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Bay K 8644 increases myocardial relaxation rate in open chest dogs: A comparison with isoproterenol
J Mol
Cell
Cardiol21
(Supplement
II) (1989)
526 THE INHIBrroRy GUANINE NUC?EGTlDE BINDING PROTEIN (G.) MEDiXL!ES THE ATTENUATION OF
CARDIAC ADExaLATE CYCL&SE (AC) ACTMTYBY SPERMINE.%. C16, B. Tantini*, P. Sac&i, ML Zanfanti and C.M. Caldarera. Department of Biochemistry, University of Bologna, *Inst. of Citcxxpholqy, CNR, Bologna (Italy). The polyamide s&e (SPM), at IpM concentration, causes a rapid decrease of basal AC activity in quiescent heart cell (HC) cultures from chick embryos. Studies have been p%formed to understarad pssible site(s) of SPM action using the enzyme from HC or from chick &xyo hearts (Cm). In vitro experiments provide evidence that the effect of SPM is progressive with time, with no apparent lag phase and inversely related tc the age of the heart and to tie dose of mnbient Mg2+. Besides, SPM strongly counteracts the stimulatory action of PGE, as well as of forskolin when added before, after or in association with the diteqene. On the countraq SPM fails to inhibit basal and stinnxlated AC in HC pretreated with pertussis toxin (which prevents Gi activation) or in the presence of 2@l Mn2+, a dose able to block the fonration of the complex between Gi and the catalytic moiety of AC. The propxal of a Gi mediation of SPM action might account for the non additive inhibitory effect of SPM and non hydrolyzable GIF analogs, as GTP yS or Gpp(NH)p, on forskolin-prestimulated AC, as well as for the failure of both the analogs to prcmote inhibition when the enzyme was preincubated with for+ lin and SPM. These findings suggest that SPM very likely ccanpetes with the analogs for the site (Gi) on stblated AC systm. Supported by a grant from Minister0 Pubblica Istruzione, Roma (40%).
527
RADIATION-INDUCED DAMAGE IN THE RAT HEART: G.D. Cilliers, I.S. Harper, MRC Centre for of Stellenbosch Hedical School, Tygerberg; Wi twatersrand, Johannesburg; MRC Research Republic of South Africa.
AN ULTRASTRUCTURAL STUDY. A. Lochner, Molecular and Cellular Biology, University Department of Radiotherapy, University of Institute for Medical Biophysics, Tygerberg,
Although clinical studies suggested that the heart is a radiosensitive organ (11, relatively little is known about radiation damage in the rat heart and no information is available regarding its effects on myocardial ultrastructure. Therefore time-se= quence as well as dose-response studies were performed to study the effects of radia= tion on myocardial ultrastructure. Wistar rats were exposed to lo-30 Gy electron irra= diation, the hearts excised at varying time intervals (1 h - 120 days) and perfusionAtria1 as well as ventricular (epi= fixed with cacodylate-buffered 2.5% glutaraldehyde. cardial and endocardial) samples were examined. Changes were observed in both myocytes and interstitium at all time intervals. The most pronounced change observed in the myocyte was that of intercalated disc damage which reached a peak at 20 days post-irra= diation. Mitochondrial damage, characterized by swelling and fenestration, was focal and relatively scarce.Swelling of capillary endothelial cells and collapse of capilla= ries were marked up to 60 days.Damage to both myocytes and interstitium receded after 60 days and the hearts exhibited an almost normal ultrastructure 120 days post-irradia= tion. 1. Stewart, J.R. et al., Radiology 89, 302, 1967.
528
BAY K 8644 INCREASES MYOCARDIAL RELAXATION RATE IN OPEN CHEST DOGS: A COMPARISON WITH ISOPROTERENOL. R.J. Gelpi, S.M. Mosca, H.E.Cingolani. Centro de Investigaciones CardioUniversidad National de La Plata, 60 y 120, 1900 La Plata, Argentina. vasculares, To determine the action of Bay K 8644 (BK) upon myocardial ielaxation,open-chest dogs were instrumented with ultrasonic crystals,a miniature pressure transducer and aortic,left atria1 and yugular vein catheters.A dose-response curve of Bay K 8644 was performed in each dog. BK lOug/kg/min increased LV systolic pressure,maximal rate of rise of LV pressure (dP/dt) from 17Olk51 to 3424+177 mmHg/sec (P
Cell
Cardiol21
(Supplement
II) (1989)
526 THE INHIBrroRy GUANINE NUC?EGTlDE BINDING PROTEIN (G.) MEDiXL!ES THE ATTENUATION OF
CARDIAC ADExaLATE CYCL&SE (AC) ACTMTYBY SPERMINE.%. C16, B. Tantini*, P. Sac&i, ML Zanfanti and C.M. Caldarera. Department of Biochemistry, University of Bologna, *Inst. of Citcxxpholqy, CNR, Bologna (Italy). The polyamide s&e (SPM), at IpM concentration, causes a rapid decrease of basal AC activity in quiescent heart cell (HC) cultures from chick embryos. Studies have been p%formed to understarad pssible site(s) of SPM action using the enzyme from HC or from chick &xyo hearts (Cm). In vitro experiments provide evidence that the effect of SPM is progressive with time, with no apparent lag phase and inversely related tc the age of the heart and to tie dose of mnbient Mg2+. Besides, SPM strongly counteracts the stimulatory action of PGE, as well as of forskolin when added before, after or in association with the diteqene. On the countraq SPM fails to inhibit basal and stinnxlated AC in HC pretreated with pertussis toxin (which prevents Gi activation) or in the presence of 2@l Mn2+, a dose able to block the fonration of the complex between Gi and the catalytic moiety of AC. The propxal of a Gi mediation of SPM action might account for the non additive inhibitory effect of SPM and non hydrolyzable GIF analogs, as GTP yS or Gpp(NH)p, on forskolin-prestimulated AC, as well as for the failure of both the analogs to prcmote inhibition when the enzyme was preincubated with for+ lin and SPM. These findings suggest that SPM very likely ccanpetes with the analogs for the site (Gi) on stblated AC systm. Supported by a grant from Minister0 Pubblica Istruzione, Roma (40%).
527
RADIATION-INDUCED DAMAGE IN THE RAT HEART: G.D. Cilliers, I.S. Harper, MRC Centre for of Stellenbosch Hedical School, Tygerberg; Wi twatersrand, Johannesburg; MRC Research Republic of South Africa.
AN ULTRASTRUCTURAL STUDY. A. Lochner, Molecular and Cellular Biology, University Department of Radiotherapy, University of Institute for Medical Biophysics, Tygerberg,
Although clinical studies suggested that the heart is a radiosensitive organ (11, relatively little is known about radiation damage in the rat heart and no information is available regarding its effects on myocardial ultrastructure. Therefore time-se= quence as well as dose-response studies were performed to study the effects of radia= tion on myocardial ultrastructure. Wistar rats were exposed to lo-30 Gy electron irra= diation, the hearts excised at varying time intervals (1 h - 120 days) and perfusionAtria1 as well as ventricular (epi= fixed with cacodylate-buffered 2.5% glutaraldehyde. cardial and endocardial) samples were examined. Changes were observed in both myocytes and interstitium at all time intervals. The most pronounced change observed in the myocyte was that of intercalated disc damage which reached a peak at 20 days post-irra= diation. Mitochondrial damage, characterized by swelling and fenestration, was focal and relatively scarce.Swelling of capillary endothelial cells and collapse of capilla= ries were marked up to 60 days.Damage to both myocytes and interstitium receded after 60 days and the hearts exhibited an almost normal ultrastructure 120 days post-irradia= tion. 1. Stewart, J.R. et al., Radiology 89, 302, 1967.
528
BAY K 8644 INCREASES MYOCARDIAL RELAXATION RATE IN OPEN CHEST DOGS: A COMPARISON WITH ISOPROTERENOL. R.J. Gelpi, S.M. Mosca, H.E.Cingolani. Centro de Investigaciones CardioUniversidad National de La Plata, 60 y 120, 1900 La Plata, Argentina. vasculares, To determine the action of Bay K 8644 (BK) upon myocardial ielaxation,open-chest dogs were instrumented with ultrasonic crystals,a miniature pressure transducer and aortic,left atria1 and yugular vein catheters.A dose-response curve of Bay K 8644 was performed in each dog. BK lOug/kg/min increased LV systolic pressure,maximal rate of rise of LV pressure (dP/dt) from 17Olk51 to 3424+177 mmHg/sec (P