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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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

In 10 patients without and 20 patients with various degrees of angiographically proven CAD 93 pacing runs were studied. Changes of PAm, of ECG, and of anginal pain serving as parameters of myocardial ischemia were correlated to the rate-pressure-product. In patients without CAD no correlations could be ascertained. In each patient with CAD determination of ischemia was achieved reproducibly. Ischemia threshold is represented by a sharp increase of PAm. Ischemia threshold seems a parameter to be preferred as compared to pain threshold. The extent of CAD (angiographically estimated) correlates well with the pacing test especially when collaterals are taken into account. After NG no substantial improvement of ischemia can be detected: Ischemia threshold before and after NG was reached at same rate pressure in each case. We conclude the atrial pacing test to be an excellent test for the provocation of myocardial ischemia. The test is also useful for estimation of the extent of CAD.

Urinary histamine was studied in 11 patients with severe atopic dermatitis and 17 controls, as well as in seven atopics prior to and 6 months following hyposensitization. No statistically significant differences were found between the groups. Urinary histamine seems to be of no value as an indicator of disease activity in atopic dermatitis.

The adenylate cyclase activator 17 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxylabd-14-en-11-one (forskolin) was studied for its beneficial effect as therapeutic agent for the treatment of dilated cardiomyopathy (DCM). In 7 DCM-patients with normal (group A) and 8 DCM-patients with pathological dP/dtmax-values (group B), we analyzed serially (computer-assisted) the pressure/volume (P/V) effects as P/V-loops (microtip catheter/Tc-99m scintigraphy) and on-line MV02 (indirectly: Bretschneider equation) under dobutamine, 10 micrograms/kg/min i.v., and forskolin, 3 micrograms/kg/min i.v. For the total group (A + B) there was no change of contractility during forskolin (p greater than 0.05); with dobutamine, however, it rose by an average of +25%. The preload decline was more pronounced with forskolin (LVEDP by -27%) as compared to dobutamine (by-19%); while left ventricular (LV-)function improved moderately only with forskolin (by +9%) and significantly (by +34%) with dobutamine. Thus, forskolin improved LV-function primarily via reduction of preload in DCM-hearts and without rising metabolic costs. Beneficial hemodynamic effects with forskolin are quantitatively less as compared to those with dobutamine (accompanied by higher MVO2-costs). It is concluded that residual myocardial reserves in DCM are mobilized by dobutamine rather than forskolin. Serial P/V-loop and on-line MVO2 registration aided in the demonstration of forskolin efficacy as compared to dobutamine.

Hemodialysis is associated with alterations in myocardial contractility, but duration and precise determinants responsible for these changes are unknown. We investigated the effect of several variables, established to influence left ventricular (LV) contractility, which normally changed during dialysis: the plasma concentrations of ionized calcium, potassium, bicarbonate, and magnesium and the removal of uremic toxins. The influence of three different isovolemic bicarbonate-dialysis procedures in 16 patients with normal (group 1) and hypertrophied myocardium (group 2) was assessed by echocardiography prior to and up to 44 h following each dialysis. During the first procedure, ionized calcium and potassium concentration decreased, but LV performance remained unchanged in both groups. The second procedure with increased ionized calcium and decreased potassium concentration resulted in an improvement of mean circumferential fiber shortening (VCF from 1.15 to 1.56 circ/s (P less than 0.001) in group 1 and from 1.05 to 1.16 circ/s (P less than 0.05) in group 2. The positive inotropic effect declined gradually up to 12 h (group 1) and 2.5 h (group 2) respectively. In the third procedure when ionized calcium was increased and potassium concentration remained unchanged contractility did not improve. Removal of uremic toxins, decrease in magnesium, and increase in bicarbonate concentrations were comparable during each procedure. These results suggest that the ionized calcium to potassium ratio is the important determinant of dialysis-related augmentation in LV contractility. In LV hypertrophy the expected contractile response is diminished indicating a depressed inotropic state.

The St. Jude medical (SJM) heart valve prosthesis presents a new bi-leaflet design which in preclinical evaluation exhibited favourable haemodynamic characteristics. Therefore clinical trials started in February 1978. The entire valve is made of pyrolytic carbon which has a poor X-ray visibility and therefore an alternative for the noninvasive routine control of valvular function and postoperative follow-up had to be found. Experimental studies in a left heart simulator provided adequate echovisualisation of both leaflets, however, depending on the direction of their motion in relation to the echobeam. Identification of both leaflets and an analysis of their motion was possible with a transducer at right angles to the leaflet axis. The experimental data were confirmed by clinical observations after implantation of the SJM prosthesis in patients. Based on the information obtained, we are providing recommendations for the implantation of the SJM prosthesis in order to achieve optimal echocardiographic visualisation of the valve and its moving parts in the postoperative follow-up.

Ein gesundes Herz bringt eine ausreichende Adaptation des HZV uber weite Frequenzbereiche zustande, d.h. signifikante HZV-Anderungen zwischen den Frequenzen 40 und 160/min finden weder in Ruhe noch unter korperlicher Belastung statt (Stein et al. 1966b). Dabei besteht eine inverse Relation zwischen Frequenz und Schlagvolumen. Mit steigender Frequenz verkleinert sich das Schlagvolumen jedoch zunachst weniger als es dem Frequenzzuwachs entspricht, so das das HZV erst ansteigt, dann gleichbleibt und erst bei Frequenzen von 160/min in Folge der Verkurzung der diastolischen Fullungsphase abnimmt, weil das Schlagvolumen nun starker absinkt, als es dem Frequenzzuwachs entspricht (Miller et al. 1962). Mit adaquater Auffullung des diastolischen Herzvolumens durch venosen Ruckstrom bei steigender Frequenz kann das HZV ansteigen. Unter korperlicher Belastung (Vatner et al. 1972 b) und unter Volumenzufuhr (Vatner et al. 1975) aber ist eine erhohte Herzfrequenz zur Erhohung des HZV notwendig (Abb. 1).

Inwieweit eine stressinduzierte regionale Funktionsstorung des Myocards bei Koronarstenose durch eine aortokoronare Bypass-Operation (AKBO) beeinflust wird, ist unzureichend untersucht. Es wurde bei 20 Pat. mit hochgradiger Stenose der LAD vor oder nach AKBO eine Stress-Ventrikulografie nach ventrikularer Stimmulation mit 170/min vorgenommen. Pat. mit stenosiertem oder verschlossenem Graft wurden ausgeschlossen. Als Kontrollgruppe dienten 6 Pat. ohne Herzerkrankung. Aus den biplanen Ventrikulogrammen wurden Vorderwandbeweglich-keit (AWM) und Ejektionsfraktion (EF) berechnet. Die Pat. wurden nach dem praoperativen Ruheventrikulogramm in Hypokinesie (AWM 10 - 30%) und Normal- kinesie (AWM > 30%) eingeteilt.