviving, p less than 0.001), an atrial rate less than or equal to 120 beats/min (1 of 12 surviving, p less than 0.005) or a ventricular rate less than or equal to 55 beats/min (3 of 21 surviving, p less than 0.001). Mean atrial and ventricular rates were higher in surviving than in nonsurviving fetuses (142 +/- 8 vs. 127 +/- 21 beats/min, p less than 0.002; 64 +/- 8 vs. 52 +/- 8 beats/min, p less than 0.001, respectively). A slow atrial rate, however, was frequently associated with left atrial isomerism.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-lipoic acid protects the retina against ischemia-reperfusion.

The aim of this study was to examine whether the antioxidant alpha-lipoic acid protects retinal neurons from ischemia-reperfusion injury. Rats were injected intraperitoneally with either vehicle or alpha-lipoic acid (100 mg/kg) once daily for 11 days. On the third day, ischemia was delivered to the rat retina by raising the intraocular pressure above systolic blood pressure for 45 min. The electroretinogram was measured prior to ischemia and 5 days after reperfusion. Rats were killed 5 or 8 days after reperfusion and the retinas were processed for immunohistochemistry and for determination of mRNA levels by RT-PCR. Ischemia-reperfusion caused a significant reduction of the a- and b-wave amplitudes of the electroretinogram, a decrease in nitric oxide synthase and Thy-1 immunoreactivities, a decrease of retinal ganglion cell-specific mRNAs and an increase in bFGF and CNTF mRNA levels. All of these changes were clearly counteracted by alpha-lipoic acid. Moreover, in mixed rat retinal cultures, alpha-lipoic acid partially counteracted the loss of GABA-immunoreactive neurons induced by anoxia. The results of the study demonstrate that alpha-lipoic acid provides protection to the retina as a whole, and to ganglion cells in particular, from ischemia-reperfusion injuries. alpha-Lipoic acid also displayed negligible affinity for voltage-dependent sodium and calcium channels.