Increased interstage morbidity and mortality following stage 1 palliation in patients with genetic abnormalities.

BACKGROUND: Hypoplastic left heart syndrome and single ventricle variants with aortic hypoplasia are commonly classified as severe forms of CHD. We hypothesised patients with these severe defects and reported genetic abnormalities have increased morbidity and mortality during the interstage period. METHODS AND RESULTS: This was a retrospective review of the National Pediatric Cardiology Quality Improvement Collaborative Phase I registry. Three patient groups were identified: major syndromes, other genetic abnormalities, and no reported genetic abnormality. Tukey post hoc test was applied for pairwise group comparisons of length of stay, death, and combined outcome of death, not a candidate for stage 2 palliation, and heart transplant. Participating centres received a survey to establish genetic testing and reporting practices. Of the 2182 patients, 110 (5%) had major genetic syndromes, 126 (6%) had other genetic abnormalities, and 1946 (89%) had no genetic abnormality. Those with major genetic syndromes weighed less at birth and stage 1 palliation. Patients with no reported genetic abnormalities reached full oral feeds sooner and discharged earlier. The combined outcome of death, not a candidate for stage 2 palliation, and heart transplant was more common in those with major syndromes. Survey response was low (n = 23, 38%) with only 14 (61%) routinely performing and reporting genetic testing. CONCLUSIONS: Patients with genetic abnormalities experienced greater morbidity and mortality during the interstage period than those with no reported genetic abnormalities. Genetic testing and reporting practices vary significantly between participating centres.

Comparison of growth and feeding method in infants with and without genetic abnormalities after neonatal cardiac surgery.

INTRODUCTION: Congenital heart disease (CHD) is multifactorial in origin, resulting from an interaction between environmental and genetic factors. Multifactorial growth delay is common in infants with CHD. The impact of a genetic abnormality and CHD on the growth of an infant is lacking in the literature. The aim of this study is to compare the growth and method of feeding following neonatal cardiac surgery in infants with normal versus abnormal genetic testing. METHODS: A retrospective chart review of neonates who underwent a Risk Adjustment in Congenital Heart Surgery IV-VI procedure between 1 January, 2006 and 22 September, 2016 was performed at our institution. Weight, length, head circumference measurements, and feeding method were collected at birth, time of neonatal surgery, and monthly up to 6 months of age. RESULTS: A total of 53 infants met inclusion criteria, of which 22 had abnormal genetic testing. Approximately 90% of infants were discharged following neonatal cardiac surgery with supplemental tube feeds. At each monthly follow-up visit, more infants were exclusively fed orally: 80% of infants with normal genetics at 5 months post-operative follow-up versus 60% of infants with abnormal genetic testing, although statistically insignificant. Growth was not different among the two groups. CONCLUSIONS: Infants with critical CHD with or without genetic abnormalities are at risk for growth delays and many need supplemental tube feeds post-operatively and throughout follow-up. Infants with genetic abnormalities are slower to achieve oral feeds and more likely to require tube feedings. It is important to have a systematic protocol for managing these high-risk infants.

Cardiomyopathy in limb girdle muscular dystrophy R9, FKRP related.

INTRODUCTION: Reported frequencies of cardiomyopathy in limb girdle muscular dystrophy R9 (LGMDR9) vary. We describe the frequency and age at onset of cardiomyopathy in an LDMDR9 cohort. METHODS: Echocardiograms from 56 subjects (157 echocardiograms) with LGMDR9 were retrospectively reviewed. The cumulative probability of having an abnormal echocardiogram as a function of age was assessed by survival analysis for interval-censored data by genotype. Correlations between cardiac and clinical function were evaluated. RESULTS: Twenty-five (45%) participants had cardiomyopathy. The median age at first abnormal echocardiogram for subjects homozygous for the c.826C>A variant was 54.2 y compared to 18.1 y for all other fukutin-related protein (FKRP) genotypes (P < .0001). There was a weak correlation between ejection fraction and 10-Meter Walk Test speed (r = 0.25), but no correlation with forced vital capacity (r = 0.08). DISCUSSION: Cardiomyopathy is prevalent among those with LGMDR9 and occurs later in subjects homozygous for the c.826C>A mutation. These data will help to guide surveillance and management.

Neuropathology of Congenital Heart Disease in an Inpatient Autopsy Cohort 2000-2017.

Background As a result of medical and surgical advancements in the management of congenital heart disease (CHD), survival rates have improved substantially, which has allowed the focus of CHD management to shift toward neurodevelopmental outcomes. Previous studies of the neuropathology occurring in CHD focused on cases preceding 1995 and reported high rates of white matter injury and intracranial hemorrhage, but do not reflect improvements in management of CHD in the past 2 decades. The purpose of this study is therefore to characterize the neuropathological lesions identified in subjects dying from CHD in a more-recent cohort from 2 institutions. Methods and Results We searched the autopsy archives at 2 major children's hospitals for patients with cyanotic congenital cardiac malformations who underwent autopsy. We identified 50 cases ranging in age from 20 gestational weeks to 46 years. Acquired neuropathological lesions were identified in 60% (30 of 50) of subjects upon postmortem examination. The most common lesions were intracranial hemorrhage, most commonly subarachnoid (12 of 50; 24%) or germinal matrix (10 of 50; 20%), hippocampal injuries (10 of 50; 20%), and diffuse white matter gliosis (8 of 50; 16%). Periventricular leukomalacia was rare (3 of 50). Twenty-six subjects underwent repair or palliation of their lesions. Of the 50 subjects, 60% (30 of 50) had isolated CHD, whereas 24% (12 of 50) were diagnosed with chromosomal abnormalities (trisomy 13, 18, chromosomal deletions, and duplications) and 16% (8/50) had multiple congenital anomalies. Conclusions In the modern era of pediatric cardiology and cardiac surgery, intracranial hemorrhage and microscopic gray matter hypoxic-ischemic lesions are the dominant neuropathological lesions identified in patients coming to autopsy. Rates of more severe focal lesions, particularly periventricular leukomalacia, have decreased compared with historical controls.

A Prospective Study Evaluating the Effects of SSRI Exposure on Cardiac Size and Function in Newborns.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the USA. We have previously shown in preclinical studies that sertraline exposure impacts cardiomyocyte development, leading to reductions in left ventricular size and cardiac function. OBJECTIVES: We hypothesized that in utero SSRI exposure will lead to reduced left ventricular dimensions and cardiac function on echocardiography immediately after birth. METHODS: Twenty term infants with and 21 term infants without in utero exposure to SSRIs underwent echocardiograms to assess cardiac size and function. The exclusion criteria for infants were prematurity, small or large for gestational age, any respiratory or cardiovascular support needed after birth, and any major congenital malformation. RESULTS: Infants exposed to in utero SSRIs had significantly reduced right ventricular dimensions in the diastole (controls 1.0 cm [0.86, 1.20], SSRI 0.89 cm [0.730, 1.05], p = 0.03), and left ventricular lengths in the diastole and systole (diastole: controls 3.4 cm [3.25, 3.65], SSRI 3.25 cm [3.10, 3.45], p = 0.03; systole: controls 2.9 cm [2.65, 3.05], SSRI 2.6 cm [2.50, 2.85], p = 0.01). No differences were observed in cardiac function. Importantly, there were no differences in maternal conditions or infant birth weight, body surface area, or gestational age. CONCLUSIONS: Our findings suggest an association between in utero exposure to SSRIs and ventricular size in infants. Given the increasing use of SSRIs during pregnancy and the importance of early life programming on future cardiovascular health, larger studies need to be completed to determine if in utero SSRI exposure impacts ventricular size.

Neonatal Growth Restriction Slows Cardiomyocyte Development and Reduces Adult Heart Size.

Prematurity is associated with reduced cardiac dimensions and an increased risk of cardiovascular disease. While prematurity is typically associated with ex utero neonatal growth restriction (GR), the independent effect of neonatal GR on cardiac development has not been established. We tested the hypothesis that isolated neonatal GR decreases cardiomyocyte growth and proliferation, leading to long-term alterations in cardiac morphology. C57BL/6 mice were fostered in litters ranging in size from 6 to 12 pups to accentuate normal variation in neonatal growth. Regardless of litter size, GR was defined by a weight below the 10th percentile. On postnatal day 8, Ki67 immunoreactivity, cardiomyocyte nucleation status and cardiomyocyte profile area were assessed. For adult mice, cardiomyocyte area was determined, along with cardiac dimensions by echocardiography and cardiac fibrosis by Masson's trichrome stain. On day 8, cardiomyocytes from GR versus control mice were significantly smaller and less likely to be binucleated with evidence of persistent cell cycle activity. As adults, GR mice continued to have smaller cardiomyocytes, as well as decreased left ventricular volumes without signs of fibrosis. Neonatal GR reduces cardiomyocyte size, delays the completion of binucleation, and leads to long-term alterations in cardiac morphology. Clinical studies are needed to ascertain whether these results translate to preterm infants that must continue to grow and mature in the midst of the increased circulatory demands that accompany their premature transition to an ex utero existence. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Acquired ventricular septal defect due to infective endocarditis.

Acquired intracardiac left-to-right shunts are rare occurrences. Chest trauma and myocardial infection are well-known causes of acquired ventricular septal defect (VSD). There have been several case reports describing left ventricle to right atrium shunt after infective endocarditis (IE). We present here a patient found to have an acquired VSD secondary to IE of the aortic and tricuspid valves in the setting of a known bicuspid aortic valve. This is the first case reported of acquired VSD in a pediatric patient in the setting of IE along with literature review of acquired left-to-right shunts.

Bovine arch anatomy influences recoarctation rates in the era of the extended end-to-end anastomosis.

OBJECTIVES: Arch branching has never been shown to influence recoarctation after extended end-to-end anastomosis via thoracotomy, yet in each study bovine arch identification is grossly underreported. This study aims to (1) assess chart review reliability in bovine arch identification; (2) determine recoarctation risk with a bovine arch; and (3) explore an anatomic explanation for recurrent arch obstruction based on arch anatomy. PATIENTS: A total of 49 consecutive patients underwent thoracotomy with extended end-to-end aortic coarctation repair at a single institution (2007-2012). METHODS: Echocardiograms from these patients were reviewed for arch anatomy and compared with the echocardiographic reports. Recurrent arch obstruction was defined as an echocardiographic gradient across the repair of 20 mm Hg or greater. For cases with angiographic images (n = 17), a scaled clamping distance between the left subclavian artery and the maximal proximal clamp location on orthogonal projections was then calculated across arch anatomies. RESULTS: Chart review identified 6.1% (3/49) of patients with a bovine arch compared with 28.6% (14/49) on targeted image review. A total of 28.6% (4/14) of patients with a bovine arch had a follow-up gradient of 20 mm Hg or greater. Only 5.7% (2/35) of patients with normal arch branching had a follow-up gradient of 20 mm Hg or greater. The mean clamping index was significantly diminished in patients with bovine arch anatomy. CONCLUSIONS: Arch anatomy often goes undocumented on preoperative imaging, yet children undergoing extended end-to-end repair with bovine arch anatomy are at a significantly increased risk of recoarctation. This may be due to a reduced clampable distance to facilitate repair. These results should be considered in the preoperative assessment, parental counseling, and surgical approach for children with discrete aortic coarctation.

Cardiac Outcomes After Perinatal Sertraline Exposure in Mice.

Selective serotonin reuptake inhibitors are prescribed to 6%-10% of pregnant women in the United States. Using an intrauterine plus neonatal exposure model to represent exposure throughout human pregnancy, we hypothesized sertraline exposure would impact intracardiac serotonin signaling and lead to small left heart syndrome in the absence of maternal psychopathology. C57BL/6 adult female mice received sertraline (5 mg·kg·d IP) or saline throughout pregnancy to time of delivery. Pups maintained exposure on postnatal days 1-14 to encompass the developmental window analogous to human gestation. Sertraline-exposed mice had increased cardiac hydroxyproline content, decreased 5-HT2B receptor mRNA levels, and increased 5-HT2A receptor and serotonin transporter mRNA levels on postnatal day 21 (P < 0.05). These changes were associated with diminished exercise capacity at 6 weeks (P < 0.05) and decreased adult shortening fraction and stroke volume at 5 months. Isolated cardiomyocytes from neonatal sertraline-exposed mice had significantly decreased proliferation, cross-sectional area, and phosphorylation of Akt (P < 0.05 vs. neonatal control mice). Perinatal sertraline exposure alters neonatal cardiac development and produces long-standing changes in adult cardiac function and exercise capacity. Further studies are needed to assess whether similar findings are present in the growing population that has been exposed to selective serotonin reuptake inhibitors during development.

Native atrial septal restriction after Fontan palliation successfully treated with transcatheter Diabolo stent.

A 6-year-old male child born with hypoplastic left heart syndrome (HLHS) was palliated with an extracardiac nonfenestrated Fontan procedure (18-mm Gore-Tex tube graft). He developed low-pressure (mean Fontan pressure 10 mmHg) protein-losing enteropathy 6 months after Fontan palliation. After initially responding to medical therapy and transcatheter pulmonary artery stent implantation, he developed medically refractory protein-losing enteropathy. At this time, his transthoracic echocardiogram showed new restriction across his native atrial septum with an 8 mmHg mean gradient. Cardiac catheterization now showed high-pressure (mean Fontan pressure 18-20 mmHg) protein-losing enteropathy and a new 6 mmHg mean gradient across the atrial septum. To avoid cardiopulmonary bypass, he underwent successful transcatheter relief of atrial septal restriction and creation of a fenestration with rapid clinical and biochemical improvement of his protein-losing enteropathy.

Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice.

Perinatal growth restriction (GR) is associated with heightened sympathetic tone and hypertension. We have previously shown that naturally occurring neonatal GR programmes hypertension in male but not female mice. We therefore hypothesized that intact ovarian function or post-ovariectomy (OVX) oestrogen administration protects GR female mice from hypertension. Utilizing a non-interventional model that categorizes mice with weanling weights below the tenth percentile as GR, control and GR adult mice were studied at three distinct time points: baseline, post-OVX and post-OVX with oral oestrogen replacement. OVX elicited hypertension in GR mice that was significantly exacerbated by psychomotor arousal (systolic blood pressure at light to dark transition: control 122 ± 2; GR 119 ± 2; control-OVX 116 ± 3; GR-OVX 126 ± 3 mmHg). Oestrogen partially normalized the rising blood pressure surge seen in GR-OVX mice (23 ± 7% reduction). GR mice had left ventricular hypertrophy, and GR-OVX mice in particular had exaggerated bradycardic responses to sympathetic blockade. For GR mice, a baseline increase in baroreceptor reflex sensitivity and high frequency spectral power support a vagal compensatory mechanism, and that compensation was lost following OVX. For GR mice, the OVX-induced parasympathetic withdrawal was partially restored by oestrogen (40 ± 25% increase in high frequency spectral power, P<0.05). In conclusion, GR alters cardiac morphology and cardiovascular regulation. The haemodynamic consequences of GR are attenuated in ovarian-sufficient or oestrogen-replete females. Further investigations are needed to define the role of hormone replacement therapy targeted towards young women with oestrogen deficiency and additional cardiovascular risk factors, including perinatal GR, cardiac hypertrophy and morning surge hypertension.

Maternal Hyperglycemia Directly and Rapidly Induces Cardiac Septal Overgrowth in Fetal Rats.

Cardiac septal overgrowth complicates 10-40% of births from diabetic mothers, but perplexingly hyperglycemia markers during pregnancy are not reliably predictive. We thus tested whether fetal exposure to hyperglycemia is sufficient to induce fetal cardiac septal overgrowth even in the absence of systemic maternal diabetes. To isolate the effects of hyperglycemia, we infused glucose into the blood supply of the left but not right uterine horn in nondiabetic pregnant rats starting on gestational day 19. After 24 h infusion, right-sided fetuses and dams remained euglycemic while left-sided fetuses were moderately hyperglycemic. Echocardiograms in utero demonstrated a thickened cardiac septum among left-sided (glucose-exposed, 0.592 ± 0.016 mm) compared to right-sided (control, 0.482 ± 0.016 mm) fetuses. Myocardial proliferation was increased 1.5 ± 0.2-fold among left-sided compared to right-sided fetuses. Transcriptional markers of glucose-derived anabolism were not different between sides. However, left-sided fetuses exhibited higher serum insulin and greater JNK phosphorylation compared to controls. These results show that hyperglycemic exposure is sufficient to rapidly induce septal overgrowth even in the absence of the myriad other factors of maternal diabetes. This suggests that even transient spikes in glucose may incite cardiac overgrowth, perhaps explaining the poor clinical correlation of septal hypertrophy with chronic hyperglycemia.

Impact of neonatal sertraline exposure on the post-myocardial infarction outcomes of adult male mice.

Neonatal exposure to a selective serotonin reuptake inhibitor (SSRI) leads to decreased left ventricular volumes and sympathetic activation in adult mice. We hypothesized this neonatal SSRI exposure-induced small left heart syndrome would increase post-myocardial infarction (MI) morbidity and mortality. C57BL/6 mice received saline or sertraline (5 mg/kg intraperitoneally) on postnatal days 1-14. At 5 months, male mice underwent coronary artery ligation and were monitored by radiotelemetry until death or 4 weeks after ligation. After ligation, SSRI-exposed mice had increased heart rates (SSRI, 516 ± 13 bpm; control, 470 ± 15 bpm; P < 0.05). SSRI-exposed mice had significant reductions in left ventricular systolic volumes both before and after coronary ligation (SSRI: baseline = 20 ± 3 µL, post-MI = 37 ± 10 µL; control: baseline = 30 ± 3 µL, post-MI = 65 ± 23 µL). Post-MI echocardiography showed significantly decreased ejection fraction in control mice (baseline = 60% ± 4%, post-MI = 41% ± 2%, P < 0.01) but not the SSRI-exposed mice (baseline = 65% ± 3%, post-MI = 53% ± 7%). Neonatal SSRI exposure did not significantly alter post-MI survival. We conclude that the preexisting SSRI-induced small left heart syndrome may provide protection from post-MI ventricular dilation.

Norwood reconstruction using continuous coronary perfusion: a safe and translatable technique.

BACKGROUND: Continuous coronary perfusion during Norwood reconstruction offers the theoretic advantage of less postoperative cardiac dysfunction. The avoidance of a cardiac and circulatory arrest period allows time for a more deliberate aortic reconstruction while the heart remains beating. This single-center study was designed to compare patient results using this method vs standard cardiac arrest for Norwood reconstruction. METHODS: A retrospective review was done of 32 patients undergoing Norwood reconstruction from November 2004 to July 2011. The operations in the most recent 16 consecutive patients were performed under deep hypothermia with constant coronary and cerebral perfusion. Continuous coronary perfusion was provided by a cannula inserted into the proximal aorta. The operations in the prior 16 consecutive patients were performed using deep hypothermia, selective cerebral perfusion, and cardioplegic arrest during aortic reconstruction. RESULTS: Survival in the beating-heart group was 87.5% (14 of 16) vs 62.5% (10 of 16) in the standard group (p = 0.22). No patients in the beating-heart group required extracorporeal membrane oxygenation vs 3 in the standard group. Postoperative cardiac function was similar for both groups. The beating-heart cohort had lower peak lactate levels (8.2 mEq/L) than the standard group (10.7 mEq/L, p = 0.022). CONCLUSIONS: This study presents the largest series of Norwood operations in which the entire aorta is augmented while delivering continuous coronary perfusion. The technique is applicable to any size aorta and represents a safe alternative because outcomes for survival, freedom from extracorporeal membrane oxygenation, postoperative cardiac function, and lactate levels were all noninferior compared with the standard technique.

Sertraline exposure leads to small left heart syndrome in adult mice.

BACKGROUND: Sertraline, a selective serotonin reuptake inhibitor (SSRI), is the most commonly prescribed therapy for maternal depression. Epidemiologic studies have linked SSRI exposure with decreased fetal growth, altered autonomic regulation, and cardiac malformations. We hypothesized that SSRI exposure decreases left-ventricular (LV) volumes and increases adult sympathetic nervous system activation, resulting in increased adult heart rates. METHODS: C57BL/6 mice received saline or sertraline (5 or 15 mg/kg/day i.p.) on postnatal days 1-14. Adult phenotypes were assessed at 5 mo. RESULTS: Sertraline-exposed mice had smaller LV internal diameters in diastole (control 4.0 ± 0.1 mm, SSRI 3.7 ± 0.1 mm, P < 0.05), decreased stroke volumes (control 46 ± 2.6 µl, SSRI 37 ± 2.3 µl, P < 0.05), higher heart rates (control 530 ± 13 beats per minute (bpm), SSRI 567 ± 6 bpm, P <0.05), and increased urinary excretion of noradrenaline (control 174 ± 29.4 ng/ml, SSRI 276 ± 35.1 ng/ml, P < 0.05). These changes were associated with increased cerebral serotonin transporter (5-HTT) expression. CONCLUSION: Neonatal sertraline exposure causes long-term changes in cardiac morphology and physiology. We speculate that early-life SSRI exposure impairs cardiomyocyte growth and central serotonin signaling, leading to a small left heart syndrome in adult mice.

Anomalous single pulmonary venous trunk.

We present a rare case of a single pulmonary venous trunk that drains all pulmonary segments to the left atrium. This anomaly may mimic pulmonary arteriovenous malformation on imaging. This report briefly discusses the embryology of the pulmonary veins and the classification of the pulmonary veins anomalies.

Programming of adult cardiovascular disease following exposure to late-gestation hyperglycemia.

BACKGROUND: In utero exposure to hyperglycemia is becoming increasingly prevalent as the number of women entering pregnancy with type II diabetes, or developing gestational diabetes, increases. Both animal studies and epidemiologic investigations have found cardiovascular abnormalities in adult offspring of hyperglycemic mothers (OHM). OBJECTIVE: We hypothesized that adult OHM would have abnormal cardiac function in vivo and increased susceptibility to ischemia. METHODS: Pregnant rats were made diabetic on day 12 of gestation. Serum glucose was monitored twice daily and insulin provided to maintain serum glucose at 200-400 mg/dl. Offspring were fostered to normal mothers after birth. Adult OHM were studied at 8-10 months of age with echocardiography to assess in vivo cardiac function and isolated hearts to determine the response to ischemia. RESULTS: Echocardiography found significant diastolic dysfunction in male OHM compared to male controls. In isolated hearts, baseline cardiac function and left ventricular compliance was significantly diminished in male OHM compared to controls. Ischemia caused a significant decline in heart function in controls and female OHM, while function in male OHM remained unchanged. CONCLUSIONS: Adult male OHM demonstrate programmed cardiac dysfunction. Given the growing number of pregnancies complicated by hyperglycemia, additional assessment of cardiac function of adults born to diabetic mothers may be warranted.

Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival.

RATIONALE: The Xin repeat-containing proteins mXinalpha and mXinbeta localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinalpha directly interacts with beta-catenin, p120-catenin, and actin filaments. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinbeta in mXinalpha-deficient hearts suggests a partial compensation. OBJECTIVE: The essential roles of mXinbeta in cardiac development and intercalated disc maturation were investigated. METHODS AND RESULTS: Ablation of mXinbeta led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinalpha. Postnatal upregulation of mXinbeta in wild-type hearts, as well as altered apoptosis and proliferation in mXinbeta-null hearts, suggests that mXinbeta is required for postnatal heart remodeling. The mXinbeta-null hearts exhibited a misorganized myocardium as detected by histological and electron microscopic studies and an impaired diastolic function, as suggested by echocardiography and a delay in switching off the slow skeletal troponin I. Loss of mXinbeta resulted in the failure of forming mature intercalated discs and the mislocalization of mXinalpha and N-cadherin. The mXinbeta-null hearts showed upregulation of active Stat3 (signal transducer and activator of transcription 3) and downregulation of the activities of Rac1, insulin-like growth factor 1 receptor, protein kinase B, and extracellular signal-regulated kinases 1 and 2. CONCLUSIONS: These findings identify not only an essential role of mXinbeta in the intercalated disc maturation but also mechanisms of mXinbeta modulating N-cadherin-mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival.

Echocardiographic assessment of cardiac morphology and function in Xenopus.

Advances using Xenopus as a model permit valuable inquiries into cardiac development from embryo to adult. Noninvasive methods are needed to study cardiac function longitudinally. The objective of this study was to evaluate the feasibility of echocardiographic studies in Xenopus and establish normative data of adult cardiac structure and function. Doppler and 2D echocardiograms and electrocardiograms were acquired from adult Xenopus laevis and X. tropicalis. Frogs were exposed to either isoflurane or tricaine to discern the effect of sedating agents on cardiac function. Cardiac dimensions, morphology, flow velocities, and electrophysiologic intervals were measured and evaluated by using bivariate and regression analyses. Normal cardiac dimensions relative to body weight and species were established by echocardiography. Normal conduction intervals were determined by electrocardiography and did not vary by body weight or species. Anesthetic agent did not affect ejection fraction or flow velocity but did alter the QRS duration and QT interval. Echocardiographic and electrocardiographic studies in Xenopus provide information about cardiac anatomy and physiology and can readily be used for longitudinal analyses of developmental inquiries. Body weight, species, and anesthetic agent are factors that should be considered in experimental design and analyses.

Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways.

BACKGROUND: Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways. METHODS: To evaluate the effects of moderate and severe maternal hyperglycemia, pregnant rats were made diabetic with an injection of 50 mg/kg of streptozotocin. Moderately well controlled maternal diabetes was achieved with twice daily glucose checks and insulin injections. No insulin was given to severely diabetic dams. Offspring of moderate and severe diabetic mothers (OMDM and MSDM, respectively) were studied on postnatal days 1 (NB1) and 21 (NB21). Echocardiograms were performed to evaluate left ventricular (LV) dimensions and function. Myocardial MAPK and apoptotic protein levels were measured by Western blot. RESULTS: OMDM had increased cardiac mass at NB1 compared to controls that normalized at NB21. OSDM demonstrated microsomia with relative sparing of cardiac mass and a dilated cardiomyopathy at NB1. In both models, there was a persistent increase in the HW:BW and significant activation of MAPK and apoptotic pathways at NB21. CONCLUSION: The degree of maternal hyperglycemia determines the type of cardiomyopathy seen in the offspring, while resolution of both the hypertrophic and dilated cardiomyopathies is associated with activation of MAPK signaling and apoptotic pathways.