Polymorphic ventricular tachycardia in a patient with hypertrophic cardiomyopathy and digitalis intoxication

SummaryWe report the case of a 74-year-old woman who presented with recurrent episodes of polymorphic ventricular tachycardia (PVT) with a normal QT interval due to digitalis intoxication (serum digoxin concentration, 5.0 ng/mL) and severe hyperkalemia (serum potassium level, 8.3 mEq/L). In addition, laboratory data showed elevated levels of blood urea nitrogen (54 mg/dL) and serum creatinine (1.57 mg/dL), suggesting dehydration. She had been treated with a combination of digoxin and eplerenone for atrial fibrillation and heart failure. The PVT resolved after treatment for hyperkalemia. Cardiac magnetic resonance imaging and left ventriculography showed left ventricular hypertrophy predominantly in the apex, suggesting apical hypertrophic cardiomyopathy (HCM). We presume that the presence of HCM was related to the occurrence of PVT in this patient with digitalis intoxication and hyperkalemia.<Learning objective: PVT with a normal QT interval caused by digitalis intoxication with hyperkalemia was observed in a patient with HCM treated with digoxin and eplerenone for atrial fibrillation and heart failure. The presence of HCM may be related to the occurrence of PVT. Combination therapy with digoxin and aldosterone receptor antagonist may predispose severe hyperkalemia, and monitoring of serum digitalis concentration and potassium level should be done strictly.

Pulmonary hypertension associated with veno-occlusive disease in systemic sclerosis: Insight into the mechanism of resistance to vasodilator

We report a case with pulmonary veno-occlusive disease (PVOD) associated with systemic sclerosis which exhibits strong resistance to pulmonary vasodilator.A 55-year-old female with severe pulmonary hypertension was admitted to our hospital to be introduced to epoprostenol infusion therapy. She was diagnosed as having pulmonary arterial hypertension (PAH) associated with systemic sclerosis at the age of 51. Several aggressive treatments with pulmonary vasodilators, including oral prostaglandin, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors, failed to improve her symptoms. We introduced continuous intravenous epoprostenol therapy from 2. μg/kg/min for her. However, pulmonary edema appeared and worsened in a dose-dependent manner. We made a diagnosis of PVOD clinically at that time. Thereafter, pulmonary edema gradually disappeared consistent with the reduction of the dose of epoprostenol infusion. She died of renal failure and infection 4. months after the introduction of epoprostenol infusion therapy. A histological examination revealed severe stenosis and occlusions of pulmonary veins as well as pulmonary arteries over a wide area. We suggest that prevalence of veno-occlusive type of disease could be one of the major mechanisms of less responsive or even refractory to pulmonary vasodilator therapies in patients with PAH associated with connective tissue disease. © 2011 Japanese College of Cardiology

Multiple noncoding exons 1 of nuclear receptors NR4A family (nerve growth factor-induced clone B, Nur-related factor 1 and neuron-derived orphan receptor 1) and NR5A1 (steroidogenic factor 1) in human cardiovascular and adrenal tissues

金沢大学医薬保健研究域医学系Objective: Nuclear receptors are involved in a wide variety of functions, including aldosteronogenesis. Nuclear receptor families NR4A [nerve growth factor-induced clone B (NGFIB), Nur-related factor 1 (NURR1) and neuron-derived orphan receptor 1 (NOR1)] and NR2F [chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), COUP-TFII and NR2F6) activate, whereas NR5A1 [steroidogenic factor 1 (SF1)] represses CYP11B2 (aldosterone synthase) gene transcription. The present study was undertaken to elucidate the mechanism of differential regulation of nuclear receptors between cardiovascular and adrenal tissues. Methods: We collected tissues of artery (n = 9), cardiomyopathy muscle (n = 9), heart muscle (noncardiomyopathy) (n = 6), adrenal gland (n = 9) and aldosterone-producing adenoma (APA) (n = 9). 5′-rapid amplification of cDNA ends (RACE) identified transcription start sites. Multiplex reverse-transcription PCR (RT-PCR) determined use of alternative noncoding exons 1 (ANEs). Results: In adrenocortical H295R cells, angiotensin II, KCl or cAMP, all stimulated CYP11B2 transcription and NR4A was upregulated, whereas NR2F and NR5A1 were downregulated. 5′-RACE and RT-PCR revealed four ANEs of NGFIB (NR4A1), three of NURR1 (NR4A2), two of NOR1 (NR4A3) and two of SF1 (NR5A1) in cardiovascular and adrenal tissues. Quantitative multiplex RT-PCR showed NR4A and NR5A1 differentially employed multiple ANEs in a tissue-specific manner. The use of ANEs of NGFIB and NURR1 was significantly different between APA and artery. Changes in use of ANEs of NGFIB and NOR1 were observed between cardiomyopathy and noncardiomyopathy. The NR4A mRNA levels in artery were high compared with cardiac and adrenal tissues, whereas the NR5A1 mRNA level in adrenal tissues was extremely high compared with cardiovascular tissues. Conclusion: NR4A and NR5A1 genes are complex in terms of alternative promoter use. The use of ANEs may be associated with the pathophysiology of the heart and adrenal gland. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

ステント摘出デバイスの開発と臨床応用

金沢大学医薬保健研究域医学系血管内治療におけるステントの使用は増加の一途であり、外科的治療と比較して入院期間の短縮など医療費軽減に寄与してきた。しかし、不適切に留置されたステントを放置することで、新たな合併症をきたす可能性が高い。今回、ステント摘出デバイスを開発し、その実用性と安全性を大型動物モデルを用いた動物実験で検証した。 当初開発したデバイスは、標的ステントまでの持込みが困難で、またステント把持力も弱かった。デバイスの改良と実験を繰返し、ステント留置直後のステントの摘出に成功した。留置後時間が経過したステントの摘出については検討できていないが、本研究では留置直後のステントは安全に摘出できる事を明らかにした。Vascular stents have become the most common procedure to gain the luminal area and to reduce the rate of restenosis in atherosclerotic arteries. However, in case of instent thrombosis and blood-flow restriction, resulting from inappropriately stent deployment or misplacement, these stents should be retrieved. Under these conditions, we have developed a novel device that could firmly grasp a stent for removal. Because the shaft of first prototype device was still 1.8 mm in diameter, the device could not be advanced into a small and tortuous artery. The aim of this study was to investigate the feasibility of this improved device with porcine coronary arteries. The forceps could catch and remove expanded stents in porcine coronary arteries without vessel damage confirmed by intravascular ultrasound. These results demonstrate that the present device can be feasible and safety for transluminal removal of foreign bodies even in small and tortuous coronary arteries in acute phase.研究課題/領域番号:25350563, 研究期間(年度):2013-04-01 – 2016-03-3