[Research on Depression in the GDR - Historical Lines of Development and Therapeutic Approaches]. / Depressionsforschung in der DDR - historische Entwicklungslinien und Therapieansätze.

BACKGROUND: Historical research has raised the issue of whether GDR psychiatry was isolated from Western influences to such an extent that an autonomous East German psychiatry developed. Taking a chronological approach and being based on a clearly defined range of topics, the objective of this paper is to identify specific contributions made by GDR psychiatry to academic research as well as the degree of its international orientation by focusing on the treatment and research on depression. METHODS: We have performed a systematic review of the East German psychiatric journal "Psychiatrie, Neurologie und medizinische Psychologie" and a screening of all psychiatric textbooks that appeared in the GDR. RESULTS: Although East German psychiatry was oriented towards Soviet as well as Western developments, some internationally used therapeutic or conceptual innovations reached East German clinics only with some delay. Yet, East German psychiatrists have also contributed their own, independent nosological and therapeutic concepts to research on depression. Pivotal figures included, among others, R. Lemke (Jena), D. Müller-Hegemann (Leipzig) or K. Leonhard (Berlin). CONCLUSION: With regard to research on depression one cannot truly speak of an autonomous East German psychiatry. Developments in East and West were largely running in parallel.

[Obesity and depression: an overview on the complex interactions of two diseases]. / Adipositas und Depression: eine Übersicht über die vielschichtigen Zusammenhänge zweier Volkserkrankungen.

Both obesity and depression are diseases of civilization with a high clinical and scientific relevance. Correlations between both diseases usually turn out to be very complex and are not always applicable to all affected patients to the same extent. Especially, dysregulations of neuroimmunological parameters and physiological regulatory processes play an important role in the development and maintenance of both obesity and mood disorders. Due to the complexity of the underlying mechanisms it is difficult to apply standardized interventions for patients in clinical practice. Therapeutic measures should always be applied in the context of current research and adapted to the individual situation of the patient.

Clinical severity and prognosis of hand eczema.

BACKGROUND: Hand eczema (HE) is a frequent, long-lasting disease with both personal and societal repercussions. Consequently, more information is needed on factors that maintain symptoms. OBJECTIVES: In this study, patients with HE were followed for 6 months from the first visit to a dermatologist to identify factors associated with severe disease and a poor prognosis. METHODS: Study participants were 799 patients with HE from nine dermatological clinics in Denmark. Severity assessment of the HE was done at baseline and at the 6-month follow-up using the Hand Eczema Severity Index (HECSI) and by patients using a self-administered photographic guide. Additional information was obtained from a baseline questionnaire. RESULTS: At baseline, 60.3% assessed their HE as moderate to very severe using the self-administered photographic guide compared with 36.1% at follow-up. The mean HECSI value decreased from 19.9 points at baseline to 11.2 points at follow-up (P < 0.001). In a multivariable logistic regression analysis, statistically significant associations with severe HE at baseline were older age (P < 0.001), atopic dermatitis (P = 0.01) and > or = 1 positive patch test (P < 0.001). Being an unskilled worker was a predictor for a poor prognosis at follow-up (P = 0.04), and the presence of frequent symptoms during the previous 12 months was associated with severe initial disease (P = 0.02) and a poor prognosis (P = 0.04). CONCLUSIONS: Overall, the disease had improved 6 months after the dermatological examination: nevertheless, many patients continued to have significant symptoms. Dermatologists should pay special attention to patients with frequent eruptions and to unskilled workers.

Incorporation of hydrophobized mineral particles in activated sludge flocs: a way to assess ballasting efficiency.

The role of mineral surface hydrophobicity in attachment to activated sludge flocs was investigated. Fluorite and quartz particles of similar granulometry were hydrophobized by adsorbing sodium oleate and dodecylamine chloride, respectively. Mineral hydrophobicity was assessed by flotation expriments. The attachment of particles to microbial flocs was determined by optical microscopy. The results indicate that hydrophobized particles are always better incorporated within activated sludge flocs than non-coated particles. A comparison with Aquatal particles used as sludge ballast reveals that hydrophobized minerals are associated with microbial flocs to the same extent.

[Effect of the imidazoline receptor agonist moxonidine on hemodynamics, coronary circulation, metabolic ischemia markers and the neurohumoral system in patients with essential hypertension. Effects of moxonidine on coronary circulation]. / Wirkung des Imidazolin-Rezeptor-Agonisten Moxonidin auf Hämodynamik, koronare Durchblutung, metabolische Ischämiemarker und neurohumorales System bei Patienten mit essentieller Hypertonie. Auswirkungen von Moxonidin auf die koronare Durchblutung.

Moxonidine is a new centrally active imidazoline-receptor agonist being effectively applied in the treatment of arterial hypertension due to its sympathicolytic potency. This is the first investigation regarding the effects of moxonidine on coronary and systemic hemodynamics, metabolic markers of ischemia and neurohumoral parameters in patients with essential hypertension (WHO I-II). We studied moxonidine (single dose of 0.4 mg p.o.) in 22 patients with left ventricular (LV) hypertrophy, ST segment depressions during exercise, pectanginal complaints and negative coronarograms. Assessments included arterial blood pressure, cardiac output, pulmonary artery pressure mean (PAPm), pulmonary capillary wedge pressure (PCWP) and coronary sinus flow (CSF) by intravascular Doppler technique. The moxonidine-induced parameter changes 2 hours later were as follows: a decrease in systolic/diastolic pressure by 28/10 mmHg, and in heart rate by 5 bpm, associated with a decline of PAPm by 17% and of PCWP by 26%. LV work was reduced by 26%, MVO2 by 18% and CSF by 16%. Average peak velocity in CS fell by 18% and coronary flow reserve (with adenosine) increased by 12%. CS-O2 saturation rose by 4%, accompanied by an increase in lactate extraction by 17%, a decrease in norepinephrine spillover by 30% and in arterial endotheline by 20%. In conclusion, moxonidine produces clinically relevant sympathicolysis with beneficial effects on hemodynamics, coronary circulation and neurohumoral parameters.

Hemodynamic, antiischemic, and neurohumoral effects of tedisamil and atenolol in patients with coronary artery disease.

Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart-rate-lowering agents, such as tedisamil, which additionally exerts antiischemic and antiarrhythmic effects by blockade of cellular repolarizing K+ currents. Forty-eight patients with stable angina pectoris were investigated (doubleblind, randomized, parallel grouped) comparing the hemodynamic, antiischemic, metabolic and neurohumoral effects of tedisamil 100 mg b.i.d. and atenolol 50 mg b.i.d. after a single dose and over 6 days of treatment. Tedisamil and atenolol produced a decrease in heart rate both at rest [day 1:-13.6 versus - 15.4 bpm; day 6: - 14.8 versus - 22.2 bpm, resp.; p > 0.05] and exercise [day 1: - 9.1 versus - 18.3 bpm; p = 0.001; day 6: - 12.0 versus - 24.8 bpm, resp.; p = 0.001], while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest [day 1: -1.01 versus -1.19 l/min; p > 0.05; day 6: - 0.86 versus - 1.10 l/min, resp.; p > 0.05] and exercise [day 1: - 0.82 versus - 1.28 l/min; p > 0.05; day 6: - 0.65 versus - 2.68 l/min, resp.; p = 0.03], while stroke volume remained unchanged. Right atrial pressure changed during exercise only: it decreased with tedisamil (-1.7 mmHg) and increased with atenolol (+ 3.7 mmHg) (p < .001). Mean pulmonary capillary wedge pressures decreased both at rest (- 0.5 mmHg) and exercise (- 6.9 mmHg) in the tedisamil group but tended to increase with atenolol on day 6 of treatment [rest: + 1.7; exercise: + 3.7 mmHg) (p = 0.03). Arterial pressure decreased under atenolol treatment only. Exercise-induced plasma norepinephrine levels were reduced by tedisamil (- 93 pg/ml) but elevated by atenolol (+ 172 pg/ml) (p = 0.001). As compared to atenolol, tedisamil produced a prolongation of QTc interval [+ 31 versus 8 ms] at initial values of 0.408 +/- 0.018 s with PQ and QRS remaining unaltered. In patients with stable angina, tedisamil (100 mg b.i.d.) as compared to atenolol (50 mg b.i.d.) generated similar hemodynamic, neurohumoral and antiischemic effects. The antiischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, was comparable to that of atenolol.

[Therapy-resistant ventricular tachycardia in a woman with primary cardiac non-Hodgkin lymphoma]. / Therapierefraktäre ventrikuläre Tachykardien bei einer Patientin mit primärem kardialen Non-Hodgkin-Lymphom.

HISTORY: A 65-year-old woman had suffered from relapsing ventricular tachycardias (VT) since 1996. FINDINGS: Physical examination was normal. An arrhythmogenic substrate was found in the right ventricular outflow tract by electrophysiological examination. Nuclear magnetic resonance imaging (MRI) showed an infiltration of the right heart. Myocardial biopsy revealed a high-grade centroblastic non Hodgkin lymphoma. The patient was now transferred to our hospital for further treatment. Lactate dehydrogenase was elevated (2,030 U/l). Echocardiography showed a thickened and more reflecting right ventricular myocardium. Bone marrow aspiration and MRI/computed tomography of abdomen and thorax excluded a generalized stage. Ventricular tachycardias were caused by a primary cardiac lymphoma. TREATMENT AND COURSE: Combined radio-chemotherapy succeeded in complete remission. High-frequency ablation and amiodarone failed. Although MRI showed no more vital lymphoma after the combined radio-chemotherapy the patient suffered from spontaneous and symptomatic relapses of VT. Therefore this patient with primary cardiac lymphoma was the first in literature to get a defibrillator (ICD). The incidence of VT decreased and up to now the patient showed no relapse of the non Hodgkin lymphoma (follow-up 23 months).

Potassium channel openers and blockers in coronary artery disease. Comparison to betablockers and calcium antagonists.

Potassium channel openers and blockers, which belong to a novel class of vasodilator drugs and to the class of specific bradycardic substances, are potential new antianginal drugs. Experimental findings in vivo suggest that bimakalim is a new substance characterized as ATP-sensitive K+ channel openers, since it exerts preferential vasodilation of the collateral circulation of the coronary vasculature and both leads to increase blood flow to ischemic areas and to attenuate the ST segment elevation caused by regional ischemia in the canine heart. Opening of KATP increases the conductivity of potassium ions which results in hyperpolarization of smooth muscle membranes, thus producing vasodilation. Tedisamil is a new bradycardic agent proven to exert antiischemic and antiarrhythmic effects by blockade of the cellular cardiac repolarization K+ currents as well as of multiple neuronal and vascular K+ currents (Ito, Ik, and K+ATP). Using right heart catheterization and exercise tolerance tests, we investigated the hemodynamic, antiischemic and neurohumoral effects of bimakalim and tedisamil in patients with angiographically proven coronary artery disease, stable angina pectoris and reproducible ST segment depression during exercise. In 50 patients with coronary artery disease, the hemodynamic and antiischemic effects of a single oral dose bimakalim of 0.1 mg, 0.3 mg and 0.6 mg were compared to placebo. In a dose-finding baseline-controlled study, a comparable collective was examined for the effects of acute i.v. administration of tedisamil 0.1, 0.2, 0.3 and 0.4 mg/kg bw. A subgroup of 8 patients receiving 0.3 mg/kg bw tedisamil i.v. was compared with a similar group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intra-individual comparison. Furthermore, in 48 patients, short-term (6 days) effects of tedisamil, 2 times 100 mg orally, were compared to 2 times 50 mg atenolol treatment. With a single oral dose of bimakalim antianginal and/or antiischemic effects were lacking, increased doses, however, induced changes in hemodynamics typical of vasodilation, i.e., a significant decrease in systolic blood pressure and a secondary chronotropic response. In contrast to bimakalim, tedisamil produced antiischemic effects and was found to have favorable hemodynamic, neurohumoral and antiischemic effects in comparison to the betablocker esmolol and atenolol in patients with coronary artery disease. Tedisamil induced a dose-dependent decrease in both heart rate and the index of myocardial oxygen consumption associated with an improvement in ST segment depression. Tedisamil as well as esmolol and atenolol showed almost equipotent antiischemic effects at the doses administered. Compared with gallopamil, both tedisamil and esmolol were superior in their effects on myocardial oxygen consumption and ST segment depression, whereas plasma lactate concentrations were more reduced by tedisamil and gallopamil.

[The type testing of light-polymerization equipment, I: the testing protocol]. / Typenprüfung von Lichtpolymerisationsgeräten I: Prüfungsprotokoll.

With the spread of light polymerisation in dentistry for curing light-activated filling and luting materials the visible-light curing unit has become a standard device in the dental office. The light intensity is the main factor for the degree of polymerisation. However, there are other factors like comfort, handling and intensity control influencing daily use. The light curing unit industry is large and always changing. Consumer information is rare and often out of date. Considering these facts the present study presents a concept of investigating light curing units. In a further study all light curing units available on the Swiss market will be investigated using this protocol. Newly released light curing units should be investigated in this manner to actualize the existing results. Initially specifications and features are summarised using a questionnaire. Several tests are performed to investigate the parameters of the units. The light intensity emitted from the curing tip is analysed by the radiant power, the radiance and the light distribution across the face of the light curing tip as a function of time. Precise radiometers and a camera for picture processing are used for these measurements. Density filters are used to reduce the radiant power. The measurements of the precise radiometer are compared with those of the integrated radiometer of the light-curing unit. In this way the precision of integrated radiometers is controlled at maximum and reduced output. For evaluating the presence and the quality of integrated voltage stabilizer, the line voltage is varied from 230 V down to 207 V and up to 244 V and the radiant power is measured. The integrated timer is measured for its accuracy in each unit. The time intervals are controlled using a stopwatch. Finally the cooling device is tested. Using a phonometer the noise of the cooling fan is measured. Furthermore, the overheating protector is controlled by recording the activating and resetting time.

[Effects of the K(+) channel blocker tedisamil on hemodynamics, myocardial ischemia and neurohumoral systems in patients with stable angina pectoris. A comparison with the beta blocker atenolol]. / Auswirkungen des K(+)-Kanalblockers Tedisamil auf Hämodynamik, Myokardischämie und neurohumorales System bei Patienten mit stabiler Angina pectoris. Ein Vergleich mit dem beta-Blocker Atenolol.

BACKGROUND: Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart rat lowering agents, such as tedisamil which additionally exerts anti-ischemic and antiarrhythmic effects by blockade of cellular repolarizing K(+) currents. METHODS AND RESULTS: 48 patients with stable angina pectoris were investigated (double-blind, randomized, parallel grouped) comparing the hemodynamic, anti-ischemic, metabolic and neurohumoral effects of tedisamil 100 mg b.i.d and atenolol 50 mg b.i.d. after a single dose and over 6 days of treatment. Tedisamil and atenolol produced a decrease in heart rate both at rest (day 1: -13.6 vs -15.4 bpm; p > 0.05; day 6: -14.8 vs -22.2 bpm; resp.; p > 0.05) and exercise (day 1: -9.1 vs -18.3 bpm; p = 0. 001; day 6: -12.0 vs -24.8 bpm, resp.; p = 0.001), while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest (day 1: -1.01 vs -1.19 l/min; p > 0.05; day 6: -0. 86 vs -1.10 l/min, resp.; p > 0.05) and exercise (day 1: -0.82 vs -1. 28 l/min; p > 0.05; day 6: -0.65 vs -2.68 l/min, resp.; p = 0.03), while stroke volume remained unchanged. Right atrial pressure changed during exercise only: It decreased with tedisamil (-1.7 mm Hg) and increased with atenolol (+3.7 mm Hg). Mean pulmonary capillary wedge pressures decreased at rest (-0.5 mm Hg) and exercise (-6.9 mm Hg) in the tedisamil group, but tended to increase with atenolol on day 6 (rest: +1.7; exercise: +3.7 mm Hg) (p = 0.03). Arterial pressure decreased under atenolol treatment only. Exercise-induced plasma norepinephrine levels were reduced by tedisamil (-93 pg/ml) but elevated by atenolol (+172 pg/ml) (p = 0. 001). As compared to atenolol, tedisamil produced a significant prolongation of QT (c) interval (+31 vs -8 ms) (p = 0.002) at initial values of 0.408 +/- 0.018 s with PQ and QRS remaining unaltered. CONCLUSIONS: In the present study, tedisamil (100 mg b.i.d. ) generated favorable hemodynamic, neurohumoral and anti-ischemic effects in patients with stable angina pectoris. The anti-ischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, is comparable to that of atenolol (50 mg b.i.d.).

High-dose enoximone to evaluate reversibility of pulmonary hypertension: is there a diagnostic value of neurohormonal measurements?

BACKGROUND: Heart transplantation is associated with a reduction of the neurohumoral activation seen in patients with severe congestive heart failure. In this study, we investigated whether pharmacologically induced complex hemodynamic improvement during assessment of reversibility of pulmonary hypertension with a phosphodiesterase inhibitor is able to induce neurohormonal changes of diagnostic importance. METHODS AND RESULTS: Twenty-one patients with New York Heart Association class III-IV heart failure underwent infusion of 3 mg/kg enoximone over a period of 30 minutes. Before and after drug infusion, we determined the plasma concentrations of atrial natriuretic peptide, endothelin-I, angiotensin-II, aldosterone, norepinephrine, epinephrine, and angiotensin-converting enzyme activity sampled from a peripheral vein and the pulmonary artery. In addition to the expected significant reduction of pulmonary hypertension and enhancement of cardiac output, increased levels of the vasoconstrictors endothelin-I, angiotensin-II, and norepinephrine were observed. Aldosterone fell after enoximone infusion; a higher baseline aldosterone level correlated to the degree of reduction of the pulmonary arteriolar resistance by enoximone. Baseline atrial natriuretic peptide levels correlated with parameters, indicating the severity of heart failure. However, the plasma concentration of this peptide did not change significantly after enoximone infusion. CONCLUSIONS: Acute hemodynamic improvement after enoximone bolus in candidates for heart transplantation is not accompanied by a reduction of the enhanced neurohumoral activity in these patients. The reaction of the investigated hormones cannot predict the individual degree of reversibility of pulmonary hypertension.

[The type testing of light-polymerization equipment, II: the 1998 status]. / Typenprüfung von Lichtpolymerisationsgeräten II: Stand 1998.

In this study 16 different light curing units, available on the Swiss market, were tested for their features, radiant power and light distribution across the face of the curing tip and components like integrated radiometer, timer and cooling device. The basis of this study was the test protocol published in the november edition (11/1999). The features of the light curing units differed from one another. The Optilux 500 had all conceivable features that it could be designated the standard in features. If all these technical options are necessary has to be decided by the consumer. However, the components such as the timer, radiometer and voltage stabilizer are important because they influence the time of irradiation and the radiant power. The radiant power (mW) i.e., the radiance (mW/cm2) were measured in 2 spectral areas which are important for visible light polymerisation. The absolute values for the standard curing tip at a voltage of 230 V lay between 143.4 and 389.7 mW for the wavelengths between 400-520 nm and between 17.7 and 41.8 mW for the wavelengths between 462-472 nm. The resultant specific radiance values were between 268.3 and 862.6 mW/cm2 in the broad spectrum of 400-520 nm and 33.5 and 95.4 mW/cm2 in the narrow spectrum of 462-472 nm. Where the standard curing tips were replaced by guides with other diameters, tips with larger entrances showed more radiant power, light guides with smaller exits also showed more radiance. Turbo tips have larger entrances than exits and therefore combine both positive effects. The intensity wasn't distributed equally across the face of the curing light guide. Characteristically there was a concentric distribution of the intensity, with the maximum found in the centre and a decrease to the margin. Corresponding to the radiance values, curing light tips with decreasing diameters showed more homogeneous distribution patterns. Only Turbo tips showed worse distribution. Comparing the light intensity at a voltage of 207 V and 244 V to the normal voltage of 230 V it was found that not all curing units had an integrated voltage stabilizer. Just 9 out of the 16 tested units had an integrated radiometer. Comparison of the evaluated radiance values to the values given by the integrated radiometer revealed an agreement in just two cases. The marginal values, programmed by the manufacturer varied between 70 and 300 mw/cm2 and lie therefore, too low.

Comparison of the potassium channel blocker tedisamil with the beta-adrenoceptor blocker esmolol and the calcium antagonist gallopamil in patients with coronary artery disease.

BACKGROUND: Tedisamil is a new bradycardic agent proven to exert anti-ischemic and antiarrhythmic effects by blockade of the different cardiac and vascular K+ currents. HYPOTHESIS: It was the aim of the present study to compare the favorable anti-ischemic effects of tedisamil, with two long established representatives in the treatment of coronary artery disease (CAD), namely, the beta1 blocker esmolol and the Ca2 antagonist gallopamil. METHODS: The hemodynamic and neurohumoral effects of the new potassium channel blocker tedisamil, an agent with negative chronotropic and class III antiarrhythmic properties, were compared with the ultra-short-acting beta1-selective adrenoceptor blocker esmolol and the calcium antagonist gallopamil. A total of 22 patients with angiographically proven CAD and reproducible ST-segment depression in the exercise electrocardiogram was included in two studies with an almost identical design and inclusion criteria. The investigation was carried out using right heart catheterization and bicycle ergometry. A subgroup of 8 patients receiving 0.3 mg/kg body weight tedisamil intravenously (i.v.) in an open dose-finding study was compared with a group of 14 patients who had received esmolol (i.v. bolus of 500 micrograms/kg, maintenance dose 200 micrograms/kg/min) and gallopamil (initial dose 0.025 mg/kg, maintenance dose 0.0005 mg/kg/h) in a second intraindividual comparison. RESULTS: Tedisamil and esmolol reduced heart rate at rest by 13% (p < 0.001), and 6% (p < 0.05), and at maximum working levels by 8% (p < 0.01) and 9% (p < 0.05), respectively. Gallopamil increased heart rate at rest by 7% (p < 0.05), with only slight changes occurring during exercise. Corresponding findings for each drug were observed for cardiac output both at rest and during exercise [tedisamil: at rest -10% (NS), max. exercise -8%; esmolol: at rest -14% (NS), max. exercise -18% (NS); gallopamil: no significant changes]. Compared with tedisamil, stroke volume was reduced by esmolol [at rest and max. workload: -9% (NS)] and gallopamil [rest: -6% (NS), max. exercise: -2% (NS)]. Of the indirect parameters of ventricular function, that is, mean capillary wedge pressure (PCWPm) and right ventricular ejection fraction, only PCWPm demonstrated significant differences between tedisamil and gallopamil (+18% and -6% at rest, +17% and -21% during exercise, respectively; p < 0.001). Compared with gallopamil, both tedisamil and esmolol were superior in their effects on rate-pressure product, myocardial oxygen consumption, and ST-segment depression, whereas plasma lactate concentration was more reduced by tedisamil and gallopamil. Tedisamil led to a fall in norepinephrine levels in particular. CONCLUSION: Tedisamil and esmolol showed almost equipotent anti-ischemic effects at the doses administered. Tedisamil acts mainly by reductions in heart rate, and esmolol, though to a lesser degree, also by reductions in systolic blood pressure. The mechanism of gallopamil is to reduce afterload and to improve coronary perfusion. At the doses applied, however, it has lower antianginal potency compared with tedisamil and esmolol.

[Acute effects of enoximone after intracoronary administration on hemodynamics, myocardial perfusion and regional wall motion]. / Akutauswirkungen von Enoximon nach intrakoronarer Applikation auf die Hämodynamik, Myokardperfusion und die regionale Wandbewegung.

The influence of intracoronary enoximone at a dose of 0.075 mg/ kg/10 min on global and regional wall motion and myocardial perfusion (Group I, n = 10) as well as on diastolic LV function (Group II, n = 8) during pacing-induced ischemia was investigated in 18 patients with significant LAD stenoses. The hemodynamic parameters were determined by left heart catheterization, the systolic and diastolic left ventricular function by echocardiography including Doppler technique, and myocardial perfusion analysis was done after intracoronary application of contrast medium. Enoximone did not change either heart rate (79 +/- 9 vs 80 +/- 9 min-1) or blood pressure (LVSP: 159 +/- 7 vs 162 +/- 5 mm Hg) at rest. In the postpacing ischemic period after enoximone, LVEDP fell from a mean of 28.9 to 18.4 mm Hg (p < 0.001), dp/dtmax increased from 1050 to 1369 mm Hg/s (p < 0.001) and regional EF from 47% to 58% (p < 0.01), while global EF remained unchanged (45% vs 47%). ST-segment depression was reduced significantly from 2.3 to 1.5 mm (p < 0.01). Enoximone induced an increase in myocardial perfusion by 129% (p < 0.001) in the stenosis-dependent myocardial areas with shortening of the wash-out half-life time of the echo contrast medium from a mean of 14 s to 5 s (p < 0.001). The isovolumetric relaxation was shortened by 13% (p < 0.05), the E wave by 5%, and dp/dtmin increased by 17% (p < 0.01). In summary, intracoronary application of enoximone led to an improvement in both systolic and diastolic LV function without concomitant peripheral effect due to regression of myocardial ischemia.

Effects of nicorandil on regional perfusion and left ventricular function.

Left ventricular function and regional perfusion were evaluated by two study designs in patient groups with stable ischemic coronary artery disease (CAD): (1) using conventional left ventricular angiographies and (2) applying myocardial contrast echocardiography. The aim of the studies was to establish the effects of sublingually or orally applied nicorandil (N) on pacing-induced myocardial ischemia (MIS). In the first angiographic study, in nine patients with ischemic CAD and with pacing-inducible MIS, the effect of N, 20 mg sublingually, on hemodynamics and regional wall motion (RWM) were studied. There were no parameter changes without MIS being induced when comparing measurements at the 7th and 14th minute after N application to control values (p > 0.05). In the 15th and 16th minutes after N, pacing-induced MIS could no longer be elicited but left ventricular pump function improved; comparing MIS with N versus MIS without N: ejection fraction improved by 21%, cardiac index by 37%, and RWM by 21%, while filling pressure fell by 41% and systemic vascular resistance fell by 29%. Thus, N-mediated "protection from ischemia" with rather improved hemodynamics and RWM corresponds with alterations that theoretically could have been expected after nitroglycerin given under the above conditions. In the second echocardiographic study, regional perfusion was assessed in 10 patients by intracoronary injection of a newly developed echo contrast medium (ECM) and measurement of ECM washout halftime (t1/2) over opacified myocardial regions of interest, which displayed wall motion abnormalities already at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

[Neurohumoral and hemodynamic effects in combination therapy of enoximone and dopamine]. / Neurohumorale und hämodynamische Effekte in der Kombinationstherapie von Enoximon und Dopamin.

Twelve patients with severe heart failure (NYHA class III-IV) were investigated by intraindividual comparison for the hemodynamic and neurohumoral effects of dopamine (3 and 6 micrograms/kg/min), enoximone (8 micrograms/kg/min), and the combination of both medications (dopamine 3 micrograms/kg/min+enoximone 8 micrograms/kg/min) using right heart catheterization. The duration of active treatment was 8 h for each substance with a subsequent washout time of 16 h. Dopamine led to a dose-dependent increase in cardiac index of 10-13% and 18-37% under 3 and 6 micrograms/kg/min, respectively (p < 0.001). Enoximone monotherapy produced a comparable increase in cardiac index between 27 and 32% (p < 0.001). Enoximone, but not dopamine, resulted in a significant decrease in mean pulmonary artery pressure (21-26%; p < 0.01), pulmonary capillary wedge pressure (24-30%; p < 0.01), and right atrial mean pressure (26-28%; p < 0.001). The systemic vascular resistance was without significant changes at low-dose dopamine therapy, decreased by 10-19% insignificantly at a dose of 6 micrograms/kg/min, and reached the level of significance with enoximone therapy (-20 to -25%; p < 0.001). There was a highly significant decrease by 49-55% in systemic vascular resistance with enoximone (p < 0.001), in contrast to dopamine. Heart rate and blood pressure remained without significant changes at low-dose dopamine, with the heart rate increasing significantly by 25% at a dose of 6 micrograms/kg/min within the first 2 h (p < 0.01). Enoximone produced a heart rate increase by 8-13% (being significant after 2 h; p < 0.05) with no changes in blood pressure. The combination therapy with dopamine and enoximone led to an additive increase in cardiac index by 35-43% (p < 0.001), a decrease in right atrial mean pressure by 28-36% (p < 0.01), a decrease in systemic vascular resistance by 27-30% (p < 0.01) and in pulmonary vascular resistance by 46-51%. An additive effect on heart rate was not observed. The respective monotherapies with low-dose dopamine and enoximone had no remarkable effect on plasma catecholamines, while dopamine at a dose of 6 micrograms/kg/min and combination therapy led to a significant increase in noradrenaline levels. There was a highly significant decrease in the plasma concentration of the atrial natriuretic factor under enoximone and combination therapy (p < 0.001) as well as a significant decrease in aldosterone (0 < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Tedisamil (KC 8857) is a new specific bradycardic drug: does it also influence myocardial contractility? Analysis by the conductance (volume) technique in coronary artery disease.

To determine whether inotropism influences the bradycardic action of tedisamil, hemodynamic assessment was performed in 13 patients with ischemic coronary artery disease including analysis of end-systolic pressure-volume relationships after an infusion of tedisamil, 0.3 mg/kg, at rest, and during paced tachycardia stress. Slope Emax fell by 14% at rest (13 patients) and by 10% during tachycardia (6/13 patients), whereas loops of end-systolic pressure-volume relationships moved rightward; all parameter changes indicated a lack of significant inotropism loss with tedisamil (p > 0.05). Although the mean heart rate decreased from 77.5 to 64.7 beats/min and QTc duration increased by 14% (p < 0.05), filling pressure and dp/dtmin remained unchanged and vascular resistance increased by 30%. Parameters of left ventricular pump function (ejection fraction, stroke volume, left ventricular efficiency) decreased slightly (between 3% and 13%), whereas left ventricular volumes increased (end-diastolic volume by 6%, end-systolic volume by 23%). The respective parameter changes during tachycardia were comparable in tendency, and angina could no longer be induced during postdrug pacing stress. We concluded that the bradycardic effects of tedisamil are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion, whereas the postdrug anginal threshold appears elevated. Thus tedisamil can be used safely in ischemic coronary artery disease.

[Is the bradycardic effect of tedisamil at the expense of the loss of the inotropic effect? A pressure-volume analysis with the conductance (volume) catheter technique in patients with coronary artery disease]. / Wird die bradykardisierende Wirkung von Tedisamil mit Inotropie-Einbusse erkauft? Eine Druck-Volumen-Analyse mit der Conductane-(Volumen-)Kathetertechnik bei Patienten mit koronarer Gefässkrankheit.

UNLABELLED: To exclude or prove potential inotropic influences from tedisamil's bradycardiac effects, our hemodynamic evaluation in 13 patients (pat.) with coronary artery disease (CAD) included analyses of end-systolic pressure-volume relationships (ESPVR) after tedisamil, 0.3 mg/kg infusion at rest and during tachycardia induced by atrial pacing. Slope Emax [mm HG/ml] fell by 14% at rest (13 pat.) and by 10% during paced tachycardia (6/13 pat.) while loops of ESPVR tended to move rightward towards larger volumes (p > 0.05): all parameter changes indicated lack of significant inotropy loss with tedisamil. While mean heart rate decreased from 77.5 to 64.7 b/min and QTc duration increased by 14% (p < 0.05), filling pressure as well as dP/dtmin remained unchanged and vascular resistance rose by 30%. Parameters of LV-pump function (ejection fraction, stroke volume) decreased slightly (between 3 and 13%), while LV-volumes increased (end-diastolic by 6%, end-systolic by 23%). The respective parameter changes during paced tachycardia were comparable in tendency. CONCLUSION: Tedisamil's bradycardic effects are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion. Thus, tedisamil can be used safely in CAD.

Effects of acetate on left ventricular function in hemodialysis patients.

Two approaches were chosen to assess the controversially debated influence of acetate on the heart in dialysis patients: (1) To separate acetate effects from influences of dialysis, acetate was infused in 12 chronic dialysis patients with normal systolic function on a dialysis-free day, and left ventricular (LV) function was assessed by LV pressure/volume loops. Hyperacetatemia (3-5 mmol/l) resulted in a decrease in LV preload (LV end-diastolic pressure decreased from 16 +/- 3 to 10 +/- 4 mm Hg, p < 0.01) but had no influence on LV contractility. (2) In 8 dialysis patients without cardiac disease, isovolemic acetate or bicarbonate dialysis was performed. During both procedures, there were comparable changes in serum electrolytes as well as in echocardiographic parameters. LV contractility measured by velocity of circumferential fiber shortening increased during acetate and bicarbonate dialysis (1.47 +/- 0.22 to 1.77 +/- 0.29, p < 0.01; 1.47 +/- 0.21 to 1.70 +/- 0.22 circ/s, p < 0.01). It is concluded that mild hyperacetatemia does not influence LV contractility and that dialysis-induced changes in serum electrolytes are responsible for the increase in LV contractility during dialysis. However, the pronounced acetate effect on LV preload implies considerable therapeutic implications.