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Comparison of the electrophysiological effects of UL-FS 49 and verapamil in canine cardiac Purkinje fibres
J Mol
Cell
Cardiol
23 (Supplement
IV)
(1991)
76
EFFECTS OF DOPROPIDIL ON CONTRACTILE EROPERTIES OF SKINNED 1FIBERS FROM FERRET PAPILLARY MUSCLES. M. Ferrfer, S. Baudet , J. Leboeuf, C. Leoty , R. Massingham, RL-CERM, Riom, France and UA CNRS 1340, Laboratory of General Physiology, E.N.V., F-44087 Nantes Cedex 03, France. The effects of dopropidil, a novel Ca++ antagonist, were investigated by using thin bundles of skinned fibers from ferret right ventricular papillary muscles. Following Triton X-100 treatment, all membranes are chemically destroyed and the sarcoplasmic reticulum is not+f+unctional. Dopropidil (lo-300 PM) shifted pCa tension curves towards lower Ca concentrations. pCa for half-maximum activation (pCa50) was increased in a reversible concentration-dependent fashion (10 PM: 0,039 +0,02; 300 PM: 0,180+0,035) as well as the partially activated tension (PAT) (pCa 5,875) (100 PM: 2,6+ij,5; 300 PM: 5,2+1,1) and the maximal activated tension (MAT) (pCa 4,5) (100 bM:-l,6+0,3; 300 PM: -2,5+0,3). Furthermore the slope at high concentrations was enhance> (Hill coef.: lO
77
A STUDY OF CORONARY HYPEREMIC RESPONSE AFTER INTRAVENOUS DIPYRIDAMOLE BY MICROSPHERES IN THE CANINE MODEL. G. Fin&. M. de Lorgeril, M. Ovize, D. Revel, JB. Plchard, M. Amiel. Laboratoire de Radiologie Experimentale URA CNRS 1216, Hopital Cardiologique, Lyon, France Dipyridamole (DPD) $ the most widely used coronary vasodilatator in nuclear medeclne and in the assessment of myocardlal perfusion by videodensitometry (VDM). We quantitate the coronary hyperemic response after DPD and its variability during the same experiment. Methods : 2 sequences [rest state/during DPD (0.75 mg/kg during 4 min and followed by 0.1 mg/kg/min] in 5 intact Beagle dogs have been realized providing for each dog 2 coronary flow reserve (CRF: hyperemic flow/basal flow). Regional myocardial blood flow (RMBF) was measured with microspheres (4 radionuclides) by the reference sample method (flow results : ml/min per g). Results : 10 CRF have been calculated 3.47*1,67 (mean+SD). The mean of delays between 2 CRF sequences for each dog was 28 min. CFR measurements obtained from the 2 sequences were 4.43, 4,2 respectively. In spite of 28 min of delay the second basal flow (1.98) was superior to 98% compared to the first (1.0). The variability of CRF in the same dog was in mean of -35% with regard to the increase of the basal flow on the 2nd sequence. Conclusions : the magnitude of the CHR is the same as papaverine (CFR:3 to 5), no maximal such as the adenosine-triphosphate (CFR:7 to 8). Its long-lasting effect is principally used to realize long image acquisition in VDM but to require a delay to steady-state more than 60 min. Several assessments during the same procedure are impossible.
78
ocMpARIs[NoFTfm-~-
cFuL-w49ntm
-IN-
~~~~.~~,B.~andA.~L.SRlithKlineB8echan, Mmrainires B, U.R., B.P. 58, 35762 St Qegoire, FYaxm% anewclass ofantiarrhy+&-cagents~~~~nlicm. Ttva Blcgical actiax3ofthebradycardic agent, UL-FS 49, a verapanil(v)derivative,uwestudiedwithstrndard microelectrode-. maUng~pcrtgNal(~)~acticn~~Enplitude(ApA)u;~lerrrt~ by ULrFs 49 (0.01 to 10 )&I). ck-l the othr hand, v (0.01 to lop) mtly decreased R'fP and APA. kzticn potmtid duratiamwereevaluatedat5Oand9C%of IrKcrea&-goxcwtratialsof the repolari=w&o aI-d -0, respectively). bthuL-Fs49andvgrohgedAPbo.
Iiomvervcnlywasebleto
ble).lhsseresultspmvidea~inmtimoftfie adalsDsllggegtthatUL-Fs49e4hlbifslessczalciun~ ie its-es antr01 O.OluN X& Y 173f18 -5fl Ap40 V-Pp -3fl (ma) UL-F!3 9 5 20531 Vezapanil 3 246&19 D?l Ap40 ULds 49 5 278 29 * pt0.05 arcwa follm by llxxs3n rrsw+nallti~ 5.26
ck==s=Ap90
elxem#@olc9licralacticnofv effectsthanVin O.l!JN
-322 +2?6 +5*2
l.OuM -1lt2 +a13 +28&6* +28?16*
10,0.$l -45f7" +13?13 +54+8* +71+20*
(ta-
Cell
Cardiol
23 (Supplement
IV)
(1991)
76
EFFECTS OF DOPROPIDIL ON CONTRACTILE EROPERTIES OF SKINNED 1FIBERS FROM FERRET PAPILLARY MUSCLES. M. Ferrfer, S. Baudet , J. Leboeuf, C. Leoty , R. Massingham, RL-CERM, Riom, France and UA CNRS 1340, Laboratory of General Physiology, E.N.V., F-44087 Nantes Cedex 03, France. The effects of dopropidil, a novel Ca++ antagonist, were investigated by using thin bundles of skinned fibers from ferret right ventricular papillary muscles. Following Triton X-100 treatment, all membranes are chemically destroyed and the sarcoplasmic reticulum is not+f+unctional. Dopropidil (lo-300 PM) shifted pCa tension curves towards lower Ca concentrations. pCa for half-maximum activation (pCa50) was increased in a reversible concentration-dependent fashion (10 PM: 0,039 +0,02; 300 PM: 0,180+0,035) as well as the partially activated tension (PAT) (pCa 5,875) (100 PM: 2,6+ij,5; 300 PM: 5,2+1,1) and the maximal activated tension (MAT) (pCa 4,5) (100 bM:-l,6+0,3; 300 PM: -2,5+0,3). Furthermore the slope at high concentrations was enhance> (Hill coef.: lO
77
A STUDY OF CORONARY HYPEREMIC RESPONSE AFTER INTRAVENOUS DIPYRIDAMOLE BY MICROSPHERES IN THE CANINE MODEL. G. Fin&. M. de Lorgeril, M. Ovize, D. Revel, JB. Plchard, M. Amiel. Laboratoire de Radiologie Experimentale URA CNRS 1216, Hopital Cardiologique, Lyon, France Dipyridamole (DPD) $ the most widely used coronary vasodilatator in nuclear medeclne and in the assessment of myocardlal perfusion by videodensitometry (VDM). We quantitate the coronary hyperemic response after DPD and its variability during the same experiment. Methods : 2 sequences [rest state/during DPD (0.75 mg/kg during 4 min and followed by 0.1 mg/kg/min] in 5 intact Beagle dogs have been realized providing for each dog 2 coronary flow reserve (CRF: hyperemic flow/basal flow). Regional myocardial blood flow (RMBF) was measured with microspheres (4 radionuclides) by the reference sample method (flow results : ml/min per g). Results : 10 CRF have been calculated 3.47*1,67 (mean+SD). The mean of delays between 2 CRF sequences for each dog was 28 min. CFR measurements obtained from the 2 sequences were 4.43, 4,2 respectively. In spite of 28 min of delay the second basal flow (1.98) was superior to 98% compared to the first (1.0). The variability of CRF in the same dog was in mean of -35% with regard to the increase of the basal flow on the 2nd sequence. Conclusions : the magnitude of the CHR is the same as papaverine (CFR:3 to 5), no maximal such as the adenosine-triphosphate (CFR:7 to 8). Its long-lasting effect is principally used to realize long image acquisition in VDM but to require a delay to steady-state more than 60 min. Several assessments during the same procedure are impossible.
78
ocMpARIs[NoFTfm-~-
cFuL-w49ntm
-IN-
~~~~.~~,B.~andA.~L.SRlithKlineB8echan, Mmrainires B, U.R., B.P. 58, 35762 St Qegoire, FYaxm% anewclass ofantiarrhy+&-cagents~~~~nlicm. Ttva Blcgical actiax3ofthebradycardic agent, UL-FS 49, a verapanil(v)derivative,uwestudiedwithstrndard microelectrode-. maUng~pcrtgNal(~)~acticn~~Enplitude(ApA)u;~lerrrt~ by ULrFs 49 (0.01 to 10 )&I). ck-l the othr hand, v (0.01 to lop) mtly decreased R'fP and APA. kzticn potmtid duratiamwereevaluatedat5Oand9C%of IrKcrea&-goxcwtratialsof the repolari=w&o aI-d -0, respectively). bthuL-Fs49andvgrohgedAPbo.
Iiomvervcnlywasebleto
ble).lhsseresultspmvidea~inmtimoftfie adalsDsllggegtthatUL-Fs49e4hlbifslessczalciun~ ie its-es antr01 O.OluN X& Y 173f18 -5fl Ap40 V-Pp -3fl (ma) UL-F!3 9 5 20531 Vezapanil 3 246&19 D?l Ap40 ULds 49 5 278 29 * pt0.05 arcwa follm by llxxs3n rrsw+nallti~ 5.26
ck==s=Ap90
elxem#@olc9licralacticnofv effectsthanVin O.l!JN
-322 +2?6 +5*2
l.OuM -1lt2 +a13 +28&6* +28?16*
10,0.$l -45f7" +13?13 +54+8* +71+20*
(ta-