Dorsal hand vein responses to the α₁-adrenoceptor agonist phenylephrine do not predict responses to the α₂-adrenoceptor agonist dexmedetomidine.

Significant inter-individual variability exists in responses of human dorsal hand veins to activation of α-adrenoceptors. Simultaneous graded infusions of the α₁- and α₂-adrenoceptor agonists phenylephrine (3.66-8000 ng/min) and dexmedetomidine (0.

Pharmacodynamic interactions of levosimendan and felodipine in patients with coronary heart disease.

Objective: The aim was to study the pharmacodynamic interactions and safety of the co-administration of the calcium sensitizer levosimendan and the calcium antagonist felodipine in patients with coronary heart disease (CHD) and with normal ejection fraction (EF).

Methods: The study was a randomized, double blind, placebo-controlled, crossover study in 24 male patients with Canadian Cardiovascular Society (CCS) class II CHD, consisting of four treatment periods, each period lasting for 7-10 days. In the first period the patients received either oral levosimendan (LS) (0.

The effect of flaxseed supplementation in processed foods on serum fatty acids and enterolactone.

Objective: The purpose was to study the effects of flaxseed supplementation as a part of daily diet on serum lipids, fatty acids and plasma enterolactone.

Design: Eighty volunteers participated in this clinical nutrition study which was carried out in a controlled, double-blind and cross-over manner. The subjects were randomized to diet sequences AB or BA.

Myocardial efficiency during levosimendan infusion in congestive heart failure.

Aims: Levosimendan, a novel calcium-dependent calcium sensitizer of the myocardial contractile proteins, also enhances diastolic relaxation and induces peripheral vasodilation by opening potassium channels. To assess the combined energetical effects of levosimendan infusion in vivo, we performed positron emission tomography in patients with decompensated chronic heart failure.

Methods And Results: Eight hospitalized patients with New York Heart Association functional class III or IV heart failure received levosimendan or placebo intravenously in a randomized double-blind cross-over study.

Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure.

Objectives: We sought to define the therapeutic dose range of levosimendan in patients with New York Heart Association class II-IV heart failure of ischemic origin.

Background: Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure.

Methods: A double-blind, placebo-controlled, randomized, multicenter, parallel-group study included 151 adult patients.

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.

Soluble and membrane-bound catechol-O-methyltransferase in normal and malignant mammary gland.

The levels of 26 kDa-soluble (S) and 30 kDa-membrane-bound (MB) catechol-O-methyltransferase (COMT) polypeptides were determined in paired samples from normal and neoplastic breast tissue of 32 patients with breast cancer. Immunohistochemical staining showed that the COMT reaction in normal mammary tissue was restricted to the epithelial cells in the ducti and lobuli, whereas in the tumors a strong reaction was also seen in the malignant cells. The amounts of COMT proteins in tumors could not be correlated with various clinical or pathological parameters.

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.

Aims: The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocardial substrate utilization of a new calcium sensitizer, levosimendan, after coronary artery bypass grafting.

Methods And Results: Twenty-three low-risk patients were included in this randomized and double-blind study. They received placebo (n = 8), 8 (n = 8) or 24 (n = 7) micrograms.

Studies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol.

Levosimendan (CAS 141505-33-1) is a calcium sensitizing drug intended for the treatment of congestive heart failure. In animal experiments levosimendan has potentiated the sedative effects of ethanol. Due to poor water solubility of the compound, ethanol is used as a diluent in the intravenous formulation.

Myocardial efficiency during calcium sensitization with levosimendan: a noninvasive study with positron emission tomography and echocardiography in healthy volunteers.

Dynamic positron emission tomography (PET) with [11C]acetate allows noninvasive assessment of myocardial oxygen consumption. In combination with echocardiography, PET enables determination of cardiac efficiency (defined as useful cardiac work per unit of oxygen consumption). We used this approach to compare the effects of levosimendan, a Ca(2+)-dependent calcium sensitizer, with dobutamine and sodium nitroprusside in healthy male volunteers.

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.

Sucralfate effervescent tablet: treatment of peptic ulcer disease and change in serum aluminium concentration.

In a single-centre randomised clinical trial, a new effervescent formulation of sucralfate was compared with the granular formulation of the drug in the treatment of peptic ulcer. The effervescent tablet had not been previously administered to human subjects. Fifty patients with endoscopically verified duodenal (40) and gastric (10) ulcers were treated with 2.

Safety of levosimendan and other calcium sensitizers.

Levosimendan belongs to a new group of heart failure drugs, the calcium sensitizers. Because these compounds are not yet available for clinical use, the adverse drug events (ADEs) during levosimendan treatment cannot be predicted in detail. To evaluate the tolerability of levosimendan in human subjects, ADEs, safety laboratory values before and after treatment, and ambulatory ECG findings have been collected from several phase I and phase II clinical studies.

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.

The effects of the COMT inhibitor entacapone on haemodynamics and peripheral catecholamine metabolism during exercise.

1. Catechol-O-methyltransferase (COMT) inhibition might be assumed to potentiate the effects of circulating catecholamines, particularly under conditions of enhanced catecholamine release. 2.

The effects of the COMT inhibitor nitecapone for one week on exercise haemodynamics and catecholamine disposition.

We have studied resting and exercise haemodynamics and catecholamine disposition after catechol-O-methyl-transferase (COMT) inhibition with nitecapone 100 mg t.d.s.

Anti-anginal therapy and quality of life. A comparison of the effects of transdermal nitroglycerin and long-acting oral nitrates.

A total of 112 male patients with severe effort-induced angina pectoris (New York Heart Association functional classes II and III) participated in a randomized open trial consisting of a 6 month phase with 3 month treatment cross-overs. The aim of the study was to compare the effect of transdermal nitroglycerin (TN) patches and long-acting oral nitrates (LAON) on quality of life (QL). During the cross-over period 30 patients (20 on TN and 10 on LAON) withdrew from the study, over half of them within the first month.

Exercise hemodynamics and catecholamine metabolism after catechol-O-methyltransferase inhibition with nitecapone.

The effect of catechol-O-methyltransferase inhibition with nitecapone (OR-462) on the hemodynamic responses to exercise and catecholamine metabolism was studied in 10 healthy male volunteers (aged 19 to 26 years). Nitecapone, a new specific and selective catechol-O-methyltransferase inhibitor, was given at increasing single oral doses up to 100 mg. Nitecapone did not influence resting or exercise heart rate, blood pressure, systolic time intervals, or plasma catecholamine levels.