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Cardiac and peripheral vascular effects of enoximone were investigated in a placebo-controlled, crossover, double-blind trial in 10 healthy volunteers. Electromechanical systole (QS2c) revealed direct positive inotropic effects and venous occlusion plethysmography of the calf arterial blood flow before and 1, 2, 3, and 4 h following 3 mg/kg of enoximone orally. Norepinephrine (7-640 ng/min) dose-response curves of a superficial human hand vein were measured, and enoximone and enoximone-sulfoxide plasma concentrations were determined at the same time points. Peak effects on all measurements were observed at 1 h and coincided with peak plasma concentrations: QS2c shortened by 36 +/- 13 ms (mean +/- SD; p less than 0.01 compared to placebo); arterial blood flow increased from 2.10 +/- 0.58 to 4.32 +/- 1.26 ml 100 ml-1 min-1 (mean +/- SD; p less than 0.01 compared to placebo); norepinephrine dose-response curves shifted to the right (p less than 0.01 with 20-320 ng/min compared to baseline), i.e., to achieve the same vasoconstriction as before enoximone a 3-to-5-times higher dose of norepinephrine was needed. In addition to its positive inotropic effects, enoximone exerts peripheral arterial dilation and diminishes the venous vasoconstriction induced by norepinephrine. The combination of these pharmacological properties could be responsible for the beneficial effects of enoximone in heart failure.

This study assesses the consequences of angiotensin I-induced afterload-stress on mitral regurgitation by two-dimensional and color-coded Doppler echocardiography. During continuous intravenous infusion of angiotensin I in increasing doses of 0.5, 2, and 4 micrograms/min, blood pressure increased significantly from 119 +/- 7/73 +/- 3 mm Hg up to 145 +/- 8/91 +/- 4 mm Hg (+22% resp. +25%; p less than 0.0001 resp. p less than 0.0001). Heart rate did not change significantly (84 +/- 2 min-1 resp. 88 +/- 4 min-1). The enddiastolic volume index, determined by two-dimensional echocardiography, did not change significantly (104 +/- 10 ml/m2 resp. 112 +/- 3 ml/m2), the endsystolic volume index increased from 57 +/- 10 ml/m2 to 75 +/- 13 ml/m2 (+32%; p less than 0.01), the ejection fraction fell from 47 +/- 4% to 36 +/- 4% (p less than 0.001). In the RAO-equivalent view the maximal jet-length, determined by color-coded Doppler echocardiography, increased from 2.6 +/- 0.2 cm to 3.9 +/- 0.3 cm (+50%; p less than 0.001), the maximal jet-area rose from 3.4 +/- 0.6 cm2 to 7.0 +/- 1.0 cm2 (+106%; p less than 0.001); in the parasternal long axis view the maximal jet-length increased from 2.3 +/- 0.2 cm to 3.5 +/- 0.3 cm (+52%; p less than 0.001), the maximal jet-area from 2.6 +/- 0.5 cm2 to 4.9 +/- 0.8 cm2 (+89%; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

To judge the influence of drugs and diseases on systolic time intervals (STI), the connection to the covariate belonging to heart frequency has to be eliminated. For this purpose, we adopt linear dependency of the interval between the R-waves in the ECG and STI. In this paper, according to different medical questions, well-fitting correction formulae are derived, based on new biometric analysis of published data. The methods used include L1-norm and L2-norm regression, rank-test connected regression Theil and Sen, and rank-scores analysis of covariance. It is concluded that the biometric methods must be well adapted to medical methods.

His-bundle electrograms were recorded in four patients with Ebstein's anomaly of the tricuspid valve. In two of the patients His potentials could only be demonstrated in the atrialized portion of the right ventricle while in the other two patients they were recorded in the right ventricle proper. The demonstration of His-potentials only in the atrialized portion of the right ventricle suggests that the origin of the free portion of the septal tricuspid valve leaflet is significantly displaced downward into the right ventricular cavity. The prolonged atrioventricular conduction time in two patients is due to conduction delay proximal to the bundle of His.

In this placebo-controlled study the cardiac effects of once daily doses of beta-methyl digoxin 0.15 mg and 0.20 mg were evaluated using noninvasive methods. In double-blind fashion, 3 groups of 15 healthy volunteers each took 0.15 mg, or 0.20 mg beta-methyl digoxin, or placebo for a period of 14 days. On the first 2 days, all volunteers received a double amount of tablets for digoxin loading. Before the start of the study and 12 h after the last dose, the following parameters were recorded: electrocardiogram (QTc, T wave amplitude), systolic time intervals (STI) (QS2c, PEP, PEPc, LVETc), and impedance cardiogram (Heather index). The mean digoxin serum concentrations were 0.648 ng/ml and 0.975 ng/ml respectively for the two doses. The typical glycoside effects were seen and there was shortening of the STI (QS2c: - 12 ms/ - 14 ms resp.), flattening of the T wave, and a rise in the Heather index. The variations between baseline values and the 2 doses were statistically significant (p less than 0.05). In most parameters, the more intense effects corresponded with the higher serum level from the 0.20 mg dose; however, the difference between the 2 doses was not statistically significant. In conclusion, the results of this study show that a positive digitalis effect is demonstrable following the relatively small dose of beta-methyl digoxin 0.15 mg once daily under long-term application in healthy volunteers.

For evaluating the degree of accuracy of the STI, a study on 120 healthy young male volunteers was performed. Under standardized conditions ecg, phonocardiogram and carotid arterial pulse were recorded. The following variables were measured: heart cycle interval (RRI), electrical systole (QT), electromechanical systole (QS2), and left ventricular ejection time (LVET). The arithmetic mean was utilized for the consecutive beats 1--5, 1--10, 1--15, and 1--20. The mean of the beats 1--20 was assumed as reference. The increase of the analysed heart cycles from 5 to 20 lead to a decrease of the standard error of RRI, which raised the degree of accuracy. The standard error for RRI decreased from 27.9 to 9.9 ms. Already the analysis of 5 consecutive beats for QT, QS2, and LVET reached the line of identity of the correlation slope compared to 20 analysed heart cycles. The standard error was very small (2.0; 2.9; and 3.0 ms). For clinical-pharmacological studies, the evaluation of 5 consecutive heart cycles for measuring STI leads to a very high degree of accuracy. For an exact measuring of RRI, it is necessary to analyse at least 20 heart cycles.

The antihypertensive effect of an oral slow release (retard) formulation of verapamil was evaluated in a negative (placebo) and positive (nifedipine) controlled study. After a run-in period of one week without antihypertensive therapy, 54 patients were classified as having mild to moderate hypertension (diastolic blood pressure 95-115 mm Hg) and assigned randomly to one of three groups (n = 18 each). These received one of the following treatments over 2 weeks: either placebo b.i.d., or a nifedipine retard preparation 20 mg b.i.d., or a verapamil retard preparation 240 mg b.i.d. Assessments of blood pressure were made at rest and during a standardized bicycle stress test. Data were recorded at baseline and at the end of each week. After one week of treatment, 1 patient receiving nifedipine and 14 patients receiving placebo dropped out of the study because their diastolic pressures were equal to or above the values before treatment. After two weeks of treatment, 13 of 18 patients on verapamil and 9 of 18 patients on nifedipine had resting diastolic pressures less than or equal to 90 mm Hg. Also systolic pressure and blood pressures during exercise were significantly lowered by both active drugs. Verapamil caused a fall in heart rate during rest and under maximal exercise. Undesired side effects from verapamil were constipation (6 of 18) and headache (1 of 18); those from nifedipine were flush or headache (5 each of 18); ankle edema, dizziness, or tachycardia were each reported by one patient. In comparison with placebo values, verapamil lengthened the atrioventricular conduction time (PQ-interval) significantly, however, PQ-interval did not exceed 0.24 s.(ABSTRACT TRUNCATED AT 250 WORDS)

We tested an assay system introduced for plasma glycoside measurements, basing on the displacement of 3-H-ouabain from Na+-K+-ATPase by unlabeled glycoside. ATPase preparations from hog, cat and guinea pig were used. Displacements were performed using 20 cardiac glycosides, genins and derivatives with different cardiac activity. Most of the glycosides and derivatives do not induce a continuous 3-H-ouabain displacement from the ATPase, but a very steep increase of unbound 3-H-ouabain between 10-minus 7 and 2 times 10-minus 7 M. Therefore this assay system shows a satisfactory discrimination only in a short concentration range. This behavior and a relatively low sensitivity make the ATPase displacement assay problematic for clinical and pharmacokinetical plasma glycoside measurements.