Hiroaki Kise

Cardiovascular Effects of Azelnidipine in Comparison with Those of Amlodipine Assessed in the Halothane‐Anaesthetized Dog

Azelnidipine is a new dihydropyridine Ca(2+) channel blocker with long plasma half-life. To understand the in vivo cardiovascular profile of azelnidipine, it was assessed in the halothane-anaesthetized, closed-chest canine model and compared with the effect of amlodipine. We administered azelnidipine in doses of 10, 20 and 70 microg/kg, i.v. or amlodipine in doses of 30, 70 and 200 microg/kg, i.v. cumulatively to the animals. The hypotensive effects of azelnidipine and amlodipine were slow in onset and long-lasted, while their extents of dose-related hypotensive effects were similar. Azelnidipine hardly affected the heart rate or plasma noradrenaline concentration at any doses, whereas the high dose of amlodipine increased these parameters. Azelnidipine as well as amlodipine tended to increase the ventricular contraction, which did not achieve statistical significance. During autonomic receptor blockade with atropine and propranolol, neither drug affected the heart rate, ventricular contraction or plasma noradrenaline concentration, although a more significant hypotensive action was observed. These results indicate that azelnidipine and amlodipine do not directly affect cardiac function. Amlodipine may induce sinus tachycardia via reflex-mediated increase in sympathetic tone. Such lack of reflex tachycardia with azelnidipine will provide potential therapeutic strategy for treatment of patients with cardiovascular diseases, being more beneficial than amlodipine.

Cardiac and Haemodynamic Effects of Tacrolimus in the Halothane-Anaesthetized Dog

Tacrolimus (FK506) is a potent immunosuppressant widely used for the treatment of patients with solid organ transplantation and autoimmune diseases. The present study investigated the cardiac, haemodynamic and electrophysiological effects of tacrolimus. Tacrolimus in doses of 0.01 and 0.1 mg/kg was infused over 10 min. with a pause of 20 min. in halothane-anaesthetized dogs under monitoring of plasma drug concentrations (n = 5). Sub-therapeutic dose of 0.01 mg/kg hardly affected any of the cardiovascular variables except that it slightly delayed the repolarization. The clinically relevant dose of 0.1 mg/kg had negative chronotropic, inotropic and dromotropic effects, and lowered blood pressure by 70 +/- 12 mmHg, effects previously ascribed to Ca(2+) channel blocking action. Tacrolimus also delayed the repolarization process in a dose-dependent and reverse use-dependent manner with an increase in electrical vulnerability. The cardiovascular effects of tacrolimus were enhanced after the cessation of drug infusion, despite a decline in the plasma concentrations. In human embryonic kidney 293 cells, however, only supratherapeutic tacrolimus concentrations (>0.1 mumol/l) inhibited hERG K(+) current with a maximum inhibition of 28% at 10 mumol/l, indicating that other mechanisms might have also operated besides direct block of ionic channel function. The present study suggests that tacrolimus has negative chronotropic, inotropic and dromotropic effects in the heart, delays repolarization and lowers blood pressure. Moreover, the monitoring of the actual drug concentration may not necessarily reflect its effects on the cardiovascular system; thus, frequent monitoring of cardiovascular variables may be essential for tacrolimus-treated patients.

Infliximab regulates monocytes and regulatory T cells in Kawasaki disease

The effect of infliximab (IFX) on immune cells has not been fully reported in Kawasaki disease (KD). To investigate the mechanism of IFX in KD, we examined changes in the abundance of CD14+CD16+ activated monocytes, regulatory T cells (Treg) cells, and T‐helper type 17 (Th17) cells following treatment with IFX.

Co-occurrence of hypertrophic cardiomyopathy and myeloproliferative disorder in a neonate with Noonan syndrome carrying Thr73Ile mutation in PTPN11

Most cases of Noonan syndrome (NS) result from mutations in one of the RAS‐MAPK signaling genes, including PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1 (MAP2K1), and CBL. Cardiovascular diseases of varying severity, such as pulmonary stenosis and hypertrophic cardiomyopathy (HCM), are common in NS patients. RAF1 mutations are most frequent in NS with HCM, while PTPN11 mutations are also well known. Thr73Ile is a gain‐of‐function mutation of PTPN11, which has been highly associated with juvenile myelomonocytic leukemia and NS/myeloproliferative disease (MPD), but has not previously been reported in HCM. Here, we report a Japanese female infant with NS carrying the PTPN11 T73I mutation with NS/MPD, complete atrio‐ventricular septal defect, and rapidly progressive HCM. No other HCM‐related mutations were detected in PTPN11, RAF1, KRAS, BRAF, and SHOC2. This patient provides additional information regarding the genotype–phenotype correlation for PTPN11 T73I mutation in NS.

Plasma Exchange Downregulates Activated Monocytes and Restores Regulatory T Cells in Kawasaki Disease: Plasma Exchange in Kawasaki Disease

In Kawasaki disease (KD), the effect of plasma exchange (PE) on immune cells has not been fully elucidated. Therefore, we examined the changes in the number of CD14+ CD16+ activated monocytes, regulatory T (Treg), and T‐helper type 17 (Th17) cells in KD patients treated with PE. The percentage of total monocytes and subclasses of lymphocytes, including CD4+ and CD8+ T cells, and CD19+ B cells, showed no significant difference before and after PE. However, the percentage of CD14+ CD16+ monocytes in total leukocytes decreased significantly after PE (1.1% ± 1.5% vs. 2.1% ± 2.3%, P < 0.05). Furthermore, while the percentage of Th17 cells in CD4+ T cells did not change, the percentage of Treg cells in CD4+ T cells increased significantly after PE (11.1% ± 5.1% vs. 8.0% ± 4.4%, P < 0.05). Therefore, PE downregulates activated monocytes and upregulates Treg cells toward normal levels and thus attenuates inflammation in KD.

Electrical storm in an infant with short-coupled variant of torsade de pointes

A 10‐month‐old infant experienced cardiac arrest caused by ventricular fibrillation (VF). His electrocardiogram (ECG) at rest was within the normal range. Amiodarone was indispensable due to its refractoriness to defibrillation. After implantable cardioverter defibrillator (ICD) implantation, ICD shock was delivered. ICD recordings documented VF and ventricular tachycardia (VT) triggered by premature ventricular contractions with an extremely short coupling interval (240 ms), which were controlled by verapamil. To the best of our knowledge, our case is the first infant with ScTdP. As the electrical storm with ScTdP occurs unpredictably, it can be a cause of sudden infant death syndrome.

Correction to: Outcomes of plasma exchange for severe dilated cardiomyopathy in children

In original publication of the article, some of the co-author’s names were not included. The correct author group is published in this article.

A Knotted Elemental Diet Tube in a Neonate: Serial Radiographs Demonstrating the Process of Loop Formation.

A 1-day-old girl with a congenital hepatoblastoma (diameter 89 mm) placed in the right hepatic lobe was admitted to our neonatal intensive care unit. Nasogastric tube feeding was initiated; however, delayed gastric emptying, possibly due to an outlet obstruction caused by the tumor, prompted us to insert a polyvinyl-chloride elemental diet (ED) tube (6.5F/120 cm; Covidien, Tokyo, Japan). The distal end of the ED tube was located at the duodenum on the 24 hospital day (Figure 1A). Radiography on the 27 hospital day indicated that the tube had slipped out from the pylorus (Figure 1B). We expected that the tube would pass through the pylorus again; however, the radiograph suggested that it formed a loop (Figure 1C) in the stomach 7

Successful Emergent Aspiration of Thrombus for Postoperative Superior Vena Cava （SVC）Obstruction Presenting Critical SVC Syndrome in Early Infancy

Successful Emergent Aspiration of Thrombus for Postoperative Superior Vena Cava (SVC) Obstruction Presenting Critical SVC Syndrome in Early Infancy Hiroaki Kise1), Hideshi Tomita1), Kazuto Fujimoto1), Takanari Fujii1), Hisako Kiguchi1), Nobuo Oyama2), Takashi Soga2), Yoshihito Hata1), Masataka Hirata1), Atsushi Itoh1), Kozo Ishino1), Shunji Sano3) 1)Cardiovascular Center, 2)Children’s Medical Center, Showa University Northern Yokohama Hospital, Yokohama, Japan 3)Department of Cardiovascular surgery, Okayama University Hospital, Okayama, Japan

A Case Report of Dysosteosclerosis Observed from the Prenatal Period

Dysosteosclerosis is a sclerosing bone dysplasia with skeletal changes resembling those of osteopetrosis. The disorder is associated with dental anomalies and occasionally mental retardation. Because of the rarity and phenotypic diversity of dysosteosclerosis, it remains unsolved whether or not the disorder is heterogeneous. We report here on an affected boy associated with brain calcification and epilepsy with developmental delay. Prenatal ultrasound revealed ventriculomegaly, and brain CT in the neonatal period showed periventricular calcifications. At 13 mo of age, he presented with generalized convulsion with developmental delay. Metaphyseal sclerosis, metaphyseal undermodeling, and oval-shaped vertebral bodies on skeletal survey warranted a diagnosis of dysosteosclerosis. Retrospective review of radiographs as a neonate showed metaphyseal radiolucency, but not metaphyseal sclerosis. Since then, neither the bone changes nor neurological symptom has progressively worsened up to 4 yr of age. Thus, it is thought that the clinical and radiological manifestations of the sclerotic disorder become obvious during infancy. Brain calcification of prenatal onset may be an essential syndromic constituent of the disorder.