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Electrophysiological and mechanical changes in ventricular myocardium of cardiomyopathic hamsters in response to alpha-adrenergic stimulation
22
L-PROPIONYLCARNITINE PREVENTS THE LYSOPHOSPHATIDYLCHOLINE-INDUCED REDlJCTTc?N (IF Si)~lIJ~ CURRENT OF GUINEA PIG VENTRICULAR CELLS Tats&o Kiyosue and Makoto Arita. 'Toshiaki Sate, Department of Physiology, Medical College of Oita, Hasama, Oita 879-56 We investigated the effects of L-propionylcarnitine (PROC), a short-chain acylcar~ nitine, on sodium current (INa) of guinea pig ventricular myocytes. The cells were perfused with low Na+ (60 mM)-Tyrcde's solution; Ca2+ and K+ currents were blocked by external Co2+ (3 r&l) and internal Cs+ (140 mM), respectively. INa was elicited by depolarizing voltage steps from a holding potential of -100 mV at a temperature of 33 the amplitude of INa at concentrations ranged from 10 to 500 %. PROC did not change pM (n=14). We reported that lysophosphatidylcholine (LPC) inhibits the INa in a" allor-nothing manner via amphiphilic intervention with the phospholipid bilayers. LPC at conce"trations more than 10 FM irreversibly depressed the INa within 0.5 - 3 min and the reduction of INa was followed by cell contracture. So we examined whether PROC could prevent such deleterious effects of LPC on INa. I" the presence of PROC (100 effects of LPC (10 or 50 PM) on INa and cell contractures were PM), the depressant was changed to PROC-free not observed for up to 5 min. However, when the solution solution, the INa began to decrease in 0.5 - 2 min and the cell contra&we occurred
eventually. These findings suggest that prevent the amphiphile-induced reduction
short-chain of INa.
acylcarnitine
(PROC) is able
to
23 CLASS III ANTIARRHWH
MIC DRUGS LI’l-l-LE AFFECT ATRIOVENTRICULAR (AV) CONDUCTION TIME, BUT PROLONG EFFECTIVE REFRACTORY PERIOD IN DOG HEARTS. Shigeru Motomura. Toshio Yamagishi. Keitaro Hashimoto. Department of Pharmacology, Yamanashi Medical College, Tamaho, Yamanashi 409-38, Japan Differential effects of class III antiarrhythmic drugs, MS-551, E-4031 and d-sotalol on atrioventricular conduction time (AVCT) and on effective refractory period (ERP) of the AV conduction system were Investigated in the in situ open-chest dog hearts. AVCT assessed as an interval between bipolar atria1 and ventricular electrograms and ERP obtained by programmed premature stimuli were evaluated using an automated AV interval meter. Basal AVCT and ERP were 119+.9 and 176f18 msec (n=16). respectively. MS-551 (3pg-lmg/kg iv), E-4031 (3lOOpg/kg iv) and d-sotalol (3pg-lmg/kg iv) only slightly affected AVCT. but markedly prolonged ERP: the percent Increases from each basal value were 4+1% of AVCT and 30f4% of ERP by lmg/kg of MS-551. 7f2% of AVCT and 28+7% of ERP by lOOpg/kg of E-403 1 and 7f lob of AVCT and 33f7% of ERP by lmg/kg of d-sotalol. These results demonstrate that MS-551 and E-4031 as well as d-sotalol possess antiarrhythmic actions by selectively prolonging the ERP of the AV conduction system without much affecting AV conduction time.
24 ELECTROPHYSIOLOGICAL AND MECHANICAL CHANGES IN VENTRICULAR MYOCARDIUMOF CARDIOMYO-
PATHIC HAMSTERS IN RESPONSETO ALPHA-ADRENERGIC STIMULATION. T. Yamashita, I. Sakuma, M. Sakurai, H. Yasuda, *H. Nakaya and +$M. Kanno. Departments of Cardiovascular Medicine and "Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. Electromechanical response to M-adrenergic stimulation of myocardium from cardiomyopathic (CM) hamster BIO 53.58 was compared with those from control Flb and CM BIO 14.6 hamsters. Action potential and developed tension (DT) were simultaneously recorded from electrically-driven left ventricular papillary muscles (PMs) of --I', Phenylephrine (PHE) concentration-dependently increased action weeks old hamsters. potential duration at 90 % repolarized level (APDzJ) and DT in BIO 53.58, Flb and BIO Although the magnitude of increase in APDoa of BIO 14.6 PMs in response to W 14.6. UM PHE was significantly greater than that of Fib PMs (LIAPD:, : 65i15 % vs lO*lO %, mean+SD), that of BIO 53.58 PMs (1715 %) was similar to that of Flb PMs. So was th? magnitude of increase in DT,ADT to 30 uM PHE in BIO 53.58, Flb and 910 14.6 PMs wa? Thus, only the myocardium of BIG 14.6 ?l+lL %, 26+-y % and 227+158 %, respectively. This may showed an enhanced electromechanical response to d-adrenergic stimulation. reflect the distinct difference between BIO 53.58 and BIO 14.6 in their progressis-an of CM disorders. S.24
L-PROPIONYLCARNITINE PREVENTS THE LYSOPHOSPHATIDYLCHOLINE-INDUCED REDlJCTTc?N (IF Si)~lIJ~ CURRENT OF GUINEA PIG VENTRICULAR CELLS Tats&o Kiyosue and Makoto Arita. 'Toshiaki Sate, Department of Physiology, Medical College of Oita, Hasama, Oita 879-56 We investigated the effects of L-propionylcarnitine (PROC), a short-chain acylcar~ nitine, on sodium current (INa) of guinea pig ventricular myocytes. The cells were perfused with low Na+ (60 mM)-Tyrcde's solution; Ca2+ and K+ currents were blocked by external Co2+ (3 r&l) and internal Cs+ (140 mM), respectively. INa was elicited by depolarizing voltage steps from a holding potential of -100 mV at a temperature of 33 the amplitude of INa at concentrations ranged from 10 to 500 %. PROC did not change pM (n=14). We reported that lysophosphatidylcholine (LPC) inhibits the INa in a" allor-nothing manner via amphiphilic intervention with the phospholipid bilayers. LPC at conce"trations more than 10 FM irreversibly depressed the INa within 0.5 - 3 min and the reduction of INa was followed by cell contracture. So we examined whether PROC could prevent such deleterious effects of LPC on INa. I" the presence of PROC (100 effects of LPC (10 or 50 PM) on INa and cell contractures were PM), the depressant was changed to PROC-free not observed for up to 5 min. However, when the solution solution, the INa began to decrease in 0.5 - 2 min and the cell contra&we occurred
eventually. These findings suggest that prevent the amphiphile-induced reduction
short-chain of INa.
acylcarnitine
(PROC) is able
to
23 CLASS III ANTIARRHWH
MIC DRUGS LI’l-l-LE AFFECT ATRIOVENTRICULAR (AV) CONDUCTION TIME, BUT PROLONG EFFECTIVE REFRACTORY PERIOD IN DOG HEARTS. Shigeru Motomura. Toshio Yamagishi. Keitaro Hashimoto. Department of Pharmacology, Yamanashi Medical College, Tamaho, Yamanashi 409-38, Japan Differential effects of class III antiarrhythmic drugs, MS-551, E-4031 and d-sotalol on atrioventricular conduction time (AVCT) and on effective refractory period (ERP) of the AV conduction system were Investigated in the in situ open-chest dog hearts. AVCT assessed as an interval between bipolar atria1 and ventricular electrograms and ERP obtained by programmed premature stimuli were evaluated using an automated AV interval meter. Basal AVCT and ERP were 119+.9 and 176f18 msec (n=16). respectively. MS-551 (3pg-lmg/kg iv), E-4031 (3lOOpg/kg iv) and d-sotalol (3pg-lmg/kg iv) only slightly affected AVCT. but markedly prolonged ERP: the percent Increases from each basal value were 4+1% of AVCT and 30f4% of ERP by lmg/kg of MS-551. 7f2% of AVCT and 28+7% of ERP by lOOpg/kg of E-403 1 and 7f lob of AVCT and 33f7% of ERP by lmg/kg of d-sotalol. These results demonstrate that MS-551 and E-4031 as well as d-sotalol possess antiarrhythmic actions by selectively prolonging the ERP of the AV conduction system without much affecting AV conduction time.
24 ELECTROPHYSIOLOGICAL AND MECHANICAL CHANGES IN VENTRICULAR MYOCARDIUMOF CARDIOMYO-
PATHIC HAMSTERS IN RESPONSETO ALPHA-ADRENERGIC STIMULATION. T. Yamashita, I. Sakuma, M. Sakurai, H. Yasuda, *H. Nakaya and +$M. Kanno. Departments of Cardiovascular Medicine and "Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. Electromechanical response to M-adrenergic stimulation of myocardium from cardiomyopathic (CM) hamster BIO 53.58 was compared with those from control Flb and CM BIO 14.6 hamsters. Action potential and developed tension (DT) were simultaneously recorded from electrically-driven left ventricular papillary muscles (PMs) of --I', Phenylephrine (PHE) concentration-dependently increased action weeks old hamsters. potential duration at 90 % repolarized level (APDzJ) and DT in BIO 53.58, Flb and BIO Although the magnitude of increase in APDoa of BIO 14.6 PMs in response to W 14.6. UM PHE was significantly greater than that of Fib PMs (LIAPD:, : 65i15 % vs lO*lO %, mean+SD), that of BIO 53.58 PMs (1715 %) was similar to that of Flb PMs. So was th? magnitude of increase in DT,ADT to 30 uM PHE in BIO 53.58, Flb and 910 14.6 PMs wa? Thus, only the myocardium of BIG 14.6 ?l+lL %, 26+-y % and 227+158 %, respectively. This may showed an enhanced electromechanical response to d-adrenergic stimulation. reflect the distinct difference between BIO 53.58 and BIO 14.6 in their progressis-an of CM disorders. S.24