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Possible role of preconditioning for the prevention of reperfusion arrhythmias
J Mel p-09-29
Crll
Cardiol
24 (Suppiemenr
1)(1992)
IN VITRO ELECTROPHYSIOLOGIC AND INOTROPIC EFFECTS OF THE NOVEL CLASS III AGENTS H 234/09 (ALMOKALANTJ, UK-68,798 (DOFRTILIDE) AND E-4031. G&an Duker, Christina Abrahamsson, Charlotte Lundberg and Leif Carlsson. Cardiovascular Pharmacology. Preclinical Research & Development, Astra Htissle, MWdal, Sweden. The electrophysiologic properties of H 234/09, UK-68,798 and E-4031 were characterized in the rabbit ventricular muscle (VM) and Purkinje fiber (PF), using a setup of dual microelectrodes for recording of action potentials in both tissues simultaneously. Effects on ventricular inotropy and refractoriness (ERPV) were studied in the cat isolated papillary muscle. All three drugs concentration-dependently prolonged the action potential duration (APD) and ERPV. The effect on APD was always larger in PF than in VM. However, at 15% prolongation of the APD in the VM, the APD prolongation in the PF was significantly (~0.05) less pronounced in the presence of H 234/09 (23f2.9%) than in the presence of UK-68,798 (47f10.96) and-TAO?1 (39*6.8%3. The maximum inotropic response (MIR;expressed as 46 of the maximum response to 3x10 M Isoprenaliue). was increased by 30f6.7.20f6.5 and 23f6.26, respectively. At the concentration causing a 20 % increase of ERPV, the inotiopic response was increased by 20%, 9% and 7% respectively. In conclusion, all Class Ill agents examined caused a delay in repolarization and an increase in refractoriness which were accompanied by a positive inotropic response. Compared to the other two drugs, H 234/09 seems to have a different profile, as it induces both: 1. a more pronounced positive inotropic response at equivalent ERPV prolongation and, 2. less dispersion of repolarization between VM and PF. This latter effect may theoretically reduce the risk for repolarization-induced proarrhythmias.
p-()g-30CATECHOLAM DEPOLARIZATION Wei-bin Shi, Department By
stable
of c&echo&nine
DAD
AFTER-
lti model induced by setylstrophanthidin, the cholinergic substances was studied in sheep disc -F Purkinje fibers. lsoprenaline (1 .0-3.0x10~8mol/L) or noradrenaline (1.5x10 mol/L) increased the amplitude of DAD and Iti significantly in a dose-dependent manner and the tr’ggered activity could be induced. Carbachol 2.0x10~6mol/L or awtylcholine -6 2.5x10 mol/L alone had little effect on DAD or a slight inhibitory effect on Iti. The amplitude of Iti was decreased from 13.4*3.6nA to 10.6*3.2nA (n=6, p
inwraction
using
I NE-CHOL I NERG I C SUBSTANCES INTERACTION ON DELAYED AND TRANSIENT INWARD CURRENT IN MYDCARDIUM Ji-ying Wu, Yuan-mou Liu, You-qiu Xu of Physiology, Shanghai Second Medical University, P.R.China and and
Pm()g-31POSSIBLE ARRHYTHMOGENIC EFFECTS OF THE CHLORIDE CURRENT IN GUINEA-PIG VENTRICULAR WYOCYTES: EXPERIMENTAL AND SIMULATION STUDIES Yuji Hirano, Noriyoshi Yamawake, Tohru Sawanobori, Masayasu Hiraoka. Dept. of Cardiovasc. Dis., M.R.I., Tokyo Medical and Dental University Possible arrhythmogenic effects of isoproterenol-activated chloride current (ICl) were examined by experimental study on isolated myocytes under various ionic environments, and by a simulation model study based on these experimental data. Application of isoproterenol (ISP,luM) to ventricular myocytes caused increased degree of membrane depolarization and higher incidence of abnormal activities, as equilibrium potential for Cl(ECl) was set to more positive potential levels. When [Kl was abnormal activities such as a e terdecreased to 2 or 3 mM, ISP elicited potentials, triggered activities and membrane oscillations in l/3 of the cells under physiological ECl. In the computer simulation model, introduction of I caused membrane depolarization and shortening of action potential 2 urations. These effects were dependent not only on EC1 but also on IKlo. With [Klo set to 2mM, the model successfully reproduced abnormal activities as observed in the experiments, when effects of ISP were introduced as increases in I Fr and activation 'k contributes to in uction of arrhythmias of IC1. We suggest th;$er;Cl under the conditions K+-conductances are decreased. S.270
Crll
Cardiol
24 (Suppiemenr
1)(1992)
IN VITRO ELECTROPHYSIOLOGIC AND INOTROPIC EFFECTS OF THE NOVEL CLASS III AGENTS H 234/09 (ALMOKALANTJ, UK-68,798 (DOFRTILIDE) AND E-4031. G&an Duker, Christina Abrahamsson, Charlotte Lundberg and Leif Carlsson. Cardiovascular Pharmacology. Preclinical Research & Development, Astra Htissle, MWdal, Sweden. The electrophysiologic properties of H 234/09, UK-68,798 and E-4031 were characterized in the rabbit ventricular muscle (VM) and Purkinje fiber (PF), using a setup of dual microelectrodes for recording of action potentials in both tissues simultaneously. Effects on ventricular inotropy and refractoriness (ERPV) were studied in the cat isolated papillary muscle. All three drugs concentration-dependently prolonged the action potential duration (APD) and ERPV. The effect on APD was always larger in PF than in VM. However, at 15% prolongation of the APD in the VM, the APD prolongation in the PF was significantly (~0.05) less pronounced in the presence of H 234/09 (23f2.9%) than in the presence of UK-68,798 (47f10.96) and-TAO?1 (39*6.8%3. The maximum inotropic response (MIR;expressed as 46 of the maximum response to 3x10 M Isoprenaliue). was increased by 30f6.7.20f6.5 and 23f6.26, respectively. At the concentration causing a 20 % increase of ERPV, the inotiopic response was increased by 20%, 9% and 7% respectively. In conclusion, all Class Ill agents examined caused a delay in repolarization and an increase in refractoriness which were accompanied by a positive inotropic response. Compared to the other two drugs, H 234/09 seems to have a different profile, as it induces both: 1. a more pronounced positive inotropic response at equivalent ERPV prolongation and, 2. less dispersion of repolarization between VM and PF. This latter effect may theoretically reduce the risk for repolarization-induced proarrhythmias.
p-()g-30CATECHOLAM DEPOLARIZATION Wei-bin Shi, Department By
stable
of c&echo&nine
DAD
AFTER-
lti model induced by setylstrophanthidin, the cholinergic substances was studied in sheep disc -F Purkinje fibers. lsoprenaline (1 .0-3.0x10~8mol/L) or noradrenaline (1.5x10 mol/L) increased the amplitude of DAD and Iti significantly in a dose-dependent manner and the tr’ggered activity could be induced. Carbachol 2.0x10~6mol/L or awtylcholine -6 2.5x10 mol/L alone had little effect on DAD or a slight inhibitory effect on Iti. The amplitude of Iti was decreased from 13.4*3.6nA to 10.6*3.2nA (n=6, p
inwraction
using
I NE-CHOL I NERG I C SUBSTANCES INTERACTION ON DELAYED AND TRANSIENT INWARD CURRENT IN MYDCARDIUM Ji-ying Wu, Yuan-mou Liu, You-qiu Xu of Physiology, Shanghai Second Medical University, P.R.China and and
Pm()g-31POSSIBLE ARRHYTHMOGENIC EFFECTS OF THE CHLORIDE CURRENT IN GUINEA-PIG VENTRICULAR WYOCYTES: EXPERIMENTAL AND SIMULATION STUDIES Yuji Hirano, Noriyoshi Yamawake, Tohru Sawanobori, Masayasu Hiraoka. Dept. of Cardiovasc. Dis., M.R.I., Tokyo Medical and Dental University Possible arrhythmogenic effects of isoproterenol-activated chloride current (ICl) were examined by experimental study on isolated myocytes under various ionic environments, and by a simulation model study based on these experimental data. Application of isoproterenol (ISP,luM) to ventricular myocytes caused increased degree of membrane depolarization and higher incidence of abnormal activities, as equilibrium potential for Cl(ECl) was set to more positive potential levels. When [Kl was abnormal activities such as a e terdecreased to 2 or 3 mM, ISP elicited potentials, triggered activities and membrane oscillations in l/3 of the cells under physiological ECl. In the computer simulation model, introduction of I caused membrane depolarization and shortening of action potential 2 urations. These effects were dependent not only on EC1 but also on IKlo. With [Klo set to 2mM, the model successfully reproduced abnormal activities as observed in the experiments, when effects of ISP were introduced as increases in I Fr and activation 'k contributes to in uction of arrhythmias of IC1. We suggest th;$er;Cl under the conditions K+-conductances are decreased. S.270