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Objective An alternative therapy for preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) is needed when cyclooxygenase inhibitors fail or where treatment is contraindicated due to coexisting renal failure, necrotizing enterocolitis, and/or intestinal perforation. No studies have evaluated the efficacy of per rectum (PR) acetaminophen. The study aimed to evaluate the efficacy of PR acetaminophen in modulating the risk of PDA ligation. Study Design A retrospective matched case–control study was conducted to compare neonates born <29 weeks' gestation with evidence of hsDA, in an era when rescue rectal acetaminophen was used (January 2014–March 2018) as a treatment strategy, versus historical controls (July 2006–August 2012). All patients underwent comprehensive echocardiography assessment of ductal shunt volume according to a standardized protocol. Acetaminophen treated neonates were matched according to demographics, gestation, preintervention echocardiography features, and comorbidities. Control patients were selected when an echocardiography was performed at an equivalent postnatal age. Infants with a genetic syndrome, severe congenital malformation, or major forms of congenital heart disease excluding small atrial septal defect or ventricular septal defect, PDA, or patent formale ovale were excluded. The primary outcome was surgical ligation of the PDA. Secondary outcomes included echocardiography indices of hemodynamic significance, the composite of death, or severe BPD (defined by ventilator dependence at 36 weeks postmenstrual age). Descriptive statistics and univariate (t -tests, Fisher's exact test, and Mann–Whitney U test) analyses were used to evaluate clinical and echocardiography characteristics of the groups and compare outcomes. Results Forty infants (20 cases and 20 controls), with similar demographic and echocardiography features, were compared. Cases received 6.8 ± 0.7 days (60 mg/kg/day) of PR acetaminophen. Responders (n = 12, 60%) had echocardiography evidence of reduced ductal diameter (2.2 mm [1.9–2.6] to 1.1 mm [0–1.7], p = 0.002), left ventricular output (363 ± 108–249 ± 61 mL/min/kg; p = 0.002) and left atrium to aortic root ratio (1.7 ± 0.3–1.3 ± 0.2; p = 0.002) following treatment. The rate of PDA ligation was 50% lower (p = 0.02) and composite outcome of death or severe bronchopulmonary dysplasia was reduced (p = 0.04) in the acetaminophen group. Conclusion Rectal acetaminophen was associated with improvement in echocardiography indices of PDA shunt volume, a 50% reduction in PDA ligation rates and a reduction in the composite outcome of death or severe BPD. Pharmacologic and further prospective clinical studies are needed. Key Points Many preterm infants encounter the clinical consequences of a hemodynamically significant PDA. The merits and optimal timing of PDA ligation remains an area of controversy amongst neonatologists. Cyclooxygenase inhibitors are associated with adverse events or are often contraindicated. [ABSTRACT FROM AUTHOR]

Objective  Epidemiological studies suggest that lactation is associated with long-term maternal health benefits. To avoid confounders in human studies, we used a previously characterized murine model to investigate the long-term effect of lactation on both cardiovascular function and adiposity. Study Design  After the delivery of the pups, CD-1 female mice were randomly divided into two groups: lactated and nonlactated (NL). Before pregnancy and at 9 months postdelivery, blood pressure was measured using a tail cuff, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography (CT), echocardiography was performed using microultrasound, and cholesterol panels and fasting blood glucose were measured. The data were analyzed using Student's t -test (significance at p  < 0.05). Results  There were no differences in baseline parameters between the two groups. At 9 months postdelivery, the NL group weighed significantly more (p  = 0.03) and demonstrated a significantly lower cardiac output (p  = 0.05) and ejection fraction (p  = 0.03). The mice in the NL group also had higher VAT (p  < 0.01) and SAT percentiles (p  = 0.03). Fasting glucose (p  = 0.01) and low-density lipoprotein (p  = 0.01) were significantly higher in the NL group at 9 months. Conclusion  Our results show the benefit of lactation is not just limited to the immediate postpartum period but it also extends into midlife in a murine model. [ABSTRACT FROM AUTHOR]

We wanted to explore whether change in LA (left atrium) size would influence LA function, or increase regurgitation in the atrioventricular valves. 595 male elite football players and 47 non-athletic controls were included. End-systolic LA volume and RA area and end-diastolic LV volume and RV area were measured by 2-dimensional (2D) echocardiography Pulsed and colour Doppler were used to estimate tricuspid and mitral regurgitations. 2D longitudinal strain of the 50 football players with the largest LA volumes were compared with the 50 players with the smallest LA volumes. The LA volumes in some athletes with large atria were more than tripled, compared to athletes with small atria. 2D strain however, could not reveal any impairment of LA function in the players with the largest atria, compared to those with the smallest LA. Tricuspid valve regurgitation was found in 343 (58 %) of the athletes, compared to 17 (36 %) of the controls (p < 0.01), while mitral regurgitation was found in 116 (20 %) football players and 7 (15 %) controls (NS). Furthermore, the RA area was significantly larger in athletes with tricuspid regurgitation compared to athletes without. The present study demonstrated a huge variation in atrial size between the athletes. This variation, however, had no impact on LA function. Tricuspid regurgitation was significantly more prevalent among the athletes, than among the controls. [ABSTRACT FROM AUTHOR]

Objective This study aims to investigate the effects of antenatalmagnesium sulfate on intestinal blood flow in preterm neonates. Study Design In this prospective case–match study, 25 preterm neonates exposed to magnesium sulfate antenatally were included (study group). Overall, 25 gestational age–matched neonates who had no exposure to magnesium constituted the control group. Serial daily Doppler flow measurements of superior mesenteric artery (SMA) were performed. The time to reach full feeds, first meconium passage were assessed. Presence of feeding intolerance or necrotizing enterocolitis was recorded. Results Blood flow velocities of SMA were not different between the groups during the first five postnatal days. However, SMA blood flow showed an increasing trend in the control group unlike the study group (control group, p < 0.001; study group, p ¼ 0.29). There was no significant difference between the two groups regarding the time to reach full feeds or first meconium passage and presence of feeding intolerance. No case of necrotizing enterocolitis was seen. Conclusion Antenatal magnesium does not significantly affect intestinal blood flow, but it seems to attenuate the increasing trend of the intestinal blood flow in the early postnatal days. However, this study failed to show any impact of this finding on clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective Bronchopulmonary dysplasia (BPD) increases the risk for developing pulmonary hypertension (PH). However, the risk factors associated with BPD-associated PH remain unclear. Our primary aim was to determine perinatal risk factors associated with the development of PH in infants with BPD. Study Design We retrospectively reviewedmedical records of 303 infants born at ≤ 28 weeks' gestation. Infants were categorized as having no,mild,moderate, or severe BPD. PH was diagnosed by echocardiogram. Data were analyzed using Fisher exact test, twosample t-test, and multivariable logistic regression. Results The incidence of PH in our cohort was 12%. Infants with PH had lower birth weights and gestational ages (p < 0.001). After controlling for confounding variables, severe BPD (p < 0.001), and higher Clinical Risk Index for Babies (CRIB) scores (p = 0.04) were associated with the development of PH. Conclusion Severe BPD increases the risk for developing PH. Higher CRIB scores correlate with PH development in infants with BPD. We speculate that CRIB scores may allow for early categorization of preterm infants with a higher likelihood of developing PH. [ABSTRACT FROM AUTHOR]

Objective Immature antioxidant and oxygen-sensing mechanisms are involved in the pathogenesis of the patent ductus arteriosus (PDA). We conducted a prospective, observational, pilot study to test the hypothesis that antioxidant activity is low at birth in preterm infants at risk for symptomatic PDA. Study Design Blood and urine samples were collected within 24 to 48 hours of life in 53 preterm infants (≤32 weeks' gestation) who developed early PDA symptoms and in 30 term (≥37 weeks' gestation) control infants. Thirty preterm infants developed hemodynamically significant PDA (hsPDA) and required pharmacologic treatment and/ or PDA ligation. For these infants, blood and urine samples were also collected at 24 hours posttreatment. Samples were analyzed for biomarkers of antioxidant activity, oxidative stress, and lipid peroxidation. Results At 24 to 48 hours after birth, plasma superoxide dismutase (SOD), urinary catalase, and plasma and urinary 8-isoPGF2α were significantly lower in preterm infants who developed hsPDA. Plasma 8-isoPGF2α levels rebounded post-PDA treatment, while urinary prostaglandin E2, plasma and urinary thromboxane B2, and plasma SOD declined. Conclusion The antioxidant status is low in preterm infants at risk for developing hsPDA. SOD may be a key antioxidant regulating functional ductus arteriosus closure. Therefore, low levels may result in persistence of a hsPDA. [ABSTRACT FROM AUTHOR]

Objective This study aims to compare the effects of early and late (routine) initiation of caffeine in nonintubated preterm neonates. Study Design A total of 21 neonates < 29 weeks gestational age were randomized to receive intravenous caffeine citrate (20 mg/kg) or placebo either before 2 hours of age (early) or at 12 hours of age (routine). This was an observational trial to determine the power needed to reduce the need for endotracheal intubation by 12 hours of age. Other outcomes included comparisons of cerebral oxygenation, systemic and pulmonary blood flow, hemodynamics, hypotension treatment, oxygen requirement, and head ultrasound findings. Results There was no difference in the need for intubation (p = 0.08), or vasopressors (p = 0.21) by 12 hours of age. Early caffeine was associated with improved blood pressure (p = 0.03) and systemic blood flow (superior vena cava flow, p = 0.04 and right ventricular output, p = 0.03). Heart rate, left ventricular output, and stroke volume were not significantly affected. Cerebral oxygenation transiently decreased 1 hour after caffeine administration. There were no differences in other outcomes. Conclusion This pilot study demonstrated the feasibility of conducting such a trial in extremely preterm neonates. We found that early caffeine administration was associated with improved hemodynamics. Larger studies are needed to determine whether early caffeine reduces intubation, intraventricular hemorrhage, and related long-term outcomes. [ABSTRACT FROM AUTHOR]

Background Electrical cardiometry (EC) is a continuous noninvasive method for measuring cardiac output (CO), but there are limited data on premature infants. We evaluated the utility of EC monitoring by comparing the results obtained using EC to measurements of CO and systemic blood flow using echocardiography (ECHO). Methods In this prospective observational study, 40 preterm neonates underwent 108-paired EC and ECHO measurements. Results There were correlations between EC-CO and left ventricular output (LVO, p < 0.005) and right ventricular output (RVO, p < 0.005) but not with superior vena cava (r = 0.093, p = 0.177). Both RVO and LVO correlated with EC with and without a hemodynamically significant ductus arteriosus (p = 0.001 and 0.008, respectively). The level of agreement was decreased in infants ventilated by high-frequency oscillation ventilators (HFOV). The bias in HFOV was also positive compared with the negative biases found in other modes of ventilation. Conclusion Given the correlation of EC with LVO, RVO, and lack of confounding effects of the ductus, our results suggest that EC has promise for trending CO in the preterm infant. However, given the limitations with mode of ventilation and the lack of correlation at low LVO values, further study is needed before this technology can be for routine use. [ABSTRACT FROM AUTHOR]

Recent attention has been focused on possible unique features of the right ventricular response to exercise. This study investigated a) the responses of right ventricular cardiac dynamics and myocardial function to a standard bout of progressive cycle exercise in healthy young males, and b) the effect of level of aerobic fitness on these responses. 14 athletically-trained males (20.4 ± 1.5 years) and 11 normally-active males (21.1 ± 1.3 years) underwent a progressive upright cycle test to exhaustion with measurement of gas exchange variables and assessment of right ventricular stroke volume, systolic and diastolic myocardial velocities, and tricuspid inflow velocities by standard Doppler echocardiographic techniques at rest, submaximal and peak exercise. Stroke volume rose initially by approximately 27 % in each group, followed by stable values to exhaustion. Values of maximal stroke index and maximal oxygen uptake were significantly greater in the trained group than the normally-active males (62 ± 10 ml m−2 , 54.3 ± 4.0 ml kg −1 min −1 ; 49 ± 7 ml m −2 , 40.3 ± 5.6 ml kg −1 min −1 , respectively). No significant differences were observed in increases in systolic or diastolic myocardial velocities, peak pulmonary outflow velocity, systolic ejection rate, or tricuspid inflow velocity between the 2 groups. The magnitude of change of these variables was similar to those previously described for left ventricular responses to similar exercise. This study revealed no unique features of right ventricular functional responses to an acute exercise challenge in young males. [ABSTRACT FROM AUTHOR]

We investigated the influence of sport modalities in resting bradycardia and its mechanisms of control in highly trained athletes. In addition, the relationships between bradycardia mechanisms and cardiac structural adaptations were tested. Professional male athletes (13 runners, 11 cyclists) were evaluated. Heart rate (HR) was recorded at rest on beat-to-beat basis (ECG). Selective pharmacological blockade was performed with atropine and esmolol. Vagal effect, intrinsic heart rate (IHR), parasympathetic (n) and sympathetic (m) modulations, autonomic influence (AI) and autonomic balance (Abal) were calculated. Plasmatic norepinephrine (high-pressure liquid chromatography) and cardiac structural adaptations (echocardiography) were evaluated. Runners presented lower resting HR, higher vagal effect, parasympathetic modulation (n), AI and IHR than cyclists (P < 0.05). Abal, sympathetic modulation (m) and norepinephrine level were similar within athletes regardless of modality. The cardiac chambers were also similar between runners and cyclists (P = 0.30). However, cyclists displayed higher septum and posterior wall thickness than runners (P = 0.04). Further analysis showed a trend towards inverse correlation between IHR with septum wall thickness and posterior wall thickness (P = 0.056). Type of sport influences the resting bradycardia level and its mechanisms of control in professional athletes. Resting bradycardia in runners is mainly dependent on an autonomic mechanism. In contrast, a cyclist’s resting bradycardia relies on a non-autonomic mechanism probably associated with combined eccentric and concentric hypertrophy. [ABSTRACT FROM AUTHOR]

Objective After the introduction of a new protocol based on the early treatment with indomethacin for patent ductus arteriosus, the objective of this study was to assess the safety and efficacy of this new practice in comparison with the safety and efficacy of the conventional treatment in a high-risk population. Study Design We conducted a retrospective cohort study including 154 newborns with an average gestational age of 26.4 weeks (1.37 standard deviation) and an average birth weight of 855 g (201.5 standard deviation). A statistically descriptive analysis was performed with SPSS Statistics Pack version 17.0. Results and Conclusions We did not find any statistically significant differences in the clinical features of the two treatment groups, nor in the main efficacy, morbidity, and mortality results. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether hemoglobin-based oxygen carrier (HBOC) could protect the heart from intense exercise-induced myocardial dysfunction. Adult male Sprague-Dawley rats were subjected to 5-h intense prolonged running on treadmill with or without HBOC pre-treatment. Immediately after exercise, the heart rate (HR) and oxygen delivery capacity of the blood were measured. After 1 h of rest, echocardiography was performed to assess the post-exercise cardiac function. Then all the hearts were isolated and perfused using the Langendorff model for 1 h. Our results proved that pronged exercise caused significant LV dysfunction, while HBOC pre-treatment attenuated such a damage, as evidenced by the increased oxygen delivery, cardiac fractional shortening (FS), rate-pressure product (RPP), ± dp/dt and coronary flow rate (CF) and decreased myocardial necrosis. The releases of cardiac enzymes, including creatine kinase-MB (CK-MB) and cardiac troponin-I (cTnI) were markedly reduced. No significant difference of cardiac infarct size was observed among groups. In addition, HBOC significantly elevated superoxide dismutase (SOD) activity and decreased hydrogen peroxide (H2O2) formation, which indicated the exercise-induced cardiac oxidative damage was inhibited. In conclusion, HBOC pre-treatment showed a promising cardioprotective effect on prolonged exercise-induced cardiac dysfunction, which was probably associated with its ability to decrease myocardium oxidative stress. [ABSTRACT FROM AUTHOR]