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Biomedical subjects

E F Grabowski

Publications and source records attributed to E F Grabowski.

17 recordsLinked to original sources

Relationship of anticoagulation and radiographic contrast agents to thrombosis during coronary angiography and angioplasty: are there real concerns?

Radiographic contrast agents are essential for the performance of coronary angiography and angioplasty. Historical data show that thrombosis-related events have occurred since coronary angiography has been performed. Newer non-ionic agents have been shown to be safer than conventional high osmolar ionic agents especially in high risk patients, but concern has been raised about a potentially increased risk of thrombosis with the use of these agents. A review of basic and clinical evidence for this perception does not support the view that an increase in thrombosis-related events has occurred as a results of non-ionic contrast media use in coronary angiographic procedures.

Angioplasty, Balloon, Coronary

Anticoagulant effects of nonionic versus ionic contrast media in angiography syringes.

To determine whether nonionic contrast media present a clotting hazard when plastic or glass injection syringes are contaminated with aspirated blood, we evaluated two nonionic (iohexol and iopamidol) and two ionic (ioxaglate and diatrizoate) contrast agents. We used a blood:contrast media ratio of 2 mL:5 mL and ten normal donors, each studied at 10, 20, 30, and 60 minutes, a parallel study of clotting and fibrinopeptide A (FPA) generation in plastic tubes, and life table analysis to estimate more accurately donor-based early clotting probabilities. While ionic contrast media are stronger anticoagulants, both nonionic and ionic media retard clotting in plastic tubes, and clotting in plastic and glass angiography syringes in comparison to saline controls. A clotting probability of 1% for nonionic agents in plastic syringes was not reached until a time (mean +/- SD) of 21.5 +/- 3.2 minutes. This contrasts with a time of 8.7 +/- 2.5 minutes for saline control. With plastic syringes, no clotting at all was observed at 10 and 20 minutes with either class of agents. Neither class of agents hastened the generation of FPA. We found no evidence, therefore, that nonionic agents either cause clots or are procoagulant.

Angiography

A hematologist's view of contrast media, clotting in angiography syringes and thrombosis during coronary angiography.

While ionic contrast media (CM) are stronger anticoagulants and antiplatelet agents, both nonionic and ionic CM retard clotting, fibrinopeptide A generation and platelet aggregation (at least by Born-O'Brien aggregometry). Thus, nonionic CM do not cause clots and thrombi. Rather, the driving force for clot or thrombus formation, when it occurs, is blood contact with and activation by the foreign surface of a syringe or catheter itself. A marked enhancement of clotting by glass syringes in comparison to plastic ones supports this view. Blood in any syringe or catheter, therefore, will clot more slowly in the presence of nonionic or ionic CM, the inhibitory effects of the latter being more profound. With respect to models of thrombosis at sites of vascular injury or stenosis, the antithrombotic effects of CM may either be transient owing to the dynamic nature of blood flow (local endothelial cell denudation model), or as in the case of ionic CM, actually to enhance local platelet aggregation (stenosis model). In these situations, preservation of the antithrombotic functions of endothelium with nonionic CM may be quite critical.

Angiography

Platelet aggregation in flowing blood at a site of injury to an endothelial cell monolayer: quantitation and real-time imaging with the TAB monoclonal antibody.

Epifluorescence videomicroscopy permits real-time imaging of platelet adhesion/aggregation to a defined microinjury of a monolayer of endothelial cells exposed to flowing blood. The fluorescent label is the TAB murine monoclonal antibody directed against human platelet GP IIB, together with a fluorescein-conjugated goat F(ab')2 against murine immunoglobulin. The combination assures specificity for platelet membranes, yet leaves platelet function intact. TAB is first added to gently mixed, citrated human blood; the second antibody is added 1 hour after the first, mixing continuing for a second hour. Bovine aortic endothelial cell monolayers (ECMs), grown on rectangular cover glasses precoated with microfibrillar collagen, comprise one wall of a flow chamber mounted on a vertical microscope stage. A loop of 6-0 sterile suture is drawn across the ECM in order to create microinjuries of width 70 +/- 15 microns (mean +/- SD) oriented in a direction transverse to flow. Platelet adhesion/aggregation is virtually absent on intact and confluent regions of the monolayer. On micro-injury sites and at shear rates of 60 to 1,080 sec-1, however, computer-enhanced images obtained by means of videomicroscopy show arrival and adherence of single platelets resulting in the formation of platelet aggregates elongated in the flow direction. When the monolayers are pretreated with 1.0 mmol/L lysine acetylsalicylate, the mean aggregate thickness increases (2P less than .05) to 260 +/- 58% (mean +/- SE, N = 6) of control, aggregates are regularly shed downstream, and the surface area of the injury site covered by platelets is augmented (2P less than .05) from 14.8 +/- 3.9% to 49.2 +/- 4.7% (mean +/- SE, N = 6). Donor ingestion of aspirin, on the other hand, leads to an increase (2P less than .01) in percent surface coverage to 42.7 +/- 8.5 without a concomitant increase in mean aggregate thickness. In parallel with the above, outflow levels of serum thromboxane and prostacyclin are measured by radioimmunoassays (RIAs) for thromboxane B2 and 6-Keto-PGF1 alpha, respectively. Thromboxane B2 is increased (2P less than .01) by monolayer pretreatment with lysine acetylsalicylate from 5.08 +/- 1.47 to 9.35 +/- 2.42, but decreased (2P less than .05) after oral aspirin to 1.21 +/- 0.38 ng/mL (mean +/- SE, N = 6). Levels of 6-Keto-PGF1 alpha were reduced (2P less than .05) by monolayer pretreatment from 0.48 +/- 0.046 to 0.36 +/- 0.016 ng/mL. Platelet adhesion/aggregation at a site of injury to an endothelial cell monolayer, therefore, can be imaged in flowing blood in real time using a monoclonal antibody approach.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Thermal excitations of a bilipid membrane.

Propagating modes of vibration of a bilipid membrane have been detected with light beating spectroscopy. The dependence of omega on q is consistent with a model of a fluid film of surface tension sigma = 2.5 +/- 0.5 dyn cm-1 surrounded by a medium with rho = 1 g cm-3 and eta = 1.01 X 10(-2) P.

Cholesterol

Platelet adhesion to foreign surfaces under controlled conditions of whole blood flow: human vs rabbit, dog, calf, sheep, pig, macaque, and baboon.

Our results reveal significant differences between mammalian species with respect to platelet adhesion to foreign surfaces exposed to heparinized, flowing blood. In particular, we have demonstrated the following: 1) At a surface shear rate characteristic of shear rates in mammalian arteries, human platelet adhesion (and that of calf, baboon, macaque, hog or sheep) is negligible in comparison to dog or rabbit platelet adhesion after 10 mins of blood flow. 2) The species differences are biomaterial dependent: the human-dog difference is present with Cuprophan or Avcothane, but absent with compressed Gore-Tex or fluorinated ethylcellulose. (The platelets of humans and dogs adhere to comparable degrees on the latter 2 biomaterials.) 3) With Cuprophan and recirculated blood, the human-dog difference persists at 30 and 180 mins. 4) By means of videomicroscopy, the species differences are unlikely only to be an artifact of the possible formation and embolization of surface-adherent aggregates. Tests for the thromboresistance of candidate biomaterials and for platelet adhesion under controlled flow conditions must therefore begin to take into account differences between humans and other species.

Animals

Human vs. dog platelet adhesion to Cuprophane under controlled conditions of whole blood flow.

It is commonly assumed that a candidate biomaterial to which nonhuman (especially dog) platelets do not readily adhere is promising for human use. This assumption has been tested in a lucite chamber in which Cuprophane membrane (Bemberg PT-150), comprising one of the chamber surfaces, is exposed to citrated or heparinized flowing dog or human blood for 10 or 20 minutes and flowing buffer for 1 minute. Following exposure, membrane specimens are carefully removed, fixed in glutaraldehyde, and mounted on a slide. Platelets at a particular axial location are counted by phase-contrast microscopy (625 X). At a shear rate of 986 sec.-1 and at 10 minutes, platelets per square millimeter (mean +/- S.E.(N) in citrate were 28,400 +/- 5,000 (6), dog; 18 +/- 3.8 (4), human. Under the same conditions, platelets per squar millimeter in heparin were 32,600 +/- 8,400 (4), dog; 7.6 +/- 1.0 (3), human. A qualitatively similar species difference was found in citrate at one shear rate and at one other exposure time. Those observations suggest that evaluations of candidate human biomaterials carried out with dog (and perhaps other nonhuman) blood must be interpreted with caution.

Animals