Brain Angiotensin II Type 1 Receptor Blockade Improves Dairy Blood Pressure Variability via Sympathoinhibition in Hypertensive Rats

Abnormal blood pressure (BP) elevation in early morning is known to cause cardiovascular events. Previous studies have suggested that one of the reasons in abnormal dairy BP variability is sympathoexcitation. We have demonstrated that brain angiotensin II type 1 receptor (AT1R) causes sympathoexcitation. The aim of the present study was to investigate whether central AT1R blockade attenuates the excess BP elevation in rest-to-active phase in hypertensive rats or not. Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with intracerebroventricular infusion (ICV) of AT1R receptor blocker (ARB), oral administration of hydralazine (HYD), or ICV of vehicle (VEH). Telemetric averaged mean BP (MBP) was measured at early morning (EM), after morning (AM), and night (NT). At EM, MBP was significantly lower in ARB to a greater extent than in HYD compared to VEH, though MBP at AM was the same in ARB and HYD. At NT, MBP was also significantly lower in ARB than in HYD. These results in MBP were compatible to those in sympathoexcitation and suggest that central AT1R blockade attenuates excess BP elevation in early active phase and continuous BP elevation during rest phase independent of depressor response in hypertensive rats

Influence of primary and secondary prevention indications on anxiety about the implantable cardioverter-defibrillator

AbstractBackgroundImplantable cardioverter-defibrillators (ICDs) have been established for primary and secondary prevention of fatal arrhythmias. However, little is known about the influence of ICD indications on quality of life (QOL) and psychological disturbances. This study aimed to examine whether there were differences in QOL and psychological distress in patients that have an ICD for primary or secondary prevention of fatal arrhythmias.MethodsA multicenter survey of 179 consecutive outpatients (29.1% primary prevention) with ICD implantations completed the Short Form-8 (SF-8), Beck Depression Inventory (BDI), Impact of Event Scale-Revised (IES-R), State-Trait Anxiety Inventory (STAI), and Worries about ICD (WAICD).ResultsPatients with an ICD for primary prevention had a higher trait anxiety score and worries about ICD score than patients with an ICD for secondary prevention (41.7±12.4 vs. 34.7±12.3, p=0.001 and 39.6±18.0 vs. 30.0±18.9, p=0.002, respectively), even after adjusting for demographic and clinical characteristics. In multivariable analysis of variance, primary prevention ICD recipients reported a poorer QOL on the vitality subscale of the SF-8.ConclusionsIn our study population, which mostly consisted of New York Heart Association (NYHA) class I and II subjects, primary prevention ICD recipients were more prone to experience worries about their ICD, anxiety, and a poorer QOL compared to secondary prevention ICD recipients. In clinical practice, primary prevention ICD patients should be closely monitored. If warranted, they should be offered psychological intervention, as anxiety and low QOL were predictors of mortality

The Overexpression of Twinkle Helicase Ameliorates the Progression of Cardiac Fibrosis and Heart Failure in Pressure Overload Model in Mice

Peer reviewe

Overexpression of TFAM or Twinkle Increases mtDNA Copy Number and Facilitates Cardioprotection Associated with Limited Mitochondrial Oxidative Stress

Background Mitochondrial DNA (mtDNA) copy number decreases in animal and human heart failure (HF), yet its role in cardiomyocytes remains to be elucidated. Thus, we investigated the cardioprotective function of increased mtDNA copy number resulting from the overexpression of human transcription factor A of mitochondria (TFAM) or Twinkle helicase in volume overload (VO)-induced HF. Methods and Results Two strains of transgenic (TG) mice, one overexpressing TFAM and the other overexpressing Twinkle helicase, exhibit an approximately 2-fold equivalent increase in mtDNA copy number in heart. These TG mice display similar attenuations in eccentric hypertrophy and improved cardiac function compared to wild-type (WT) mice without any deterioration of mitochondrial enzymatic activities in response to VO, which was accompanied by a reduction in matrix-metalloproteinase (MMP) activity and reactive oxygen species after 8 weeks of VO. Moreover, acute VO-induced MMP-2 and MMP-9 upregulation was also suppressed at 24 h in both TG mice. In isolated rat cardiomyocytes, mitochondrial reactive oxygen species (mitoROS) upregulated MMP-2 and MMP-9 expression, and human TFAM (hTFAM) overexpression suppressed mitoROS and their upregulation. Additionally, mitoROS were equally suppressed in H9c2 rat cardiomyoblasts that overexpress hTFAM or rat Twinkle, both of which exhibit increased mtDNA copy number. Furthermore, mitoROS and mitochondrial protein oxidation from both TG mice were suppressed compared to WT mice. Conclusions The overexpression of TFAM or Twinkle results in increased mtDNA copy number and facilitates cardioprotection associated with limited mitochondrial oxidative stress. Our findings suggest that increasing mtDNA copy number could be a useful therapeutic strategy to target mitoROS in HF.Peer reviewe

Bionic Cardiology : A New Therapeutic Modality for Cardiology in the 21st Century

近年の医学の進歩はめざましく,従来は難治と思われた幾多の疾患が救われるようになってきた.このような医学の進歩は2つの要因に支えられている.一つは遺伝子関連の科学に支えられた分子生物学である.分子生物学の進歩により,特定の疾患に関しては原因遺伝子が突き止められ,その遺伝子情報を元に治療薬剤の開発が可能になってきた.もう一つの要因はコンピュータ,ITに象徴されるハイテクである.当初はレントゲンや心電計などの極めて単純な医療技術しか存在しなかったが,その後の進歩は目覚ましく,昨今の医療はこれらの医療機器の存在を除外しては考えられない状態になっている.しかしながら医療機器は,極端なまでに診断装置としての応用に止まっている.近年のマイクロプロセッサに象徴されるハードウエアの高機能化やナノ化,さらに情報や信号処理の論理の発展により,これらのハイテクを難治性疾患の治療に応用するバイオニック医学の可能性が開けてきた.バイオは命,遺伝子など生物系を表し,ニックは電子,工学,IT等ハイテクを象徴している.バイオニック医学は生命科学と先端工学を融合させることにより,従来の医学体系では治療が困難であった疾患の治療を目指す全く新たな医療体系であ