The Experts below are selected from a list of 2586 Experts worldwide ranked by ideXlab platform
Caspar J Ruegg - One of the best experts on this subject based on the ideXlab platform.
-
replacement of troponin i in slow twitch skeletal muscle alters the effects of the Calcium Sensitizer emd 53998
Pflügers Archiv: European Journal of Physiology, 1998Co-Authors: Harald Kogler, C Plathow, Eman Alhillawi, Ian P Trayer, Caspar J RueggAbstract:We extracted troponin-I (TnI) from skinned rat and rabbit soleus muscle fibres using a modification of the method described by Strauss et al. (FEBS Lett 310:229–234, 1992) for replacement of TnI in cardiac preparations. Incubation of soleus muscle fibres with 10 mmol/l vanadate virtually completely abolished the Ca2+dependence of force. Immunoblot analysis revealed that more than 80% of TnI had been extracted from the preparations. The Ca2+dependence of force was restored by incubation with a complex of cardiac TnI (cTnI) and troponin-C (cTnC). We examined the effects of the Ca2+-sensitizing compound EMD 53998 on isometric tension in native porcine cardiac and rabbit soleus skinned fibres as well as soleus in which the endogenous slow skeletal TnI (ssTnI) had been replaced by cTnI (soleus–cTnI). It was found that 10 µmol/l EMD 53998 in native soleus increased maximum Ca2+-activated force to 120±1.4% of control. In soleus–cTnI fibres, maximum force was increased to only 105±0.9%, which was similar to the effect observed in cardiac muscle (108±0.6%). In cardiac muscle, 10 µmol/l EMD 53998 induced a leftward shift of the pCa-tension relation by 0.65 log units. In native soleus, ΔpCa was only 0.40. Again, the effect of EMD 53998 on soleus–cTnI (ΔpCa=0.56) more closely resembled the response found in cardiac muscle than that observed in native soleus muscle. The apparent TnI-isoform dependence of the effects elicited by EMD 53998 suggests that its actions are modulated by the regulatory proteins of the thin filament.
-
the Calcium Sensitizer emd 53998 antagonizes phosphate induced increases in energy cost of isometric tension in cardiac skinned fibres
European Journal of Pharmacology, 1994Co-Authors: John D Strauss, Christel Bletz, Caspar J RueggAbstract:Abstract We have investigated whether a Ca 2+ -sensitizing substance, the thiadiazinone derivative EMD 53998, can alter the ratio of ATPase activity to force, i.e. the tension cost in skinned fibres of swine cardiac trabecula in which the tension cost was increased by inorganic phosphate. In the presence of 10 mM inorganic phosphate (P i ) and thapsigargin 20 μM, EMD 53998 reduced the energy cost of isometric tension over the entire range of activating Ca 2+ concentrations, resulting in a consistent change in slope (∼ 20% decrease) of the ATPase/force relation. We confirmed that in the absence of added phosphate and at maximal Ca 2+ activation EMD 53998 had little if any effect on tension cost. We had previously reported that the effects of EMD 53998 and P i on Calcium sensitivity and maximum isometric tension are mutually antagonistic and our new energy data now support the proposal that EMD 53998 functio lly antagonizes the effects of P i on crossbridges. The decrease in the slope of the relation between ATPase and force caused by EMD 53998 may be interpreted to reflect either a decrease in the rate of ‘detachment’ ( g app ) of crossbridgesor an increase in average force per crossbridge, as predicted by classical crossbridge models. Since the P i release step of the crossbridge cycle is associated with the rate of ‘attachment’ ( f app ) rather than g app , we conclude that the decrease in tension cost with EMD 53998 most likely reflects an increased force per crossbridge. The mechanism of action for this Ca 2+ -sensitizing compound may then involve redistribution of crossbridge states around the P i release step, which may possibly be due to a lowered affinity of crossbridges for phosphate.
-
the positive inotropic Calcium Sensitizer emd 53998 antagonizes phosphate action on cross bridges in cardiac skinned fibers
European Journal of Pharmacology, 1992Co-Authors: John D Strauss, C Zeugner, Caspar J RueggAbstract:The diazinone derivative EMD 53998 sensitizes skinned myocardial fibers to Ca2+ and enhances maximal Calcium-activated force (pCa = 4.5) by approximately 100%, the EC50 is 10 μM in the absence and about 30 μM in the presence of added inorganic phosphate (10 mM). Although concentrations of added phosphate as low as 0.5 mM inhibit force, at high concentrations of EMD 53998 (≥ 50 μM), phosphate only inhibits at concentrations exceeding 20 mM. These data suggest that the effects of EMD 53998 and phosphate are mutually antagonistic. Importantly, both TMD 53998 and phosphate had similar effects on force generation in troponin I-depleted (Ca2+-independent) skinned fibers, thus demonstrating that these compounds are likely to affect cross-bridges directly and not via the Ca2+-regulatory system.
Markku S Nieminen - One of the best experts on this subject based on the ideXlab platform.
-
Review Evidence-based use of levosimendan in different clinical settings
2016Co-Authors: Leonardo De Luca, Markku S Nieminen, Wilson S. Colucci, Barry M. Massie, Ischaemic Heart DiseaseAbstract:Levosimendan is a new Calcium Sensitizer and K-ATP channel opener. Compared with other inodilators, it improves myocardial contractility without increasing oxygen requirements and induces peripheral and coronary vasodilation with a potential anti-stunning, anti-ischaemic effect. The documentation regard-ing levosimendan is one of the largest ever on the safety and efficacy of a new pharmacological agent in acute heart failure syndromes. Recent experiences in small-scale studies and randomized clinical trials have led to greater interest in the use of this drug for the support of impaired cardiac function also in patients with ischaemic heart disease and cardiogenic or septic shock. It is also demonstrated that this drug could be used as bridge therapy for the peri-operative phase of cardiac surgery in both adult and paediatric populations. This review summarizes the evidence from published scientific literature regarding the use of levosimendan in various clinical settings
-
effects of a new Calcium Sensitizer levosimendan on haemodynamics coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting
European Heart Journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P<0·05). Cardiac output increased by 0·7 and 1·6l.min−1(P<0·05 for both) after 8 and 24μg.kg−1of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42ml/(P=0·054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly. Conclusion Despite improved cardiac performance, levosimendan did not increase myocardial oxygen con-sumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.
-
Effects of a new Calcium Sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.
European heart journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P
-
hemodynamic and neurohumoral effects of levosimedan a new Calcium Sensitizer at rest and during exercise in healthy men
American Journal of Cardiology, 1995Co-Authors: Stig Sundberg, Jyrki Lilleberg, Markku S Nieminen, Lasse LehtonenAbstract: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)
-
dose range study of a new Calcium Sensitizer levosimendan in patients with left ventricular dysfunction
Journal of Cardiovascular Pharmacology, 1995Co-Authors: J Lilleberg, Stig Sundberg, Markku S NieminenAbstract: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.
Jyrki Lilleberg - One of the best experts on this subject based on the ideXlab platform.
-
The Calcium Sensitizer levosimendan and cardiac arrhythmias: an analysis of the safety database of heart failure treatment studies.
Scandinavian cardiovascular journal : SCJ, 2004Co-Authors: Jyrki Lilleberg, Vesa Ylönen, Lasse Lehtonen, Lauri ToivonenAbstract:Background—Levosimendan is a Calcium Sensitizer that increases the contractility of the myofilaments and is considered not to affect cardiac electrophysiology. We assessed its potential to generate cardiac arrhythmias by analysing ECG recordings from clinical studies on intravenously administered levosimendan in heart failure patients. Methods and results—The database consisted of continuous 1‐day recordings, of which 366 were during levosimendan and 142 during placebo comparison. Supraventricular (SVT) and ventricular tachycardia (VT) were defined as ≥3 premature complexes at a rate ≥120/ min. No difference appeared between levosimendan and control groups in the occurrence of atrial fibrillation (12% vs 13%), SVT (28% vs 30%), or VT (41% vs 44% of all recordings; all p = NS). Also the frequency of VT was similar (0.55 ± 3.89 vs 0.20 ± 1.08 episodes/h; p = NS). No torsade de pointes or sustained VT occurred. Conclusion—Short‐term levosimendan therapy of heart failure showed no tendency to increase cardiac...
-
effects of a new Calcium Sensitizer levosimendan on haemodynamics coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting
European Heart Journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P<0·05). Cardiac output increased by 0·7 and 1·6l.min−1(P<0·05 for both) after 8 and 24μg.kg−1of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42ml/(P=0·054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly. Conclusion Despite improved cardiac performance, levosimendan did not increase myocardial oxygen con-sumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.
-
Effects of a new Calcium Sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.
European heart journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P
-
hemodynamic and neurohumoral effects of levosimedan a new Calcium Sensitizer at rest and during exercise in healthy men
American Journal of Cardiology, 1995Co-Authors: Stig Sundberg, Jyrki Lilleberg, Markku S Nieminen, Lasse LehtonenAbstract: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)
-
Pharmacokinetics and pharmacodynamics of simendan, a novel Calcium Sensitizer, in healthy volunteers
Clinical pharmacology and therapeutics, 1994Co-Authors: Jyrki Lilleberg, Markku S Nieminen, Saila Antila, Marianne Karlsson, Pertti J PentkäinenAbstract:Objective To assess pharmacokinetics and correlation of pharmacokinetics and pharmacodynamics of simendan, a new Calcium-sensitizing compound aimed at the treatment of congestive heart failure, in healthy volunteers. Methods Simendan was administered to eight healthy subjects in seven different doses, and its concentrations in plasma and proportions of enantiomers (levosimendan and dextrosimendan) were determined. Hemodynamic effects were measured by M-mode echocardiography. Results The area under the plasma concentration time–curve increased linearly and correlated with dose (p < 0.001). The volumes of distribution were small (mean Vc, 8.5 to 14.1 L; VSS, 12.8 to 28.4 L) and elimination fairly fast (mean t½β, 0.83 to 1.77 hours). There were only minor differences between the pharmacokinetic profiles of the enantiomers of simendan. The increase in maximal ejection fraction (EF) correlated significantly with the plasma concentrations of simendan (p < 0.01; r2 = 0.33). However, the correlation coefficient was higher between estimated concentrations of simendan in peripheral compartment and ejection fraction; r2 was 0.79 (p < 0.01) and 0.94 (p < 0.001) after 2 and 5 mg doses, respectively. One subject after 5 mg simendan and one subject after 10 mg simendan had transient vasovagal reactions consisting of decreases in heart rate and blood pressure. Conclusions Simendan has favorable and predictable hemodynamic actions. The pharmacokinetic profile facilitates rapid dose adjustments during intravenous administration. Clinical Pharmacology and Therapeutics (1994) 56, 554–563; doi:10.1038/clpt.1994.177
Markku Salmenperä - One of the best experts on this subject based on the ideXlab platform.
-
effects of a new Calcium Sensitizer levosimendan on haemodynamics coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting
European Heart Journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P<0·05). Cardiac output increased by 0·7 and 1·6l.min−1(P<0·05 for both) after 8 and 24μg.kg−1of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42ml/(P=0·054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly. Conclusion Despite improved cardiac performance, levosimendan did not increase myocardial oxygen con-sumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.
-
Effects of a new Calcium Sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.
European heart journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P
Juha Akkila - One of the best experts on this subject based on the ideXlab platform.
-
Electrophysiologic Effects of a Calcium Sensitizer Inotrope Levosimendan Administered Intravenously in Patients with Normal Cardiac Function
Journal of cardiovascular pharmacology, 2000Co-Authors: Lauri Toivonen, Juha Akkila, Stig Sundberg, Matti Viitasalo, Lasse LehtonenAbstract:Summary: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 new Calcium Sensitizer levosimendan on haemodynamics coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting
European Heart Journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P<0·05). Cardiac output increased by 0·7 and 1·6l.min−1(P<0·05 for both) after 8 and 24μg.kg−1of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42ml/(P=0·054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly. Conclusion Despite improved cardiac performance, levosimendan did not increase myocardial oxygen con-sumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.
-
Effects of a new Calcium Sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.
European heart journal, 1998Co-Authors: Jyrki Lilleberg, Juha Akkila, A Kuitunen, L Lehtonen, K Verkkala, S Mattila, Markku S Nieminen, L. Heikkilä, Markku SalmenperäAbstract:Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial 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) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P
-
Myocardial efficiency during Calcium sensitization with levosimendan: A noninvasive study with positron emission tomography and echocardiography in healthy volunteers
Clinical pharmacology and therapeutics, 1997Co-Authors: Heikki Ukkonen, Juha Akkila, Lasse Lehtonen, Markku Saraste, M. Juhani Knuuti, Pertti Lehikoinen, Kjell Någren, Liisa-maria Voipio-pulkkiAbstract: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. The effects of levosimendan on k(mono), an index of oxygen consumption, and cardiac efficiency were neutral, whereas the hemodynamic profile was consistent with balanced inotropism and vasodilatation. Dobutamine enhanced cardiac efficiency at the expense of increased oxygen requirement, but the effects of nitroprusside on k(mono) and cardiac efficiency were neutral. This study shows the feasibility of PET in phase 1 pharmacodynamic studies and suggests potential energetical advantages of Calcium sensitization with levosimendan.
