缺血性与非缺血性心肌病左心室延迟收缩的比较研究

摘要：目的应用组织多普勒探讨左心室延迟收缩模型是否与缺血病因相关。方法选择74例正常人，年龄（40±14）岁，66％男性；48例非缺血性心肌病患者，年龄（55±12）岁，63％男性，ORS宽度（148±35）ms，52％完全性左束支传导阻滞，左心室射血分数（LVEF）29％±10％；43例缺血性心肌病患者，年龄（58±12）岁。64％男性，QRS宽度（151±28）ms，44％完全性左束支传导阻滞,LVEF 31％±13％。分别进行组织多普勒检查。测量12个左心室节段中QaS起始到收缩速度峰值的时间间期（Ts），计算其标准差（Ts—SD）为心室内失同步参数,并计算各节段间Ts的差值。结果正常组、非缺血性心肌病组和缺血性心肌病组的Ts—SD分别为（22．7±10．5）ms、（45．3±15．6）ms和（45．5±17．0）ms。正常组下壁和后壁的Ts显著长于侧壁和前壁[（154．0±34．2）ms、（151．1±32．3）ms比（129．6±29．0）ms，（124．9±24．9）ms；P〈0．05]。在非缺血性心肌病和缺血性心肌病组中,各节段的Ts均较正常组延长（P〈0．05）。在非缺血性心肌病组．下壁的Ts最长，前壁的Ts最短。收缩最延迟位于左心室下壁、后壁、侧壁和其他室壁的比例分别为42％、26％、16％、16％。在缺血性心肌病组，收缩最延迟位于左心室下壁、后壁、侧壁和其他室壁的比例分别为13％、31％、25％、31％。两组的构成比差异存在统计学意义（P〈0．05）。结论缺血性心肌病组和非缺血性心肌病组的左心室延迟收缩部位不同。     

起搏QRS波时限与左心结构和功能的关系

目的探讨长期右室心尖起搏患者的起搏QRS时限与左心结构、左心室收缩功能及心室间不同步的关系。方法长期右室心尖部起搏患者共105例,通过常规体表心电图测得起搏QRS（pQRS）时限,运用常规心脏超声心动图检测主动脉根部内径（AO）、左房内径（LAD）、收缩末期左心室内径（LVDs）、舒张末期左心室内径（LVDd）、室间隔厚度（IVST）、左室后壁厚度（LVPWT）及左室射血分数（LVEF）,分析pQRS时限与以上各心超指标的关系。结果 pQRS时限与LVDd、LVDs及IVST呈正相关（r分别为0.334、0.385和0.289,前两者P〈0.01,后者P〈0.05）,与LVEF负相关（r=-0.312,P〈0.05）;pQRS时限与LAD的相关性更显著（r=0.595,P〈0.01）。以pQRS时限≥180ms诊断左房扩大时,敏感度和特异度分别为86.49%和67.74%。结论对于长期右室心尖部起搏的患者,pQRS时限与左心大小及左心室收缩功能相关;pQRS时限延长（≥180ms）,提示左心房扩大。     

Ulnar and tibial bending stiffness as an index of bone strength in synchronized swimmers and gymnasts

The purpose of this study is to compare a mechanical property of bone in world-class female athletes with different loading histories. Bone bending stiffness or EI (E is the modulus of elasticity and I, the moment of inertia) was measured noninvasively with the mechanical response tissue analyzer, that analyzes the response of bone to a vibratory stimulus. We evaluated the ulna, ulnar width, wrist density and tibia in 13 synchronized swimmers (SYN), eight gymnasts (GYM) and 16 untrained women (UNT) of similar age. Muscle strength in the flexors and extensors at elbows and knees was measured in the athletes. SYN were taller than GYM or UNT (168±0.7 vs. 152±1.1 or 157±1.2 cm, P< 0.01). Ulnar EI, Nm², was similar in SYN and GYM (41±5.4 vs. 42±4.2, NS) and 50% higher than in UNT (27±2.1, P<0.05). Ulnar EI, Nm² was related to ulnar width (r=0.497, P<0.002, n=37) but not to wrist density. Tibial EI, Nm², in SYN and GYM (270±42 vs. 285±49, NS) was similar and more than twice as high as in UNT (119±6; p<0.05). Knee flexor strength measured at 60° s^–1 and elbow extensor strength at 200° s^–1 correlated with tibial EI (r=0.44 and 0.41, P<0.05). In spite of different loading histories, the tibiae and ulnas of world-class athletes showed similar high values for bending stiffness that exceeded values in untrained women. EI in the ulna could be related to bone width and in the tibia, to muscle strength.     

Doppler echocardiographic analysis of diastolic left ventricular function in dialysis patients and its relation to intradialytic hypotension

Summary Doppler echocardiography was used to evaluate left ventricular relaxation and filling in 20 patients on chronic maintenance hemodialysis. In comparison with 11 normal controls hemodialysed patients showed a marked prolongation of isovolumic relaxation period (83±23 ms vs 67±11 ms,P<0.01). Peak velocity of early diastolic filling was similar in both groups, but peak velocity of late ventricular filling due to atrial contraction was substantially increased in dialysis patients (66±23 cm/s vs 37±7 cm/s,P<0.01) and the ratio late to early peak velocity was significantly enlarged (0.97±0.35 vs 0.58±0.19,P<0.01). Although left ventricular mass index, as determined by Echo, was markedly increased in dialysis patients, no significant correlation was found between ventricular mass and indexes of diastolic function. When patients were divided into two groups on the basis of development of hypotension during dialysis clinical and echocardiographic characteristics were similar, although patients with dialysis hypotension (n=9) were significantly older (53±9 years) than normotensiv patients (n=11, 42±14 years,P<0.05). Indexes of diastolic function showed a great overlap between the two groups, but ratio late to early peak velocity was significantly greater in patients with intradialytic hypotension (1.13±0.35 vs 0.83±0.32,P<0.05). It is concluded that dialysis patients exhibit significant alterations of left ventricular relaxation and diastolic filling as assessed by Doppler echocardiography which might be independent of left ventricular hypertrophy. Impaired diastolic function might contribute to intradialytic hypotension.Abbreviations DEF deceleration of early diastolic flow - IVRP isovolumic relaxation period - peakA peak velocity of late left ventricular filling - peakE peak velocity of early left ventricular filling     

Improved relationship between left and right ventricular electrical activation after cardiac resynchronization therapy in heart failure patients can be quantified by body surface potential mapping

OBJECTIVES:

Few studies have evaluated cardiac electrical activation dynamics after cardiac resynchronization therapy. Although this procedure reduces morbidity and mortality in heart failure patients, many approaches attempting to identify the responders have shown that 30% of patients do not attain clinical or functional improvement. This study sought to quantify and characterize the effect of resynchronization therapy on the ventricular electrical activation of patients using body surface potential mapping, a noninvasive tool.

METHODS:

This retrospective study included 91 resynchronization patients with a mean age of 61 years, left ventricle ejection fraction of 28%, mean QRS duration of 182 ms, and functional class III/IV (78%/22%); the patients underwent 87-lead body surface mapping with the resynchronization device on and off. Thirty-six patients were excluded. Body surface isochronal maps produced 87 maximal/mean global ventricular activation times with three regions identified. The regional activation times for right and left ventricles and their inter-regional right-to-left ventricle gradients were calculated from these results and analyzed. The Mann-Whitney U-test and Kruskall-Wallis test were used for comparisons, with the level of significance set at p≤0.05.

RESULTS:

During intrinsic rhythms, regional ventricular activation times were significantly different (54.5 ms vs. 95.9 ms in the right and left ventricle regions, respectively). Regarding cardiac resynchronization, the maximal global value was significantly reduced (138 ms to 131 ms), and a downward variation of 19.4% in regional-left and an upward variation of 44.8% in regional-right ventricular activation times resulted in a significantly reduced inter-regional gradient (43.8 ms to 17 ms).

CONCLUSIONS:

Body surface potential mapping in resynchronization patients yielded electrical ventricular activation times for two cardiac regions with significantly decreased global and regional-left values but significantly increased regional-right values, thus showing an attenuated inter-regional gradient after the cardiac resynchronization therapy.     

Echocardiographic assessment of right ventricular function in responders and non-responders to cardiac resynchronization therapy

Introduction

The aim of this study was to determine whether baseline right ventricular (RV) function assessed by standard echocardiography may indicate patients who will respond to cardiac resynchronization therapy (CRT).

Material and methods

The data of 57 patients (54 men, 95%), aged 66.4 ±8.7 years with heart failure (HF) having a CRT device implanted were collected. All patients had left ventricular ejection fraction (LVEF) ≤ 35% and QRS complex duration ≥ 120 ms. Echocardiographic examination with tissue Doppler imaging techniques and complex RV evaluation were performed at baseline and three months after CRT onset.

Results

Three months after CRT implantation, patients responding to CRT, defined as a reduction of left ventricle end-systolic volume (LVESV) of at least 10% (n = 34), compared to patients with a reduction of LVESV of less than 10% (n = 23), had at baseline a smaller right atrium diameter (47.85 ±11.33 mm vs. 52.65 ±8.69 mm; p = 0.028), higher TAPSE (14.56 ±2.57 mm vs. 13.04 ±2.93 mm; p = 0.030) and lower grade of tricuspid valve regurgitation (1.82 ±0.97 vs. 2.3 ±0.88; p = 0.033).

Conclusions

This study showed that there are differences in baseline right ventricular function between responders and non-responders to CRT. Yet in our study, none of the baseline RV parameters provided any value in identifying patients who would respond to CRT.     

Evaluation of left ventricular dyssynchrony using combined pulsed wave and tissue Doppler imaging

Introduction

The combination of pulsed wave (PW) and tissue Doppler imaging (TDI) has been proposed as a new method to assess left ventricular (LV) mechanical dyssynchrony (LVMD), but results have not been validated. We investigated the correlation of a combination of PW and TDI with a positive response to cardiac resynchronization therapy (CRT).

Material and methods

We studied 108 consecutive patients who received CRT. Patients with atrial fibrillation were excluded. The time difference (T_PW-TDI) between onset of QRS to the end of LV ejection by PW (T_PW) and onset of QRS to the end of the systolic wave in LV basal segments with greatest delay by TDI (T_TDI) was measured before CRT and during short-term and long-term follow-up.

Results

The T_PW-TDI interval before CRT was 74 ±48 ms. Intra-observer variabilities for T_PW and T_TDI were 1.5 ±0.24% and 1 ±0.17%. Inter-observer variabilities for T_PW and T_TDI were 1 ±0.36% and 1 ±0.64%, respectively. T_PW-TDI > 50 ms was defined as the cutoff value for diagnosis of LVMD by receiver operating curve (ROC) analysis. During follow-up of 15 ±11 months, the sensitivity and specificity of TP_PW-TDI to predict a positive response to CRT were 98% and 82%, respectively. The area under the ROC curve was 0.92. There was a significant agreement between LVMD determined by T_PW-TDI and the positive response to CRT (κ=0.80).

Conclusions

Left vertricular dyssynchrony detected by the method combining PW and TDI demonstrated a high reproducibility, sensitivity, specificity and agreement with a positive response to CRT.     

Contractile reserve assessed by dobutamine test identifies super-responders to cardiac resynchronization therapy

Introduction

In this study, we sought to determine whether myocardial contractile reserve (CR) assessed by dobutamine stress echocardiography (DSE) can identify patients who experience nearly complete normalization of left ventricular (LV) function after the implantation of a cardiac resynchronization therapy (CRT) pacemaker.

Material and methods

The study group consisted of 55 consecutive patients with non-ischemic dilated cardiomyopathy, LV ejection fraction (LVEF) < 35%, and prolonged QRS complex duration, who were scheduled for CRT pacemaker implantation. The DSE (20 µg/kg/min) was performed in all patients. The CR assessment was based on a change in the wall motion score index (ΔWMSI) and ΔLVEF during DSE. Super-response was defined as an increase in LVEF to > 50% and reduction in left ventricular end-systolic dimension to < 40 mm 12 months following the CRT implantation.

Results

A total of 7 patients (12.7%) were identified as super-responders to CRT. When compared to non-super-responders, these patients had significantly higher values of the dobutamine-induced change in ΔWMSI (1.031 ±0.120 vs. 0.49 ±0.371, p < 0.01), and ΔEF (17.9 ±2.2 vs. 8.8 ±6.2, p < 0.01). Receiver operating characteristic analysis showed that dobutamine-induced changes in ΔWMSI ≥ 0.7 and ≥ 14% for ΔEF are the best discriminators for a super-response. Patients with ΔWMSI ≥ 0.7 and ΔEF ≥ 14% are significantly less often hospitalized (p < 0.01) for worsening of heart failure during 28.5 ±3.0 months of the follow-up.

Conclusions

Contractile reserve assessed by DSE can identify patients with dilated cardiomyopathy who are likely to experience near normalization of LV function following CRT.     

Plasma levels of atrial natriuretic peptide are raised in essential hypertension during low and high sodium intake

Summary Plasma levels of -human atrial natriuretic peptide (hANP) were measured in 17 patients with primary hypertension (11 females, 6 males, aged 22–61; blood pressure systolic 154±7 mmHg, diastolic 92±4 mmHg) and in 9 normotensive controls (4 males, 5 females, aged 20–71; blood pressure systolic 117±4 mmHg, diastolic 76±2 mmHg) during unrestricted sodium diet, at the 4th day of a low sodium intake (40–60 mEq/day) and at the 6th day of sodium loading (280–320 mEq/day) both after an overnight rest and after 4 h of upright posture. In the controls, plasma levels of hANP at 8:00 a.m. were lowered from 73±11 to 49±7 pg/ml during low sodium diet and increased to 128±37 pg/ml after high salt intake. Plasma ANP levels were significantly lower after 4 h of upright posture during unrestricted, low and high sodium intake. In the hypertensive group, plasma ANP levels were elevated during unrestricted diet (203±43 pg/ml), during the low sodium period (139±31 pg/ml), and after high sodium intake (267±63 pg/ml) compared to the controls. All levels were lowered by upright posture. The absolute decrease was more pronounced compared to the normotensives, the relative decline was similar in both groups. In the hypertensives, plasma ANP levels significantly correlate with systolic and diastolic blood pressure (r=0.468,r=0.448,P<0.05) and with urinary aldosterone during unrestricted diet (r=0.536,P<0.05). There was an inverse correlation between plasma ANP levels and plasma renin concentration during low and high sodium intake (r=–0.469,r=–0.496,P<0.05).These studies demonstrate raised circulating plasma ANP levels in patients with essential hypertension. The modulation of ANP by different sodium intake and by upright posture is maintained similar to the changes in plasma ANP in normotensive controls. Raised ANP levels in the hypertensives are correlated with low renin secretion and high aldosterone excretion. High ANP levels, therefore, might indicate sodium retention in essential hypertension.Abbreviation ANP atrial natriuretic peptide Supported by a grant from Ministerium für Wissenschaft und Forschung, NRW     

Functional differences in type-I fibres from two slow skeletal muscles of rabbit

The present study addressed the question of whether the slow fibres of mammalian skeletal muscle, containing the myosin heavy chain MHCI (type-I fibres), are a functionally homogeneous population. We compared various properties of Ca²⁺-activated, skinned, type-I fibres from the soleus and semitendinosus muscles of a rabbit. Soleus type-I fibres showed significantly faster kinetics of stretch activation, measured as the time-to-peak of the stretch-induced, delayed force increase, t₃, than semitendinosus fibres (1239±438 ms, n=136, vs. 1600±409 ms, n=208 respectively) (means±SD, 22 °C). Similarly, the speed of unloaded shortening at 15 °C was faster in soleus than in semitendinosus fibres [0.79±0.16 fibre lengths (FL) s^–1, n=44, vs. 0.65±0.15 FL s^–1, n=35 respectively]. The kinetics of stretch activation were more temperature sensitive in semitendinosus than in soleus fibres. Finally, the generation of steady-state isometric force was more sensitive to Ca²⁺ in semitendinosus than in soleus fibres: [pCa₅₀ (–log [Ca²⁺] for half-maximal activation) at 22 °C: 6.29±0.15, n=28, vs. 6.19±0.10, n=18 respectively]. These results suggest strongly that there is no functional homogeneity within type-I fibres of different muscles. The observed differences might reflect the existence of more than one functionally different slow myosin heavy chain isoforms or other modifications of contractile proteins.     

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: Preliminary report

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 ± 18.1 pg/ml vs. 57.2 ± 11.9 pg/ml). IL-6 level was significantly elevated (91.6 ± 46.9 pg/ml vs. 45 ± 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 ± 19 mg/l vs. 3 ± 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = –0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established. On the other hand, a negative correlation between IL-10 and serum level of CRP (r = –0.76, p < 0.05), AGP (r = –0.64, p < 0.05) and ACT (r = –0.38, p < 0.05) was also observed. Moreover, these relationships were maintained when patients treated with MTX, IMG, or NSAID were analyzed independently. According to the data thus far obtained, it seems that IL-10 decreases IL-6 production, and thereby indirectly affects the acute phase response, decreasing CRP, AGP, and ACT concentration in RA patients.Abbreviations ACT -1-antichymotrypsin - AGP ₁-acid glycoprotein - APP acute phase protein - CRP C-reactive protein - CSF colony stimulating factor - IFN interferon - IL interleukin - IMG intramuscular gold - MTX methotrexate - NSAID non-steroidal anti-inflammatory drug - RA rheumatoid arthritis     

The effect of training on responses of Β-endorphin and other pituitary hormones to insulin-induced hypoglycemia

Summary We studied whether the previously reported intensified -endorphin response to exercise after training might result from a training-induced general increase in anterior pituitary secretory capacity. Identical hypoglycemia was induced by insulin infusion in 7 untrained (Skeletal muscle enzyme activity, fiber composition and in relation to distance running performance 49±4 ml · (kg · min)^–1, mean and SE) and 8 physically trained (Skeletal muscle enzyme activity, fiber composition and in relation to distance running performance 65±4 ml · (kg · min)^–1) subjects. In response to hypoglycemia, levels of -endorphin and prolactin immunoreactivity in serum increased similarly in trained (from 41±2 pg · ml^–1 and 6±1 pg · ml^–1 before hypoglycemia to 103±11 pg · ml^–1 and 43±9 pg · ml^–1 during recovery, P<0.05) and untrained (from 35±7 pg · ml^–1 and 7±2 pg · ml^–1 to 113±18 pg · ml^–1 and 31±8 pg · ml^–1 P<0.05) subjects. Growth hormone (GH) was higher 90 min after glucose nadir in trained (61±13 mU · l^–1) than in untrained (25±6 mU · l^–1) subjects (P<0.05). Levels of thyrotropin (TSH) changed in neither of the groups. It is concluded that, in contrast to what has been formerly proposed, training does not result in a general increase in secretory capacity of the anterior pituitary gland. TSH responds to hypoglycemia neither in trained nor in untrained subjects. Finally, differences in -endorphin responses to exercise between trained and untrained subjects cannot be ascribed to differences in responsiveness to hypoglycemia.     

Neuromuscular,anaerobic, and aerobic performance characteristics of elite power athletes

Summary Various aspects of neuromuscular, anaerobic, and aerobic performance capacity were investigated in four powerlifters, seven bodybuilders, and three wrestlers with a history of specific training for several years. The data (means ± SD) showed that the three subject groups possessed similar values for maximal isometric force per unit bodyweight (50.7±9.6, 49.3±4.1, and 49.3±10.9 N/kg, respectively).However, significant (P<0.05) differences were observed in the times for isometric force production, so that e.g., times to produce a 30% force level were shorter for the wrestlers and bodybuilders (28.3±3.1 and 26.4±6.6 ms) than that (53.3±23.7 ms) for the powerlifters. Utilization of elastic energy by the wrestlers was significantly (P<0.05) better than that of the other two subject groups, as judged from differences between the counter-movement and squat jumps at 0, 40, and 100 kg's loads. No differences were observed between the groups in anaerobic power in a 1-min maximal test, but the values for max were higher (P<0.05) among the wrestlers and bodybuilders (57.8±6.6 and 50.8±6.8 ml·kg^–1·min^–1) as compared to the powerlifters (41.9±7.2 ml ·kg^–1·min^–1). Within the limitations of the subject sample, no differences of a statistical significancy were observed between the groups in fibre distribution, fibre areas, or the area ratio of fast (FT) and slow (ST) twitch fibres in vastus lateralis. In all subjects the vertical jumping height was positively (P<0.01) correlated with the FT fibre distribution, and negatively with the time of isometric force production (P<0.05). Maximal force was correlated (P<0.001) with thigh girth. Muscle cross-sectional area did not correlate with mean fibre area. It was assumed that the selected aspects of neuromuscular, anaerobic, and aerobic performance capacity may be influenced by muscle structure, but also specifically and/or simultaneously by training lasting for several years.     

Imaging the coronary venous drainage system using electron-beam CT

This study describes the appearance of the coronary sinus and its tributary veins as visualized on ECG-triggered electron-beam computed tomography (CT) and investigates their spatial relationship to other cardiac structures. Thirty-two patients were examined with ECG-triggered electron-beam CT (exposure time 100 ms, slice thickness 1.5 mm) after intravenous contrast agent administration. The entire heart was imaged the appearance of the coronary sinus and its tributary veins were evaluated. In all 32 patients the anterior interventricular veinand the posterior interventricular vein drained into the coronary sinus. The small cardiac vein was visualized in five patients, a posterior vein of the left ventriclein three and the left marginal vein in eleven. The coronary sinus of all 32 patients had a average length of 30 mm ± 10 mm (mean ± SD), range 21–40 mm and a diameter of 9 mm ± 5 mm (mean ± SD), range 4–14 mm. The results of our work show that if the entire heart volume is scanned usingECG-triggered electron-beam CT, the delineation and the differentiation of the major cardiac veins is possible on transverse cross sections in a way which corresponds to the anatomical literature. Hence to the similar enhancement and similar diameter of coronary veins and arteries on contrast-enhanced electron-beam CT studies, the radiologist should be familiar with the cross-sectional anatomy of the major cardiac veins to prevent possible misinterpretation.     

Silent period to transcranial magnetic stimulation: construction and properties of stimulus–response curves in healthy volunteers

Silent period (SP) is widely used in transcranial magnetic stimulation studies. Methodologically, SP is usually elicited at stimulus intensities corresponding to a certain percentage of corticomotor threshold. Because this approach might lead to factitious SP changes, the present study was designed to develop, in a stepwise manner, a method for investigating SP independently of corticomotor threshold. First, stimulus–response (S–R) curves of SP against stimulus intensity (SI) were constructed and quantitatively described in healthy volunteers. Second, various methodological issues such as the optimum model for describing the relationship between SP duration and SI and the importance of the type of stimulating coil were addressed. Finally, the proposed method and a commonly used method (eliciting SPs at 130% MT SI) were directly compared for a group of epileptic patients for whom administration of oxcarbazepine resulted in significant corticomotor threshold elevation. Twenty-one subjects (eleven females, median age, 38 years) were studied. SPs were obtained with a figure-of-eight coil using a standardized procedure (recording, FDI). Pilot experiments indicated that at least four trials were required, at each intensity level, to estimate the mean SP duration within 10% of the true mean. Therefore, SPs were determined from the average of four trials with 5% increments from 5 to 100% maximum SI. In a second set of experiments, SPs were obtained for fifteen subjects using a circular coil. In a third set of experiments, eight epileptic patients were studied before and after administration of oxcarbazepine (mean dose 1553 mg, range 900–1800 mg). The S–R curves were fitted to a Boltzman function and to first-order to fourth-order polynomial and sigmoid functions. The Boltzman function described the data accurately (R²=0.947–0.990). In addition, direct comparison of the six models with an F-test proved the superiority of the first. The best-fit parameters of the reference curve, i.e. the maximum and minimum values, the slope, and V₅₀ (the SI at which SP duration is halfway between Min and Max) were 230.8±3.31 ms (x±SEM), –11.51±3.31 ms, 11.56±0.65%, and 49.82±0.65%, respectively. When the curves obtained with the circular coil were compared with those obtained with the figure-of-eight coil, there were differences between V₅₀ (51.69±0.72 vs 47.95±0.82, P<0.001) and SP threshold (31.15 vs 24.77, P<0.01) whereas the other best-fit values did not differ significantly. Oxcarbazepine increased corticomotor threshold from 45.3±5.8% at baseline to 59.4±10.4% (P<0.001). According to the commonly used method, the drug significantly prolonged SP (from 117.6±42.4 ms to 143.5±46.5 ms, P<0.001) and, consequently, enhanced brain inhibition. In contrast, study of the SP curves led to the conclusion that oxcarbazepine does not affect the Max value and slope but significantly increases V₅₀ and SP threshold (from 54.5±4.9% to 59.9±7.2% and from 29.1±6.4% to 34.6±6.8%, respectively, P<0.01). These findings imply that oxcarbazepine does not enhance brain inhibitory mechanisms. Thus, in situations characterized by significant changes in corticomotor threshold the proposed method provides results clearly different from a commonly used approach. It is concluded that S–R curves obtained with a figure-of-eight coil in 5% increments and fitted to a Boltzman function provide an accurate, comprehensive, and clinically applicable method for exploring SP.Presented in part at the meeting of the EFNS, Helsinki, September 2003     

Kein Einfluß von Digitalis auf Sexual-und Nebennierenrindenhormone bei gesunden Probanden und bei Patienten mit Herzinsuffizienz

Summary Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7±7.7 vs 35.4±3.2 pg/ml) nor estradiol (35.8±6.4 vs 32.2±3.9 pg/ml) nor testosterone (6.32±0.74 vs 6.45±0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55±0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147±24 vs 142±19 pg/ml) and free estradiol (657±77 vs 615±78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128±18 to 389±18 ng/ml) and testosterone (from 5.96±0.90 to 10.33±1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150–210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took -methyldigoxin (n=8), -acetyldigoxin (n=20) and digitoxin (n=7) from 1 to 9 (x:1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound. However, our studies showed that sexual hormones are correlated to cardiac performance: with decreasing cardiac index, testosterone (r: 0.86;P<0.01) and estradiol (r: 0.68;P<0.05) decreased significantly. We conclude that digoxin does not exert any influence on plasma sexual steroids. Since no competition between digoxin and estradiol receptors was found, it may even be the digitalis compound of choice when feminization is expected due to other complications. Furthermore, on digoxin the adrenal gland is capable of synthesizing cortisol sufficiently.

Unterstützt durch die Deutsche Forschungsgemeinschaft (Kl 346)     

End-tidal carbon dioxide monitoring indicates recovery from cardiogenic shock in patients receiving percutaneous cardiopulmonary support

The aim of this study was to examine the prognostic value of monitoring end-tidal carbon dioxide (ETCO₂) levels for patients in cardiogenic shock undergoing percutaneous cardiopulmonary support (PCPS). Fifteen patients in whom PCPS was used to treat cardiogenic shock were enrolled in this study. For hemodynamic measurements, a thermodilution catheter was inserted into the pulmonary artery and an infrared absorption sensor was placed in the main stream of exhaled air between the respiration tube and the respirator to measure ETCO₂ levels. Nine patients (group II, 60%) died of multiple organ failure. In the six survivors (group I), there was a significant increase in average ETCO₂ level from 8.8 ± 3.9 mmHg before treatment to 20.5 ± 2.1 mmHg 24 h after the start of PCPS compared with values in group II patients (8.8 ± 3.9 mmHg, P = 0.0411). Also, serum lactate concentrations fell significantly in group I patients (group I 2.8 ± 0.47 mmol/l, group II 9.0 ± 2.31 mmol/l, P = 0.0435). The mean ETCO₂ level in group I patients gradually returned to 23 mmHg, which was within the normal healthy range; these patients were successfully weaned from PCPS. These results suggest that, in cardiogenic shock patients, ETCO₂ level is a possible index of cardiac recovery during PCPS support.     

Corticospinal activation of internal oblique muscles has a strong ipsilateral component and can be lateralised in man

Trunk muscles receive corticospinal innervation ipsilaterally and contralaterally and here we investigate the degree of ipsilateral innervation and any cortical asymmetry in pairs of trunk muscles and proximal and distal limb muscles. Transcranial magnetic stimulation (TMS) was applied to left and right motor cortices in turn and bilateral electromyographic (EMG) recordings were made from internal oblique (IO; lower abdominal), deltoid (D; shoulder) and first dorsal interosseus (1DI; hand) muscles during voluntary contraction in ten healthy subjects. We used a 7-cm figure-of-eight stimulating coil located 2 cm lateral and 2 cm anterior to the vertex over either cortex. Incidence of ipsilateral motor evoked potentials (MEPs) was 85% in IO, 40% in D and 35% in 1DI. Mean (± S.E.M.) ipsilateral MEP latencies were longer (P<0.05; paired t-test) than contralateral MEP latencies (contralateral vs. ipsilateral; IO: 16.1±0.4 ms vs. 19.0±0.5 ms; D: 9.7±0.3 ms vs. 15.1±1.9 ms; 1DI: 18.3±0.6 ms vs. 23.3±1.4 ms), suggesting that ipsilateral MEPs were not a result of interhemispheric current spread. Where data were available, we calculated a ratio (ipsilateral MEP areas/contralateral MEP areas) for a given muscle (IO: n=16; D: n=8; 1DI: n=7 ratios). Mean values for these ratios were 0.70±0.20 (IO), 0.14±0.05 (D) and 0.08±0.02 (1DI), revealing stronger ipsilateral drive to IO. Comparisons of the sizes of these ratios revealed a bias towards one cortex or the other (four subjects right; three subjects left). The predominant cortex showed a mean ratio of 1.21±0.38 compared with 0.26±0.06 in the other cortex (P<0.05). It appears that the corticospinal control of IO has a strong ipsilateral component relative to the limb muscles and also shows hemispheric asymmetry.     

Secretion of growth hormone and thyroid-stimulating hormone in patients with dementia

We studied the growth hormone (GH) response to GH-releasing hormone (GHRH) and the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in four groups of patients with dementia and examined whether GH and TSH secretion is altered in patients with Alzheimer's disease. The four groups included those with Alzheimer's disease (n=28), parkinsonism with dementia (n=10), progressive supranuclear palsy with dementia (n=10), and dementia of vascular origin (n=28). The results showed no differences among the four groups in GH response to GHRH (12.2 ± 2, 10.7 ± 2, 8.9 ±1.1, and 9.9 ± 1.9 g/ml, respectively); there was no correlation between GH response to GHRH and sex, stage of the disease, or cerebral atrophy. The proportion of patients with exaggerated, normal, or lower GH response was similar in the four groups. There were also no differences among the groups in terms of TSH response to TRH (9.2 ±0.9, 11.1 ± 1, 11.1 ± 1, and 10.3 ± 1 mU/ml, respectively), nor was there a correlation between TSH response to TRH and sex, stage of the disease, cerebral atrophy, or GH response to GHRH. The proportion of those with exaggerated, normal, or lower TSH response was similar in the four groups. Cerebrospinal somatostatin levels were similar in Alzheimer's disease and vascular dementia patients. These findings indicate that neither GH response to GHRH nor TSH response to TRH provides a useful diagnostic adjunt in Alzheimer's disease patients.Abbreviations AD Alzheimer's disease - PD parkinsonism with dementia - PSP progressive supranuclear palsy - VD dementia of vascular origin - GH growth hormone - GHRH growth hormone releasing hormone - TRH thyrotropin releasing hormone - TSH thyroid stimulating hormone Correspondence to: J.M. Gomez     

Histamine release with intravenous narcotics: Protective effects of H1 and H2-receptor antagonists

Summary High dose narcotic anesthesia with fentanyl or morphine is not associated with significant direct myocardial depression. Morphine is reported to produce arteriolar dilatation and a decrease in SVR (probably due to histamine release) while fentanyl is not. Studies were undertaken to determine if morphine or fentanyl caused histamine release; if such a release correlated with hemodynamic changes, and if H₁ and H₂ antagonists could provide protection. In a randomized double blind study of 40 patients in 4 groups, patients who received morphine (1 mg/kg) demonstrated significant increases in plasma histamine (880±163 to 7,437±2,684 pg/ml–p<0.01) accompanied by an increase in CI (2.4±0.2 to 3.0±0.2 l/min/m²–p<0.01) and decreases in (88±4 to 61±4 torr–p<0.01) and SVR (15.5±1 to 9.0±1 torr-l-min^–1 p<0.01). The prior administration of H₁ (dyphenhydramine 1 mg/kg) and H₂ (cimetidine 4 mg/kg) antagonists provided significant protection (SVR 17.4±1 to 14.6±1 torr-l-min^–1–p<0.05) although histamine increased comparably (1,059±22 to 7,653±4,242 pg/ml–p<0.05). In a separate study, seven patients receiving fentanyl 50 µg/kg showed no histamine changes (935±51 to 685±51 pg/ml) and no significant hemodynamic response. Eight patients receiving morphine 1 mg/kg again showed significant increases in plasma histamine (880±163 to 7,480±2,230 pg/ml–p<0.05) which collelated with the decrease in SVR (r=0.81). These data demonstrate that morphine releases histamine in amounts which correlate with the hemodynamic changes seen. Prior administration of H₁ and H₂ histamine antagonists provide significant protection — more so than either alone. Fentanyl produced no histamine release which may account for much of the cardiovascular stability reported with this drug.