Biomedical subjects

S Sundberg

Publications and source records attributed to S Sundberg.

At least 19 recordsLinked to original sources

PubMed2003

Pharmacokinetic-pharmacodynamic interrelationships of intravenous and oral levosimendan in patients with severe congestive heart failure.

OBJECTIVE: To assess the pharmacokinetic-pharmacodynamic (PK-PD) interrelations after a 6-hour continuous infusion and a 2 mg single oral dose of levosimendan in patients with congestive heart failure (CHF). METHODS: This was an open-label, non-randomized Phase II trial in 29 patients with New York Heart Association (NYHA) class III-IV CHF, comprising 2 study days. On the first day, patients were given 6-hour levosimendan infusion with the dose 0.2 microg/kg/min. After a 1-week washout, the patients received a 2 mg single oral dose of levosimendan. Heart rate-corrected electromechanical systole QS2i was the primary variable. Secondary variables were heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) and 24-hour ambulatory ECG (Holter). RESULTS: QS2i shortened from 515 ms at baseline to 506 ms at the end of 6-hour infusion (p = 0.007). After 2 mg single dose, QS2i shortened at 2 h after drug intake from 532 ms at baseline to 525 ms (p = 0.006). The effect was similar also at 8 h (532 ms vs 526 ms, p = 0.017). Mean of maximum shortening of QS2i observed during the infusion was 22 ms (p < 0.0001) and 17 ms after 2 mg single oral dose (p < 0.0001). The concentration-effect loops for QS2i showed a clear counter-clockwise hysteresis with both modes of administration. sBP and dBP decreased both during infusion and after 2 mg oral dose. HR remained unchanged during both modes of administration. CONCLUSIONS: Both 6-hour infusion and 2 mg single dose of levosimendan showed that levosimendan possesses moderate inotropic and vasodilatory effects in patients with severe congestive heart failure, which could be described as counter-clockwise hysteresis. It seemed that the vasodilatory effect appeared earlier than the inotropic effect.

Administration, Oral↗

PubMed2000

Electrophysiologic effects of a calcium sensitizer inotrope levosimendan administered intravenously in patients with normal cardiac function.

Provocation of fatal cardiac arrhythmias has limited the use of inotropic agents as heart failure therapy. Calcium sensitization of the myofilaments might increase inotropy without influencing cardiac electrophysiology unless modified by ancillary properties of the drugs. Electrophysiologic effects of a calcium sensitizer inotrope levosimendan were examined in short-term intravenous administration in humans. Variables were determined in 10 patients with normal cardiac function during a preceding control phase and levosimendan infusion yielding a high therapeutic concentration of 110 (+/-22) microg/L. Levosimendan increased heart rate by 9 beats/min (p < 0.01) on average and shortened the sinus node recovery time and AH interval. At the tested cycle lengths, levosimendan shortened the effective refractory periods in the atrioventricular node by 40-63 ms (p < 0.05), in the atrium by 22-33 ms (p < 0.001), and in the ventricle by 5-9 ms (p < 0.005) on average. Levosimendan increased ventricular monophasic action potential duration by 9-17 ms at 50% (p < 0.001) and by 5-15 ms (p = 0.07) at 90% levels of repolarization on average. The QT interval during spontaneous rhythm and atrial pacing remained unchanged although increased slightly when corrected to sinus rate (p < 0.001). The observations indicate that levosimendan in short-term administration facilitates impulse formation and conduction in cardiac slow-response tissue, enhances recovery of excitability in the myocardium, and may delay ventricular repolarization. The effects on the ventricle were not substantial, and therefore the likelihood of provoking serious cardiac arrhythmias is not estimated to be high.

Action Potentials↗

PubMed2000

Test tube's end.

Explore the source record for details and available documents.

Genetic Techniques↗

PubMed1999

Separation of linoleic acid oxidation products by micellar electrokinetic capillary chromatography and nonaqueous capillary electrophoresis.

In this work the suitability of micellar electrokinetic capillary chromatography (MEKC) and nonaqueous capillary electrophoresis (CE) to the analysis of the primary oxidation products of linoleic acid was studied with uncoated fused-silica capillaries. The primary autoxidation products of linoleic acid are the four hydroperoxide isomers 13-hydroperoxy-cis-9, trans-11-octadecadienoic acid, 13-hydroperoxy-trans-9, trans-11-octadecadienoic acid, 9-hydroperoxy-trans-10,cis-12-octadecadienoic acid, 9-hydroperoxy-trans-10, trans-12-octadecadienoic acid. Addition of a surfactant such as sodium dodecyl sulfate (SDS) or sodium cholate (SC) into the running buffer (20-30 mM 3-(cyclohexylamino)-1-propanesulfonic acid (CAPS) or ammonium acetate, pH 9.5-11) was required to enhance the water solubility of the sample and selectivity of the separation. MEKC proved to be a promising new technique for the separation of the primary oxidation products of lipids giving results comparable to high performance liquid chromatography (HPLC). Partial separation of hydroperoxide isomers was also achieved using nonaqueous CE with methanol-acetonitrile-sodium cholate as running buffer.

Chromatography, Micellar Electrokinetic Capillary↗

PubMed1998

Aerobic endurance exercise or circuit-type resistance training for individuals with impaired glucose tolerance?

The role of physical activity in the prevention of non-insulin-dependent diabetes mellitus (NIDDM) is of utmost importance. The aim of the present study was to evaluate the metabolic effects of aerobic endurance exercise and circuit-type resistance training in subjects with impaired glucose tolerance (IGT). Twenty-two individuals participated in the study. Fourteen subjects were enrolled in the aerobic endurance exercise part of the study; seven exercised regularly for six months, while seven served as controls. Maximal aerobic capacity (VO2max) was measured and insulin sensitivity and insulin secretion were assessed by a frequently sampled intravenous glucose tolerance test (FSIVGTT). Eight subjects participated in a circuit-type resistance training program for three months. Insulin sensitivity and substrate oxidation were then assessed using the euglycemic insulin clamp technique combined with indirect calorimetry. The aerobic endurance exercise program caused in increase in VO2max (21.6 +/- 1.9 to 25.4 +/- 2.4 ml/kg.min; p < 0.05) and HDL-cholesterol (1.14 +/- 0.06 to 1.23 +/- 0.08 mmol/l; p < 0.05), but no change in insulin sensitivity nor insulin secretion occurred. However, comparing the changes between the intervention and control group, the differences disappeared. Circuit-type resistance training increased insulin sensitivity (glucose disposal) by 23% (p < 0.05), primarily due to a 27% increase in non-oxidative glucose metabolism. Both circuit-type resistance training and aerobic endurance exercise seem to have beneficial effects in subjects with impaired glucose tolerance. However, by improving insulin sensitivity, circuit-type resistance training may postpone the manifestations of NIDDM in these high-risk individuals and should therefore be included in an exercise program for IGT subjects.

Blood Glucose↗

PubMed1998

The effect of prolonged doxycycline therapy on Chlamydia pneumoniae serological markers, coronary heart disease risk factors and forearm basal nitric oxide production.

Chronic Chlamydia pneumoniae infection, characterized by elevated levels of C. pneumoniae IgG and IgA antibodies and immunocomplexes, is associated with myocardial infarction and angiographically verified coronary heart disease. C. pneumoniae organisms have also been found in coronary atheromas, but not in healthy vessels. We investigated the effect of 4 months' doxycycline therapy on serological markers of C. pneumoniae infection and coronary risk factors. Thirty-four non-smoking men, aged 57.9 (+/- 5.2) years, who had mild hypertension or moderate hypercholesterolaemia and a previous coronary bypass, were randomly assigned to receive doxycycline or matching placebo for 4 months. Acetylsalicylic acid and beta-blocker were the only other medications allowed. Patients were examined physically and by laboratory tests; their basal nitric oxide production was determined by blood flow responses to intra-arterial monomethyl-L-arginine at baseline and at 2 and 4 months. The tests were also taken at 6 months after medication. At entry, the demographic, clinical, blood flow and laboratory measurements were similar in both groups, with the exception of fibrinogen and triglyceride levels, which were higher in the placebo group. No significant changes were found in any of the parameters during the treatment. Thus extended doxycycline therapy did not affect C. pneumoniae antibodies or coronary heart disease risk factors. We conclude that doxycycline monotherapy may not be sufficient to eradicate chronic C. pneumoniae infection.

Adult↗

PubMed1998

Integrated pharmacokinetics and pharmacodynamics of the novel calcium sensitizer levosimendan as assessed by systolic time intervals.

BACKGROUND: Levosimendan is a new calcium sensitizer, acting calcium-dependently on cardiac troponin C. In the present study pharmacokinetic-pharmacodynamic interrelations of levosimendan were assessed. SUBJECTS AND METHODS: Ten healthy subjects (22-27 years) were given single doses of 2 mg of levosimendan in 4 different formulations: intravenous (i.v.), conventional tablet (CT), conventional capsule (CC), and slow-release tablet (SR) on different days. Systolic time intervals and impedance cardiography were recorded up to 4 hours post drug. Plasma concentrations of levosimendan and its metabolite OR-1855 were analyzed using HPLC. Hysteresis loops were constructed by connecting the effect-concentration points in time order. In addition, pharmacokinetic-pharmacodynamic modelling was performed with the i.v. data. RESULTS: The i.v. administration, giving a maximal levosimendan concentration of 180 ng x ml(-1), increased heart rate by 8 beats min(-1) and cardiac output by 18%. It shortened heart rate corrected electromechanical systole QS2i by 23 ms, indicating a fairly strong positive inotropic effect. The conventional oral formulations (giving maximal drug concentrations of about 70-80 ng x ml(-1)) increased heart rate by 4-5 beats min(-1) and cardiac output by 5-8%, while QS2i shortened by 9-13 ms. The SR formulation resulted in low drug concentrations and generally weaker effects than the other formulations. The bioavailability of CT and CC was 83 and 87%, while that of SR was only 31%. QS2i showed counter-clockwise hysteresis after all formulations (p < 0.01). The mean equilibration half-time (ln(2)/k(e0)) after i.v. administration was 9.6 min. Only after SR, OR-1855 was detected in appreciable amounts in plasma, the highest value being 2.2 ng x ml(-1) which occurred 24 hours after drug intake. CONCLUSION: In conclusion, the pharmacokinetic-dynamic behavior of the inotropy index QS2i indicates an equilibration delay of levosimendan, which most probably reflects the time the drug requires to distribute from plasma to its cardiac site of action. The deviant kinetic-dynamic profile of the oral slow-release formulation suggests a different absorption pattern of levosimendan from this formulation.

Administration, Oral↗

PubMed1996

COMT inhibition by entacapone does not affect growth hormone or prolactin secretion in healthy volunteers.

We studied the effects of entacapone, a novel inhibitor of the enzyme catechol-O-methyltransferase (COMT), on spontaneous and levodopa (LD) modulated secretion of growth hormone (GH) and prolactin (PRL) in 12 healthy male volunteers. The study had a double-blind, cross-over design with two experimental settings. In the first setting the subjects received a single oral dose of 400 mg of entacapone or matching placebo in a randomized order. In the second setting, a single oral dose of 300 mg of LD and 75 mg of carbidopa was administered concomitantly with either 400 mg of entacapone or matching placebo in a randomized order. Entacapone had no effect on resting levels of GH, but PRL concentrations in plasma were slightly lower after entacapone than after placebo. As expected, LD/carbidopa increased the concentration of GH and decreased that of PRL. The effects of LD were not influenced by concomitant administration of entacapone. Compared with the administration of LD/carbidopa together with placebo, concomitant administration of entacapone increased the AUC of LD by 29% and reduced the AUC of 3-O-methyldopa (a metabolite of LD produced by COMT) by 69%. Entacapone appears not to enhance the effects of LD on hypothalamic-pituitary function, although the LD dose used may have been bigger than optimal for detection of a small modulatory influence.

Adult↗

PubMed1996

Simultaneous inhibition of catecholamine-O-methylation by entacapone and neuronal uptake by imipramine: lack of interactions.

OBJECTIVE: We have evaluated the effects of simultaneous inhibition of catechol-O-methyltransferase (COMT) by entacapone and of neuronal monoamine reuptake by imipramine on haemodynamics and catecholamine metabolism, and the safety and tolerability of the drug combination in healthy women. METHODS: In a randomized, single-dose, single-blind, cross-over study, 12 healthy women were given placebo, entacapone (200 mg), imipramine (75 mg) or entacapone and imipramine in combination. Heart rate, blood pressure, systolic time intervals, and plasma concentrations of catecholamines and their metabolites were measured at rest and during exercise. RESULTS: The only drug-related effect on haemodynamics was an increase in heart rate during exercise after imipramine. The increase in heart rate after the combination of entacapone and imipramine was similar to that after imipramine alone. Entacapone alone had no effects on haemodynamics. Imipramine and entacapone had no significant effects on the plasma concentrations of noradrenaline and adrenaline. No interactions between entacapone and imipramine were detected.

Adrenergic Uptake Inhibitors↗

PubMed1996

Simultaneous inhibition of catechol-O-methyltransferase and monoamine oxidase A: effects on hemodynamics and catecholamine metabolism in healthy volunteers.

OBJECTIVE: To evaluate the effects of simultaneous pharmacologic inhibition of catechol-O-methyltransferase (COMT) and monoamine oxidase type A (MAO-A) on hemodynamics and catecholamine metabolism in healthy volunteers at rest and during exercise. BACKGROUND: Entacapone, a COMT inhibitor, is studied as an adjunct to levodopa treatment in patients with Parkinson's disease. Moclobemide, an MAO-A inhibitor, is already in clinical use as an antidepressant. It is likely that entacapone and moclobemide will be used concomitantly in the future in patients who have both Parkinson's disease and depression. It was therefore considered to be important to investigate the tolerability of combined COMT and MAO-A inhibition with entacapone and moclobemide. DESIGN AND METHODS: This was a randomized, single-dose, double-blind crossover study of 12 healthy male volunteers. The treatments were either placebo, 200 mg entacapone, 150 mg moclobemide, or the combination of entacapone and moclobemide in single doses. Heart rate, blood pressure, impedance cardiography, and plasma concentrations of catecholamines and their metabolites were measured both at rest and during submaximal standardized bicycle exercise. RESULTS: Entacapone and moclobemide (either alone or in combination) did not change heart rate, blood pressure, or any hemodynamic parameter at rest or during exercise compared with placebo. Neither were the concentrations of norepinephrine and epinephrine in plasma influenced. Both drugs had the expected effects on catecholamine metabolite concentrations in plasma. The decrease in the concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) induced by moclobemide was not potentiated by entacapone. CONCLUSION: The combined use of therapeutic single doses of entacapone and moclobemide in healthy volunteers did not affect the hemodynamics or concentrations of unconjugated norepinephrine and epinephrine in plasma. Other mechanisms are capable of regulating the concentrations of norepinephrine and epinephrine in circulating blood (and apparently also at receptors in the heart and vascular tissue) when both COMT and MAO-A activity are inhibited to a significant extent. This was also the case during marked sympathetic stimulation. The changes in the catecholamine metabolite concentrations provide evidence of effective COMT and MAO inhibition. Concentrations of MHPG in plasma are determined mainly by MAO-A activity because COMT inhibition did not have an additional effect on the moclobemide-induced decrease in plasma MHPG.

Administration, Oral↗

PubMed1996

Management of common pediatric fractures.

Pediatric fractures are seen commonly in emergency departments. Pediatricians are usually the first physicians to assess injured children. Pediatricians should be comfortable in evaluating the fracture and interpreting radiographs prior to consulting an orthopedist. An understanding of the differences between pediatric and adult bone makes the assessment of children and their radiographs easier. Musculoskeletal injuries, fractures, and sprains are common, most of which require minimal care. Growth plate injuries, however, pose a risk for permanent deformity and must be managed with care.

Arm Injuries↗

PubMed1996

Assessment of cardiac performance: short- and medium-term variability of impedance cardiography at rest and during dynamic exercise.

Short- and medium-term variability of impedance cardiography at rest and during exercise at a heart rate of 155-160 beats/min were assessed in 12 healthy men aged 21-28 years. Two consecutive measurements within 1 min were performed 4 times at 2-hour intervals on 2 days 14 days apart. Ejection fraction was the most reproducible of all impedance cardiography parameters, the CV ranging from 3.3-5.9%. The short-term reproducibility of cardiac output and stroke volume at rest was good, the between-repeats coefficient of variation (CV) being 4-6%. The reproducibility weakened with longer time span (between-day CV being about 12%) and higher heart rates (exercise). However, even the between-day reproducibility at rest was as good as that of heart rate. Between-day CV during exercise were about 20%.

Adult↗

PubMed1995

Hemodynamic and neurohumoral effects of levosimendan, a new calcium sensitizer, at rest and during exercise in healthy men.

Levosimendan is a novel inodilator that increases the calcium sensitivity of troponin C in a calcium-dependent way. Cardiac function (impedance cardiography, systolic time intervals), neurohumoral responses at rest and during exercise at 2 workloads, and peripheral blood flow (plethysmography) were studied in 14 healthy young men. Vehicle and 2 doses of levosimendan (6.5 micrograms/kg, low dose [LD]; and 25 micrograms/kg, high dose [HD]) were given intravenously in a crossover study. Measurements taken 15 minutes after a supine rest showed HD levosimendan shortened electromechanical systole (QS2i) by 16 ms maximally (p < 0.001), and decreased systemic vascular resistance by 25% (p < 0.001), compared with baseline values. Diastolic blood pressure fell by 9 mm Hg (p < 0.01). When the changes after vehicle were compared with the changes after HD levosimendan, the difference was 2.1 L/min after 25 micrograms/kg (p < 0.001), caused by an increase in stroke volume, with the heart rate being unaffected. Leg blood flow increased by 35% (p < 0.001). During exercise at the lower workload, HD levosimendan increased cardiac output by 1.5 L/min (p < 0.05), compared with that caused by vehicle, by an increase in heart rate, with the stroke volume being unchanged. Electromechanical systole was shortened significantly (20 ms, p < 0.001 after HD; 12 ms, p < 0.01 after LD). At the higher workload, no effects on electromechanical systole or cardiac output compared with that associated with administration of vehicle were seen, but the mean heart rate increased (p < 0.001, LD and HD) and mean diastolic blood pressure decreased (p < 0.01, HD).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

The effect of entacapone on the disposition and hemodynamic effects of intravenous isoproterenol and epinephrine.

BACKGROUND: Entacapone is a potent, selective catechol-O-methyltransferase (COMT) inhibitor. Entacapone could potentiate the hemodynamic effects of exogenously administered catecholamines, which are substrates of the COMT enzyme. DESIGN AND METHODS: Originally, the study was to follow a placebo-controlled, randomized crossover design. Because of two cases of ventricular arrhythmia, a decision was made to terminate the study before its completion. Six subjects went through the isoproterenol and epinephrine infusions while taking placebo and five other subjects while taking entacapone. The actual design was thus one with two parallel groups with random allocation and double-blind drug administration. The subjects were given either a single dose of 400 mg entacapone or placebo 30 minutes before the start of isoproterenol or epinephrine infusions. Four dosages of epinephrine (1.5, 3, 6, or 12 micrograms/min) and isoproterenol (0.5, 1, 1.5, or 2 micrograms/min) were infused (5 minutes for each level). Heart rate and blood pressure were measured and ECG was monitored. The concentrations of isoproterenol and epinephrine in plasma were determined by HPLC. RESULTS: The maximal increase in heart rate during isoproterenol infusion after entacapone administration (40 +/- 11 beats/min, mean +/- SD) was statistically greater (p = 0.0496) than after placebo administration (27 +/- 7 beats/min). The increase in heart rate during epinephrine infusion was 25 +/- 13 beats/min after entacapone administration and 14 +/- 9 beats/min after placebo administration (p = 0.127). There were no statistically significant differences between entacapone and placebo in blood pressure or in plasma concentrations of isoproterenol and epinephrine. CONCLUSION: We conclude that entacapone may potentiate the chronotropic and arrhythmogenic effects of exogenously administered isoproterenol and epinephrine.

Adult↗

PubMed1995

Variation in plethysmographically measured limb blood flow using two study designs.

Ingestion of food is known to influence peripheral blood flow. In clinical drug trials it is important to obtain values which do not fluctuate because of exogenous factors. In the study reported here, the variability of limb blood flow was assessed using two study designs: after a light standard breakfast with nothing more to eat (Day A); and after an overnight fast followed by a heavy non-standardized lunch (Day B). Calf and forearm blood flow (BF), venous capacity (VC) and maximal venous outflow (MVO) were measured by means of strain-gauge venous occlusion plethysmography in 10 young healthy subjects six times during a period of 8 h. The most stable values were recorded from the calf on Day A, when no statistically significant variation occurred in any of the parameters. Mean values for calf BF ranged from 3.9 to 4.3 ml min-1 100 ml-1 (SEM 0.3-0.4) at the different time points on Day A. The corresponding values for VC were 3.4-3.7 ml 100 ml-1 (SEM 0.2-0.3) and for MVO were 100-112 ml min-1 100 ml-1 (SEM 7-10). Within-subject coefficients of variation were 13-16%. After lunch on Day B, both calf and forearm BF increased significantly, by 40-60%, as compared with prelunch values, and remained at about this level throughout the rest of the day. The corresponding postlunch increase in VC was 25-40%, and that in MVO was 20-25%. A study design in which the subjects ate a light, standard breakfast before the start of measurements and fasted thereafter gave fairly stable plethysmographic results.

Adult↗

PubMed1995

Dose-range study of a new calcium sensitizer, levosimendan, in patients with left ventricular dysfunction.

Levosimendan, a new drug that sensitizes troponin-C to calcium and selectively inhibits phosphodiesterase III, was administered to 24 patients with ischemic heart disease and ejection fraction below 40%. In a placebo-controlled, crossover, double-blind study, each patient received two intravenous doses of levosimendan on 2 consecutive study days. The doses were 0.25 mg (n = 6), 0.5 mg (n = 11), 1 mg (n = 12), 2 mg (n = 12), and 4 mg (n = 5). After 0.25 mg and 0.5 mg, cardiac output increased by 0.49-0.67 L/min (p < 0.05) due to an increase in stroke volume of 6-11 ml. After 2 and 4 mg, cardiac output increased by 0.61-0.88 L/min due to an increase in heart rate of 6-12 beats/min. The baseline filling pressures, i.e., right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP), were within the normal range. RAP decreased significantly (p < 0.05) after 2 and 4 mg and PCWP after 0.5, 1, 2, and 4 mg. The most profound decreases were observed 10 min after infusion of 4 mg, from 5.0 to 3.2 mm Hg in RAP and from 9.8 to 6.0 mm Hg in PCWP. Total peripheral resistance decreased significantly only after 2 and 4 mg, by 13 and 21%, respectively. However, there were no statistically significant changes in pulmonary vascular resistance. It is concluded that levosimendan has a hemodynamically favorable action after 0.25 and 0.5 mg but that decreases in filling pressures probably prevented the increase in stroke volume and caused a reflex increase in heart rate after 2 and 4 mg.

Aged↗

PubMed1994

Hemodynamic effects of the novel cardiotonic drug simendan: echocardiographic assessment in healthy volunteers.

Simendan is a novel cardiotonic drug with mixed properties, including calcium sensitization. Simendan was given intravenously to eight healthy volunteers in doses from 0.1 to 10.0 mg to define its safety and dose-response effects. Its effects on myocardial function were recorded by echocardiography with simultaneous measurement of heart rate (HR) and blood pressure (BP). A linear dose response was observed in all echocardiographic indices. Fractional shortening increased from a basal value of 29.5% to 32.4% (p < 0.05), 34.7% (p < 0.001), and 39.4% (p < 0.001) 10 minutes after doses of 1.0, 2.0, and 5.0 mg of simendan, respectively. The mean velocity of maximal circumferential fiber shortening increased from the baseline of 2.22 lengths/sec to 2.7 lengths/sec after the 2.0 mg dose (p < 0.05) and to 3.31 lengths/sec after the 5.0 mg dose (p < 0.001). Mean BP decreased slightly and mean HR increased only by 5.2 beats/min after the 5.0 mg dose. Because of the potent effect seen on hemodynamic indices and due to two vasovagal reactions, 10 mg was given to two subjects only. These results revealed that simendan has hemodynamic effects that can be explained by positive inotropy as well as vasodilatation, in agreement with preclinical findings. Further studies with patients disabled by heart failure are warranted.

Adult↗

PubMed1994

Haemodynamic dose-efficacy of levosimendan in healthy volunteers.

Levosimendan is a new calcium-sensitiser intended for the treatment of congestive heart failure. The results of preclinical studies indicate it has positive inotropic and vasodilator effects. In the open study reported here up to 5 mg levosimendan and vehicle were administered to 8 healthy male volunteers at one- to 2-week intervals. Efficacy was evaluated using M-mode echocardiography, and by measuring systolic time intervals, recording ECG and measuring blood pressure. For almost all haemodynamic parameters except heart rate (HR) the maximum effect was seen 10 or 20 min after drug infusion. Effects 10 min after infusion of drug and vehicle were compared. HR was significantly increased 10 min only after infusion of 5 mg: significant increases were seen 60 min after infusions of 2, 3 and 5 mg (4, 8 and 17 beats.min-1, respectively). Diastolic blood pressure was significantly lower after doses of 1 mg or more. The decrease after 5 mg was 17 mmHg. Systolic blood pressure tended to increase. Fractional shortening (FS) and ejection fraction (EF) increased significantly after doses of 1 mg and higher. EF 10 min after infusion of vehicle was 54%. It increased to 73% after 5 mg. Decreases in electromechanical systole (QS2i) 10 min after 2, 3 and 5 mg were significant. There were no clinically significant adverse events or changes in laboratory safety values. The changes in QS2i, FS, EF and blood pressure indicate that levosimendan has positive inotropic and vasodilator effects in healthy subjects.

Adult↗