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Objectives: We tested a newly developed 4-dimensional (4D) right ventricular (RV) analysis method for computing RV volumes for both 3-dimensional (3D) ultrasound (US) and magnetic resonance (MR) images., Background: Asymmetry and the anatomical complexity of the RV make accurate determination of RV shape and volume difficult., Methods: Thirty patients, 14 with grossly normal cardiac anatomy and 16 with major congenital heart disease, were studied at the same visit with both 3D echocardiography (echo) and magnetic resonance imaging (MRI) for RV size and function. Ultrasound images were acquired on a Philips 7500 system (Philips Medical Systems, Andover, Massachusetts) with a matrix-array transducer (real-time 3D echo) with full volume sweeps from apical and subcostal views. Sagittal, 4-chamber, and coronal views were derived for contour detection (all 12 to 24 slices). The MR images were acquired with a 3-T MRI magnet with segmented cine-loop gradient echo sequences in short- and rotated long-axis views to cover the RV inflow, body, and outflow tract. The RV volumes were analyzed with the new software applicable to 3D echo MR images., Results: New software aided delineation of the RV free wall, tricuspid valve, RV outflow tract, and apex on 3D echo volumes. Although there was a slightly higher variability measuring right ventricular ejection fraction (RVEF) and volumes obtained by US compared with MRI, both imaging methods showed closely correlated results. The RVEF was measured with 4% variability for US and 5% variability for MRI with a correlation coefficient of r = 0.91. The RV end-diastolic volume was measured at 70.97 +/- 15.0 ml with 3D US and at 70.06 +/- 14.8 ml with MRI (r = 0.99), end-systolic volume measured 39.8 +/- 10.4 ml with 3D US and 39.1 +/- 10.2 ml with MRI (r = 0.98)., Conclusions: The new RV analysis software allowed validation of the accuracy of 4D echo RV volume data compared with MRI.

The regulation of nitrogen metabolism in the amino acid producer Corynebacterium glutamicum was subject of research for several decades. While previous studies focused on single enzymes or pathways, the publication of the C. glutamicum genome sequence gave a fresh impetus to research, since a global investigation of metabolism and regulation networks became possible based on these data. This communication summarizes the advances made by different studies, in which global analysis approaches were used to characterize the C. glutamicum nitrogen starvation response. A combination of bioinformatics approaches, transcriptome and proteome analyses as well as chemostat experiments revealed new insights into the nitrogen control network of C. glutamicum. C. glutamicum reacts to a limited nitrogen supply with a rearrangement of the cellular transport capacity, changes in metabolic pathways for nitrogen assimilation and amino acid biosynthesis, an increased energy generation and increased protein stability. With the aid of chemostat experiments, in which different growth rates were obtained by nitrogen limitation, general starvation effects could be distinguished from specific nitrogen limitation-dependent changes. The core adaptations on the level of transcription are controlled by the master regulator of nitrogen control, the TetR-type protein AmtR. This global regulator governs transcription of at least 33 genes via binding to a palindromic consensus motif (AmtR box). Genes with AmtR box-containing promoters were identified by genome-wide screening and validated, besides by other methods, by transcriptome analyses using DNA microarrays.

Pulmonary artery agenesis and hypoplasia of the homolateral lung occasionally occurs as an isolated lesion, but more often has associated congenital cardiac anomalies. We present a case where pulmonary artery agenesis was the sole lesion in an asymptomatic child. Pulmonary artery agenesis should be suspected in asymptomatic patients if a plain chest X-ray shows asymmetric lung fields, lung hypoplasia, or hyperinflation of the contralateral lung. Echocardiography is the best tool to establish the diagnosis. In our opinion, invasive procedures, such as cardiac catheterization, may be postponed if there is no echocardiographic evidence of pulmonary hypertension.

Cyclic nucleotide-gated (CNG) channels are a family of ion channels activated by the binding of cyclic nucleotides. Endogenous channels have been used to measure cyclic nucleotide signals in photoreceptor outer segments and olfactory cilia for decades. Here we have investigated the subcellular localization of cGMP signals by monitoring CNG channel activity in response to agonists that activate either particulate or soluble guanylyl cyclase. CNG channels were heterologously expressed in either human embryonic kidney (HEK)-293 cells that stably overexpress a particulate guanylyl cyclase (HEK-NPRA cells), or cultured vascular smooth muscle cells (VSMCs). Atrial natriuretic peptide (ANP) was used to activate the particulate guanylyl cyclase and the nitric oxide donor S-nitroso-n-acetylpenicillamine (SNAP) was used to activate the soluble guanylyl cyclase. CNG channel activity was monitored by measuring Ca2+ or Mn2+ influx through the channels using the fluorescent dye, fura-2. We found that in HEK-NPRA cells, ANP-induced increases in cGMP levels activated CNG channels in a dose-dependent manner (0.05-10 nM), whereas SNAP (0.01-100 microM) induced increases in cGMP levels triggered little or no activation of CNG channels (P < 0.01). After pretreatment with 100 microM 3-isobutyl-1-methylxanthine (IBMX), a nonspecific phosphodiesterase inhibitor, ANP-induced Mn2+ influx through CNG channels was significantly enhanced, while SNAP-induced Mn2+ influx remained small. In contrast, we found that in the presence of IBMX, both 1 nM ANP and 100 microM SNAP triggered similar increases in total cGMP levels. We next sought to determine if cGMP signals are compartmentalized in VSMCs, which endogenously express particulate and soluble guanylyl cyclase. We found that 10 nM ANP induced activation of CNG channels more readily than 100 muM SNAP; whereas 100 microM SNAP triggered higher levels of total cellular cGMP accumulation. These results suggest that cGMP signals are spatially segregated within cells, and that the functional compartmentalization of cGMP signals may underlie the unique actions of ANP and nitric oxide.

Nitrogen is an essential component of nearly all of the complex macromolecules in a bacterial cell, e.g. proteins, nucleic acids, and cell wall components. Accordingly, most prokaryotes have developed elaborate control mechanisms to provide an optimal supply of nitrogen for cellular metabolism and to cope with situations of nitrogen limitation. In this communication, a global analysis of the Corynebacterium glutamicum nitrogen starvation response by transcriptional profiling using DNA microarrays is presented. Our results show that C. glutamicum reacts to nitrogen starvation with a rearrangement of the cellular transport capacity, changes in metabolic pathways concerning nitrogen assimilation and amino acid biosynthesis, and a decreased capacity for protein synthesis.

Background: Extracorporeal life support has assumed a very effective role in the support of patients with refractory heart failure after repair of congenital heart disease, with hospital survival between 37% and 42%. We reviewed our results of different applications of extracorporeal life support in the last 2 years., Methods: Between January 2001 and October 2003, 671 patients underwent surgery for congenital heart disease at our institution. We retrospectively reviewed the hospital and clinic charts of the patients who required extracorporeal life support postoperatively, and studied the factors associated with survival., Results: Thirty-six patients (5.36%) received extracorporeal life support after surgery, between 1 day and 8 years of age (age < 30 days, n = 34). We divided the patients into four groups. Group 1 consisted of 13 patients who were electively placed on ventricular support without an oxygenator (univentricular assist device) after repair of single-ventricle disease. Group 2 consisted of 16 patients who required extracorporeal membrane oxygenation after surgery for failed hemodynamics. Group 3 consisted of 2 patients who required left ventricle support (left ventricular assist device) after surgery for two-ventricle disease but who did not require biventricular (extracorporeal membrane oxygenation) support. Group 4 consisted of 5 patients who required conversion from ventricular assist device to extracorporeal membrane oxygenation. Overall, 28 patients were weaned successfully (78%), and 24 survived to discharge (67%). Hospital survival in groups 1, 2, 3, and 4 was 100%, 50%, 100%, and 20%, respectively. Univariate factors associated with survival were age, weight, ventricular assist device type, duration, single-ventricle disease, reexploration, number of complications, and specific complications such as sepsis, renal failure, and pulmonary failure., Conclusions: Extracorporeal life support utilization was expanded to include different applications with different outcomes. The extracorporeal life support registry should be altered to reflect those changes.

Theresponse of Corynebacterium glutamicum to ammonium limitation was studied by transcriptional and proteome profiling of cells grown in a chemostat. Our results show that ammonium-limited growth of C. glutamicum results in a rearrangement of the cellular transport capacity, changes in metabolic pathways for nitrogen assimilation, amino acid biosynthesis, and carbon metabolism, as well as a decreased cell division. Since transcription at different growth rates was studied, it was possible to distinguish specific responses to ammonium limitation and more general, growth rate-dependent alterations in gene expression. The latter include a number of genes encoding ribosomal proteins and genes for F(o)F(1)-ATP synthase subunits.

Objective: Placement of oversized pulmonary ventricle-pulmonary artery conduits is routinely performed to decrease conduit failure in children. However, this practice has recently been challenged as somatic outgrowth may not be the main determinant of allograft failure in children. Our objective was to determine whether placement of oversized homografts for extracardiac pulmonary ventricle (PV) outflow tract reconstruction improves longevity in young children., Methods: We reviewed 102 consecutive PV-PA conduits inserted in 70 patients less than 18 years between 1984 and 2003. Conduits placed in an anatomic position (n=23) as part of a Ross operation, were excluded. Conduits were initially stratified into two age groups: Group 1, those placed in patients 10 years. Normalization of conduit size to patient's body surface area at the time of insertion (z-value) was then performed to divide the conduits into oversized (O/S) and non-oversized (NO/S) groups. Determinants of conduit failure and allograft longevity were then compared between groups., Results: Seventy-nine extracardiac conduits were placed, and 57 of these were in patients under 10 years of age. The majority had a diagnosis of tetralogy of Fallot (n=38), truncus arteriosus (n=19), pulmonary atresia with ventricular septal defect (n=12), or D-TGA with pulmonary stenosis and ventricular septal defect (n=7). Thirty-seven conduits were oversized (O/S) based on z-value, and 42 were non-oversized (NO/S), and the mean age at initial homograft placement was 7.0+/-7.5 years. Overall, oversizing conferred no significant advantage with respect to actuarial freedom from homograft replacement at 1, 5, or 10 years (96, 79, and 21%, O/S vs 93, 60, and 24%, NO/S), P=0.44. Oversizing was more frequent in Group 1 than Group 2 (53 vs 32%), and conduit failure was also more frequent with 49% requiring reoperation during the study period vs 38% in Group 2. In the subset of patients

Objective: Aortic valvotomy is widely used for the treatment of congenital aortic stenosis in children. We sought to evaluate whether the predominant post-valvotomy physiology, aortic insufficiency (AI) or aortic stenosis (AS) independently affected patient outcome., Methods: From 1972-2002, 57 children with congenital aortic stenosis underwent valvotomy. We divided age-matched patients with residual lesions based on their predominant pathology into three groups: Group I (n=14), patients with moderate AI; Group II (n=14), patients with moderate AS, and Group III (n=14), patients with combined AI and AS. Fifteen patients with severe AI or mild residual lesions following valvotomy were excluded from analysis., Results: mean freedom from aortic valve replacement (AVR) was 11.2+/-1.7 years in Group I and 21.5+/-3.9 years in Group II, P=0.05. AVR was required in 11 patients (79%) in Group I vs. only 5 (36%) in Group II, P=0.05. Group III was intermediate, with 9 (64%) requiring AVR. At the time of AVR, patients with aortic stenosis had significantly higher fractional shortening % than those with insufficiency or combined lesions, (Group 1: 38.2+/-7.9 vs. Group II: 46.3+/-5.5 vs. Group III: 39.2+/-3.7, P=0.007). Patients in Group II also had less severely dilated ventricles (mm) than those in the other groups, (Group 1: 50.2+/-12.5 vs. Group II: 39.5+/-8.3 vs. Group III: 49.0+/-8.1, P=0.030)., Conclusions: patients with predominant AI following valvotomy are more likely to need AVR sooner than those with residual stenosis without AI. Therefore, cautious use of repeat valvotomy using maneuvers to avoid AI (small balloons), may prolong freedom from aortic valve replacement in those patients with significant residual AS.

In order to utilize different nitrogen sources and to survive situations of nitrogen limitation, microorganisms have developed several mechanisms to adapt their metabolism to changes in the nitrogen supply. In this communication, the use of creatinine as an alternative nitrogen source in Corynebacterium glutamicum, the identification of a membrane protein involved in creatinine uptake, the transcriptional regulation of the corresponding gene, and expression regulation of the gene encoding the creatinine deaminase are reported. As shown by mutant analyses, RNA hybridization experiments and real-time PCR, the expression of two genes, crnT and codA, is increased in response to nitrogen limitation, and regulation depends on the global nitrogen regulator AmtR. In addition, synthesis of creatinine deaminase during nitrogen starvation was shown by two-dimensional gel electrophoresis and MALDI-TOF-MS followed by peptide mass fingerprint analysis.

Human mutations in Nkx2-5 lead to progressive cardiomyopathy and conduction defects via unknown mechanisms. To define these pathways, we generated mice with a ventricular-restricted knockout of Nkx2-5, which display no structural defects but have progressive complete heart block, and massive trabecular muscle overgrowth found in some patients with Nkx2-5 mutations. At birth, mutant mice display a hypoplastic atrioventricular (AV) node and then develop selective dropout of these conduction cells. Transcriptional profiling uncovered the aberrant expression of a unique panel of atrial and conduction system-restricted target genes, as well as the ectopic, high level BMP-10 expression in the adult ventricular myocardium. Further, BMP-10 is shown to be necessary and sufficient for a major component of the ventricular muscle defects. Accordingly, loss of ventricular muscle cell lineage specification into trabecular and conduction system myocytes is a new mechanistic pathway for progressive cardiomyopathy and conduction defects in congenital heart disease.

Background: Although excellent survival following the Norwood procedure for palliation of hypoplastic left heart syndrome (HLHS) is being achieved by some, most centers, especially the ones with small surgical volume and limited experience, continue to struggle with initial results. Survivors often showed evidence of significant neurologic injury. The early postoperative care is labor-intensive as attempts are made to balance the systemic and pulmonary circulation for these infants. We report our experience with routine use of mechanical circulatory assist to support the increased cardiac output requirements present following Norwood procedure., Methods: Eighteen consecutive infants undergoing Norwood operation for HLHS (Oregon Health & Science University [OHSU] 13; University of Louisville [UL] 5) were placed on a ventricular assist device (VAD) immediately following modified ultrafiltration in the operating room using the cardiopulmonary bypass (CPB) cannulas that were in the right atrium and the neoaorta. VAD flows were maintained at approximately 200 mL x kg(-1) x min(-1) and the patients were transported to the intensive care unit (ICU). Patients operated at OHSU also received neurodevelopmental testing before their Glenn procedure, approximately 4 to 6 months following their Norwood operation., Results: All patients were stable on VAD support and no attempt was made to balance the systemic and pulmonary circulation. The ventilator was manipulated to achieve systemic Pa0(2) between 30 and 45 mm Hg and PaC0(2) between 35 and 45 mm Hg. Evidence of hypoperfusion (increasing lactates) was managed by increasing the VAD flow. Lactates normalized [< 2 mmol/L]) by 1.8 +/- 1.1 days following surgery. Average time of VAD support was 3.1 +/- 1.0 (range, 2 to 5 days) and average time until chest closure was 3.4 +/- 1.5 (range, 2 to 8 days). There were two cases of postoperative bleeding (11.1%) requiring reexploration and one case of mediastinitis (5.5%) in a patient who has now gone on to successful Glenn. Sixteen of the eighteen patients survived (hospital survival mean 89% with a 95% confidence interval of 63.9% to 98.1%; 12/13 OHSU [92.3%]; 4/5 UL [80%]). Neurodevelopmental testing using the Mullen Scales of Early Learning and the Vineland Adaptive Behavior Scale were normal for all infants tested., Conclusions: Routine postoperative use of VAD can support the increased cardiac output demands of infants following Norwood operation and results in a stable postoperative convalescence that does not require aggressive ventilator or inotrope manipulation. Although not a panacea, this strategy can simplify postoperative management, lead to excellent hospital survival, and possibly augment cerebral oxygen delivery, resulting in improved neurologic outcomes for this challenging group of patients.

Circulating natriuretic peptides such as atrial natriuretic peptide (ANP) counterbalance the effects of hypertension and inhibit cardiac hypertrophy by activating cGMP-dependent protein kinase (PKG). Natriuretic peptide binding to type I receptors (NPRA and NPRB) activates their intrinsic guanylyl cyclase activity, resulting in a rapid increase in cytosolic cGMP that subsequently activates PKG. Phosphorylation of the receptor by an unknown serine/threonine kinase is required before ligand binding can activate the cyclase. While searching for downstream PKG partners using a yeast two-hybrid screen of a human heart cDNA library, we unexpectedly found an upstream association with NPRA. PKG is a serine/threonine kinase capable of phosphorylating NPRA in vitro; however, regulation of NPRA by PKG has not been previously reported. Here we show that PKG is recruited to the plasma membrane following ANP treatment, an effect that can be blocked by pharmacological inhibition of PKG activation. Furthermore, PKG participates in a ligand-dependent gain-of-function loop that significantly increases the intrinsic cyclase activity of the receptor. PKG translocation is ANP-dependent but not nitric oxide-dependent. Our results suggest that anchoring of PKG to NPRA is a key event after ligand binding that determines distal effects. As such, the NPRA-PKG association may represent a novel mechanism for compartmentation of cGMP-mediated signaling and regulation of receptor sensitivity.

In this study, the advantage of a novel measuring device for the online determination of oxygen and carbon dioxide transfer rates in shaking-flasks is reported for glucose oxidation by Gluconobacter oxydans. In this fermentation process, this device was used for the characterization of the oxidation pattern of different strains. G. oxydans NCIMB 8084 forms 2,5-diketogluconate from d-glucose in a multi-stage process via three different membrane-bound dehydrogenases. This strain was chosen for a scale-up of the process from shaking-flasks to a 2-l stirred vessel. An enhancement of 2,5-diketogluconate production was realized by controlling the pH at different levels during the fermentation.

Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented.

The natriuretic peptides (NPs) constitute a family of polypeptide hormones that regulate mammalian blood volume and blood pressure. The ability of the NPs to modulate cardiac hypertrophy and cell proliferation as well is now beginning to be recognized. The NPs interact with three membrane-bound receptors, all of which contain a well-characterized extracellular ligand-binding domain. The R1 subclass of NP receptors (NPR-A and NPR-B) contains a C-terminal guanylyl cyclase domain and is responsible for most of the NPs downstream actions through their ability to generate cGMP. The R2 subclass lacks an obvious catalytic domain and functions primarily as a clearance receptor. This review focuses on the signal transduction pathways initiated by ligand binding and other factors that help to determine signalling specificities, including allosteric factors modulating cGMP generation, receptor desensitization, the activation and function of cGMP-dependent protein kinase (PKG), and identification of potential nuclear or cytoplasmic targets such as the mitogen-activated protein kinase signalling (MAPK) cascade. The inhibition of cardiac growth and hypertrophy may be an important but underappreciated action of the NP signalling system.

Atrial natriuretic factor (ANF) inhibits proliferation in non-myocardial cells and is thought to be anti-hypertrophic in cardiomyocytes. We investigated the possibility that the anti-hypertrophic actions of ANF involved the mitogen-activated protein kinase signal transduction cascade. Cultured neonatal rat ventricular myocytes treated for 48 h with the alpha(1)-adrenergic agonist phenylephrine (PE) had an 80% increase in cross-sectional area (CSA). ANF alone had no effect but inhibited PE-induced increases in CSA by approximately 50%. The mitogen-activated protein kinase/ERK kinase (MEK) inhibitor PD098059 minimally inhibited PE-induced increases in CSA, but it completely abolished ANF-induced inhibition of PE-induced increases. ANF-induced extracellular signal-regulated protein kinase (ERK) nuclear translocation was also eliminated by PD098059. ANF treatment caused MEK phosphorylation and activation but failed to activate any of the Raf isoforms. ANF induced a rapid increase in ERK phosphorylation and in vitro kinase activity. PE also increased ERK activity, and the combined effect of ANF and PE appeared to be additive. ANF-induced ERK phosphorylation was eliminated by PD098059. ANF induced minimal phosphorylation of JNK or p38, indicating that its effect on ERK was specific. ANF-induced activation of ERK was mimicked by cGMP analogs, suggesting that ANF-induced ERK activation involves the guanylyl cyclase activity of the ANF receptor. These data suggest that there is an important linkage between cGMP signaling and the mitogen-activated protein kinase cascade and that selective ANF activation of ERK is required for the anti-hypertrophic action of ANF. Thus, ANF expression might function as the natural defense of the heart against maladaptive hypertrophy through its ability to activate ERK.

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Beyond infancy, blood cyst of the aortic valve is not known to occur. We describe a 16-year-old girl who had aortic valve stenosis and regurgitation and giant blood cyst of the aortic valve. Serial echocardiograms over a 12-year period demonstrated gradual enlargement of the cyst.

A rotational data acquisition system was used to create three-dimensional images from thoracic and subxiphoid echocardiographic windows in children with various types of subaortic stenosis. Thirteen patients, ranging in age from 2 days to 17 years, were examined. Subaortic obstruction was caused by a discrete fibrous ridge in six patients, hypertrophic cardiomyopathy in two patients, subaortic tunnel in two patients, and septal malalignment, restrictive VSD, and abnormal suture placement each in one patient. Unique views could be obtained equivalent to surgical or autopsy dissections, and allowed more complete understanding of morphology than conventional imaging techniques.

To study the effect of atrial natriuretic peptide (ANP) on vascular permeation of albumin in the fetus, ANP (167-600 ng/min) was infused into eight ovine fetuses and saline vehicle was infused into eight twin controls (gestational age 127 +/- 3 d) over a 50-min period. Using two different radiolabeled albumin markers, we determined the tissue to blood isotope ratio (TBIR), an index of albumin permeation, and the albumin clearance. Although ANP had no hemodynamic effect, a marked increase in the hematocrit was observed in ANP-infused fetuses compared with initial values (0.37 +/- 0.04 vs 0.42 +/- 0.04, p < 0.005) but was unchanged in the twin fetuses receiving saline vehicle (0.35 +/- 0.03 versus 0.35 +/- 0.02). TBIR and albumin permeation were increased in combined tissues of ANP-infused fetuses compared with saline controls (TBIR: 1.49 +/- 0.58 versus 1.29 +/- 0.3, p < 0.001; albumin clearance: 1091 +/- 1279 versus 827 +/- 1464 nL/g/min, p < 0.01). In individual tissues, TBIR was significantly increased in skin (2.88 +/- 0.67 versus 1.55 +/- 0.35, p < 0.02), muscle (1.6 +/- 0.27 versus 1.24 +/- 0.26, p < 0.02), adrenal (1.33 +/- 0.10 versus 1.13 +/- 0.15, p < 0.02), bone (1.67 +/- 0.45 versus 1.20 +/- 0.40, p < 0.02), kidney (1.52 +/- 0.25 versus 1.24 +/- 0.26, p < 0.03), and gut (1.69 +/- 0.20 versus 1.39 +/- 0.34, p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Three hundred twenty-two consecutive operations between December 1985 and December 1989 for 10 types of low-risk congenital cardiac malformations were reviewed to determine the hospital charge and postoperative length of stay. Multiple regression analysis of variance was used to predict the influence of the primary diagnosis and various preoperative parameters. The average hospital charge was $27,262 +/- $20,644 and the postoperative length of stay was 9.3 +/- 8.3 days. Age at operation alone did not influence the dependent variables. The diagnosis of atrial septal defect (p = 0.002) or coarctation of the aorta (p = 0.002) decreased the mean charge, whereas the 8 other primary diagnoses did not significantly influence the mean charge. Other preoperative factors found to be predictive of increased hospital charge were: the date of operation (p < 0.001), cyanosis (p = 0.008), previous thoracic surgery (p = 0.02), failure to thrive (p < 0.001), associated major extra cardiac anomalies (p < 0.001), oxygen requirement (p = 0.02), and distance > 100 miles from home to hospital (p = 0.05). A primary diagnosis of atrial septal defect decreased the mean postoperative length of stay by 3.1 days (p < 0.001). Other preoperative conditions increased the mean postoperative length of stay: major extracardiac malformation (p < 0.001), failure to thrive (p < 0.001), and oxygen requirement (p = 0.003). Charge and length of stay equations were generated which may assist in the prediction of resource utilization in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

The newborn has an attenuated response to saline fluid challenge. We studied the response of endogenous atrial natriuretic peptides (ANF) to 10% body weight graded isotonic saline volume expansion (VE) in 14 anesthetized neonatal lambs which were either 1 day old or 7 days old. Plasma ANF values were unchanged at 3.3% and 10% VE compared with control values (56 +/- 28 vs. 66 +/- 17 and 66 +/- 37 pg/ml, not significant) in the 1-day-old lambs, whereas values increased significantly at both 3.3% and 10% VE (47 +/- 40 vs. 99 +/- 57 and 96 +/- 73, P = 0.022 and P = 0.018, respectively) in the 7-day-old lambs. No relationship existed between right atrial (RAP) or pulmonary capillary wedge pressures (PCWP) and plasma ANF in the 1-day-old lambs; however, a significant correlation existed (RAP, P = 0.015; PCWP, P = 0.022) in the 7-day-old lambs. In general, renal function was improved in the 7-day-old lambs compared with the 1-day-old lambs, but only changes in fractional sodium excretion were significantly different (P = 0.017). We speculate that ANF unresponsiveness in the 1-day-old lamb is related to physiological transitions during the birth process and that the maturation of the renal response to VE may require maturation of the atrial mechanism which permits ANF secretion.

The effects of intravenous verapamil (0.15 mg/kg) and propranolol (0.2 mg/kg) with regard to atrioventricular (AV) conduction and tachycardia termination during paroxysmal atrial tachycardia were compared in 2 groups of infants (verapamil n = 14, propranolol n = 18, mean age 80 +/- 21 days, range 1 to 364). Using transesophageal recording techniques, tachycardia cycle length, AV intervals and ventriculoatrial intervals were measured before and after drug administration. Both intravenous propranolol and verapamil significantly prolonged tachycardia cycle length and AV interval (cycle length--propranolol 230 +/- 30 to 262 +/- 33 ms, p less than 0.05, verapamil 223 +/- 38 to 245 +/- 32 ms, p less than 0.05; AV interval--propranolol 98 +/- 26 to 126 +/- 38 ms, p less than 0.05, verapamil 96 +/- 19 to 109 +/- 24 ms, p less than 0.05). Neither drug prolonged the ventriculoatrial interval. Tachycardia terminated after intravenous verapamil in 11 of 14 infants (79% efficacy rate). Tachycardia terminated in 0 of 18 after intravenous propranolol (0% efficacy rate). In 8 infants an atrial deflection was recorded on the esophageal electrocardiogram at the time of tachycardia termination after intravenous verapamil, which suggested that tachycardia terminated by block occurring in the AV node. In 2 infants a ventricular deflection was recorded at the time of tachycardia termination after verapamil, which suggested that block occurred in the accessory connection. Both drugs prolonged tachycardia cycle length by prolonging AV conduction to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS)

The pulmonary valve and left ventricular outflow tract of 214 hearts with d-transposition of the great arteries (d-TGA) were visually inspected (126 of 214 with intact ventricular septum and 88 of 214 with ventricular septal defect [VSD]). Pulmonary stenosis (PS), either valvular, subvalvular, or in combination, was present in 26 cases and was found to be more common in the presence of a VSD (20.5%) than intact ventricular septum (6.3%). PS occurred more commonly in the presence of a supracristal VSD than an infracristal VSD (70%, 7 of 10 vs 15%, 10 of 66). Further, infracristal or supracristal VSDs were associated with different types of pulmonary obstruction. In seven of ten cases with infracristal VSD and PS, the stenosis was caused by an anomaly of an atrioventricular valve. In six of seven cases with supracristal VSD and PS, the latter was caused by membranous encirclement of the left ventricular outflow tract.