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The role of platelet-activating factor in spontaneous platelet aggregation developing during extracorporeal circulation in anaesthetized beagle dogs
FIemh,
F., Magyar, IL and Filep *, J.
Department of Pharmaco&namics and * Pathophysiologv, Semmelweis Uniuersity Medical School. Budapest, P. 0. B. 370. H-1445, Hungary
When arterial blood of beagle dogs is directed through a metal screen by a peristaltic pump, there is a spontaneous increase in filter pressure as a consequence of spontaneous platelet aggregation (1). Gur aim was to study the role of platelet-activating factor (PAF) in spontaneous platelet aggregation on the filter. Administration of PAP proximal to the filter (final concentration in the flowing blood: 10s7 M; duration of infusion: 30 se@ resulted in an immediate increase in filter pressure. The filter occlusion time decreased from 356 f 56 set to 132 + 20 set (n = 4, p < 0.001) during PAF infusion. This proaggregatory action of PAF was blocked by infusion of a specific PAF-antagonist, BN 52021 (2) (final concentration in the flowing blood: IO-’ M) proximal to the filter before and during PAF administration. However, infusing BN 52021 in itself, failed to block the increase in filter pressure. BN 52021 was administered intravenously (2 mg/kg) in six anaesthetized animals, in order to evaluate the role of endogenously generated PAF in spontaneous platelet aggregation. The efficacy of PAF antagonist was characterized by changes in filter occlusion time (FOT), filter occlusion rate (FOR) and the pressure stabilizing concentration (PSC) of prostacyclin (PGI,), infused proximal to the filter, which proved to be the most sensitive marker of filter occlusion (1). There were no significant changes in filter occlusion time and filter occlusion rate after administration of PAF-antagonist (before BN 52021: FOT (s) = 282 f 42; FOR (mmHg/s) = 2.1 i- 0.3; after BN 52021: FOT (s) = 304 + 53: FOR (mmHg/s) = 1.9 f. 0.2). However, in the presence of BN 52021 the PSC of PGI, was markedly decreased (before BN 52021: PSC-PGIz (nM) = 3.2 f 0.4; after BN 52021: PSC-PG12 (nM) = 1.2 f 0.2) (p c 0.05). Therefore, we conclude that while exogenous PAF injected into the filter-loop markedly enhanced the propagation of spontaneous platelet aggregation on the filter, the blockage of the effect of endogenously generated PAF (by pretreatment with BN 52021) is not enough to prevent filter occlusion. However, decrease in the amount of PGI, that is necessary for pressure stabilization after RN 52021 treatment suggests, that endogenously generated PAF might be an additional factor in the platelet activation during extracorporeal circulation. This finding might has therapeutic relevances. erences
HermBn, F.. 1986. Thrombosis Research, 44. 575. Braquet. P.. 1985. Blood Vessels 6, 559.
g as fibrinogen Huang, T.-F., Wang, W.-J. and Ouyang, C. Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Tarwan, People’s Republic of China
By means of Fractogel TSK-50, CM-Sephadex C-50 column chromatography, gel filtration on Sephadex G-75 and Sephacryl G-200 cohmms and reverse phase HPLC, an antiplatelet peptide, arietin was purified from the venom of Bitis ariems. Arietin is a single chain, Arg-Gly-Asp (RGD) containing peptide with molecular weight of 8,500
F., Magyar, IL and Filep *, J.
Department of Pharmaco&namics and * Pathophysiologv, Semmelweis Uniuersity Medical School. Budapest, P. 0. B. 370. H-1445, Hungary
When arterial blood of beagle dogs is directed through a metal screen by a peristaltic pump, there is a spontaneous increase in filter pressure as a consequence of spontaneous platelet aggregation (1). Gur aim was to study the role of platelet-activating factor (PAF) in spontaneous platelet aggregation on the filter. Administration of PAP proximal to the filter (final concentration in the flowing blood: 10s7 M; duration of infusion: 30 se@ resulted in an immediate increase in filter pressure. The filter occlusion time decreased from 356 f 56 set to 132 + 20 set (n = 4, p < 0.001) during PAF infusion. This proaggregatory action of PAF was blocked by infusion of a specific PAF-antagonist, BN 52021 (2) (final concentration in the flowing blood: IO-’ M) proximal to the filter before and during PAF administration. However, infusing BN 52021 in itself, failed to block the increase in filter pressure. BN 52021 was administered intravenously (2 mg/kg) in six anaesthetized animals, in order to evaluate the role of endogenously generated PAF in spontaneous platelet aggregation. The efficacy of PAF antagonist was characterized by changes in filter occlusion time (FOT), filter occlusion rate (FOR) and the pressure stabilizing concentration (PSC) of prostacyclin (PGI,), infused proximal to the filter, which proved to be the most sensitive marker of filter occlusion (1). There were no significant changes in filter occlusion time and filter occlusion rate after administration of PAF-antagonist (before BN 52021: FOT (s) = 282 f 42; FOR (mmHg/s) = 2.1 i- 0.3; after BN 52021: FOT (s) = 304 + 53: FOR (mmHg/s) = 1.9 f. 0.2). However, in the presence of BN 52021 the PSC of PGI, was markedly decreased (before BN 52021: PSC-PGIz (nM) = 3.2 f 0.4; after BN 52021: PSC-PG12 (nM) = 1.2 f 0.2) (p c 0.05). Therefore, we conclude that while exogenous PAF injected into the filter-loop markedly enhanced the propagation of spontaneous platelet aggregation on the filter, the blockage of the effect of endogenously generated PAF (by pretreatment with BN 52021) is not enough to prevent filter occlusion. However, decrease in the amount of PGI, that is necessary for pressure stabilization after RN 52021 treatment suggests, that endogenously generated PAF might be an additional factor in the platelet activation during extracorporeal circulation. This finding might has therapeutic relevances. erences
HermBn, F.. 1986. Thrombosis Research, 44. 575. Braquet. P.. 1985. Blood Vessels 6, 559.
g as fibrinogen Huang, T.-F., Wang, W.-J. and Ouyang, C. Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Tarwan, People’s Republic of China
By means of Fractogel TSK-50, CM-Sephadex C-50 column chromatography, gel filtration on Sephadex G-75 and Sephacryl G-200 cohmms and reverse phase HPLC, an antiplatelet peptide, arietin was purified from the venom of Bitis ariems. Arietin is a single chain, Arg-Gly-Asp (RGD) containing peptide with molecular weight of 8,500