dc.creator GIORGIO, TODD DONALD 2007-05-09T19:44:31Z 2007-05-09T19:44:31Z 1987 https://hdl.handle.net/1911/16058 A rotational viscometer was modified to permit continuous measurement of platelet aggregation, dense granule release and intracellular calcium ion concentration during exposure to uniform shear stress in either the presence or absence of added chemical agonists. The shear stress intensity applied to a platelet suspension influences both the concentration of single, unaggregated platelets and the population volume distribution of formed aggregates in samples with and without added ADP. Direct evidence supports the postulate that large platelet aggregates formed in response to chemical and/or mechanical stimulus can dissociate into smaller particles upon additional shear stress exposure. The rate of platelet dense granule release is approximately a constant function of applied shear stress intensity in the absence of added chemical agonists. Addition of 0.2 or 2.0 $\mu$M ADP accelerates the rate of dense granule release in a concentration dependent way which is also potentiated by increased shear stress intensity. Application of shear stress alone results in bulk phase concentrations of ADP which are insufficient to induce aggregation in a stirred platelet suspension. Platelet ADP surface concentrations estimated from the continuously measured luminescence response indicate that application of shear stress alone results in local ADP concentrations which are sufficient to cause platelet aggregation which is consistent in rate and extent with that observed in response to ADP added to a stirred platelet sample. Increased intracellular calcium ion concentration ( (Ca$\sp{2+}$) $\sb{\rm i}$) is correlated with the formation of irreversible platelet aggregation. Platelet aggregation which occurs in response to 0.2 $\mu$M added ADP and/or low intensity shear stress is reversible and not accompanied by a rise in (Ca$\sp{2+}$) $\sb{\rm i}$. Inhibitors of ADP induced platelet activation (creatine phosphate/creatine phosphokinase, apyrase, 5$\sp\prime$-p-fluorosulfonylbenzoyl adenosine) were effective in reducing, but not abolishing, shear stress induced aggregation. A mechanism for shear stress induced aggregation is postulated which implicates elevated platelet surface concentration of ADP as the primary mediator. This postulate is extended to indicate that the initiation step in this response is a shear stress dependent local elevation of (Ca$\sp{2+}$) $\sb{\rm i}$. application/pdf eng Biomedical engineering CONTINUOUS MEASUREMENT OF SHEAR STRESS INDUCED PLATELET ACTIVATION Thesis Text Bioengineering Engineering Rice University Doctoral Doctor of Philosophy GIORGIO, TODD DONALD. "CONTINUOUS MEASUREMENT OF SHEAR STRESS INDUCED PLATELET ACTIVATION." (1987) Diss., Rice University. https://hdl.handle.net/1911/16058.
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