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V Mitrovic

Publications and source records attributed to V Mitrovic.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Effects of the K(+) channel blocker tedisamil on hemodynamics, myocardial ischemia and neurohumoral systems in patients with stable angina pectoris. A comparison with the beta blocker atenolol].

BACKGROUND: 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. METHODS AND RESULTS: 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; p > 0.05; day 6: -14.8 vs -22.2 bpm; resp.; p > 0.05) 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; p > 0.05; day 6: -0. 86 vs -1.10 l/min, resp.; p > 0.05) and exercise (day 1: -0.82 vs -1. 28 l/min; p > 0.05; 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. CONCLUSIONS: 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.).

Adrenergic beta-Antagonists↗
PubMed1999

High-dose enoximone to evaluate reversibility of pulmonary hypertension: is there a diagnostic value of neurohormonal measurements?

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.

Angiotensin II↗
PubMed1998

Comparison of the potassium channel blocker tedisamil with the beta-adrenoceptor blocker esmolol and the calcium antagonist gallopamil in patients with coronary artery disease.

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.

Adrenergic beta-Antagonists↗
PubMed1997

Hemodynamic and autonomic effects of intravenous saterinone in patients with chronic heart failure.

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 < 0.05) and an increase in heart rate (p = 0.05). Filling pressures also decreased during saterinone, but this was statistically significant only for pulmonary capillary wedge pressure, whereas the cardiac index remained unaffected. Plasma neurohormones (norepinephrine, epinephrine, and renin activity) were not significantly influenced by saterinone. HRV analysis revealed no significant effect of saterinone on autonomic tone. These results suggest that intravenous saterinone has a significant vasodilating effect in patients with moderate to severe chronic heart failure (CHF), without exerting an adverse effect on the autonomic nervous system, as demonstrated by assessment of plasma neurohormones and HRV analysis.

Aged↗
PubMed1996

Hemodynamic and hormonal effects of quinaprilat in patients with congestive heart failure.

OBJECTIVE: To assess the pharmacodynamic activity and safety of rising single and multiple doses of intravenous quinaprilat compared with placebo in patients with New York Heart Association (NYHA) class III and IV congestive heart failure who were receiving digitalis or diuretic therapy or both. METHODS: Patients were randomly assigned to three treatment groups to receive low (0.5 to 1.0 mg), medium (1.0 and 2.5 mg), or high (5.0 and 10.0 mg) single intravenous doses of quinaprilat or placebo on day 1. On the basis of responses observed on day 1, the three treatment groups received stable multiple intravenous doses of either quinaprilat or placebo every 6 hours on days 2 and 3. Hemodynamic measurements, hormonal assessments, and safety were evaluated before and at specified intervals during the study. RESULTS: Compared with placebo, single and multiple doses of quinaprilat increased cardiac index and reduced pulmonary capillary wedge pressure, mean arterial pressure, systemic vascular resistance, and right atrial pressure in a dose-related manner. No clinically important change in heart rate was observed. Hemodynamic changes after multiple-dose quinaprilat administration were similar to those observed after single doses and were generally sustained during the 6-hour dosing interval. Relative to placebo, quinaprilat reduced plasma angiotensin converting enzyme (ACE) activity, angiotensin II concentration, and aldosterone concentration and increased plasma renin activity; no prominent changes in plasma catecholamine and atrial natriuretic peptide concentrations were observed. There were no clinically important drug-related changes in the safety parameters. CONCLUSIONS: Single and multiple intravenous doses of 0.5 to 10 mg quinaprilat are well-tolerated and produce favorable dose-dependent hemodynamic effects and hormonal changes consistent with those expected of an ACE inhibitor in patients with NYHA class III and IV congestive heart failure.

Adult↗
PubMed1996

The influence of Albunex on the pulmonary circulation in patients with pulmonary hypertension or left heart failure.

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.

Albumins↗
PubMed1996

[Hemodynamic and humoral effects of parenteral therapy with intravenously administered ACE inhibitor quinaprilat in patients with advanced heart failure].

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% (p < 0.05) and simultaneously decreased both peripheral vascular resistance by 25% (p < 0.05) and left ventricular filling pressures by 33% (p < 0.05). There was a dose-related decrease in mean right atrial pressure by 47% (p < 0.05) 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 (p < 0.05) 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.

Adult↗
PubMed1996

[Acute effects of enoximone after intracoronary administration on hemodynamics, myocardial perfusion and regional wall motion].

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 (p < 0.001), dp/dtmax increased from 1050 to 1369 mm Hg/s (p < 0.001) and regional EF from 47% to 58% (p < 0.01), while global EF remained unchanged (45% vs 47%). ST-segment depression was reduced significantly from 2.3 to 1.5 mm (p < 0.01). Enoximone induced an increase in myocardial perfusion by 129% (p < 0.001) 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 (p < 0.001). The isovolumetric relaxation was shortened by 13% (p < 0.05), the E wave by 5%, and dp/dtmin increased by 17% (p < 0.01). 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.

Adult↗
PubMed1996

[The new potassium channel blocker tedisamil and its hemodynamic, anti-ischemic and neurohumoral effect in patients with coronary heart disease].

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%, p < 0.001) and maximum exercise (-9%, p < 0.05). There was a consecutive fall of CO (by 10%, p < 0.05), 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 (p < 0.05) 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; p < 0.05). Plasma catecholamine levels fell in a dose-dependent way by a maximum of 115-150 pg/ml (p < 0.01) on treatment with 0.4 mg/kg BW. QTc was found significantly prolonged by 16% (p < 0.001) 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% (p < 0.001) 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.

Aged↗
PubMed1995

Determination of monoamine oxidase B activity by high-performance liquid chromatography with electrochemical detection.

A sensitive high-performance liquid chromatography method with electrochemical detection for measuring monoamine oxidase B activity in blood platelets is described. Dopamine is used as substrate and is incubated with isolated platelets and aldehyde dehydrogenase to convert dihydroxyphenylacetaldehyde to dihydroxyphenylacetic acid (DOPAC). The acid and the added internal standard hydrocaffeic acid are separated from dopamine and the incubation mixture by extraction with 5 ml of ethyl acetate-toluene (5:1, v/v). The organic phase is evaporated under nitrogen stream and the residue dissolved in 0.1 M citric acid. Dihydroxyphenylacetic acid and the internal standard dihydrocaffeic acid are then separated on a Eurosphere 100-C18 5 microns column. The mobile phase used was a mixture of sodium acetate, citric acid, and acetonitrile at pH 2.5. The standard curve was linear from 125 pg to 10 ng. Absolute recovery of DOPAC was 85 +/- 3.8% and of hydrocaffeic acid 87 +/- 4.1%. The method presented is sensitive (detection limit 8.0 pg of DOPAC injected) and reproducible (coefficient of variation 0.4-1%) with good accuracy (94-98%).

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effects of nicorandil on regional perfusion and left ventricular function.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Steady-state plasma kinetics of slow-release propafenone, its two isomers and its main metabolites.

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.

Acetylation↗
PubMed1994

[Anti-ischemia effects of gallopamil and esmolol in an intra-individual comparison in patients with coronary heart disease].

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.

Adrenergic beta-Antagonists↗
PubMed1994

Steady-state plasma concentrations of propafenone--chirality and metabolism.

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.

Adult↗
PubMed1994

[Neurohumoral and hemodynamic effects in combination therapy of enoximone and dopamine].

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 (p < 0.001). Enoximone monotherapy produced a comparable increase in cardiac index between 27 and 32% (p < 0.001). Enoximone, but not dopamine, resulted in a significant decrease in mean pulmonary artery pressure (21-26%; p < 0.01), pulmonary capillary wedge pressure (24-30%; p < 0.01), and right atrial mean pressure (26-28%; p < 0.001). 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%; p < 0.001). There was a highly significant decrease by 49-55% in systemic vascular resistance with enoximone (p < 0.001), 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 (p < 0.01). Enoximone produced a heart rate increase by 8-13% (being significant after 2 h; p < 0.05) with no changes in blood pressure. The combination therapy with dopamine and enoximone led to an additive increase in cardiac index by 35-43% (p < 0.001), a decrease in right atrial mean pressure by 28-36% (p < 0.01), a decrease in systemic vascular resistance by 27-30% (p < 0.01) 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 (p < 0.001) as well as a significant decrease in aldosterone (0 < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Rapid and sensitive assay of dobutamine in plasma by high-performance liquid chromatography and electrochemical detection.

A sensitive and specific high-performance liquid chromatographic method with electrochemical detection was developed for measuring dobutamine in human plasma samples. Following an external standard method, 0.1 ml of EDTA-glutathione plasma was diluted on ice with 0.2 ml of a 5% trichloracetic acid solution. The mixture was centrifuged, filtered, and 30 microliters were injected. Assessment was done by electrochemical detection. The assay was linear from 1 to 400 ng/ml plasma. For determination of dobutamine we also used a liquid-liquid extraction method routinely applied for plasma catecholamines. Liquid-liquid extraction requires application of 100-1000 microliters of plasma. The standard curve was linear from 0.1 to 600 ng/ml. Absolute recovery of dobutamine was 90 +/- 3% with the liquid-liquid extraction procedure and 91 +/- 3% with the protein precipitation method. For both methods dobutamine was separated on Nova-Pak C18 columns. The mobile phase used was 0.1 molar phosphate buffer-acetonitrile (80:20, v/v) with 1-octanesulfonic acid and triethylamine as ion-pair reagents. The pH was adjusted to 2.7.

Chromatography, High Pressure Liquid↗
PubMed1993

Tedisamil (KC 8857) is a new specific bradycardic drug: does it also influence myocardial contractility? Analysis by the conductance (volume) technique in coronary artery disease.

To determine whether inotropism influences the bradycardic action of tedisamil, hemodynamic assessment was performed in 13 patients with ischemic coronary artery disease including analysis of end-systolic pressure-volume relationships after an infusion of tedisamil, 0.3 mg/kg, at rest, and during paced tachycardia stress. Slope Emax fell by 14% at rest (13 patients) and by 10% during tachycardia (6/13 patients), whereas loops of end-systolic pressure-volume relationships moved rightward; all parameter changes indicated a lack of significant inotropism loss with tedisamil (p > 0.05). Although the mean heart rate decreased from 77.5 to 64.7 beats/min and QTc duration increased by 14% (p < 0.05), filling pressure and dp/dtmin remained unchanged and vascular resistance increased by 30%. Parameters of left ventricular pump function (ejection fraction, stroke volume, left ventricular efficiency) decreased slightly (between 3% and 13%), whereas left ventricular volumes increased (end-diastolic volume by 6%, end-systolic volume by 23%). The respective parameter changes during tachycardia were comparable in tendency, and angina could no longer be induced during postdrug pacing stress. We concluded that the bradycardic effects of tedisamil are selectively generated without impairing either ventricular pump function or contractility in a clinically relevant fashion, whereas the postdrug anginal threshold appears elevated. Thus tedisamil can be used safely in ischemic coronary artery disease.

Aged↗