Hemodynamic and humoral effects of the novel calcium antagonist Ro 40-5967 in patients with hypertension.

The tolerability and hemodynamic and humoral effects of the structurally novel calcium antagonist Ro 40-5967 were investigated in 64 patients with hypertension. In a double-blind, placebo-controlled study, ascending oral doses of 50, 100, 150, or 200 mg were administered once daily for 8 days in a solution. Ro 40-5967 was well tolerated up to 150 mg, but treatment was stopped in one patient in the 200 mg group because of bradycardia. Blood pressure was dose-dependently reduced over the full 24-hour dosing period with more pronounced effects on day 8 than on day 1. The maximum blood pressure reduction was obtained after 150 mg (supine blood pressure, -34/-25 mm Hg, p less than 0.001). Despite a slight decrease in supine heart rate, cardiac output increased. PQ time was dose-dependently increased and concentration-effect analysis showed that relevant atrioventricular conduction disturbances occur only at concentrations much higher than those required to reduce blood pressure. Changes in catecholamines, plasma renin activity, and aldosterone were small and inconsistent. In conclusion, Ro 40-5967 has a long-lasting antihypertensive effect after once-daily administration.

Efficacy and tolerability of the renin inhibitor Ro 42-5892 in patients with hypertension.

The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 [(S)-alpha-](t-butylsulfonyl)-methyl]hydrocinnamamido]-N-[1S , 2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-imi dazole-4- propionamide] was studied. Forty-nine patients with moderate essential hypertension were randomly assigned to three groups that entered an 8-day double-blind oral treatment period: daily administration of placebo (group A), 300 mg Ro 42-5892 (group B), or 600 mg Ro 42-5892 (group C). Four hours after the last oral drug intake, placebo was administered intravenously to subjects in group A and 100 mg Ro 42-5892 was administered intravenously to subjects in groups B and C. Sitting systolic and diastolic blood pressures were measured on days 1 and 8 with a blood pressure device. On day 1, systolic blood pressure maximally decreased by 13.3 +/- 9.3, 20.2 +/- 11.2, and 24.1 +/- 11.3 mm Hg in groups A, B, and C, respectively (mean +/- SD; p < 0.01 for group A versus group C). Diastolic blood pressure maximally decreased 9.4 +/- 5.7, 13.9 +/- 8.7, and 11.8 +/- 5.7 mm Hg (difference not significant). On day 8, systolic blood pressure maximally decreased 19.5 +/- 16.5, 26.5 +/- 17.4, and 30.5 +/- 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 +/- 5.0, 16.2 +/- 9.0, and 17.9 +/- 12.7 mm Hg (difference not significant) compared with pretreatment values. Intravenous drug administration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy.

Pharmacokinetics and hemodynamic effects of tiapamil: exercise performance, thallium stress scintigraphy, and radionuclide ventriculography.

The pharmacokinetic behavior and hemodynamic effects of tiapamil, a calcium antagonist, were studied in 16 cardiac patients during an eight-day treatment course, giving oral doses of 600 mg daily. The hemodynamic effects were investigated using exercise performance tests, thallium stress scintigraphy, and radionuclide ventriculography. The areas under the plasma concentration-time curve after the final dose were greater than after the first dose for both tiapamil (+53 per cent) and its metabolite (+24 per cent). One possible explanation is that tiapamil undergoes saturable intestinal wall metabolism. Alternatively, like verapamil, it may undergo a saturable hepatic elimination process. The hemodynamic test series showed that, despite increasing the exercise tolerance, tiapamil significantly reduced the rate-pressure product, an index of myocardial oxygen requirement. Regional myocardial perfusion clearly improved. Ventriculography showed a significant increase in ejection fraction (+18 per cent), cardiac index (+12 per cent), and stroke volume index (+19 per cent). At the same time, the measured mean arterial pressure decreased significantly by about 10 per cent and the calculated peripheral vascular resistance, by about 19 per cent.

[The submaximal ergometric load test in hypertensive patients during physical training and treatment with debrisoquin (author's transl)]. / Der submaximale ergometrische Belastungsversuch bei Hypertonikern unter Bewegungstherapie und Behandlung mit Debrisoquin

A standardized simple submaximal ergometric load test was used to investigate the effects of active physical training combined with physical-balneological therapy over a 4-week period in 68 hypertensive patients. The systolic and diastolic blood pressure decreased slightly (6 and 4% respectively), without any further medication, although the resting heart rate remained virtually unchanged. The identical examination regimen was applied to 2 groups of hypertensive patients (total 61), who were additionally treated for 3 weeks with respective doses of 30 mg or 40 mg debrisoquin daily, as a hypotensive agent. This additional treatment caused an optimum reduction in blood pressure (14 to 17%) and a decrease in heart rate (8 to 15%) at rest and during exercise. In summary, the additional pharmacological supporting measure intensifies the beneficial effects of exercise treatment in reducing high blood pressure and moreover, in decreasing heart rate values at rest and during work performance. The same physical load is performed more economically under conditions of lowered myocardial effort and reduced oxygen demand.

[Comparable ergometric examinations before and after administration of practolol and bunitrolol (author's transl)]. / Vergleichende ergometrische Untersuchungen nach Anwendung von Practolol und Bunitrolol

By means of a standardized, single-level ergometric load of 1.5 watt/kg body weight, the effects of a new beta-adrenergic receptor blocking agent bunitrolol (o-(2-hydroxy-3-tertiary butylamino)-propoxy)-benzonitrile) was compared with the well-known cardiovascular properties of practolol during an intraindividual therapeutic crossover trial after intravenous administration. In the absence of any side-effects, bunitrolol shows a higher degree of beta-adrenergic receptor bocking activity than practolol, with a distinct specificity towards myocardial receptors and very low cardiodepressive properties at rest. Bunitrolol caused a marked reduction (33%) in exercise-induced myocardial work effort, whilst practolol achieved a reduction of only 17% under equal conditions. Thus, the same physical work load is performed after bunitrolol more economically by decreasing both heart rate and blood pressure. The circulatory effects of an intravenous dose of 5 mg bunitrolol seems to be twice as effective as 10 mg practolol. This implies that beta-adrenergic receptor blockade by bunitrolol during work performance is four times as effective as practolol. The observed marked effect of bunitrolol on the diastolic blood pressure is discussed.

[The influence of mexiletin on ventricular arrhythmias during ergometric exercise (author's transl)]. / Zur Beeinflussung ventrikulärer Herzrhythmusstörungen durch Mexiletin im Verlauf ergometrischer Belastungsprüfungen.

Wireless telemetric ECG observations and suitably-graded ergometric loads to reach an age-dependent maximum heart rate of about 130/min. are suited for the critical examination of released ventricular arrhythmias requiring therapeutic aid. In the recovery period after ergometric exercise the incidence of ventricular arrhythmias is twice as great as at rest or during normal physical activity. Even in the recovery period distinct ST depressions were observed. The hypothesis that myocardial ischaemia predisposes to ventricular arrhythmias as a result of electrophysiological instability is apparently supported by these findings. Mexitil--a potent class I antiarrhythmic drug--significantly reduced the incidence of ventricular arrhythmias at rest, normal physical activity and after ergometric loading during initial intravenous therapy followed by continuous oral administration over a three-week period at a daily dosage of 600 to 800 mg. No significant haemodynamic effects were observed, especially with respect to the pump function of the heart during oral or intravenous therapeutic administration.

[Blood pressure analysis by means of an ultrasonic blood pressure monitor during the course of rehabilitative treatment (author's transl)]. / Blutdruckanalysen im Verlauf von Rehabilitationsheilverfahren gemessen mit einem ultraschallenergetisch betriebenen Blutdruckmessgerät

A statistic evaluation of the daily blood pressure values at rest during a 4-week period of active training combined with physiotherapy and medical baths indicated a decrease of 20 mm Bg in systolic pressure and of 9 mm Hg in diastolic pressure in patients with hypertension of various grades. The resting blood pressure shows a tendency to become normalized during the course of this therapy with phases of maximum negative decline. However, a standardized simple submaximla ergometric load test carried out weekly demonstrated that there were only minimal changes in systolic and diastolic blood pressure during exercise. In comparison with observations made in other spas, these results demonstrate a uniform reaction of the human organism to this particular form of irritative therapy independent of the particular features of the spas and the special constituents of the waters.

[Clinical observations during accumulative oral glycoside therapy with meproscillarin (author's transl)]. / Klinische Beobachtungen während einer akkumulativen oralen Glykosidtherapie mit Meproscillarin.

In heart failure of the severity degrees II and III according to Friedberg's classification, administration of a daily maintenance dose of 0.5--0.75 mg of 14-hydroxy-3beta-[(4-O-methyl-alpha-L-rhamnopyranosyl)oxy]-14beta-bufa-4,20,22-trienolide (mesproscillarin, Clift) induces a cumulative blood level of 1--1.5 mg after 8--10 days. This level eliminates manifestations of heart failure both clinically and with regard to objective criteria. Increased heart rate returns to normal particularly in types of the tachycardiac atrial fibrillation. The frequency corrected QT-time is significantly reduced by about 30 ms. The relative heart volume decreases. The heart's work is increased by about 15%. No side effects are observed under this oral accumulative glycoside therapy.

Ergometric and hemodynamic studies on a new cardiotonic agent AR-L 115 BS.

The cardiotonic agent, 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazol[4,5-b]pyridine (AR-L 115BS), increases cardiac contractility and lowers cardiac pre- and afterload. These properties were shown to favourably influence hemodynamics at rest and under exercise in patients with coronary heart disease and angina pectoris. Although it reduces pre- and afterload, unlike isosorbide dinitrate it does not improve exercise tolerance in symptom limited ergometry. There was, however, no worsening of exercise tolerance. It appears that the decrease in oxygen consumption due to a decreased pre- and afterload is compensated for by an increase in oxygen requirement during contractility.

Hemodynamic effects of calcium antagonists in cardiac patients.

Hemodynamic studies were carried out after cardiac catheterization with a floatation catheter in the pulmonary artery and cannulation of the brachial artery for the calculation of cardiac output by means of the Fick principle. Continuous pressure recordings were carried out at rest and under submaximal treadmill exercise in the supine body position in 5 homogeneous groups of 12 patients, all with disorders due to coronary disease. In a control test, hemodynamic investigations were carried out at rest before medication, under stress and after recovery. Similar tests were performed after intravenous administration of either isotonic saline as placebo, tiapamil (1.1 and 1.6 mg/kg) or verapamil (0.07 and 0.14 mg/kg). It was shown that there was a marked dose-related reduction in peripheral vascular resistance with a maximum effect occurring at 2-5 min after the intravenous administration of tiapamil (1.1 and 1.6 mg/kg) reaching 23 and 39%, respectively, or verapamil (0.07 and 0.14 mg/kg) attaining 28 and 39%, respectively, at rest and, to a similar extent, under stress conditions. In patients with sinus rhythm, the mean arterial pressure was reduced. Cardiac outputs and stroke volumes were increased at rest as well as under stress. There was no evidence of a depressant action of the drug on hemodynamic variables. An interplay of simultaneous changes in preload and afterload seems to be responsible for the effects obtained. The doses used were those commonly employed in the termination of supraventricular tachyarrhythmias. However, a potential depressant effect of tiapamil in patients with markedly reduced ventricular function is not excluded by this study.

The antihypertensive effect of lexotan (bromazepam)- a new benzodiazepine derivative.

Clinical observations led to the assumption that there is an antihypertensive effect of bromazepam in patients suffering from mild benign hypertension. Because of this observation we studied the antihypertensive effect of bromazepam by means of a standardized simple submaximal ergometric load performed weekly over a 4-week period of observation. A control group of 68 hypertensive patients without any drug therapy but under active physical training combined with physiotherapy and medicinal baths showed only a slight decrease in systolic and diastolic blood pressure at rest (about 4%). Furthermore, the pulse frequency did not change. In contrast, there was a distinct and significant decrease in blood pressure at rest and during exercise after a 3-week period of additional treatment with bromazepam, especially in hypertensive patients. One group of 68 hypertensive patients receiving 9 mg bromazepam daily showed a mean reduction in blood pressure by 14.4% systolic and 12.7% diastolic at rest, and during exercise by 7.5% systolic and 6.8% diastolic. The heart remained practically unchanged. A somewhat slighter decrease of the blood pressure values was seen in an additional group of 31 hypertensive patients receiving 6 mg bromazepam per day and in a group of 30 normotensive patients receiving 9 mg bromazepam daily. The calculated indices such as the product of heart rate and mean systolic pressure and the tension time index in the groups receiving bromazepam pointed to a better economic work performance under reduced myocardial pressure effort and reduced oxygen demand on the myocardium. The possible action of bromazepam in reducing blood pressure will be discussed.

[Problems of medical documentation in the hospital]. / Probleme der medizinischen Dokumentation im Krankenhaus.

Problems of medical documentation arise from an explosive increase of data-volumes, complexity and multiplicity in data-management. The causality of that development, the possibility of computerized support in repetitive data-management, the economic, organizing and scientific problems are widely discussed. Solving the problems in the hospital a potent middle-ranged computer offers his services under certain circumstances. To obtain an efficient support following details are to take into consideration: reduction in manipulation-time, program-organization under medical demands, safe transfer of data and text by application of modern and potent database management systems as a tool of organizing, combining and retrieving informations.