Influence of Obstructive Sleep Apnea on Diastolic Heart Failure

Heart failure is frequently complicated by obstructive sleep apnea, which raises blood pressure and arrhythmiaand worsens prognosis. However, the incidence and influence of obstructive sleep apnea in patientswith diastolic heart failure is unknown. We hypothesized that patients with diastolic heart failurecomplicated by obstructive sleep apnea may have a worse outcome compared to those without obstructivesleep apnea. The study included 49 patients with an ejection fraction ≥ 50 %, of whom 34 had diastolic heartfailure and 15 did not have diastolic heart failure. The patients were examined in a sleep study and byechocardiography. Brain natriuretic peptide (BNP) levels were determined at admission and 1, 6 and 12months thereafter. The prevalence of obstructive sleep apnea in patients with diastolic heart failure( 18/34,53 %) was significantly higher than that in those without diastolic heart failure (3/15, 20 %)(p=0.032).BNP levels were high at admission in patients with diastolic heart failure, but then decreased gradually inthose without obstructive sleep apnea. However, BNP in patients with diastolic heart failure and obstructivesleep apnea remained high and was significantly elevated compared to the level in patients without obstructivesleep apnea at 6 and 12 months after admission. Patients with diastolic heart failure and obstructivesleep apnea showed prolongation of elevated BNP, indicating that complication of diastolic heart failure byobstructive sleep apnea may aggravate cardiac function

Hemodynamic Effects of Positive end-expiratory Pressure on Right Ventricular Diastolic Function in Patients with Acute Myocardial Infarction

The effects of positive end-expiratory pressure (PEEP) on the right ventricular (RV) diastolic function in patients with congestive heart failure (CHF) due to acute myocardial infarction (AMI) are unknown. The aim in this study was to investigate PEEP associated variations in RV diastolic function in CHF due to AMI. The subjects comprised the control group (26 subjects) and the AMI group (36 subjects) classified as 20 patients with pulmonary capillary wedge pressure (PCWP) < 18 mmHg (CHF-low PCWP group) and 16 patients with PCWP≧18mmHg (CHF-high PCWP group). PEEP was applied for 30 minutes at 0, 5, 10 and 15 cmH_20. Two-dimensional echocardiography with continuous and pulse wave Doppler studies was performed. RV diastolic functional parameters included the ratio of peak early tricuspid valve filling and peak atrial filling velocities, the decelation time of the tricuspid E valve and the RV isovolumic relaxation time. In the control and CHF-low PCWP groups, right atrial pressure, mean pulmonary arterial pressure (mPAP), total pulmonary resistance (TPR) and systemic vascular resistance (SVR) increased, output (CO) decreased and RV diastolic functional parameters worsened significantly at the transition from 10 to 15 cmH_20 PEEP. In the CHF-high PCWP group, mPAP, TPR and SVR decreased, while CO increased and RV diastolic functional parameters improved significantly at the transition from 10 to 15 cmH_20 PEEP. From these findings, it is clear that PEEP induced hemodynamic deterioration and reduces RV diastolic function in intact and mildly failing hearts. On the other hand, in severely failing hearts, PEEP effers hemodynamic improvement and ameliorates RV diastolic function. It appears possible to predict responses to PEEP by determining RV diastolic function in CHF. Therefore, we conclude that evaluation of the RV diastolic function during PEEP is highly important in terms of recognizing the effectiveness of PEEP therapy in CHF

Effects of Norepinephrine on Left Ventricular Hemodynamics and Myocardial Blood Flow in Rats with and without Calcium Overload

Heart failure patients have been shown to have an increased blood norepinephrine concentration, and patients with a high norepinephrine concentration have a poor prognosis. Norepinephrine is a catecholamine with α_1 and β_1 effects, which lead to a vasoconstrictive action and enhancement of myocardial contraction. However, the consequences of norepinephrine-induced changes in myocardial blood flow in heart failure patients remain unknown. In this study, the influence of norepinephrine on hemodynamics and blood flow in the left ventricular myocardium was investigated using rats with and without a calcium load. Norepineph-rine without a calcium load induced a 29.3% reduction of myocardial blood flow (MBF), but had no significant effect on ejection fraction (EF) and left ventricular end-diastolic pressure (LVEDP). With simultaneous calcium administration, norepinephrine induced a 33.2% reduction of MBF and increased LVEDP significantly, but caused no reduction in EF. These results suggest that norepinephrine decreases MBF but has no effects on systolic function, and increases LVEDP and decreases MBF more markedly in combination with calcium

A Novel Cardioprotective Drug, K201 (JTV519), Induces Prolongation of QT and QTc Intervals, but not Torsades de Pointes

K201 (JTV-519; 4-[-3{1-(4-benzyl) piperidinyl} propionyl]-7-methoxy-2, 3, 4, 5-tetrahydro-1, 4-ben-zothiazepine), is a multi-channel blocker and a ryanodine receptor stabilizer that exhibits strong cardiopro-tective and antiarrhythmic effects. In this study, we examined how intravenous infusion of K201 without an α-agonist prolongs the QT interval in chloralose-anaesthetized rabbits, and whether the maximum dose of K201 given concomitantly induces torsades de pointes. The QT interval was significantly prolonged in the group receiving 6-hour infusion of K201 at 20 μg/kg/min, but the QTc interval was not prolonged (n=5). With infusion of K201 at 0 (vehicle; n=5), 40 (n=6), 100 (n=6), 200 (n=6) and 400 μg/kg/min (n=5), blood pressure and HR were decreased, and prolongation of PQ, QRS complex, QT and QTc intervals occurred dose-dependently. The QTc interval was significantly prolonged from 211.5±11.9 ms of the baseline to 319.9±31.1 ms at a concentration of 400 μg/kg/min, which is the maximum dose of K201, but tors-ades de pointes was not induced at this dose. These results show that K201, which has a suppressive effect on Ca^ leakage from the sarcoplasmic reticulum and an α_1-adrenoceptor-blocking effect, does not induce torsades de pointes, although it causes prolongation of the QT interval

マンセイ シンフゼン カンジャ ノ ジュウショウド ニヨル ヤカン ムコキュウ ト テイサンソ ケッショウ ノ ヒカク

慢性心不全(CHF)患者の重症度による夜間の酸素飽和度(SaO_2)と無呼吸の比較について検討を行うために安定した慢性軽症心不全患者6例(男4例,女2例63±5.2歳,左室駆出率:49.8±3.4%,NYHA class:IかII,mild-CHF群)と安定慢性重症心不全患者11例(男9例,女2例,62±11.9歳,左室駆出率:25.6±8.6%,NYHA class:III,severe-CHF群)患者を対象とし,両群を比較することにより検討を行った.全例において室内空気下にパルスオキシメーターを用いて24時間のSaO_2と脈拍数を連続記録した.そして夜間のSaO_2が3%あるいは4%以上低下した1時間あたりの回数(3%ODI,4%ODI),SaO_2の最低値を各々分析した.さらにポリソムノグラフィーを用いてSaO_2と睡眠に関する全てのデータを連続的に記録分析した.その結果,severe-CHF群のODIはmild-CHF群に比して有意に高値であった(4%ODI;5.8±5.1 vs 0.6±0.5,p<O.01.3%ODI;8.6±7.1 vs 1.0±O.9,p<0.01.).severe-CHF群のSaO_2の最低値はmild-CHF群に比して有意に低かった(82.2±7.1 vs 91.7±1.0%,p<0.01).severe-CHF群の夜間無呼吸は全例にみられ,大多数が中枢型であった(74.0±3.6%).以上より安定した重症心不全では夜間に低酸素血症と無呼吸がみられ,これらが臨床病像の悪化に影響していることが示唆される.Background : Patients with chronic heart failure (CHF) commonly experience Cheyne- Stokes respiration, central apnea, or obstructive apnea during sleep associated with oxygen desaturation. Nocturnal oxygen therapy and nasal continuous positive airway pressure (NCPAP) reduce sleep-disordered breathing in stable CHF. However, the relation between sleep apnea and nocturnal desaturation inpatients with severe, stable CHF in Japan is unknown. Objectives : To examine nocturnal oxygen saturation (SaO_2) and sleep apnea in Japanese patients with severe, stable CHF. Methods : The subjects were 11 patients with severe, stable CHF (9 men and 2 women, LVEF=25.6±8.6%, NYHA class=III, severe CHF group) and 6 with mild, stable CHF (4 men and 2 women, LVEF=49.8±3.4 %, NYHA class=I or II, mild CHF group). SaO_2 was continuously recorded with a pulse oximeter under room air, and 4 % and 3 % SaO_2 dip rate per hour (GDIs) and the SaO_2 nadir were analyzed. In addition, SaO_2 and sleep variables were continuously recorded with a polysomnograph. Results : ODI frequency in the severe CHF group was significantly higher than that in the mild CHF group (4% ODI, 5.8±5.1 vs 0.6±0.5 times/hour, respectively, p<0.01;3 % ODI, 8.6±7.1 vs 1.0±0.9 times/hour, respectively, p<0.01.). SaO_2 nadir in the severe CHF group was significantly lower than that in the mild CHF group (82.2±7.1 vs 91.7±1.0 %, p<0.01). All severe patients had sleep apnea, predominantly of the central type (74.0±3.6%). Conclusion : The frequency of nocturnal hypoxemia and apnea increases in patients with severe, stable CHF. Nocturnal hypoxemia and apnea may adversely effect the clinical status of these patients

ラット ニオケル カルシウム フカカ ノ ノルエピネフリン ニヨル キュウセイ サシツ カクチョウ ショウガイ : サシツ ケッコウ ドウタイ ナラビニ シンゾウ チョウオンパホウ ニヨル ケントウ

拡張不全は左室収縮の低下を伴わない心不全で,左室収縮の低下による収縮不全とは病態,基礎疾患,予後が異なることが明らかにされつつある.しかし,その発生メカニズムについては十分に解明されていない.本研究では雄性ラット42匹を用い,対照群,塩化カルシウム投与群,ノルエピネフリン投与群,塩化カルシウム投与後,塩化カルシウム+ノルエピネフリン投与群において,左室血行動態,左室拡張障害について検討をおこなった.4群でチップ付き圧カテーテルを左室内へ挿入し,また別の4群で心臓超音波法により左室駆出率を測定した.さらに別に拡張早期急速流人期血流速波形(E波),拡張後期流人速波形(A波),E波減速時間(DCT),組織ドプラ法で拡張早期僧帽弁輪速度(Ea波)を測定した.その結果,塩化カルシウム群,ノルエピネフリン群では左室拡張末期圧は変化を認めなかったが,塩化カルシウム+ノルエピネフリン投与群で左室拡張末期圧は著しい上昇を認めた.また,塩化カルシウム+ノルエピネフリン群では左室駆出率は対照群と有意差を認めなかったが,E波,DCT,Ea波は対照群に比し有意な減少を認めた.以上より,塩化カルシウム負荷下でのノルエピネフリン投与で急激な心臓拡張障害が惹起され,心臓の拡張障害の発生にノルエピネフリンが関与している可能性が示唆された.In diastolic dysfunction, cardiac cells in the diastolic phase do not rapidly or completely return to the normal state of relaxation. However, the detailed mechanism remains unknown. To develop an acute diastolic dysfunction model in the rat, norepinephrine (30μg/kg/min) with calcium (12mg/kg/min) was administered for 20 minutes, following 20-minute administration of calcium, compared with the control group. A cardiovascular mikro-tip pressure transducer catheter was inserted into the left ventricle, and the intraventricular pressure and left ventricular end-diastolic pressure were determined. Early diastolic mitral annular velocity (Ea), E and A waves, deceleration time (DCT) and left ventricular ejection fraction were estimated using tissue Doppler imaging and echocardiography. In the norepinephrine with calcium group, no significant change in left ventricular pressure was found, but left ventricular end-diastolic pressure was markedly increased. On echocardiography, no change was found in left ventricular ejection fraction, but the E wave, DCT and Ea wave were decreased, in comparison with the control, calcium alone and norepinephrine alone groups. The results of this study could indicate that norepinephrine administration with calcium causes acute diastolic dysfunction in the rat