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Leukoaraiosis is a change in brain white matter with characteristic manifestation in MR and CT head scans. Common leukoaraiosis risk factors include aging and arterial hypertension. A quarter of symptomatic ischemic infarcts belongs to small blood vessel disease group and could be presented as lacunar infarcts. These two crucial pathophysiological mechanisms are in the root of cognitive dysfunction related to small blood vessel disease. 60 lacunar infarct patients were examined and parameters for groups with and with-out leukoaraiosis were determined. It was found that leukoaraiosis incidence was highest in the group of women older than 70. Neurological assessment was scored on NIH-NINDS scale, functional status was scored with Barthelo index, and cognitive status was determined using Mini Mental State Examination (MMSE) and Alzheimer Disease Assessment Scale Late (ADAS-L). Correlation analysis of these parameters on significance level of *p

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group.

Bei der Behandlung der akut dekompensierten Herzinsuffizienz stehen seit Kurzem neue Therapiekonzepte bereit. Die Wirkweise der neuen Substanzen wird uber Guanylatzyklase vermittelt. cGMP entsteht aus Guanosintriphosphat. Hierfur sind 2 Isoenzyme der Guanylatzyklase verantwortlich: Eine ist in die Plasmamembran eingelagert und wird durch natriuretische Peptide stimuliert. Die andere findet sich im Zytosol bestimmter Zellen. Es handelt sich um ein Ham-Protein, das durch Stickstoffmonoxid aktiviert wird. Nesiritide und Ularitide sind natriuretische Peptide, die an der plasmamembrangebundenen Guanylatzyklase wirken und vasodilatatorische, natriuretische und diuretische Effekte aufweisen. Cinaciguat aktiviert die Synthese von cGMP, indem es die zytosolische Guanylatzyklase in seinem NO-unempfindlichen, eisenoxydierten oder Ham-freien Zustand erkennt und bindet. Diese Substanz wirkt sehr gut unter oxidativem Stress. Vorlaufige Studien mit Cinaciguat zeigen eine beachtliche Verbesserung der Hamodynamik und eine deutliche Symptomlinderung unter Aufrechterhaltung der Nierenfunktion.

BACKGROUND AND OBJECTIVE Blood pressure values resulting from measurements by the patients themselves have greater diagnostic and prognostic significance than those measured by the physician, assuming, however, that measurement is taken correctly. As self-measurement of blood pressure has meanwhile become a widespread practice. The question arises to what extent the rules on exact measurement of blood pressure are known to the patient. PATIENTS AND METHODS The answers to questions on five rules on self-measurement of blood pressure (resting period prior to measurement, time of measurement and intake of morning medication, left or right arm for measurement, level of measuring point and width of cuff) given by 500 hypertensive patients (373 men, 127 women, mean age 59.2 +/- 10.2 years) were evaluated. RESULTS Three patients only were in the position to answer all five questions correctly. 19 % were unable to give any right answer. Patients showed highest information levels concerning the resting period before measurement. Approximately half of them (51 %) knew that a pause of three minutes has to be kept. Only one in three, however, was familiar with the fact that morning measurement has to be taken prior to the intake of antihypertensives (32 %) choosing the arm that shows higher blood pressure values. 28 % were informed that the measuring point has to lie at the height of the heart. Only 4 % were able to answer the question on the width of the cuff correctly. CONCLUSION Our findings show that the rules on correct self-measurement of blood pressure are unknown to most of the hypertensive patients. This may be due to the fact that they are insufficiently informed and trained.

Moxonidin ist ein neuer zentral wirksamer Imidazolin-Rezeptor-Agonist, der aufgrund seiner sympathikolytischen Wirkung effektiv zur Behandlung der arteriellen Hypertonie eingesetzt wird. Die vorliegende Arbeit ist die erste Untersuchung uber die Auswirkungen von Monoxidin auf die koronare und systemische Hamodynamik, metabolische Ischamiemarker und neurohumorale Parameter bei Patienten mit einer essentiellen Hypertonie vom Schweregrad WHO I–II. Die Auswirkungen von Monoxidin nach Einzelgabe von 0,4 mg p.o. wurden an 22 Hochdruckpatienten mit linksventrikularer Hypertrophie, ST-Streckensenkungen wahrend der Belastung, pectanginosen Beschwerden und unauffalligen Koronararterien untersucht. Untersuchungsparameter waren der arterielle Blutdruck, das Herzzeitvolumen, der mittlere Pulmonalarterien- und der pulmonalkapillare Verschlussdruck sowie der Koronarsinusflow mittels intravaskularer Dopplertechnik. Die durch Monoxidin induzierten Parameteranderungen nach 2 Stunden stellten sich wie folgt dar: Der systolische/diastolische Blutdruck sank im Mittel um 28/10mmHg und die Herzfrequenz um 5/min. Gleichzeitig sank der PAPm um 17% und der PCWP um 26%. Der linksventrikulare Schlagarbeitsindex sank um 26%, MVO2 um 18% und der CSF um 16%. Die mittlere Spitzengeschwindigkeit im Koronarsinus fiel um 18% und die Koronarreserve (nach Adenosingabe) stieg um 12%. Die CS-O2-Sattigung stieg um 4%. Parallel hierzu kam es zu einem Anstieg der Laktatextraktion um 17% und zu einem Abfall des Noradrenalin Spillover um 30% und der arteriellen Endothelinkonzentration um 20%. Zusammenfassung: Moxonidin bewirkt eine klinisch relevante Sympathikolyse mit gunstigen Auswirkungen auf Hamodynamik, koronare Durchblutung, metabolische Ischamiemarker und neurohumorale Parameter.

Klinische Limitationen bei der Behandlung der stabilen Angina pectoris mittels Betablocker fuhrten zur Entwicklung von alternativen frequenzsenkenden Substanzen wie beispielsweise dem K+-Kanalblocker Tedisamil, der neben antiischamischen auch antiarrhythmische Eigenschaften aufweist. In der vorliegenden Untersuchung (doppelblinder, randomisierter Gruppenvergleich) wurden die hamodynamischen, antiischamischen, metabolischen und neurohumoralen Auswirkungen von 2× 100 mg Tedisamil und 2× 50 mg Atenolol als Monotherapie bei 48 Patienten mit stabiler Angina pectoris uber einen Zeitraum von 6 Tagen verglichen. Tedisamil und Atenolol fuhrten zu einer Senkung der Herzfrequenz sowohl in Ruhe (Tag 1: –14 vs –15 min-1; p > 0,05; Tag 6: –15 vs –22 min-1; p > 0,05) als auch unter Belastung (Tag 1: –9 vs –18 min-1; p = 0,001; Tag 6: –12 vs –25 min-1; p = 0,001) bei gleichzeitiger Erhohung der Angina-pectoris-Schwelle. Das Herzzeitvolumen wurde unter beiden Substanzen sowohl in Ruhe (Tag 1: –1,01 vs –1,19 l/min; p > 0,05; Tag 6: –0,86 vs –1,01 l/min; p > 0,05) als auch unter Belastung (Tag 1: –0,82 vs –1,28 l/min; p > 0,05); Tag 6: –0,65 vs –2,68 l/min; p = 0,03) gesenkt, wobei das Schlagvolumen unverandert blieb. Der rechtsatriale Druck anderte sich nur unter Belastung mit einem Abfall unter Tedisamil (–1,7 mm Hg) und einem Anstieg unter Atenolol (+3,7 mm Hg) (p = 0,001). In der Tedisamil-Gruppe fiel der mittlere pulmonalkapillare Verschlusdruck am 6. Behandlungstag sowohl in Ruhe (–0,5 mm Hg) als auch unter Belastung (–6,9 mm Hg), zeigte jedoch unter Atenolol eine Tendenz zum Anstieg (Ruhe: +1,7 mm Hg; Belastung: +3,7 mm Hg) (p = 0,03). Eine Senkung des arteriellen Druckes zeigte sich nur unter Behandlung mit Atenolol. Wahrend die belastungsinduzierten Noradrenalin-Plasmaspiegel nach Tedisamil-Gabe gesenkt wurden (–93 pg/ml), zeigte sich unter Atenolol eine Erhohung (+172 pg/ml) (p = 0,001). Nach Tedisamil fand sich eine im Vergleich zu Atenolol signifikante Verlangerung des QTc-Intervalls (+31 vs –8 ms) 8p = 0,002) bei einem Ausgangswert von 0,408 ± 0,018 und unveranderten PQ- und QRS-Zeiten. In der vorliegenden Studie zeigte Tedisamil gunstige hamodynamische, metabolische und neurohumorale Effekte bei Patienten mit stabiler Angina pectoris. Die antiischamische Wirkung von Tedisamil, gemessen an der ST-Strecken-Senkung und der Angina-pectoris-Schwelle, ist mit der von Atenolol vergleichbar.

A grid of experimental alloys containing nominally 17% Cr and 7.5% Ni in combination with low (0.01%) and high (0.1%) nitrogen and low (0.004%) and high (0.01%) sulfur was prepared with co...

Electronprobe microanalysis of the magnesium matrix in a series of Mg-Fe alloys was used to measure the concentration of Fe in solid solution in Mg. The “solubility limit” was found to be approximately 55 ppm (by weight) at 400°C and 28 ppm at 500°C. Thermodynamic evaluation of these data suggests that the equilibrium has. been established with a phase other than high-purity αFe and semiquantitative analysis by transmission electron microscopy has confirmed that the precipitates are Fe containing dissolved Si. Resume La micro analyse par sonde electronique d'une mat rice de magnesium a ete utilisee sur une serie d'alliages Mg–Fe pour mesurer la concentration de Fe en solution solide dans le magnesium. La limite de solubilite se situe environ a 55 ppm (poids) a 400°C et 28 ppm a 500°C. L'evaluation thermodynamique de ces donnees suggere que l'equilibre s'est etabli, laissant une phase autre que le fer-α de haute purete, et l'analyse semi-quantitative par microscopie electronique en transmission a c...

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary summarizes the results and recommendations of this working group.

The initiation of localized corrosion with alloys exhibiting passive behavior has been studied extensively by the authors; first, with austenitic stainless steels and, more recently, with martensitic stainless steel and nickel. In all cases, it was observed that a go/no-go corrosion initiation threshold existed as a function of temperature, and a theoretical approach was developed to explain the stability boundary as the environment became more aggressive due to an increase in temperature or chloride concentration or a decrease in pH. Because magnesium and magnesium alloys are expected to show passive behavior at high pH, it was decided to expand this approach to investigate the localized corrosion resistance of magnesium alloys. The ranking of alloys by this go/no-go methodology addresses only the resistance to the initiation of localized corrosion and not the subsequent kinetics of attack. EXPERIMENTAL PROCEDURE

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.

This study examines the relationships between distorted cognitions, motivation, and alexithymia on problem gambling in poker players (n = 96). Respondents completed questionnaires containing the Canadian Problem Gambling Index, Gambling Motivation Scale, Gambler’s Beliefs Questionnaire, and Toronto Alexithymia Scale-20. The results suggest that problem gambling is significantly related to distorted cognitions, non-self-determined motivation, and difficulty identifying feelings. Implications are drawn for the development of more relevant intervention, prevention, and treatment strategies.

Les hormones peptidiques, qui appartiennent a la famille des peptides natriuretiques (NP), jouent un role important dans le maintien de la fonction cardiaque et renale en regulant le volume hydrique, la pression arterielle et la concentration en sodium. Les principaux membres de cette famille sont les peptides natriuretiques auriculaires (peptides natriuretiques de type A ou cardiodilatine, ANP), ľurodilatine (URO), les peptides natriuretiques cerebraux (peptides natriuretiques de type B, BNP) et les peptides natriuretiques de type C (CNP). ďun point de vue physiologique, ces molecules ont generalement une action vasodilatatrice, natriuretique et diuretique et regulent ľhemostasie sodique et hydrique — des effets qui en font des candidats prometteurs pour le traitement des troubles cardiovasculaires et renaux. Ce chapitre porte sur la biochimie, la physiologie et le potentiel therapeutique des principaux peptides natriuretiques en soulignant leur importance clinique dans le traitement du syndrome ďinsuffisance cardiaque (IC) aigue.

We use the data collected by the Lung Image Database Consortium (LIDC) for modeling the radiologists' nodule interpretations based on image content of the nodule by using decision trees. Up to 4 radiologists delineated nodule boundaries and provided ratings for nine nodule characteristics (lobulation, margin, sphericity, etc). Therefore, there can be up to 4 instances per nodule in our data set. However, to learn a good predictive model, the data set should have only one instance per nodule. In this study, we investigate several approaches to combine delineated boundaries and ratings from multiple observers. From our experimental results, we learned that the thresholded p-map analysis approach with the probability threshold PrGt=0.75 provides the best predictive accuracies for the nodule characteristics. In the long run, we expect that the predictive model will improve radiologists' efficiency and reduce inter-reader variability.

The corrosion behavior of test welds on the hull of the M.V. Arctic was monitored for 30 months. An excellent correlation was found between these data and laboratory tests lasting 6 months in the case of free-corrosion tank tests and 15 days in the case of galvanostatic anodic dissolution tests.

After a rapid increase in infusion rate of adrenaline to elevate the initial heart rate by more than 15 %, a continuous infusion was sustained in order to maintain elevated adrenaline plasma levels. A

Blood pressure values resulting from measurements by the patients themselves have greater diagnostic and prognostic significance than those measured by the physician, assuming, however, that measurement is taken correctly. As self-measurement of blood pressure has meanwhile become a widespread practice. The question arises to what extent the rules on exact measurement of blood pressure are known to the patient.The answers to questions on five rules on self-measurement of blood pressure (resting period prior to measurement, time of measurement and intake of morning medication, left or right arm for measurement, level of measuring point and width of cuff) given by 500 hypertensive patients (373 men, 127 women, mean age 59.2 +/- 10.2 years) were evaluated.Three patients only were in the position to answer all five questions correctly. 19 % were unable to give any right answer. Patients showed highest information levels concerning the resting period before measurement. Approximately half of them (51 %) knew that a pause of three minutes has to be kept. Only one in three, however, was familiar with the fact that morning measurement has to be taken prior to the intake of antihypertensives (32 %) choosing the arm that shows higher blood pressure values. 28 % were informed that the measuring point has to lie at the height of the heart. Only 4 % were able to answer the question on the width of the cuff correctly.Our findings show that the rules on correct self-measurement of blood pressure are unknown to most of the hypertensive patients. This may be due to the fact that they are insufficiently informed and trained.

Some medications have been shown to produce reductions in hs-CRP levels after initiating therapy. Whereas the role of the renin-angiotensin system in the inflammatory process has been documented in more detail during the last few years, the impact of an ACE-inhibitor therapy on this process has not been fully understood so far. The aim of this study was to investigate the effect of a therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on hs-CRP plasma concentrations in patients with atherosclerosis.A total of 24 patients were enrolled in this prospective, uncontrolled, open-label multicenter study. Inclusion criteria were documented atherosclerosis, baseline high-sensitivity C-reactive protein between 3 and 12 mg/l, LDL-Cholesterolor =150 mg/dl and no previous treatment with ACE inhibitors or angiotensin receptor blockers. Ten patients, pretreated with statins, and 10 patients not previously treated with statins were eligible for statistical analysis. Baseline high-sensitivity C-reactive protein was significantly decreased from 3.99+/-1.61 mg/l (mean+/-SD) to 2.72+/-1.19 mg/l (-32%) after 3 months treatment with 10 mg ramipril daily (p=0.0002). The decrease was more pronounced in patients who had not been treated with statins previously (-1.50 mg/l+/-1.44 mg/l) compared to those who were pretreated (-0.90 mg/l+/-0.93 mg/l).The ACE inhibitor ramipril administered in a daily dose of 10 mg to patients with atherosclerosis reduces the high-sensitivity C-reactive protein concentration. This effect may contribute to cardiovascular risk reduction mediated by ramipril aside from the blood pressure lowering effect.

In patients with atrial septal defects of the secundum-type (ASD), exercise tolerance is reduced. Generally, ASD closure is recommended in symptomatic patients and in patients with a relevant left-to-right shunt (Qp/Qs1.5). Only few data are available concerning objective parameters of cardiopulmonary exercise capacity. The aim of this study was to evaluate exercise capacity as achieved by ergospirometry in adult patients with an ASD at baseline and in the long-term following transcatheter closure.Thirty consecutive patients (8 male; mean age 43.4 years; defect size 23.5 mm; pulmonary-to-systemic flow ratio (Qp/Qs) 1.94) performed exercise testing on a supine bicycle ergometer. At baseline, oxygen consumption at maximal exercise (VO(2) peak) was 14.3 ml/min kg, oxygen consumption at the anaerobic threshold (VO(2)-AT) was 11.2 ml/min/kg and maximal achieved workload was 86 Watt. At one and six months after ASD-closure, there was no relevant increase of the VO(2) peak, the VO(2)-AT or the maximal workload. After 12 months, there was a significant increase of the VO(2) peak (15.1 ml/min/kg, p = 0.049), the VO(2)-AT (13 ml/min/kg, p0.001) and the maximal workload (99 Watt, p0.01). An increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT) could be seen in 24 out of 30 patients and was independent of shunt volume (Q(p)/Q(s)or = 2, 1.95 ml/ min/kg; Q(p)/Q(s)2, 2.13 ml/min/ kg; ns), defect size (defector = 24 mm, 2.0 ml/min/kg; defect24 mm, 1.5 ml/min/kg; ns), age (ageor = 44 years, 1.97 ml/min/kg; age44 years, 1.66 ml/min/kg; ns), gender (female 1.56 ml/min/ kg; male 1.91 ml/min/kg; ns) and of the existence of a residual shunt. Highly symptomatic patients had a tendency to have greater benefit from ASD-closure as compared to mildly symptomatic patients (NYHA 0/I 1.85 ml/min/kg; NYHA II 1.5 ml/min/ kg; NYHA III 2.7 ml/min/kg; ns). There was no correlation between shunt volume, shunt size, pulmonal arterial pressure and increase of the oxygen consumption at the anaerobic threshold (Delta VO(2) AT).There is no relevant improvement in exercise capacity early (1-6 months) after interventional ASD-closure, but late after ASD-closure (12 months) exercise capacity improves significantly. This improvement can be found in almost all patients independent of gender, age, symptoms, shunt volume and defect size.

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.

Standardized extracts of Crataegus leaves and blossoms are said to have positive inotropic, positive dromotropic and negative bathmotropic effects. Clinical trials produce evidence for an improvement of symptoms in patients with congestive heart failure (NYHA II). In this trial the efficacy of a standardized extract of fresh Crataegus berries (Rob 10) on exercise tolerance and quality of life was studied in 88 patients. In a three-month placebo-controlled, randomized, double-blind trial these patients were treated with Rob 10 (3 x 25 drops daily). Total exercise time in bicycle ergometry was defined as primary efficacy variable, while quality of life (Minnesota Questionnaire), Dyspnea-Fatigue Index and the assessment of dyspnea by the patient on a visual analogous scale were chosen as secondary parameters. Investigations were performed after a two week placebo run-in period as well as 6 and 12 weeks after the onset of the study. Treatment with Rob 10 led to a increase of exercise time of 38.9 s vs placebo (95% confidence interval 5.7-72.1 s). Quality of life improved accordingly in favour of Rob 10. In the Minnesota Questionnaire, the total score fell by 31% (30.6 vs 44.1) under Rob 10 vs 18% (34.6 vs 42.4) under placebo. The Dyspnea-Fatigue Index demonstrated an increase of the total score of 12% (9.41 vs 8.37) vs 8% (8.92 vs 8.26) under administration of placebo. According to findings of the assessment of dyspnea by the patient, dyspnea decreased by 11% (50.5 vs 56.6 mm) vs 4% (54.8 vs 57.3 mm) under placebo. The present study proves the efficacy and safety of a standardized extract of fresh Crataegus berries (Rob 10) in patients with congestive heart failure (NYHA II) regarding the parameters evaluated.

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.

To investigate the hemodynamic effects of the selective endothelin (ET)A receptor antagonist LU135252 in patients with congestive heart failure (CHF).Nonselective ET(A/B( receptor antagonists improve hemodynamics in patients with CHF. Since ET(B( receptors mediate the release of nitric oxide and the clearance of ET-1, selective ET(A) antagonists are of special interest.The hemodynamic effects of a single oral dose of the selective ET(A) receptor antagonist LU135252 (1, 10, 30, 100 or 300 mg) were investigated in a multicenter study involving 95 patients with CHF (New York Heart Association II-III) with an ejection fractionor = 35%.Baseline ET-1 positively correlated with pulmonary vascular resistance, pulmonary capillary wedge pressure (PCWP), and mean pulmonary artery pressure (MPAP, r = 0.37-0.50, p0.0004) but were inversely related to cardiac index (CI; r = -0.36, p = 0.0004). LU135252 dose dependently increased CI and decreased mean arterial pressure and systemic vascular resistance (p0.03-0.0002), while heart rate remained constant or decreased slightly. Pulmonary capillary wedge pressure, MPAP, pulmonary vascular resistance and right atrial pressure also decreased significantly (p0.035-0.0001). Two hours after LU135252, plasma ET-1 did not significantly increase after 1 mg but did so by 23% (p = 0.003), 29% (p = 0.0018), 56% (p0.0001) and 101% (p0.0001) after 10, 30, 100 and 300 mg, respectively, while plasma catecholamines remained constant.In patients with CHF, a single oral dose of the selective ET(A) receptor antagonist LU135252 improves hemodynamics in a dose-dependent manner without activation of other neurohumoral systems and is well tolerated over a wide dose range.

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.

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.).

Die Geschichte der Therapie der koronaren Herzkrankheit begann nicht erst mit der Einfuhrung der Nitrite und Nitrate im 19. Jahrhundert, sondern bereits viel fruher, als Menschen zum ersten Mal bewust die Symptome der koronaren Durchblutungsstorung wahrnahmen und versuchten, die Ursache zu finden, um ihr Kranksein zu erleichtern. Der geschichtliche Verlauf hat gezeigt, das der Wissensstand uber die koronare Herzkrankheit gleichzeitig die Grundlage der Therapie war. Um diese geschichtliche Beziehung zu wahren, soil beim histori schen Ruckblick nicht nur auf die Therapie, sondern auch auf den Erkenntnisstand der jeweiligen Zeit eingegangen werden.

Der Wirkmechanismus der Phosphodiesterase-III-Hemmstoffe ist recht komplex und setzt die genaue Kenntnis der intrazellularen Prozesse voraus, so das vorab die Beschreibung der physiologischen Regulation der Myokardkontraktion erfolgt.

In this study, the hemodynamic and neurohumoral/autonomic effects of intravenous saterinone (a selective phosphodiesterase type III inhibitor, with additional alpha(1)-blocking properties) were evaluated. In a double-blind, placebo-controlled design, 36 patients with moderate to severe heart failure were studied (saterinone, n = 24; placebo, n = 12). Invasive hemodynamic measurements, by using right-heart catheterization, were performed, as well as measurement of plasma neurohormones and analysis of heart rate variability (HRV), to study drug influences on neurohumoral activation and autonomic tone. Systemic vascular resistance significantly decreased during saterinone infusion, accompanied by a decrease in systemic blood pressure (both p values

Thirty-two patients with angiographically proven coronary artery disease and reproducible ST-segment depression in the exercise ECG took part in this open dose-finding study on the hemodynamic and anti-ischemic effects of tedisamil, using right heart catheterization and bicycle exercise testing. Tedisamil--a bispidine derivative--is a new potassium channel blocking agent with negative chronotropic (i.e., direct effects on sinus node automaticity) and class III antiarrhythmic properties. Four groups of 8 patients each received rising doses of 0.1, 0.2, 0.3, and 0.4 mg/kg BW tedisamil intravenously. Being well tolerated, tedisamil was found to be dose-linear with the dose of 0.3 mg/kg BW having the most favorable anti-ischemic effects accompanied by a significant decrease in heart rate at rest (-13%, p0.001) and maximum exercise (-9%, p0.05). There was a consecutive fall of CO (by 10%, p0.05), while stroke volume remained unaltered. Despite singular significant changes, PCWPm and RV-EF, as indirect parameters of ventricular function, showed different responses without a clear tendency. PAPm increased slightly in accordance with peripheral and pulmonary vascular resistance, being significant at 3.3 mm Hg (p0.05) only at the dose of 0.4 mg/kg BW. Mean arterial pressure demonstrated a slight increase at rest (9% at 0.4 mg/kg BW; p0.05). Plasma catecholamine levels fell in a dose-dependent way by a maximum of 115-150 pg/ml (p0.01) on treatment with 0.4 mg/kg BW. QTc was found significantly prolonged by 16% (p0.001) on 0.4 mg/kg BW. During treatment with 0.3 mg/kg BW, tedisamil produced a dose-dependent reduction of ST segment depression at a maximum of 42% (p0.001) as well as a decrease in myocardial oxygen consumption, pressure rate product, and plasma lactate concentrations. In conclusion, tedisamil lowered heart rate and showed favorable hemodynamic, anti-ischemic, and neurohumoral effects in patients with coronary artery disease.

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.

The hemodynamic and neurohumoral effects of single and multiple doses of intravenous quinaprilat were assessed and compared with placebo in a double-blind design. The study group included 50 patients aged between 33 and 76 years with NYHA Class III and IV heart failure. The patients were randomized into three treatment groups to receive low (0.5 and 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) intravenous doses of quinaprilat or placebo on day 1, and, based on the responses, q6h on two further days. The hemodynamic parameters were determined by right-heart catheterization. Quinaprilat is the active metabolite of quinapril, an ACE inhibitor with high affinity for the angiotensin converting enzyme, which is formulated for oral application. Compared with placebo, single and multiple doses of quinaprilat increased cardiac index by 25% (p0.05) and simultaneously decreased both peripheral vascular resistance by 25% (p0.05) and left ventricular filling pressures by 33% (p0.05). There was a dose-related decrease in mean right atrial pressure by 47% (p0.05) without significant heart rate changes (-3-5 bpm). The mean artery pressure showed a dose-related maximum decrease of 4-9 mm Hg 45-60 min after single-dose quinaprilat and of 7-10 mm Hg (p0.05) after repetitive dosing. Maximum changes were observed 15-90 min after drug application. The hemodynamic changes after multiple-dose quinaprilat were similar to those observed following single doses and generally persisted during the total observation period of 6 h. Compared with placebo, quinaprilat reduced ACE activity and angiotensin II and aldosterone concentrations, and increased plasma renin activity. There were no significant changes with regard to plasma catecholamines and the atrial natriuretic factor, although a slight decrease could be observed. The study results obtained in patients with advanced heart failure support both the safety and favorable hemodynamic and neurohumoral effects of intravenous quinaprilat over an observation period of 3 days.

To determine the safety of the ultrasound contrast agent Albunex, its influence on right and left heart haemodynamics in patients with pulmonary artery hypertension or left heart failure was assessed after intravenous injection. Patients with a left ventricular ejection fraction smaller than 40% or a systolic pulmonary artery pressure greater than 40 mmHg received 0.08 and 0.22 ml.kg -1 Albunex and 10 ml albumin in random order during right heart catheterization and transthoracic echocardiography. Right atrial, systolic and diastolic pulmonary artery and capillary wedge pressures were measured at 3 min and 5 min and cardiac output at 5 min after the intravenous injection of Albunex and control. The mean differences of pre- and postinjection values and their confidence intervals were tabulated and significance was anticipated if the confidence interval did not include 0. Significant changes to pre-injection values could be observed in diastolic pulmonary artery pressure 5 min after the injection of albumin and 0.08 ml.kg -1 Albunex, and in right atrial pressure 5 min after the injection of 0.22 ml. kg -1 Albunex only. Since intermediate opacification of the left ventricle was seen in only four patients with 0.22 ml.kg -1 Albunex, in the patients studied higher doses of Albunex and their safety need to be assessed.

Steady-state plasma kinetics of propafenone (CAS 54063-53-5), the S- and R-enantiomers, and the two main metabolites were investigated in a double-blind, placebo-controlled dose-finding study using a slow-release formulation of propafenone at three different dose regimens (2 x 225 mg, 2 x 325 mg, and 2 x 425 mg). The study included a total of 24 patients (18 m, 6 f) with symptomatic ventricular arrhythmia. Since statistically valuable data was limited by a considerable portion of undetectable plasma concentrations among patients having received verum, kinetics could be followed up only in a group of 14 patients (10 m, 4 f) over a period of 12 h under steady state conditions. All patients were phenotyped prior to the study by measuring the ratio of sparteine/dehydrosparteine and three poor metabolizers were identified. A detailed description of the analytical methods used is given. With the low dose, a mean plasma level of 87 +/- 16 ng propafenone per ml plasma was obtained, with the medium dose a level of 243 +/- 34 ng/ml and with the higher dose 334 +/- 71 ng/ml were reached. All three doses of the slow-release preparation resulted in a smoothened and thus therapeutically favorable plasma concentration curve, independently from phenotype. With regard to the two propafenone enantiomers, a preferential clearance of the R-form (S/R = 2.08 +/- 0.19) could be confirmed without observing a change in the S/R ratio with time.

In a selected group of 86 patients (60 males, 26 females) with symptomatic ventricular arrhythmias, possible interactions between metabolic and chiral effects at steady-state were investigated by comparing the plasma levels of propafenone, its major metabolites and the 2 structural isomers. The antiarrhythmic drug propafenone is metabolized--besides a minor dealkylation pathway--mainly via 5-hydroxylation. It is a well-known phenomenon that this oxidative pathway is not shared by all individuals to the same extent. We were able to verify among our subjects the portion of so-called poor metabolizers reported in the literature for the total population. Propafenone was administered as a slow release formulation at 3 different dose regimens (2 x 225 mg, 2 x 325 mg and 2 x 425 mg). The crude drug is a racemic mixture of equal amounts of R- and S-forms. During treatment, the plasma S and R ratio was shifted towards the S-isomer due to preferential clearance of the R-form. It was further found that neither a genetic disposition (gender, metabolic phenotype) nor age or the dose applied had any influence on the measured plasma isomer ratio.

To compare the hemodynamic, antiischemic, metabolic, and neurohumoral effects of intravenous esmolol (beta 1 blocking agent) and gallopamil (verapamil-like calcium channel blocker), 14 patients with angiographically proven CAD and reproducible ST segment depression were studied at rest and during exercise under control conditions and after an intravenous bolus injection of esmolol (0.5 mg/kg/1 min, followed by an infusion with 0.2 mg/kg/min) or gallopamil (0.025 mg/kg/3 min). In contrast to gallopamil, esmolol significantly reduced systolic blood pressure (175.7 vs. 160 mm Hg) and heart rate (107.4 vs. 96.9 min-1) during exercise as well as cardiac output (11.57 vs. 9.38 l/min) and significantly enhanced systemic vascular resistance both at rest (1241 vs. 1479 dynes.s.cm-5) and during exercise (805 vs. 947 dynes.s.cm-5). On the other hand, exercise filling pressures and lactate levels (3.66 vs. 3.05 mmol/l) were significantly reduced by gallopamil only. Thus, the significant improvement of exercise tolerance by both esmolol and gallopamil is based on different mechanisms of action: esmolol improves myocardial ischemia by appreciably reducing myocardial oxygen consumption, whereas gallopamil primarily improves oxygen supply and ventricular performance. Plasma catecholamines, atrial natriuretic factor, and aldosterone levels as well as plasma renin activity were identically influenced by esmolol and gallopamil, respectively. A reflex activation of the sympathetic system did not occur.

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.

The hemodynamic, clinical, and neurohumeral effects of a prolonged (6-days) intravenous enoximone-infusion therapy were evaluated in 12 patients suffering from severe cardiac failure due to dilated cardiomyopathy. The loading dose of enoximone was 1.5 mg/kg. The maintenance dose during the two phases of constant intravenous infusion were 4 and 8 mcg/kg/min, respectively. The enoximone infusion therapy produced sustained salutary effects on cardiac hemodynamics and on clinical status in every patient. The enoximone infusion therapy caused a decrease in mean pulmonary artery pressure by 38%, an increase in cardiac index by 60%, the pulmonary and systemic vascular resistance decreased by 61% and 37%, respectively. Side effects and therapy-related cardiac arrhythmias were not observed.Enoximone infusion therapy provides sustained salutary hemodynamic and clinical effects in patients with severe cardiac failure.

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.