Therapeutic Research

Background：QT dispersion is considered as a predictor of prognosis in patients with heart failure. Renin−angiotensin system is one of worsening factors to heart failure. Hypothesis：We designed a prospective study to determine whether combination therapy of an ACE inhibitor and an angiotensin I I receptor blocker, valsartan, more improves QT dispersion in patients with chronic heart failure（CHF）. Method：A tissue−selective ACE inhibitor（quinapril or trandolapril）or valsartan was administered to 26 patients with CHF for 3 months in a single−blind manner, and then to the ACE inhibitor group（n＝14）valsartan was concomitantly administered and to the valsartan group（n＝12）an ACE inhibitor was concomitantly administered. We performed echocardiography, Holter ECG, and measurements of endocrine hormones for both groups and compared the results. Results：A tissue−selective ACE inhibitor and valsartan significantly reduced QT dispersion by 41％ and 58％, respectively. Additive administration of valsartan to an ACE inhibitor significantly improved QT dispersion by 28％, whereas additive effect of an ACE inhibitor to valsartan exhibited no further improvement. Similar results were observed in Lown’s classification. Conclusion：The results demonstrated that adding valsartan to an ACE inhibitor was beneficial to improving QT dispersion and ventricular arrhythmia, whereas adding an ACE inhibitor to valsartan did not show any additive clinical benefit.

We examined the effects of combination therapy of an ACE inhibitor and angiotensin I I receptor blocker on hemodynamics and left ventricular mass（LVM）in patients with chronic heart failure. A tissue−selective ACE inhibitor（quinapril or trandolapril）or valsartan was administered to 26 patients demonstrating New York Heart Association（NYHA）classification I I moderate to I I I for 3 months in a single−blind manner. Valsartan was concomitantly administered to the primary ACE inhibitor group（n＝14）and to the primary valsartan group （n＝12）, ACE inhibitor was concomitantly administered for another 3 months. We performed echocardiography and measured endocrine hormones to compare the results. Left ventricular end−diastolic diameter（LVDd）significantly decreased from 59±8 to 53± 12 mm in the ACE inhibitor group and from 58±6 to 51±7 mm in the valsartan group while ejection fraction（EF）significantly increased from 30±7 to 48±13％ in the ACE inhibitor group and from 32±5 to 53±11％ in the valsartan group. Administration of valsartan on an ACE inhibitor significantly improved LVDd and EF by 11％ and 25％, respectively, whereas additive administration of an ACE inhibitor to valsartan showed no further improvement. Similar results were obtained for left ventricular mass index（LVMI）. Additional administration of valsartan to a tissue−selective ACE inhibitor could further improve cardiac function and reduce LVM, whereas additional administration of a tissue−selective ACE inhibitor to valsartan exhibited no similar effect.

目的：急性期市中病院におけるカンジダ血症の頻度と分離菌，感受性，予後を明らかにすること。患者および方法：高松病院（179 床）において，2003 年 6 月 1 日から 2006 年 2 月 28 日までに血液から真菌が検出された症例について臨床的・微生物学的データをレトロスペクティブに調査した。微生物学的検査は検査会社にて実施され，菌種同定は VITEK YBCsystem，API20CAUX または API32ID（ビオメリュー）を使用し，感受性検査は「ASTY」（極東製薬）を用いた。結果：329 例の菌血症・真菌血症例中，15 例（4.6％）がカンジダ血症であった。平均年齢79.5 歳，男性 8 名，女性 7 名であった。基礎疾患は悪性疾患（7 名），脳梗塞症（3 名），慢性腎不全（1 名），その他（4 名）であった。分離菌は Candida albicans（5 名），C. parapsilosis（5名），C. tropicalis（2 名），C. glabrata（2 名），non−identified Candida species（1 名）であった。中心静脈カテーテル（CVC）先端培養検査が実施された 12 例のうち 4 例（33.3％）は，血液と同一のカンジダ属が検出された。13 例（86.7％）は真菌性眼内炎に対する眼科的検査が実施されていなかった。カンジダ血症発症後，30 日以内にカンジダ血症が原因で死亡した症例が 9 例（60.0％）認められた。fluconazole の感受性結果は 11 例が感受性，残り 4 例が用量依存的感受性であった。結論：高齢者および CVC 留置症例においては，市中病院においてもカンジダ血症の可能性を常に考慮し，血液培養の実施，CVC 留置例における抜去および先端培養提出，そして十分量の抗真菌薬投与を行い，真菌性眼内炎に対する眼科的検査が必要であると考える。

安定期 COPD の管理薬として，長時間作用型吸入抗コリン薬や長時間作用型β2刺激薬の使用がガイドラインで推奨されている。今回，軽症 24 例，中等症 30 例計 54 例に対する臭化チオトロピウム水和物製剤（以下，チオトロピウム）およびツロブテロール貼付剤（以下，ツロブテロール）の肺機能および臨床効果を評価した。中等症症例においては，両剤ともに息切れ，ピークフロー値の有意な改善が認められた。肺機能に関しては，チオトロピウム（スピリーバ）使用群において有意な改善を示したが，ツロブテロール（ホクナリンテープ）使用群においては有意な改善は認められなかった。軽症症例においては，チオトロピウム使用群で肺機能，息切れ，ピークフロー値の有意な改善がみられたが，ツロブテロール使用群においては有意な変化は認められなかった。チオトロピウムはツロブテロールに比較し，肺機能および臨床症状に対し高い効果を示した。チオトロピウムは軽症から COPD 治療の第一選択薬として使用を考慮できると考えられた。

Electrophysiological effects of flecainide acetate, a potent class Ic antiarrhythmic agent,on spontaneous action potentials and membrane currents were studied using small preparation（s 0.2×0.2×0.1 mm）of rabbit sinoatria（l SA）node. Flecainide（1, 3, 10μM）progressively decreased maximal diastolic potential, rate of diastolic depolarization and maximal rate of depolarization, and prolonged action potential duration and diastolic interval in a concentration− dependent manner. At 10μM, the spontaneous activity ceased in 3 of the 6 preparations. In voltage clamp experiments using double microelectrode techniques, 10μM flecainide reduced the L−type Ca2＋ current（ICa,L）obtained on step depolarization from −40 to 0mV by 25±6％（p＜0.05, n＝5）, the delayed rectifying K＋ current （IK）tail obtained on repolarization from ＋10 to −60mV by 50±7％（p＜0.05, n＝4）, and the hyperpolarization− activated inward current（Ih）at −90mV by 9±1％（p＜0.05, n＝4）, respectively. The steady−state inactivation curve for ICa,L was shifted toward more negative potentials by 3.7± 0.5mV（p＜0.05, n＝4）without causing a significant change in the slope factor by 10μM flecainide. 10μM flecainide caused a marked use− or frequency−dependent block of ICa,L in a frequency−dependent manner. Recovery of ICa,L from inactivation was retarded（time constant＝1536±299ms）at a holding potential of −40mV in the presence of 10μM flecainide（n＝5）. The steady−state activation curve for IK was shifted toward more negative potentials by 5.0±1.6mV（p＜0.05, n＝4）without causing a significant change in the slope factor by 10μM flecainide. These results suggest that （1）flecainide exerts a negative chronotropic action by decreasing ICa,L, IK and Ih in rabbit SA node（, 2）the drug has a higher affinity both to the inactivated state of the L−type Ca2＋ channel and to the activated state of the delayed rectifying K＋ channel than to the resting state of these channels, and（3）recovery Therapeutic Research vol. 28 no. 11 2007 2267 Key words：Flecainide, Class Ic antiarrhythmic agent, Action potential, Ionic currents, Sinoatrial node Correspondence：Tomoaki Saeki. Department of Cardio−Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho−cho, Mizuho−ku, Nagoya, 467−8601, Japan, Fax 052−852−3796 Original Paper Electrophysiological Effects of Flecainide Acetate on the Spontaneous Action Potentials and Membrane Currents in Isolated Rabbit Sinoatrial Node Tomoaki Saeki Nobuyuki Ohte Genjiro Kimura Department of Cardio−Renal Medicine and Hypertension,Nagoya City University Graduate School of Medical Sciences kinetics of flecainide from L−type Ca2＋ channel inactivation was slow and therefore the drug showed a marked use− or frequency−dependent block of ICa,L.