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Power generation systems based on fuel cell technology are an interesting option for mobile auxiliary power units (APU). Hydrogen for the fuel cell can be supplied from conventional fuels, such as diesel fuel. Mobile APUs must possess high efficiencies in order to be compact, lightweight, and capable of supply hydrogen on dynamic demand. Microstructured reactors have increased mass and heat transport rates as well as space time yields compared to conventional reactors. Therefore, they potentially meet the requirements of these mobile systems. The presented work examines and evaluates the application of microstructured devices for the steam reforming of diesel fuel by applying a Rh/CeO2 catalyst system. A microstructured reactor was designed where the heat for the endothermic steam reforming reaction was supplied in adjacent microchannels via catalytic combustion of hydrogen, which is potentially substituted in a complete APU system by use of the anode off gases of the fuel cell which contains less hydrogen and is of different composition. Dynamic experiments performed with this prototype reactor revealed a very fast response of the reaction on transients in reactant feed. A constant reformate flow was reached within 35 s. Reformate usually contained 70 vol% of hydrogen in the dry product gas.

The procedure following the washcoating of three different Ni catalyst systems (MgO, Al2O3, and CeO2/Al2O3 supported) on pretreated Fecralloy® microchanneled foils under controlled milling times and viscosities of the slurries is described. The activity of the prepared coatings is also presented. Four different series of coated foils were prepared: one per each catalyst system, keeping constant the average particle size on 5 μm, and one extra series to study the effect of reducing the average particle size of the MgO-supported catalyst system to 3 μm. For each coating, scanning electron microscopy pictures were taken and specific surface areas and average densities of the catalyst layers were estimated. Finally, each series of coated foils was stacked and tested in a microreactor for the methane steam reforming (MSR) reaction under different conditions.

Clinical data, function and compliance of left ventricle as well as regional wall motion were analysed in 17 patients with preoperatively limited left-ventricular function and signs of myocardial ischaemia after complete revascularisation surgery. Recatheterisation after 5.2 months on average after surgery showed improvement by one NYHA class, an increase of mean left-ventricular enddiastolic pressure, which was interpreted as "improved status of ischaemia", a decrease of left-ventricular compliance by 30%, of enddiastolic volume by 14% and of endsystolic volume by 20% (P less than 0.05). Loss of function occurred in 3 out of 92 bypasses. Up to the time of reporting, 22.4 months postoperatively, all patients have survived in a relatively satisfactory clinical state. All parameters of left-ventricular function as well as regional wall motion showed a tendency for improvement after surgery in the majority of patients. However, pre- and postoperative mean values were not significantly different (P greater than 0.05). Thus, despite clearcut improvement of clinical state and "ischaemia index", improvement of left-ventricular function and regional wall motion are not consistently demonstrable. The reasons of this discrepancy cannot be ascertained by this investigation. The quality of the surgical intervention and the sensitivity of parameter assessment cannot be held responsible.

The A1555G mutation in the 12S rRNA gene of human mitochondrial DNA causes maternally inherited, nonsyndromic deafness, an extreme case of tissue-specific mitochondrial pathology. A transgenic mouse strain that robustly overexpresses the mitochondrial 12S ribosomal RNA methyltransferase TFB1M (Tg-mtTFB1 mice) exhibits progressive hearing loss that we proposed models aspects of A1555G-related pathology in humans. Although our previous studies of Tg-mtTFB1 mice implicated apoptosis in the spiral ganglion and stria vascularis because of mitochondrial reactive oxygen species-mediated activation of AMP kinase (AMPK) and the nuclear transcription factor E2F1, detailed auditory pathology was not delineated. Herein, we show that Tg-mtTFB1 mice have reduced endocochlear potential, indicative of significant stria vascularis dysfunction, but without obvious signs of strial atrophy. We also observed decreased auditory brainstem response peak 1 amplitude and prolonged wave I latency, consistent with apoptosis of spiral ganglion neurons. Although no major loss of hair cells was observed, there was a mild impairment of voltage-dependent electromotility of outer hair cells. On the basis of these results, we propose that these events conspire to produce the progressive hearing loss phenotype in Tg-mtTFB1 mice. Finally, genetically reducing AMPK α1 rescues hearing loss in Tg-mtTFB1 mice, confirming that aberrant up-regulation of AMPK signaling promotes the observed auditory pathology. The relevance of these findings to human A1555G patients and the potential therapeutic value of reducing AMPK activity are discussed.

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.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.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).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.

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.

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.

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. Echocardiographic evaluations were performed at rest and during MIS with and without the effects of 20 mg of oral N. The t1/2 shortened significantly by 60% and was accompanied by a decrease in filling pressure from 18±9 to 7±3 mmHg. The perfused myocardial area increased by 75%, displaying a partially regained wall motion in previously hypokinetic areas, which resulted in an augmentation of regional ejection fraction. Concomitantly, the degree of coronary stenoses was reduced by 21% (p

We analysed end-systolic pressure-volume relations (ESPVR), using the conductance technique, to study the potential inotropic effects of (1) PDE inhibitor drugs, (2) class 1 anti-arrhythmic drugs and (3) PTCA-induced myocardial ischaemia (MIS). The question of contractility involvement is of clinical importance, since with inotropy-induced rise in MVO2 there is a risk of MIS, should any of the cardiotonic drugs (amrinone, enoximone, piroximone) be used in patients with CAD. Accordingly, we analysed their haemodynamic effects, identified improved contractility as one factor of these drugs' mode of action and proved their inability to induce MIS. Anti-arrhytmic drugs may cause cardiodepression, a risk theoretically well recognized but clinically poorly defined. We monitored the haemodynamics of six class 1 anti-arrhythmic drugs and found that drug-induced moderate impairments of contractility (at rest and during tachycardia) proved significant, but clinically asymptomatic, and did not differ significantly from drug to drug. PTCA provides routine models of MIS in man. We analysed ESPVR and haemodynamics during MIS with PTCA and coronary angiography (CORO) and the induced diminished LV function during CORO v PTCA appeared quantitatively less. Inotropy impairment was rather modest during ischaemia: dP/dtmax was reduced by 11%, slope k of the ESPVR by 14%, while the EDV was increased by 67%. All changes were reversible about 90 s after PTCA balloon occlusion and 20 s after CORO.

Improved contractility after applying piroximone (PIR) a new phosphodiesterase III inhibitor drug, is difficult to prove clinically. However, augmented contractility could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). Analysis of the end-systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular (LV) function allows for differentiation of PIR's effects: contractility vs. unloading. We therefore analyzed ESPVR and LV function in 16 CAD patients before and after PIR, 0.75 mg/kg intravenously. Emax increased by 39% (9/16 patients) and loops of the ESPVR (16 patients) moved leftward, indicating improved contractility. The difference in percent change PIR versus control (16 patients) demonstrated augmentation of LV function via unloading: LV volumes decreased (ESV by 37%, EDV by 19%), LV-filling pressure by 34%, and systemic vascular resistance by 19%; dP/dtmax increased by 28%, LV efficiency by 24%, cardiac index by 21%, and ejection fraction by 13%. Pacing-induced anginal threshold increased by 47% after PIR while the ischemic postpacing LV-filling pressure and ST-segment changes tended to normalize under the drug's influence. Thus, PIR improved LV function both by unloading and by positive inotropy. Lack of PIR-induced angina and an increased anginal threshold indicate that the drug can be used safely in CAD patients as well. The analysis of ESPVR proved to be safe and reliable in identifying contractility during the diagnostic cardiac catheterization routine.

Twenty-four patients with angiographically documented coronary artery disease, chronic stable angina, and reproducible ST-segment depression took part in this openlabel, baseline-controlled study on the hemodynamic, antiischemic, metabolic, and neurohumoral effects of tedisamil following IV doses of 0.1, 0.2, and 0.3 mg/kg (eight patients in each dose group). Tedisamil produced a dose-dependent decrease in both heart rate [rest: 2.4, 7.5 (p .01), resp.]. While cardiac output was found decreased due to the heart-rate reduction both at rest [−8.5%, −5.7%, and −10.2% (p

To determine whether alterations of left ventricular (LV) structure are associated with improved LV function under chronic clonidine monotherapy (300-450 g/day) of essential hypertension, 11 male patients (age range 47-61 years) were followed for 5.4 +/- 0.9 months using echocardiography and Doppler echocardiography. Blood pressure decreased from a mean of 168/105 to 150/96 mmHg (p less than 0.01), heart rate remained unchanged (73 +/- 10 vs. 71 +/- 10 beats/min). LV muscle mass decreased from 350 +/- 73 to 297 +/- 56 g (p less than 0.02), LV volume/muscle mass ratio increased from 0.58 +/- 0.13 to 0.69 +/- 0.12 ml/g (p less than 0.005). Ejection time increased from 276 +/- 17 to 296 +/- 17 ms (p less than 0.01), whereas no significant change was found for pre-ejection period, ejection fraction, cardiac index and LV dimensions. Doppler analysis revealed improved isovolumic relaxation time (116 +/- 17 vs. 84 +/- 28 ms; p less than 0.05), but no change in isovolumic contraction duration, maximal inflow velocities, time-velocity integrals and their duration, rate of acceleration and deceleration of early and atrial filling, and of their ratios. It is concluded that no reliable improvement in diastolic or systolic LV function is observed in chronic clonidine monotherapy of essential hypertension despite a normalization of blood pressure and a regression of LV hypertrophy.

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.

International audience; The role of mineral surface hydrophobicity on attachment to activated sludge flocs was investigated. Fluorite and quartz particles of similar granulometry were hydrophobized by adsorbing sodium oleate and docecylamine 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.

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.

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.; p0.05] 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; p0.05; day 6: - 0.86 versus - 1.10 l/min, resp.; p0.05] and exercise [day 1: - 0.82 versus - 1.28 l/min; p0.05; 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.

A 65-year-old woman had suffered from relapsing ventricular tachycardias (VT) since 1996.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.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, 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.

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.

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.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; p0.05; day 6: -14.8 vs -22.2 bpm; resp.; p0.05) 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; p0.05; day 6: -0. 86 vs -1.10 l/min, resp.; p0.05) and exercise (day 1: -0.82 vs -1. 28 l/min; p0.05; 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.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.).

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. (Am Heart J 1999;137:887-94.)

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.

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 (p0.001), dp/dtmax increased from 1050 to 1369 mm Hg/s (p0.001) and regional EF from 47% to 58% (p0.01), while global EF remained unchanged (45% vs 47%). ST-segment depression was reduced significantly from 2.3 to 1.5 mm (p0.01). Enoximone induced an increase in myocardial perfusion by 129% (p0.001) 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 (p0.001). The isovolumetric relaxation was shortened by 13% (p0.05), the E wave by 5%, and dp/dtmin increased by 17% (p0.01). 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.

Die klinisch-kardiologische Routine profitiert von moglichst vollstandigen Einsichten in den Wirkungsmechanismus der Medikamente auf die Ventrikelfunktion. Der Nachweis von Anderungen der myokardialen Inotropie aber gerat oft nur fehlerhaft und unzuverlassig wegen des Aufwandes und der technischen Unzulanglichkeiten der damit verbundenen methodischen Bedingungen [75, 76]. An den folgenden 4 klinischen Untersuchungen kardiovaskularer Interventionen soll die Bedeutung des Problems vorgestellt werden, nicht nur die konventionelle Hamodynamik mit ihren Anderungen, sondern auch die der Kontraktilitat unter den Bedingungen der klinisch-diagnostischen Routine korrekt nachzuweisen. Anhand der Untersuchungsergebnisse soll eine praktikable Losungsmoglichkeit fur die Inotropiemessung unter klinischen Bedingungen erlautert werden.

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 (p0.001). Enoximone monotherapy produced a comparable increase in cardiac index between 27 and 32% (p0.001). Enoximone, but not dopamine, resulted in a significant decrease in mean pulmonary artery pressure (21-26%; p0.01), pulmonary capillary wedge pressure (24-30%; p0.01), and right atrial mean pressure (26-28%; p0.001). 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%; p0.001). There was a highly significant decrease by 49-55% in systemic vascular resistance with enoximone (p0.001), 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 (p0.01). Enoximone produced a heart rate increase by 8-13% (being significant after 2 h; p0.05) with no changes in blood pressure. The combination therapy with dopamine and enoximone led to an additive increase in cardiac index by 35-43% (p0.001), a decrease in right atrial mean pressure by 28-36% (p0.01), a decrease in systemic vascular resistance by 27-30% (p0.01) 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 (p0.001) as well as a significant decrease in aldosterone (00.05).(ABSTRACT TRUNCATED AT 400 WORDS)

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 (p0.05): 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% (p0.05), 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.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.

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, p0.01) 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, p0.01; 1.47 +/- 0.21 to 1.70 +/- 0.22 circ/s, p0.01). 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.

Positive inotropy requires a rise in myocardial oxygen consumption (MVO2); as far as PDE-III-inhibitors' beneficial hemodynamic effects, increases in contractility are controversial, in part probably because accurate proving is rather tedious. The clinician, however, requires a clear concept of whether or not enoximone (EN), for example, carries the risk of myocardial ischemia when used in patients with coronary artery disease. Using the analysis of pressure-volume relations, we recently established contractility-increasing as a partial effect of EN. There are indications suggesting that the inotropy-induced added increase in MVO2 of the PDE-III-inhibitor drugs could be compensated for by the simultaneous vasodilation and changes in compliance, so that as a net effect an unchanged MVO2 might result. Since, on the other hand, PDE-III-inhibitor drugs have been said to generate antiischemic properties, further clinical investigations with EN clearly seemed indicated and they are the subject of the present report: In five patient groups with stabile angina (AP) studied the following parameters and methods, respectively, were used for the evaluation of EN-induced changes of the anginal threshold: exercise, using pacing and ergometry; PA- and PC-pressure measurements; MVO2, indirectly assessed; hemodynamic profile and regional wall motion as assessed in the immediate post pacing phase; ST- T-segment evaluation; thalium-201 perfusion scintigraphy; myocardial perfusion, indirectly assessed. Lack of EN-induced AP (ischemia) and an increased AP threshold indicated that the drug can be used safety in patients with heart failure, including that due to coronary artery disease.

Das Forschungszentrum Karlsruhe (FZK) ist eine der grosten naturund ingenieurwissenschaftlichen Forschungseinrichtungen in Europa. Seine Forschungsund Entwicklungsprogramme sind von offentlichem Interesse und erstrecken sich auf die Gebiete der industriellen Vorlaufforschung bis hin zur Produktund Verfahrensentwicklung, der Vorsorgeund der naturwissenschaftlichen Grundlagenforschung. Dabei kooperiert das FZK mit Partnern aus Wissenschaft und Wirtschaft. Die Universitat Karlsruhe und das Forschungszentrum haben kurzlich das Karlsruher Institut fur Technologie (KIT) gegrundet. KIT verbindet die Starken beider Partner. Das Institut fur Mikroverfahrenstechnik (IMVT) ist eines der 22 Institute des FZK. Dessen Forschung befasst sich mit chemischen Reaktionen und Grundoperationen der Verfahrenstechnik in Komponenten und Systemen, deren charakteristische Abmessungen zwischen 1 lm und 1 mm liegen und sehr hohe Stoffund Warmetransportraten aufweisen. Im Rahmen des normalen Arbeitsalltags werden sowohl nationale als auch internationale Forschungsprojekte bearbeitet. Zu den Aufgaben der Mitarbeiter gehoren die Konzeption von Versuchsanlagen, die Inbetriebnahme sowie die Auswahl, Durchfuhrung und Auswertung von Experimenten und die Entwicklung geeigneter Mikrostrukturapparate. Modellierung und Simulation der Reaktionen liefern ein Verstandnis der ablaufenden Prozesse im Inneren der Apparate. Resultate werden bei Projekttreffen besprochen und als Beitrag in wissenschaftlichen Zeitschriften oder in Vortragen auf weltweiten Konferenzen veroffentlicht.

To evaluate cardiodepressive risks of antiarrhythmic treatment with ajmaline, we monitored, in addition to conventional hemodynamic parameters, end systolic pressure-volume relations (ESPVR) to assess potential negative inotropic effects. Twelve patients (CAD without ischemia; EF = 60 +/- 3%) underwent hemodynamic analysis with and without the influence of ajmaline (1 mg/kg, i.v.) both 1) at rest (paced heart rate of 90 bpm) and 2) during tachycardia of 160 bpm. As a result, LV-pump function was found to have diminished moderately: EF by 23% vs 10%, respectively; stroke volume by 10% vs 0%; cardiac work by 5% vs 16%, and dP/dtmax by 14% vs 19%. While preload increased under the influence of ajmaline (LVEDP by 17% vs 30%), the LV-volumes increased (EDV by 18% vs 12%; ESV by 58% vs 21%), afterload remained unchanged. Ajmaline caused the loops of the ESPVR to move rightward and the slope k of the ESPVR to decrease, thus indicating loss of inotropy during the influence of the antiarrhythmic agent. Thus, ajmaline showed a tendency to generate cardiodepressive effects in patients with normal LV-function, and to depress contractility in single cases that clinically had no consequences. The conductance technique proved useful and safe in the assessment of inotropic drug effects by analyzing the ESPVR within the catheterization laboratory routine.

To determine whether ajmaline (A) can be safely applied in coronary artery disease (CAD), changes of left ventricular (LV) function after acute ajmaline application were analyzed by pulsed Doppler echocardiography in 10 CAD patients. LV pressures in systole and end-diastole and LVEF remained normal and comparable. Doppler normalized peak filling rate (p less than 0.02), peak early/atrial filling velocity (E/A) ratio (p less than 0.01) and E-deceleration (p less than 0.05) increased. The increase in E/A and in E-deceleration relative to base values was directly correlated (p less than 0.001). PEP increased, LVET remained unchanged. LV diastolic filling is improved after acute application of ajmaline in patients with CAD and normal systolic function; its application may be advised not only for therapy of arrhythmia but also to improve left ventricular diastolic mechanics in these patients.

In congestive heart failure (CHF), even today, pharmacotherapy renders primarily only symptomatic improvement. The success of the treatment is basically dependent on the degree of functional myocardial impairment, that is, the condition of the inadequately treatable underlying disease. Treatment should be differentially oriented to the nature of the LV dysfunction as systolic or diastolic whereby the latter may account for 20 to 40% of those with CHF. In the case of diastolic LV dysfunction, because of the impaired compliance, vasodilators are not beneficial since small changes in volume may cause marked changes in filling pressures and vice versa. Additionally, inotropic substances are unfavorable since they further increase filling pressure and impedance, that is, diastolic LV function may become more compromised. For systolic LV dysfunction both vasodilators and positive inotropic substances can be employed. Some unsettled issues remaining include the appropriate time to begin treatment, the most suitable form of combined treatment and the best dosing regimens. Digitalis, as dobutamine, increases measured contractility; those seen to profit from digitalis include symptomatic patients with LV dilatation and impaired pump function as well as patients with supraventricular tachyarrhythmias. Prior to use of positive inotropic drugs in CHF, consideration should be given to whether favorable acute effects can be maintained during longterm treatment, adverse reactions such as arrhythmogenicity are acceptable, and the actions on myocardial oxygen balance. New nonglycoside positive inotropic agents which can also be administered orally, acutely improve hemodynamics; these include catecholamine derivatives, phosphodiesterase inhibitors (PDH). Both substance groups increase contractility but arrhythmogenicity as well, in general via increased concentrations of intracellular cyclic AMP. Reservations regarding the use of positive inotropic drugs for CHF have been supported by the results of studies showing that beta 1 agonists such as prenalterol and beta 2 agonists such as salbutamol or pirbuterol, due to down-regulation of beta-receptor density, are not capable of maintaining improved contractility during chronic treatment; intermittent dobutamine treatment resulted in higher mortality; beta-blockers without intrinsic sympathomimetic activity reduced mortality in patients with CHF after myocardial infarction while on use of beta-receptor blockers with intrinsic sympathomimetic activity, this favorable effect was not observed; during chronic PDH treatment, there was an unfavorable one-year mortality rate (50 to 100%); a controlled study with amrinone did not show a higher mortality than placebo. For most PDH, it is not known with certainty at which therapeutically effective dose the positive inotropic effect can best be realized and whether the acute hemodynamic effects are not predominantly attributable to the vasodilatory properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Forty-eight patients with a positive patch test to potassium dichromate 0.5% were retested after 4-7 years; 38 patients (79%) still had a positive patch test. Chromate allergy seems to be persistent. In 72% of the cases a history of occupational exposure to chromates could be proved.

The evidence of subendocardial ischemia was studied during isoproterenol stress in seven patients with aortic valve disease before (group A) and approximately 6 months after Bjork-Shiley valvular replacement (group B), in seven patients with coronary artery disease (group C), and in seven patients without heart disease (group D). Ejection fraction, thermodilution coronary sinus flow, and lactate metabolism were determined at rest and during isoproterenol stress. Potential subendocardial blood supply was estimated from a diastolic pressure-time index (DPTI), calculated from aortic and left ventricular pressure curves, and oxygen demand, estimated from the tension-time index (TTI). The ratio of DPTI/TTI was used to estimate the supply-demand relationship. Impaired left ventricular myocardial function was apparent by a lack of increase of the ejection fraction during stress in groups A and C as compared to controls. After aortic valvular replacement (group B) during stress, an adequate increase of the ejection fraction, a normal stress response of the O2 supply-demand ratio, and a lactate extraction rather than production (all p>0.05) were found. During isoproterenol infusion (at equal heart rates and normal coronary sinus flow) a significant lactate production and decreased O2 supply-demand ratio in group A and C patients were induced, but not in group B and D patients. The more massive lactate production in group A as opposed to group C reflected subendocardial ischemia of the hypertrophic left ventricle as compared to the more regional and nonuniform distribution of ischemic areas in coronary artery disease. The results of this study suggest that ischemia and cardiac failure can be induced by isoproterenol stress in coronary artery disease as well as in hypertrophic myocardium caused by aortic stenosis. Aortic valvular replacement repaired the ischemic response found in aortic valve disease 6 months prior to surgery. Stress-induced lactate production rather than coronary sinus flow changes allow discrimination between ischemic and nonischemic myocardium. A critical DPTI/TTI ratio (≤0.4) indicates ischemia in hypertrophic myocardium caused by aortic valve disease, but this concept does not apply to ischemia caused by coronary artery disease.

Practolol was injected intravenously at 3 dose levels (5, 15 and 25 mg total dose) in patients with ischemic heart disease and in non-cardiac cases. The influence of practolol on the P-Q interval at rest and at paced rates (atrial stimulation) of 110, 125 and 140 beats/min was studied: only the 15 mg dose produced a significant prolongation of the P-Q interval of normal patients at rest and at paced rates. No significant P-Q changes were found in patients with ischemic heart disease at all dose levels. It is concluded that practolol has no measurable direct effect on A-V conduction and that patients with ischemic heart disease are not more sensitive as regards A-V conduction.

A congenital syndrome affecting the skin, oral mucosa and bulbar conjunctiva is reported in father and son. Skin lesions consisted of brownish papules with central keratotic plugs. Trauma was able to provoke lesions. In addition, changes of oral mucosa with premature loss of the teeth, and recurrent eye symptoms with conjunctivitis were present. Histological examination of specimens from skin, oral mucosa and conjunctiva revealed a uniform picture of dyskeratosis (single cell keratinization). The symptoms reported do not seem to fit into any of the existing muco-cutaneous syndromes. An autosomal dominant mutation is suggested as the cause of the disease.

In the first part of this presentation, data is reported on the hemodynamic effects of forskolin given to patients with dilated cardiomyopathy in a concentration of 3 micrograms/kg/min and 4 micrograms/kg/min. At the lower dosage, forskolin had no effect on dP/dtmax, cardiac index, ejection fraction, or myocardial oxygen consumption. With small dosages of dobutamine, however, an increase of all four parameters has been observed in the same group of patients. Systemic vascular resistance and left ventricular enddiastolic pressure fell with forskolin given at the lower concentration. Forskolin administered at a dosage of 4 micrograms/kg/min induced an increase in dP/dtmax by 19% and a 16% rise in heart rate. However, these changes were associated with symptomatic flush syndromes. Therefore, forskolin may serve as a vasodilating substance in lower concentrations, but cannot be used as a positive inotropic compound because of the subjective symptoms. In the second part, a study is reported in which an anti-ischemic effect of the phosphodiesterase inhibitor enoximone was observed in patients with proven significant coronary heart disease. With respect to the hemodynamic parameters, the most striking findings were the decreases in left ventricular enddiastolic pressure and systemic vascular resistance. Furthermore, when left ventricular stroke work index was plotted as a function of the left ventricular enddiastolic pressure, enoximone shifted the left ventricular function curve to the left. Therefore, the anti-ischemic effect of enoximone may not only be due to a reduction in preload and afterload but may rather reflect an effect on diastolic compliance. Studies with intracoronary injections of enoximone and animal experiments support this hypothesis.

Stress evaluation was carried out in 26 patients approximately 7 months after aortic valve replacement with Björk-Shiley valves (13 patients) and St. Jude medical valves (13 patients). During isoproterenol infusion (0.3 micrograms/kg/min), cardiac output increased by a factor of 1.5 and aortic valve area decreased by 50% for both valve groups, while transvalvular gradients (rest: 7 +/- 2 vs 10 +/- 5 mm Hg, p greater than 0.05) increased by 42 +/- 18 vs 51 +/- 18 mm Hg (p greater than 0.05), i.e., to levels of moderate aortic stenosis. However, during pacing stress these values progressively decreased with rising heart rates. In other postoperative evaluations that included ergometric stress with isoproterenol and pacing, induced hemodynamic changes after aortic valve replacement were predictable and consistent with regard to both direction and magnitude, and they differed characteristically according to the type of stress used. We conclude that no functional differences between Björk-Shiley and St. Jude medical valves can be claimed. Standardized evaluation with isoproterenol is a sensitive stress test of prosthetic valvular hemodynamics. Because of the apparent magnification of residual obstruction after aortic valve replacement, it has advantages over pacing.

In a case of rheumatic valve disease atrial sounds could be heard and recorded on the phonocardiogram during atrial flutter at a rate of 260/min and an atrioventricular block of 3:1 and 5:1. The atrial flutter sounds were also recorded in the apex-cardiogram and as a slight but rapid motion of the anterior mitral valve leaflet in the echocardiogram. These atrial sounds were recorded both in systole and diastole and disappeared after cardiac failure had been treated and sinus rhythm restored. This case and 19 others reported in the medical literature indicate that for atrial sounds to become audible requires high-grade atrioventricular block and increased atrial contractions with increased ventricular filling. The sounds have been proven to originate in the atrium, the characteristics of the sound being similar to those of an opening snap.

Twelve arrhythmias that occurred during and following surgery for acquired heart disease were studied in a group of 52 randomly selected patients. In cases of aortic and mitral valve replacement, Björk-Shiley prosthetic valves were used, and procain-magnesium-aspartate solution was applied for cardiac arrest. Registration and analysis of rhythm disturbances were carried out at 10 different time intervals, spaced narrowly in the intra-and early postoperative phases, then more widely up to the 96th hour of observation. Arrhythmic incidence and occurrence per case and phase are given, thereby allowing an account of transient arrhythmias as well. The peak occurrence of serious rhythm disturbance was found, intraoperatively, at about the time of aortic cross-clamping and release (ischaemic effect) with the exception of the mitral-commissurotomy group. The 1st-6th postbypass hours showed an arrhythmia trough, followed by a 2nd peak (9th-96th postoperative hour) made up of less serious arrhythmias (electrolyte- and acid-base disturbances; digitalis effects). All 12 arrhythmia types, as well as the five separately considered ventricular arrhythmias of the "first arrhythmia peak", did not reveal any significant relation to: patients' age, N.Y.H.A. criteria, pre-operative PAm or the duration of anaesthesia, surgery and bypass time.

Three patients with recurring attacks of supraventricular tachycardia and no electrocardiographic evidence of the Wolff-Parkinson-White syndrome (WPW syndrome) were studied using intracardiac recordings and atrial stimulation. The findings are interpreted as evidence of a concealed WPW syndrome. In all patients there was antegrade block of the anomalous atrioventricular (A-V) pathway while retrograde conduction was unimpaired and allowed the initiation of the observed reciprocating tachycardias. The diagnosis was based on the assumption that the ventricular myocardium was an essential link in the re-entry circuit. The three most important findings to support this assumption are: 1) retrograde conduction time, measured by the Q-A' interval (Q in ECG to atrial echo), and the rate of tachycardia were dependent on the mode of intraventricular conduction: 2) the first Q-A' interval of the tachycardia was independent of the A-H interval (initiation of atrial impulse to first activation of the His bundle) of the initiating premature atrial depolarization (PAD); 3) there was retrograde conduction following a ventricular premature beat during tachycardia at a time when the A-V node and/or the bundle of His would be refractory.

Electrophysiological studies were performed in a patient with a short P-R interval and a small delta wave. The findings suggest that ventricular pre-excitation resulted from an infranodal bypass (Mahaim type). As the functional properties of the pathway were evaluated, impaired conductivity (suggested by rather long refractory periods) became apparent at frequency stress. The pathway could easily be blocked by Ajmaline. This demonstrated an unexpected early diastolic improvement in conductivity; i.e. a supernormal phase of conduction. Due to this supernormal phase, Mahaim-fiber conduction was present when block in the anterior division of the left bundle branch, or even trifascicular block occurred. Thus the effects of exclusive Mahaim-fiber conduction on ventricular activation were documented.