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Martin Schlepper - One of the best experts on this subject based on the ideXlab platform.

  • The new potassium channel blocker tedisamil and its hemodynamic, anti-ischemic and neurohumoral effect in patients with coronary heart disease
    Zeitschrift fur Kardiologie, 1996
    Co-Authors: Veselin Mitrovic, Eckart Oehm, R. Strasser, Martin Schlepper, Heinz F. Pitschner
    Abstract:

    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 Antiischemic 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 Antiischemic 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, Antiischemic, and neurohumoral effects in patients with coronary artery disease.

  • Hemodynamic and Antiischemic effects of tedisamil in humans
    Cardiovascular Drugs and Therapy, 1992
    Co-Authors: V. Mitrovic, E Oehm, A Liebrich, J Thormann, Martin Schlepper
    Abstract:

    Twenty-four patients with angiographically documented coronary artery disease, chronic stable angina, and reproducible ST-segment depression took part in this openlabel, baseline-controlled study on the hemodynamic, Antiischemic, metabolic, and neurohumoral effects of tedisamil following IV doses of 0.1, 0.2, and 0.3 mg/kg (eight patients in each dose group). Tedisamil produced a dose-dependent decrease in both heart rate [rest: 2.4, 7.5 (p .01), resp.]. While cardiac output was found decreased due to the heart-rate reduction both at rest [−8.5%, −5.7%, and −10.2% (p

  • Antiischemic and hemodynamic effects of an oral single dose of 150 mg of the phosphodiesterase inhibitor enoximone in patients with coronary artery disease ― relation to plasma concentration
    Cardiovascular drugs and therapy, 1991
    Co-Authors: V. Mitrovic, O. Petrovic, Hassan Bahavar, J. Neuzner, Hans Armin Dieterich, Martin Schlepper
    Abstract:

    The hemodynamic and Antiischemic effects of a 150-mg single oral dose of the PDE inhibitor enoximone were correlated with the plasma levels of enoximone and its sulfoxide metabolite. Twenty-one patients with angiographically documented coronary artery disease were investigated by exercise testing 1 and 2 hours after drug administration. The control group consisted of 15 patients with proven coronary artery disease and stable reproducible angina pectoris on exercise. The enoximone group included 14 responders with therapeutic plasma concentrations 2 hours after drug intake and significantly reduced mean pulmonary artery pressures on exercise (from 42.4 ± 8.6 to 30.9 ± 11.2 mmHg, p < 0.05). Compared to basal exercise values, responders showed a reduced ST-segment depression by 1 hour after drug intake (2.1 ± 1.2 vs. 1.3 ± 3 mm, p < 0.05) and minimal values after 2 hours (0.9 ± 1.0 mm, p < 0.01) at comparable workloads. There were no significant changes in heart rate, blood pressure, cardiac output, and systemic vascular resistance. No significant improvement in the hemodynamic parameters and ST-segment depression was found in nonresponders with plasma concentrations below 100 ng/ml and 500 ng/ml for enoximone and its metabolite, respectively. In summary, oral administration of enoximone in patients with coronary artery disease led to favorable acute hemodynamic and Antiischemic effects at sufficiently high plasma levels of enoximone and its sulfoxide metabolite.

Giovanni Gambassi - One of the best experts on this subject based on the ideXlab platform.

  • Antiischemic therapy in patients with coronary heart disease living in long term care
    Pharmacotherapy, 1999
    Co-Authors: Kate L. Lapane, Marilyn M. Barbour, Anne Van Haaren, Giovanni Gambassi
    Abstract:

    We evaluated Antiischemic therapy in elderly nursing home residents with a diagnosis of coronary heart disease (CHD) using a population-based data base with over 300,000 residents (1992-1995) of all Medicare/Medicaid-certified nursing homes of five states. We identified 72,263 patients age 65 years or older with a diagnosis of CHD. We examined data collected with the federally mandated Minimum Data Set, drug information, and Medicare hospital claims. Antiischemics were defined as beta-adrenergic blockers, long-term nitrates, and calcium channel blockers. We determined factors associated with use of the drugs by logistic regression. Antiischemic therapy was inversely related to age and cognitive and physical functioning, but positively associated with recent hospitalization and concomitant cardiovascular diseases. beta-Adrenergic blockers were least likely to be administered regardless of age, gender, or cognitive or physical function. We conclude that Antiischemic therapy in nursing home residents may not be optimal.

  • Antiischemic Therapy in Patients with Coronary Heart Disease Living in Long‐term Care
    Pharmacotherapy, 1999
    Co-Authors: Kate L. Lapane, Marilyn M. Barbour, Anne Van Haaren, Giovanni Gambassi
    Abstract:

    We evaluated Antiischemic therapy in elderly nursing home residents with a diagnosis of coronary heart disease (CHD) using a population-based data base with over 300,000 residents (1992-1995) of all Medicare/Medicaid-certified nursing homes of five states. We identified 72,263 patients age 65 years or older with a diagnosis of CHD. We examined data collected with the federally mandated Minimum Data Set, drug information, and Medicare hospital claims. Antiischemics were defined as beta-adrenergic blockers, long-term nitrates, and calcium channel blockers. We determined factors associated with use of the drugs by logistic regression. Antiischemic therapy was inversely related to age and cognitive and physical functioning, but positively associated with recent hospitalization and concomitant cardiovascular diseases. beta-Adrenergic blockers were least likely to be administered regardless of age, gender, or cognitive or physical function. We conclude that Antiischemic therapy in nursing home residents may not be optimal.

V. Mitrovic - One of the best experts on this subject based on the ideXlab platform.

  • Potassium channel openers and blockers in coronary artery disease. Comparison to betablockers and calcium antagonists.
    Herz, 2000
    Co-Authors: V. Mitrovic, Jochen Thormann, Heinz F. Pitschner, Eckart Oehm, Christian Hamm
    Abstract:

    Potassium channel openers and blockers, which belong to a novel class of vasodilator drugs and to the class of specific bradycardic substances, are potential new antianginal drugs. Experimental findings in vivo suggest that bimakalim is a new substance characterized as ATP-sensitive K+ channel openers, since it exerts preferential vasodilation of the collateral circulation of the coronary vasculature and both leads to increase blood flow to ischemic areas and to attenuate the ST segment elevation caused by regional ischemia in the canine heart. Opening of KATP increases the conductivity of potassium ions which results in hyperpolarization of smooth muscle membranes, thus producing vasodilation. Tedisamil is a new bradycardic agent proven to exert Antiischemic and antiarrhythmic effects by blockade of the cellular cardiac repolarization K+ currents as well as of multiple neuronal and vascular K+ currents (Ito, Ik, and K+ATP). Using right heart catheterization and exercise tolerance tests, we investigated the hemodynamic, Antiischemic and neurohumoral effects of bimakalim and tedisamil in patients with angiographically proven coronary artery disease, stable angina pectoris and reproducible ST segment depression during exercise. In 50 patients with coronary artery disease, the hemodynamic and Antiischemic effects of a single oral dose bimakalim of 0.1 mg, 0.3 mg and 0.6 mg were compared to placebo. In a dose-finding baseline-controlled study, a comparable collective was examined for the effects of acute i.v. administration of tedisamil 0.1, 0.2, 0.3 and 0.4 mg/kg bw. A subgroup of 8 patients receiving 0.3 mg/kg bw tedisamil i.v. was compared with a similar 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 intra-individual comparison. Furthermore, in 48 patients, short-term (6 days) effects of tedisamil, 2 times 100 mg orally, were compared to 2 times 50 mg atenolol treatment. With a single oral dose of bimakalim antianginal and/or Antiischemic effects were lacking, increased doses, however, induced changes in hemodynamics typical of vasodilation, i.e., a significant decrease in systolic blood pressure and a secondary chronotropic response. In contrast to bimakalim, tedisamil produced Antiischemic effects and was found to have favorable hemodynamic, neurohumoral and Antiischemic effects in comparison to the betablocker esmolol and atenolol in patients with coronary artery disease. Tedisamil induced a dose-dependent decrease in both heart rate and the index of myocardial oxygen consumption associated with an improvement in ST segment depression. Tedisamil as well as esmolol and atenolol showed almost equipotent Antiischemic effects at the doses administered. Compared with gallopamil, both tedisamil and esmolol were superior in their effects on myocardial oxygen consumption and ST segment depression, whereas plasma lactate concentrations were more reduced by tedisamil and gallopamil.

  • Hemodynamic and Antiischemic effects of tedisamil in humans
    Cardiovascular Drugs and Therapy, 1992
    Co-Authors: V. Mitrovic, E Oehm, A Liebrich, J Thormann, Martin Schlepper
    Abstract:

    Twenty-four patients with angiographically documented coronary artery disease, chronic stable angina, and reproducible ST-segment depression took part in this openlabel, baseline-controlled study on the hemodynamic, Antiischemic, metabolic, and neurohumoral effects of tedisamil following IV doses of 0.1, 0.2, and 0.3 mg/kg (eight patients in each dose group). Tedisamil produced a dose-dependent decrease in both heart rate [rest: 2.4, 7.5 (p .01), resp.]. While cardiac output was found decreased due to the heart-rate reduction both at rest [−8.5%, −5.7%, and −10.2% (p

  • Antiischemic and hemodynamic effects of an oral single dose of 150 mg of the phosphodiesterase inhibitor enoximone in patients with coronary artery disease ― relation to plasma concentration
    Cardiovascular drugs and therapy, 1991
    Co-Authors: V. Mitrovic, O. Petrovic, Hassan Bahavar, J. Neuzner, Hans Armin Dieterich, Martin Schlepper
    Abstract:

    The hemodynamic and Antiischemic effects of a 150-mg single oral dose of the PDE inhibitor enoximone were correlated with the plasma levels of enoximone and its sulfoxide metabolite. Twenty-one patients with angiographically documented coronary artery disease were investigated by exercise testing 1 and 2 hours after drug administration. The control group consisted of 15 patients with proven coronary artery disease and stable reproducible angina pectoris on exercise. The enoximone group included 14 responders with therapeutic plasma concentrations 2 hours after drug intake and significantly reduced mean pulmonary artery pressures on exercise (from 42.4 ± 8.6 to 30.9 ± 11.2 mmHg, p < 0.05). Compared to basal exercise values, responders showed a reduced ST-segment depression by 1 hour after drug intake (2.1 ± 1.2 vs. 1.3 ± 3 mm, p < 0.05) and minimal values after 2 hours (0.9 ± 1.0 mm, p < 0.01) at comparable workloads. There were no significant changes in heart rate, blood pressure, cardiac output, and systemic vascular resistance. No significant improvement in the hemodynamic parameters and ST-segment depression was found in nonresponders with plasma concentrations below 100 ng/ml and 500 ng/ml for enoximone and its metabolite, respectively. In summary, oral administration of enoximone in patients with coronary artery disease led to favorable acute hemodynamic and Antiischemic effects at sufficiently high plasma levels of enoximone and its sulfoxide metabolite.

Veselin Mitrovic - One of the best experts on this subject based on the ideXlab platform.

  • Hemodynamic, Antiischemic, and Neurohumoral Effects of Tedisamil and Atenolol in Patients with Coronary Artery Disease
    Cardiovascular Drugs and Therapy, 2000
    Co-Authors: Veselin Mitrovic, Aleksandra Miskovic, Matthias Straub, Jochen Thormann, Heinz Pitschner, Christian Hamm
    Abstract:

    Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart-rate-lowering agents, such as tedisamil, which additionally exerts Antiischemic and antiarrhythmic effects by blockade of cellular repolarizing K^+ currents. Forty-eight patients with stable angina pectoris were investigated (doubleblind, randomized, parallel grouped) comparing the hemodynamic, Antiischemic, 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 versus −15.4 bpm; day 6: −14.8 versus −22.2 bpm, resp.; p > 0.05] and exercise [day 1; −9.1 versus −18.3 bpm; p = 0.001; day 6; −12.0 versus −24.8 bpm, resp.; p = 0.001], while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest [day 1: −1.01 versus −1.19 l/min; p > 0.05; day 6: −0.86 versus −1.10 l/min, resp.; p > 0.05] and exercise [day 1: −0.82 versus −1.28 l/min; p > 0.05; day 6: −0.65 versus −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 mmHg) and increased with atenolol (+3.7 mmHg) (p < .001). Mean pulmonary capillary wedge pressures decreased both at rest (−0.5 mmHg) and exercise (−6.9 mmHg) in the tedisamil group but tended to increase with atenolol on day 6 of treatment [rest: +1.7; exercise: +3.7 mmHg) (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 prolongation of QT_c interval [+31 versus 8 ms] at initial values of 0.408 ± 0.018 s with PQ and QRS remaining unaltered. In patients with stable angina, tedisamil (100 mg b.i.d.) as compared to atenolol (50 mg b.i.d.) generated similar hemodynamic, neurohumoral and Antiischemic effects. The Antiischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, was comparable to that of atenolol.

  • The new potassium channel blocker tedisamil and its hemodynamic, anti-ischemic and neurohumoral effect in patients with coronary heart disease
    Zeitschrift fur Kardiologie, 1996
    Co-Authors: Veselin Mitrovic, Eckart Oehm, R. Strasser, Martin Schlepper, Heinz F. Pitschner
    Abstract:

    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 Antiischemic 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 Antiischemic 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, Antiischemic, and neurohumoral effects in patients with coronary artery disease.

  • hemodynamic and Antiischemic effects of tedisamil in humans
    Cardiovascular Drugs and Therapy, 1992
    Co-Authors: Veselin Mitrovic, E Oehm, A Liebrich, J Thormann, M. Schlepper
    Abstract:

    Twenty-four patients with angiographically documented coronary artery disease, chronic stable angina, and reproducible ST-segment depression took part in this openlabel, baseline-controlled study on the hemodynamic, Antiischemic, metabolic, and neurohumoral effects of tedisamil following IV doses of 0.1, 0.2, and 0.3 mg/kg (eight patients in each dose group). Tedisamil produced a dose-dependent decrease in both heart rate [rest: 2.4, 7.5 (p .01), resp.]. While cardiac output was found decreased due to the heart-rate reduction both at rest [−8.5%, −5.7%, and −10.2% (p<.05), respectively] and during exercise (2–8%), being significant only at rest in the highest dose group, stroke volume remained unaltered. Pulmonary artery pressure, pulmonary capillary wedge pressure, right-ventricular ejection fraction, and pulmonary vascular resistance were without significant changes. Blood pressure and systemic vascular resistance tended to increase, associated with a decrease in plasma catecholamines (20–40%). Tedisamil produced a dose-dependent prolongation of QTc duration [+2%, +6%, +12% (p<.05), respectively] with PQ and QRS unaltered. The elimination half-life of tedisamil IV ranges between 6.8 and 7.8 hours. In conclusion, tedisamil, at a dose of 0.3 mg/kg IV, was well tolerated and was found to have favorable hemodynamic and Antiischemic effects in patients with ischemic heart disease.

Christian Hamm - One of the best experts on this subject based on the ideXlab platform.

  • Hemodynamic, Antiischemic, and Neurohumoral Effects of Tedisamil and Atenolol in Patients with Coronary Artery Disease
    Cardiovascular Drugs and Therapy, 2000
    Co-Authors: Veselin Mitrovic, Aleksandra Miskovic, Matthias Straub, Jochen Thormann, Heinz Pitschner, Christian Hamm
    Abstract:

    Clinical drawbacks of beta-blocker treatment in stable angina have motivated researchers to provide alternative heart-rate-lowering agents, such as tedisamil, which additionally exerts Antiischemic and antiarrhythmic effects by blockade of cellular repolarizing K^+ currents. Forty-eight patients with stable angina pectoris were investigated (doubleblind, randomized, parallel grouped) comparing the hemodynamic, Antiischemic, 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 versus −15.4 bpm; day 6: −14.8 versus −22.2 bpm, resp.; p > 0.05] and exercise [day 1; −9.1 versus −18.3 bpm; p = 0.001; day 6; −12.0 versus −24.8 bpm, resp.; p = 0.001], while anginal threshold increased. Cardiac output decreased with tedisamil and atenolol at rest [day 1: −1.01 versus −1.19 l/min; p > 0.05; day 6: −0.86 versus −1.10 l/min, resp.; p > 0.05] and exercise [day 1: −0.82 versus −1.28 l/min; p > 0.05; day 6: −0.65 versus −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 mmHg) and increased with atenolol (+3.7 mmHg) (p < .001). Mean pulmonary capillary wedge pressures decreased both at rest (−0.5 mmHg) and exercise (−6.9 mmHg) in the tedisamil group but tended to increase with atenolol on day 6 of treatment [rest: +1.7; exercise: +3.7 mmHg) (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 prolongation of QT_c interval [+31 versus 8 ms] at initial values of 0.408 ± 0.018 s with PQ and QRS remaining unaltered. In patients with stable angina, tedisamil (100 mg b.i.d.) as compared to atenolol (50 mg b.i.d.) generated similar hemodynamic, neurohumoral and Antiischemic effects. The Antiischemic efficacy of tedisamil, as measured by ST segment depression and angina threshold, was comparable to that of atenolol.

  • Potassium channel openers and blockers in coronary artery disease. Comparison to betablockers and calcium antagonists.
    Herz, 2000
    Co-Authors: V. Mitrovic, Jochen Thormann, Heinz F. Pitschner, Eckart Oehm, Christian Hamm
    Abstract:

    Potassium channel openers and blockers, which belong to a novel class of vasodilator drugs and to the class of specific bradycardic substances, are potential new antianginal drugs. Experimental findings in vivo suggest that bimakalim is a new substance characterized as ATP-sensitive K+ channel openers, since it exerts preferential vasodilation of the collateral circulation of the coronary vasculature and both leads to increase blood flow to ischemic areas and to attenuate the ST segment elevation caused by regional ischemia in the canine heart. Opening of KATP increases the conductivity of potassium ions which results in hyperpolarization of smooth muscle membranes, thus producing vasodilation. Tedisamil is a new bradycardic agent proven to exert Antiischemic and antiarrhythmic effects by blockade of the cellular cardiac repolarization K+ currents as well as of multiple neuronal and vascular K+ currents (Ito, Ik, and K+ATP). Using right heart catheterization and exercise tolerance tests, we investigated the hemodynamic, Antiischemic and neurohumoral effects of bimakalim and tedisamil in patients with angiographically proven coronary artery disease, stable angina pectoris and reproducible ST segment depression during exercise. In 50 patients with coronary artery disease, the hemodynamic and Antiischemic effects of a single oral dose bimakalim of 0.1 mg, 0.3 mg and 0.6 mg were compared to placebo. In a dose-finding baseline-controlled study, a comparable collective was examined for the effects of acute i.v. administration of tedisamil 0.1, 0.2, 0.3 and 0.4 mg/kg bw. A subgroup of 8 patients receiving 0.3 mg/kg bw tedisamil i.v. was compared with a similar 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 intra-individual comparison. Furthermore, in 48 patients, short-term (6 days) effects of tedisamil, 2 times 100 mg orally, were compared to 2 times 50 mg atenolol treatment. With a single oral dose of bimakalim antianginal and/or Antiischemic effects were lacking, increased doses, however, induced changes in hemodynamics typical of vasodilation, i.e., a significant decrease in systolic blood pressure and a secondary chronotropic response. In contrast to bimakalim, tedisamil produced Antiischemic effects and was found to have favorable hemodynamic, neurohumoral and Antiischemic effects in comparison to the betablocker esmolol and atenolol in patients with coronary artery disease. Tedisamil induced a dose-dependent decrease in both heart rate and the index of myocardial oxygen consumption associated with an improvement in ST segment depression. Tedisamil as well as esmolol and atenolol showed almost equipotent Antiischemic effects at the doses administered. Compared with gallopamil, both tedisamil and esmolol were superior in their effects on myocardial oxygen consumption and ST segment depression, whereas plasma lactate concentrations were more reduced by tedisamil and gallopamil.