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Biomedical subjects

M L Rand

Publications and source records attributed to M L Rand.

62 records · Page 4Linked to original sources
PubMed1985

Effects of plasmin on rabbit platelets.

The effects of plasmin have been examined because platelets may be exposed to plasmin in vivo and treatment of platelets with plasmin shortens platelet survival. Rabbit plasmin was prepared by urokinase activation of plasminogen immobilized on lysine-Sepharose. Plasmin caused rabbit platelets to aggregate and release the contents of their amine storage granules, but aggregation was slower than in response to ADP or thrombin. EDTA, prostaglandin E1, or creatine phosphate/creatine phosphokinase were inhibitory, but indomethacin was not. Deaggregation did not occur when platelets had been aggregated by a concentration of plasmin that caused extensive release of granule contents. EDTA or prostaglandin E1 caused deaggregation. Low concentrations of ADP and plasmin acted synergistically in causing platelet aggregation. Plasmin decreased the amounts of platelet membrane glycoproteins that stained with periodic acid-Schiff reagent; glycoprotein I was more susceptible than glycoprotein II and III. Concentrations of plasmin that induced the release of amine storage granule contents also released PAS-staining granule glycoproteins. Platelets incubated with plasmin, washed and resuspended, were not aggregated by ADP, but were aggregated strongly by the combination of fibrinogen and ADP, and bound 125I-fibrinogen to a greater extent than untreated platelets. Platelets preincubated with a high concentration of plasmin were unresponsive to thrombin, but were sometimes aggregated by fibrinogen. Plasmin decreased the buoyant density and increased the median size of platelets. Thus plasmin, as well as ADP and thrombin, may contribute to the density shift observed in platelets from rabbits in which thrombosis and continuous vessel injury have been induced.

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PubMed1985

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP.

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.

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PubMed1983

Survival of density subpopulations of rabbit platelets: use of 51Cr-or 111In-labeled platelets to measure survival of least dense and most dense platelets concurrently.

The origin of the density heterogeneity of platelets was studied by measuring the survival of density subpopulations of rabbit platelets separated by discontinuous Stractan density gradient centrifugation. When a total population of 51Cr-labeled platelets was injected into recipient rabbits, the relative specific radioactivity of the most dense platelets decreased rapidly. In contrast, that of the least dense platelets had not changed 24 hr after injection, and then decreased slowly. To distinguish between the possibilities that most dense platelets are cleared from the circulation more quickly than least dense platelets or that platelets decrease in density as they age in the circulation, the concurrent survival of least dense and most dense platelets, labeled with either 51Cr or 111In-labeled total platelet populations, determined concurrently in the same rabbits, were identical, calculated from 1 hr values as 100%. However, the 1-hr recovery of 111In-labeled platelets was slightly but significantly less than that of 51Cr-labeled platelets. Therefore, we studied the survival of 51Cr-labeled least dense and 111In-labeled most dense platelets as well as that of 111In-labeled least dense and 51Cr-labeled most dense platelets. Mean 1-hr recovery of least dense platelets, labeled with either isotope (78% +/- 7%, SD) was similar to that of most dense platelets, labeled with either isotope (77% +/- 8%; SD). Mean survival of least dense platelets was 47.3 +/- 18.7 hr (SD), which was significantly less than that of most dense platelets (76.1 +/- 21.6 hr; SD) (p less than 0.0025). These results indicate that platelets decrease in buoyant density as they age in the circulation and that most dense platelets are enriched in young platelets, and least dense in old. Thus, the events that affect platelets as they age in the circulation contribute to platelet density heterogeneity, although they may not be the sole cause of it.

Animals↗
PubMed1983

Changes in the properties of platelets from rats with experimentally induced shortened platelet survival.

Platelet survival is shortened in experimental animals in which indwelling aortic catheters have been placed. We have examined the properties of platelets harvested from rats on day 1 or day 6 after insertion of indwelling aortic catheters. Platelets taken from these animals at 6 days (but not at 1 day) survived in normal rats or in rats with indwelling catheters for a significantly longer time than platelets from sham-operated rats. The catheters caused a persistent fall in the platelet count, an increase in the proportion of platelets in the most dense fraction after separation on discontinuous Stractan density gradients, and a decrease in mean sialic acid and protein per 10(9) platelets, but not change in modal size as determined with a Coulter Counter Channelyzer. No significant differences in the sensitivity to aggregating and release-inducing agents (ADP, thrombin, or collagen) were observed. It seems likely that chronic damage of the vessel wall shortened platelet survival and increased platelet turnover, although the increase in platelet production was not sufficient to maintain the platelet counts at the same values as in the sham-operated animals. The prolonged survival times in recipient rats of platelets from rats with indwelling aortic catheters indicate that a population of predominantly young platelets exists in these animals. Their increased density supports this conclusion.

Animals↗
PubMedDate not supplied

Platelet function in Watanabe heritable hyperlipidemic rabbits. Decreased sensitivity to thromboxane A2.

The characteristics of platelets from seven 5-7-month-old homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits (plasma cholesterol, 13.9 +/- 1.7 mM, mean +/- SEM) were compared with those of platelets from normocholesterolemic age/weight- and sex-matched control rabbits (plasma cholesterol, 2.2 +/- 0.3 mM). Whole-blood platelet count and platelet size and protein content were not different in the two groups of rabbits, and the platelets from the WHHL rabbits were not enriched in cholesterol as indicated by identical mean cholesterol:phospholipid molar ratios (C/P). Responses of washed platelets stimulated with various agonists were studied to determine the effects of the genetically determined hypercholesterolemia on the various pathways of platelet aggregation in the absence of plasma components. In platelets from WHHL rabbits compared with controls, aggregation induced by ADP (0.5-5 microM) did not differ; collagen-induced (0.25-1.5 micrograms/ml) responses (aggregation, secretion of carbon-14-labeled serotonin from the amine storage granules of prelabeled platelets, and thromboxane A2 [TxA2] formation) were significantly less extensive; with aspirin-treated platelets, aggregation and secretion of granule contents induced by the TxA2 mimetic U46619 (0.25-1 microM) were significantly less extensive; and thrombin-induced (0.005-0.1 unit/ml) responses of untreated platelets (aggregation, secretion of granule contents, and TxA2 formation) or aspirin-treated platelets (aggregation and secretion of granule contents) did not differ. These observations are in direct contrast with previous studies of platelets from rabbits with diet-induced hypercholesterolemia, in which responses to TxA2 and thrombin were enhanced. Platelets from WHHL rabbits are hyposensitive to aggregation induced by TxA2.

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