Cinaciguat Prevents Postnatal Closure of Ductus Arteriosus by Vasodilation and Anti-remodeling in Neonatal Rats.

Closure of the ductus arteriosus (DA) involves vasoconstriction and vascular remodeling. Cinaciguat, a soluble guanylyl cyclase (sGC) activator, was reported with vasodilatory and anti-remodeling effects on pulmonary hypertensive vessels. However, its effects on DA are not understood. Therefore, we investigated whether cinaciguat regulated DA patency and examined its underlying mechanisms. In vivo, we found that cinaciguat (10 mg/kg, i.p. at birth) prevented DA closure at 2 h after birth with luminal patency and attenuated intimal thickening. These anti-remodeling effects were associated with enhanced expression of cyclic guanosine monophosphate (cGMP) in DA. Ex vivo, cinaciguat dilated oxygen-induced DA constriction dose-dependently. Such vasodilatory effect was blunted by KT-5823, a PKG inhibitor. In DA smooth muscle cells (DASMCs), we further showed that cinaciguat inhibited angiotensin II (Ang II)-induced proliferation and migration of DASMCs. In addition, cinaciguat inhibited Ang II-induced mitochondrial reactive oxygen species (ROS) production. Finally, Ang II-activated MAPKs and Akt were also inhibited by cinaciguat. In conclusion, cinaciguat prevents postnatal DA closure by vasodilation and anti-remodeling through the cGMP/PKG pathway. The mechanisms underlying anti-remodeling effects include anti-proliferation and anti-migration, with attenuation of mitochondrial ROS production, MAPKs, and Akt signaling. Thus, this study implicates that sGC activation may be a promising novel strategy to regulate DA patency.

Developing New Health Material: The Utilization of Spray Drying Technology on Avocado (Persea Americana mill.) Seed Powder.

Avocado (Persea Americana Mill.) generates byproducts, especially the avocado seeds. Hence, the aim of this study was to investigate the potential utilization of avocado seed as a very important, high phenolic content, climacteric fruit with unique characteristics and high nutritional properties. As such, theantioxidative test is conducted, then spray drying is used to produce avocado seed powder. The objective of this study was to develop an avocado seed powder using the spray drying technique by investigating the solution stability with different avocado seed extract concentrations, and to determine the physical properties of spray dried avocado powder that consists of powder yield, moisture, water activity, solubility, and color. The avocado seed extract was mixed with maltodextrin and water and homogenized for 10 min at 8000 rpm. The avocado seed solution was then spray dried with different inlet temperatures and feed flow rates. The spray dried avocado seed powder was analyzed for its yield, moisture content, water activity, solubility, and color. It was reported that the solution with the least avocado extract concentration (10 g) had the best stability in terms of presence of solute particles and color. The avocado seed powder obtained from this experiment had yield ranges from 24.46-35.47%, moisture content ranges from 7.18-7.96%, water activity ranges from 0.27-0.34, solubility ranges from 55.50-79.67 seconds, L* value ranges from 38.38-41.05, a* value ranges from 6.20-7.25, and b* value ranges from 13.33-15.17. In addition, increasing inlet temperature resulted in an increase in powder yield, solubility, a* value, and b*value, as well as a decrease in moisture, water activity, and L* value. Meanwhile, increasing the feed flow rate resulted in an increase in powder yield, moisture, water activity, and all L*, a*, b* values, as well as a decrease in solubility. In conclusion, spray drying technology is able to develop avocado seed powder.

Traumatic Ventricular Septal Defect in a 1-Year-Old Boy After Accidental Chest Compression by an Adult.

We report a 1-year-old boy with a delayed diagnosis of traumatic ventricular septal defect (VSD) related to chest compression. His cardiac function was stable after adequate medical treatment. Spontaneous closure of traumatic VSD occurred to this patient at the age of 4 years. This is a rare case of traumatic VSD associated with accidental chest compression, which is similar to rupture of the ventricular septum after blunt chest trauma. It should be kept in mind that traumatic VSD and concomitant thoracic injuries can develop during chest compression. The clinician should pay attention to the potential risk of traumatic VSD in patients experiencing chest compression. Echocardiography is a convenient and effective tool for serial follow-up examination and avoiding the delayed diagnosis. Troponin I level can be a useful screening test. Conservative management of traumatic VSD with hemodynamic stability is recommended because of possible spontaneous closure.

Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure.

The ductus arteriosus (DA) connects the main pulmonary artery and the aorta in fetal circulation and closes spontaneously within days after birth in normal infants. Abnormal patent DA (PDA) causes morbidities and mortality, especially in preterm infants. Closure of the DA is a complex interactive process involving two events: functional and anatomic closure. Functional closure by smooth muscle contraction was achieved through the regulatory factors of vaso-reactivity. These factors include oxygen sensing system, glutamate, osmolality, prostaglandin E2, nitric oxide, and carbon monoxide. Anatomic closure by vascular remodeling involved several vascular components including endothelium, extracellular matrix, smooth muscle cells, and intraluminal blood cells. Despite advances in understanding of PDA pathogenesis, the molecular mechanism for regulation of DA closure is complex and not fully understood. In this article we review recent evidence regarding the molecular mechanisms of DA closure.

Abnormal biventricular performance in asymptomatic adolescents late after repaired Tetralogy of Fallot: Combined two-dimensional speckle tracking and three-dimensional echocardiography study.

BACKGROUND: The aim of this prospective study was to assess biventricular performance in asymptomatic adolescents with repaired tetralogy of Fallot (TOF) using 2D speckle tracking and real time 3D echocardiography simultaneously. METHODS: We studied 31 patients with repaired TOF (M/F: 22/9, age: 16.1 ± 6.1 yrs) who had history of cardiac surgery with mean follow-up duration of 12.8 years, and 32 age- and sex-matched normal individuals (M/F: 23/9, age: 16.6 ± 5.1 yrs). All subjects underwent speckle tracking and 3D echocardiography, electrocardiogram, treadmill, and blood sampling for measurement of brain natriuretic peptide (BNP). RESULTS: Compared to the control group, the TOF group had higher BNP level (31.8 ± 21.4 vs 14.1 ± 12.4 pg/ml, p < 0.01), lower peak oxygen consumption (8.4 ± 1.7 vs 9.9 ± 1.6 ml/kg/min, p < 0.05), and longer QRS duration (126 ± 30 vs 82 ± 9 ms, p < 0.01). Patients with repaired TOF had significantly impaired right ventricle (RV) global and all six regional longitudinal strain and strain rate than normal controls. Left ventricle (LV) global and mainly apical regional longitudinal strain and strain rate were reduced in patients with repaired TOF. There was a significant correlation of global longitudinal strain (r = 0.456, p = 0.01) and global time to peak longitudinal strain (r = 0.484, p < 0.01) between LV and RV in patients with repaired TOF. In terms of 3D echo cardiographic volume data, patients with repaired TOF had lower LV stroke volume index (p < 0.05), but higher RV end diastolic volume index (p < 0.01), RV end systolic volume index (p < 0.01), RV stroke volume index (p < 0.01), and pulmonary regurgitation fraction (p < 0.01) than normal controls. CONCLUSION: Our results suggest asymptomatic adolescents with repaired TOF had abnormal biventricular myocardial performance, as demonstrated by combined 2D speckle-tracking and 3D echocardiography. The implications of these findings for management of adolescents late after repaired TOF remain to be determined.