Effectiveness of a portable device and the need for treatment of mild-to-moderate obstructive sleep-disordered breathing in patients with cardiovascular disease

SummaryBackground and purposeIn Japan, there are two sleep-disordered breathing (SDB)-related problems, which include diagnosing SDB using a portable device (PD) and treating mild-to-moderate SDB (mm-SDB) using continuous positive airway pressure (CPAP) for severe SDB (s-SDB) in obstructive sleep apnea (OSA) patients. Our aims were to evaluate the effectiveness of a PD in diagnosing SDB in patients with cardiovascular disease (CVD), and to assess the difference between mm-SDB [apnea-hypopnea index (AHI): 20–40h−1] and s-SDB (AHI: >40h−1) using brain natriuretic peptide (BNP) in OSA patients.Methods and subjectsAfter their underlying CVD was treated, full-night sleep studies using polysomnography (PSG) and PD were performed on the same day.ResultsEighty-three patients underwent full-night PSG simultaneously with PD. The average duration of the sleep study was 8.6±6.2 days. There was a tendency for a higher AHI value obtained with PSG (PSG, 28.9±24.3h−1; PD, 22.3±16.7h−1; p=0.05). However, the specificity and sensitivity of diagnosing SDB using PD were 86% and 81%, respectively. Using PD, twenty-nine OSA patients had mm-SDB and eleven patients had s-SDB. The BNP value was higher in the mm-SDB patients (318±550pg/ml) than in the s-SDB patients (202±160pg/ml).ConclusionsThe PD was effective in diagnosing SDB in patients with CVD. The BNP value was higher in the mm-SDB patients. Therefore, they need to be treated with CPAP to treat underlying CVD

Blunted Expression of PPARa in Mice with FABP-4 and -5 Deficiency under Acute Cold Exposure

Brown Adipose Tissue (BAT) is a nonshivering thermogenesis organ during cold exposure. Peroxisomal proliferator activated receptor alpha (PPARa) is the member of the nuclear hormone receptor superfamily and primarily expressed in BAT and liver. PPARa is coordinated with uncoupling protein 1 (UCP1) to regulate fatty acid metabolism in BAT. Fatty acid binding protein (FABP)-4 and-5 play role in adaptive response under fasting and cold exposure. The purpose of this study was to investigate the expression of PPARa in mice with FABP4/5 deficiency (DKO). Wildtype (WT) and DKO mice were exposed to cold for 2 hours under fed or 20 hours-fasted conditions. BAT was collected and further mRNA level of PPARa was examined using quantitative real-time PCR. As the result, PPARa gene expression in WT mice were increased 50% and 100% in fed and fasted condition respectively after cold exposure. There was no alteration in PPARa expression in  BAT of DKO mice. As conclusion, The functional FABP-4 and -5 are necessary to modulate PPARa gene expression in Brown Adipose Tissue under acute cold exposure  Keywords: Acute cold exposure; FABP4; FABP5; Fasting  PPAR

Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension

Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-β receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1fl/fl mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1fl/fl mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-β signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening

Relationships between Cytokine Profiles and Signaling Pathways (IκB Kinase and p38 MAPK) in Parainfluenza Virus-Infected Lung Fibroblasts

Respiratory viruses such as parainfluenza virus (PIV) in individuals with certain genetic predispositions in early life are associated with the induction of wheezing, which can progress to the development of asthma. It has been suggested that aberrant production of various cytokines due to viral infection are associated with virus-induced asthma. However, the mechanisms of how respiratory viruses induce and exacerbate asthma have yet to be clarified. To examine cytokine responses to PIV infection, we assessed 27 cytokine levels released from PIV-infected human fetal lung fibroblasts. In addition, we examined relationships between these cytokine responses and signaling pathways (IκB kinase and p38 MAPK) in PIV-infected cells. At 24 h after infection, PIV-infected cells significantly released a number of cytokines, namely, proinflammatory cytokines [interleukins (IL)-1β, IL-6, and tumor necrosis factor-α], anti-inflammatory cytokine (IL-1ra), Th1 cytokines (interferon-γ, and IL-2), Th2 cytokines (IL-4, IL-5, and IL-10), granulopoiesis-inducing cytokines (granulocyte colony-stimulating factor and granulocyte–macrophage colony-stimulating factor), neutrophil recruitment-inducing cytokines (IL-8 and interferon-inducible protein-10), and eosinophil recruitment-inducing cytokines (eotaxin and regulated on activation normal T-cell expressed and secreted). PIV infection enhanced phosphorylation of both IκB and p38 MAPK, but not Akt, in the cells. Signaling pathway inhibitors, BMS-345541 (a specific IκB kinase inhibitor) and SB203580 (a specific p38 MAPK inhibitor), significantly suppressed release of these cytokines from PIV-infected cells. The results indicate that PIV infection induces aberrant production and release of various cytokines through IκB kinase and p38 MAPK pathways in human lung fibroblasts. Overproduction and imbalance of these cytokines may be partially associated with the pathophysiology of virus-induced asthma

The Upregulation of <i>Carnitine Palmitoyltransferase 1a</i> (<i>CPT1a</i>) Expression under Prolonged Fasting in CD36 Knockout Mice

Food deprivation is one of the extreme conditions that mammals have to survive. The majority of the tissues, excluding the brain and red blood cells, depend on the fatty acids (FA) utilization to produce energy. We recently showed in mice lacking for CD36 (CD36−/−), the uptake of FA is limited with dramatically increased of glucose uptake in heart and skeletal muscle in fasted condition, indicating a compensatory mechanism of organ to fulfill an energy demand. The liver is the central tissue maintaining metabolic homeostasis in fasted state. Synthesize adenosine triphosphate (ATP) in the mitochondria via beta-oxidation was mediated by carnitine palmitoyltransferase 1a (CPT1a). The objective of this research was to explore the role of CD36 in CPT1a expression in the fasted state. This research was conducted at Gunma University Japan in 2015. The method was in vivo-experimental, that we used CD36−/− and wild-type (WT) mice, as a control. The gene expression of CPT1a was measured by real-time PCR. Fasting condition up regulated mRNA expression of CPT1a in both WT and CD36−/− mice in 24 h and 48 h. However in CD36−/− mice, the mRNA expression of CPT1a in 24 h fasted state was lower very significantly than WT mice (p<0.01). We demonstrate that CD36 deficiency up regulate CPT1a gene expression, suggested that CD36 is essential for nutrient homeostasis when requirement for FA is increased and obtainability of nutrient is inadequate.   PENINGAKTAN EKSPRESI GEN CARNITINE PALMITOYLTRANSFERASE 1A (CPT1A) PADA CD36 KNOCKOUT MICE DALAM KEADAAN PUASA Kekurangan makanan adalah salah satu kondisi ekstrem yang harus dihindari oleh mamalia. Sebagian besar jaringan, kecuali otak dan sel darah merah sangat bergantung pada pemanfaatan langsung asam lemak untuk menghasilkan energi. Penelitian kami sebelumnya menunjukkan pada mencit dengan defisiensi CD36 (CD36−/−), serapan asam lemak terbatas karena peningkatan pengambilan glukosa hati dan otot rangka secara signifikan dalam kondisi puasa yang mengindikasikan mekanisme kompensasi organ untuk memenuhi kebutuhan energi. Hati adalah jaringan sentral yang menjaga homeostasis metabolik tubuh dalam keadaan berpuasa. Sintesis adenosine triphosphate (ATP) di mitokondria melalui beta-oksidasi dimediasi oleh carnitine palmitoyltransferase 1a (CPT1a). Tujuan penelitian ini mengetahui peran CD36 dalam ekspresi CPT1a dalam keadaan puasa. Penelitian ini dilakukan di Universitas Gunma Jepang pada tahun 2015. Metode penelitian ini adalah eksperimental in vivo dengan menggunakan mencit CD36−/− dan wild type (WT) sebagai kontrol. Ekspresi gen CPT1a diukur dengan real-time PCR. Puasa meningkatkan ekspresi mRNA CPT1a pada mencit WT dan CD36−/− baik setelah puasa selama 24 jam dan 48 jam. Namun, pada mencit CD36−/−, ekspresi mRNA CPT1a dalam keadaan setelah dipuasakan 24 jam lebih rendah daripada mencit WT (p<0,01). Penelitian ini menunjukkan bahwa defisiensi CD36 mengatur ekspresi gen CPT1a sehingga CD36 sangat diperlukan untuk homeostasis nutrisi ketika kebutuhan asam lemak meningkat dan kemungkinan ketersediaan nutrisi terbatas

Characteristics of systolic and diastolic potentials recorded in the left interventricular septum in verapamil-sensitive left ventricular tachycardia

We studied the electrophysiological characteristics of systolic (SP) and diastolic (DP) potentials recorded during sinus rhythm (SR) in the left interventricular septum of a 27 year-old woman presenting with verapamil-sensitive idiopathic left ventricular tachycardia (VT). During SR, and during VT, SP was activated from ventricular base-to-apex, and DP from apex-to-base. SP and DP were both detected at the site of successful ablation during SR, whereas during VT, DP was detected away from the earliest activation site. Thus, SP apparently reflected a critical component of the reentrant circuit, while DP reflected the activation of a bystander pathway

A case of a middle-aged patient with a ventricular septal defect complicated by severe pulmonary hypertension-stepwise surgical repair with pulmonary vasodilators-

We report a case of ventricular septal defect (VSD) in which we attempted to treat pulmonary arterial hypertension (PAH) with the goal of VSD closure in an adult with suspected Eisenmenger syndrome in childhood. Four years previously (age 41 years), she was referred to our department due to repeated hemoptysis requiring further treatment of PAH. We started combination therapy with several pulmonary vasodilators. Two years later, her pulmonary vascular resistance (PVR) was improved but still not at the level where VSD closure was possible. To control the increased PA flow resulting from intensive PAH treatment and to reduce the risk of hemoptysis, we performed pulmonary artery banding (PAB). As the risk of hemoptysis decreased, a prostacyclin analog was introduced, and the dose was increased. More than 1 year after PAB, active vasoactivity testing became positive, suggesting that the pulmonary vascular lesion was now “reversible”. We performed VSD closure and atrial septal defect creation even though her PVR was still high. After the operation, her exercise capacity was remarkably improved. We suggest that stepwise surgical repair with pulmonary vasodilators is an important treatment option for select patients with VSD with severe PAH.Learning objectiveAdvances in pulmonary arterial hypertension (PAH) treatment have led to the use of a “treat-and-repair” strategy to close the intracardiac shunt after PAH treatment in select patients with adult congenital heart disease. In our case, ventricular septal defect (VSD) closure was achieved with stepwise surgical repair and a combination of pulmonary vasodilators, even though long-standing severe PAH with persistent hemoptysis remained. Even after a long period of exposure to high blood flow, this strategy may reduce pulmonary vascular resistance and permit eventual closure of the VSD

Irregular atrial flutter following pulmonary vein isolation for persistent atrial fibrillation

AbstractA 65-year-old man with a history of refractory paroxysmal atrial fibrillation (AF) underwent catheter ablation for persistent AF lasting 2 months. AF was not terminated after complete isolation of the 4 pulmonary veins (PV). Instead, it was transformed to a sustained atrial tachyarrhythmia with beat-to-beat variability in the atrial cycle length. A 12-lead electrocardiogram during tachycardia showed negative flutter-like waves in the inferior leads. Entrainment pacing along the tricuspid annulus confirmed the diagnosis of irregular cavotricuspid isthmus (CTI)-dependent typical atrial flutter (AFL). Linear ablation of the CTI terminated AFL and restored sinus rhythm

Typical atrial flutter with atypical flutter wave morphology due to abnormal interatrial conduction

We report a case of typical counterclockwise atrial flutter (AFL) with conduction block from right to left atrium along the coronary sinus (CS) musculature, confirmed by discontinuous CS activation sequence during pacing near the ostium and differential right atrial pacing. AFL was associated with an atypical flutter wave morphology, due to the detour of the activation wavefront from right to left atrium via alternate interatrial electrical connections, such as Bachmann&#8217;s bundle, the interatrial septum, or both. (Cardiol J 2011; 18, 4: 450&#8211;453