Platelet Survival and Function in Animals with Prosthetic Mitral Valve: The Effect of Nafazatrom

1984 ◽  
Vol 52 (02) ◽  
pp. 099-101
Author(s):  
H Al-Mondhiry ◽  
W S Pierce ◽  
W Richenbacher
Keyword(s):  
Platelet Aggregation ◽  
Heart Valves ◽  
Ex Vivo ◽  
Oral Drug ◽  
Prosthetic Heart Valves ◽  
Antithrombotic Agent ◽  
Mitral Valves ◽  
Platelet Survival ◽  
Survival Studies ◽  
And Function

SummaryThromboembolism remains a serious problem in patients with prosthetic heart valves. Previous studies documented a number of platelet abnormalities in such patients and correlated the occurrence of thromboembolic complications with short platelet survival. We have studied platelet survival and platelet aggregation in eight goats fitted with prosthetic mitral valves and repeated the studies following treatment with nafazatrom, a potent antithrombotic agent. Eleven survival studies in eight animals showed a platelet survival not significantly different from control (6.52 ± 0.72 vs. 6.94 ± 0.81 days). Following seven to ten days of oral drug administration, platelet survival in the test animals was 7.34 ± 0.96 days, significantly longer than pretreatment results (p <0.01). Animals with the shortest pretreatment platelet survival achieved substantial prolongation of platelet life span following drug treatment. The drug caused no change in ex vivo platelet aggregation.

The Influence of Ascorbic Acid on Platelet Structure and Function

1975 ◽  
Vol 34 (01) ◽  
pp. 050-062
Author(s):  
Dale H Cowan ◽  
Richard C Graham ◽  
Patricia Shook ◽  
Ronda Griffin
Keyword(s):  
Ascorbic Acid ◽  
Open Channel ◽  
Channel System ◽  
Short Intervals ◽  
Platelet Survival ◽  
Artifactual Changes ◽  
Survival Studies ◽  
And Function ◽  
Induced Aggregation ◽  
Platelet Structure

SummaryTo determine the effect on platelet behavior of transient exposure of platelets to ascorbic acid, studies of platelet function and ultrastructure were done before exposure to ascorbic acid at pH 6.5, during exposure to pH 6.5, and after restoration of pH to pre-acidifìcation levels. The effect of ascorbic acid (A. A.) was compared to that of HCl and citric acid (C. A.). ADP- and collagen-induced aggregation of normal platelets were significantly impaired by both A. A. and C. A. but were less affected by HCl. The release of 14C-serotonin was significantly reduced by each agent. The ultra-structure of normal platelets brought to pH 6.5 by A.A. was normal. After neutralization, there was marked dilatation of the open channel system and loss of the disc shape. When platelets were brought to pH 6.5 by A. A., then neutralized, the aggregates which formed after stimulation by ADP or collagen were smaller than normal, the platelets were less closely approximated, and degranulation was less complete. The data show that exposure of platelets to ascorbic acid for short intervals impairs their function when measured after restoration of pH to levels compatible with maximal responses. Platelet survival studies using autologous platelets labelled with 51Cr in the presence or absence of ascorbic acid showed that the recovery of normal platelets was unaffected by ascorbic acid, whereas recovery of platelets from patients with idiopathic thrombocytopenic purpura, idiopathic thrombocythemia, and alcohol-related thrombocytopenia was markedly reduced. The injury resulting from the use of ascorbic acid in preparing platelets for studies of platelet survival in patients with disorders affecting platelets may impair the recovery of the cells, resulting in artifactual changes in the survival studies.

Dipyridamole Inhibits Platelet Aggregation in Whole Blood

1983 ◽  
Vol 50 (04) ◽  
pp. 852-856 ◽  
Author(s):  
P Gresele ◽  
C Zoja ◽  
H Deckmyn ◽  
J Arnout ◽  
J Vermylen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Significant Negative Correlation ◽  
Significant Inhibition ◽  
Oral Drug ◽  
Human Blood Samples ◽  
Induced Aggregation

SummaryDipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine- 5’-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p <0.001). A statistically significant inhibition of both collagen (p <0.0025) and ADP-induced (p <0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37° C with dipyridamole (3.9 μM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood.Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.

scholarly journals Antithrombotic effect of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor in an experimental animal model

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 783-786 ◽  
Author(s):  
BS Coller ◽  
JD Folts ◽  
LE Scudder ◽  
SR Smith
Keyword(s):  
Monoclonal Antibody ◽  
Animal Model ◽  
Platelet Aggregation ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Platelet Glycoprotein ◽  
Antithrombotic Effect ◽  
Antithrombotic Agent ◽  
Antithrombotic Effects ◽  
Platelet Thrombus

A murine monoclonal antibody directed at the platelet glycoprotein IIb/IIIa complex, which blocks platelet aggregation ex vivo, was tested for its antithrombotic effects in an established animal model of acute platelet thrombus formation in partially stenosed arteries. Infusion of 0.7 to 0.8 mg/kg of the F(ab')2 fragment of the antibody completely blocked new thrombus formation despite multiple provocations, making it the most potent antithrombotic agent tested in this model.

scholarly journals Left heart simulator for evaluation of prosthetic heart valves: behavior of tricuspid bioprosthetic mitral valves during diastole

2018 ◽  
Vol 51 (27) ◽  
pp. 134-139
Author(s):  
Ovandir Bazan ◽  
Jayme Pinto Ortiz ◽  
Antonio Braulio Neto ◽  
Jurandir Itizo Yanagihara
Keyword(s):  
Heart Valves ◽  
Prosthetic Heart Valves ◽  
Left Heart ◽  
Mitral Valves

scholarly journals Antithrombotic Activity of a Potent, New Agent, 6,7-Dichloro-1,2,3,5-Tetrahydroimidazo[2,1-B] Quinazolin-2-One Hydrochloride Monohydrate

1977 ◽  
Author(s):  
J. S. Fleming ◽  
J. P. Buyniski
Keyword(s):  
Platelet Aggregation ◽  
Animal Models ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Oral Dosage ◽  
Antithrombotic Agent ◽  
Duration Of Action ◽  
Antithrombotic Activity ◽  
Small Vessels ◽  
Hydrochloride Monohydrate

A potent, new anti-thrombotic agent, 6 ,7-dichloro-l,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one hydrochloride monohydrate (BL-4162A) has been evaluated for activity against induced platelet aggregation in a series of in vitro and ex vivo experiments using platelet rich plasma (PRP) from various species including man. In addition, the compound’s potential utility as an antithrombotic agent has been tested in various in vivo animal models including two models of induced thrombosis involving both large and small vessels. Aggregometry was employed to test the ability of BL-4162A to inhibit platelet aggregation induced by aggregating agents such as ADP, collagen, thrombin and antigen-antibody complexes. The compound’s antithrombotic activity was evaluated in small vessels using the biolaser-rabbit ear chamber technique while the effect of BL-4162A on large vessel thrombosis was assessed against electrically-induced carotid artery thrombosis in dogs. Results indicate that BL-4162A inhibits platelet aggregation in the range of 0.08 to 0.68 pg/ml. Platelet antiaggregating activity was also observed in ex vivo aggregometry studies in dogs and rats at oral doses in the range of 1 to 10 mg/kg. Of particular interest, is the fact that BL-4162A effectively inhibited thrombosis in both animal models employed over the same oral dosage range. Results of the above investigations as well as an appreciable duration of action suggest that BL-4162A may be an important candidate for clinical evaluation in thromboembolism.

scholarly journals Platelet Suppression Therapy in Arterial Disease: Present Status

1977 ◽  
Author(s):  
J. A. Blakely
Keyword(s):  
Secondary Prevention ◽  
Heart Valves ◽  
Case Reports ◽  
Myocardial Infarct ◽  
Arterial Disease ◽  
Preliminary Evidence ◽  
Prosthetic Heart Valves ◽  
Prosthetic Valves ◽  
Survival Studies ◽  
Cerebral Ischemic

Arterial disease is a severe test of clinical trials methodology. Results to date have defined areas for further study, but clinical indications are not established. Dipyridamole reduces emboli from prosthetic heart valves but applicability to less thrombogenic valves is uncertain. Transient cerebral ischemic attacks are physiologically appropriate and there is preliminary evidence of reduced attacks with Sulfinpyrazone, none with Dipyridamole, and favorable case reports with Aspirin. Effects on stroke and death in patients presenting with TIA or stroke are under study. Sulfinpyrazone has failed to prolong patency time after peripheral vascular surgery. Administration of aspirin and of Sulfinpyrazone to elderly populations has shown no detectable benefit from Aspirin, and has suggested that Sulfinpyrazone should be further studied in patients recovered from thrombotic stroke. The greatest potential benefit may be secondary prevention of myocardial infarct, but to date efficacy has neither been demonstrated nor excluded. Studies in progress include: ASA and/or Sulfinpyrazone and TIA, stroke and death in patients with TIA; ASA with and without Dipyridamole in patients with TIA: Sulfinpyrazone and survival after recovery from thrombotic stroke; Secondary prevention of myocardial infarct with ASA, ASA or ASA + Dipyridamole, Sulfinpyrazone, and Clofibrate; Sulfinpyrazone, ASA, and ASA with anticoagulants and emboli from prosthetic valves. Platelet survival studies may permit selection of populations likely to benefit and assessment of adequacy of therapy.Hypotheses tested by clinical trial must be distinguished from hypotheses formulated from retrospective analysis, and methods must permit effects of treatment to be distinguished from differences in risk.

Platelet survival in patients with prosthetic heart valves

1974 ◽  
Vol 33 (7) ◽  
pp. 840-844 ◽  
Author(s):  
R.Kenneth Stuart ◽  
John W. McDonald ◽  
Suraj P. Ahuja ◽  
John C. Coles
Keyword(s):  
Heart Valves ◽  
Prosthetic Heart Valves ◽  
Platelet Survival

scholarly journals SIBS triblock copolymers in cardiac surgery: in vitro and in vivo studies in comparison with ePTFE

2020 ◽  
Vol 21 (4) ◽  
pp. 67-80
Author(s):  
M. A. Rezvova ◽  
E. A. Ovcharenko ◽  
P. A. Nikishev ◽  
S. V. Kostyuk ◽  
L. V. Antonova ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Heart Valves ◽  
Ex Vivo ◽  
Calcium Content ◽  
Positive Control ◽  
Prosthetic Heart Valves ◽  
Solution Casting Method ◽  
Cell Adhesion And Proliferation

Implantation of polymeric heart valves can solve the problems of existing valve substitutes – mechanical and biological. Objective: to comprehensively assess the hemocompatibility of styrene-isobutylene-styrene (SIBS) triblock copolymer, synthesized by controlled cationic polymerization in comparison with expanded polytetrafluoroethylene (ePTFE) used in clinical practice. Materials and methods. SIBS-based films were made by polymer solution casting method; in vitro biocompatibility assessment was performed using cell cultures, determining cell viability, cell adhesion and proliferation; tendency of materials to calcify was determined through in vitro accelerated calcification; in vivo biocompatibility assessment was performed by subcutaneous implantation of rat samples; hemocompatibility was determined ex vivo by assessing the degree of hemolysis, aggregation, and platelet adhesion. Results. The molecular weight of synthesized polymer was 33,000 g/mol with a polydispersity index of 1.3. When studying cell adhesion, no significant differences (p = 0.20) between the properties of the SIBS polymer (588 cells/mm2) and the properties of culture plastics (732 cells/mm2) were discovered. Cell adhesion for the ePTFE material was 212 cells/mm2. Percentage of dead cells on SIBS and ePTFE samples was 4.40 and 4.72% (p = 0.93), respectively, for culture plastic – 1.16% (p < 0.05). Cell proliferation on the ePTFE surface (0.10%) was significantly lower (p < 0.05) than for the same parameters for SIBS and culture plastic (62.04 and 44.00%). Implantation results (60 days) showed the formation of fibrous capsules with average thicknesses of 42 μm (ePTFE) and 58 μm (SIBS). Calcium content in the explanted samples was 0.39 mg/g (SIBS), 1.25 mg/g (ePTFE) and 93.79 mg/g (GA-xenopericardium) (p < 0.05). Hemolysis level of red blood cells after contact with SIBS was 0.35%, ePTFE – 0.40%, which is below positive control (p < 0.05). Maximum platelet aggregation of intact platelet-rich blood plasma was 8.60%, in contact with SIBS polymer – 18.11%, with ePTFE – 22.74%. Conclusion. In terms of hemocompatibility properties, the investigated SIBS polymer is not inferior to ePTFE and can be used as a basis for development of polymeric prosthetic heart valves.

scholarly journals Selection of donor platelets for alloimmunized patients using a platelet-associated IgG assay

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 444-450
Author(s):  
TJ Myers ◽  
BK Kim ◽  
M Steiner ◽  
MG Baldini
Keyword(s):  
Platelet Aggregation ◽  
Serotonin Release ◽  
The Other ◽  
Hla Typing ◽  
Survival Times ◽  
Platelet Survival ◽  
Quantitative Immunofluorescence ◽  
Survival Studies ◽  
Selection Of ◽  
Sensitive Method

A quantitative immunofluorescence platelet-associated immunoglobulins (PA-IgG) assay was used to detect alloimmunity to platelets in 8/12 multitransfused patients and to perform platelet crossmatching in the 8 alloimmunized patients. The correct separation of multitransfused patients into alloimmune and nonalloimmune groups was substantiated with chromium-51-labeled platelet survival studies. For 5 alloimmunized patients, compatible and incompatible donor platelets were demonstrated by PA-IgG crossmatching and were confirmed by platelet survival studies. With the other 3 alloimmunized patients, only studies with 5 of these incompatible donor platelets showed markedly reduced survival times on 4 occasions. PA-Igg compatible donor platelets survived 3.5- 8.7 days, while PA-IgG incompatible platelets showed survival times of 0.1–2.4 days. Overall, PA-IgG testing correctly indicated survival results on 15/17 occasions (88%), whereas platelet aggregation, serotonin release, and lymphocytotoxicity testing showed correct predictions for only 41%-59% of the survival studies. PA-IgG testing predicted which times, thus indication patients with platelet-specific alloantibodies. the PA-IgG assay provides a sensitive method to detect platelet alloantibodies and to perform platelet crossmatching, which can complement HLA typing in the selection of donor platelets for alloimmunized patients.

Selection of donor platelets for alloimmunized patients using a platelet-associated IgG assay

Blood ◽  
1981 ◽  
Vol 58 (3) ◽  
pp. 444-450 ◽  
Author(s):  
TJ Myers ◽  
BK Kim ◽  
M Steiner ◽  
MG Baldini
Keyword(s):  
Platelet Aggregation ◽  
Serotonin Release ◽  
The Other ◽  
Hla Typing ◽  
Survival Times ◽  
Platelet Survival ◽  
Quantitative Immunofluorescence ◽  
Survival Studies ◽  
Selection Of ◽  
Sensitive Method

Abstract A quantitative immunofluorescence platelet-associated immunoglobulins (PA-IgG) assay was used to detect alloimmunity to platelets in 8/12 multitransfused patients and to perform platelet crossmatching in the 8 alloimmunized patients. The correct separation of multitransfused patients into alloimmune and nonalloimmune groups was substantiated with chromium-51-labeled platelet survival studies. For 5 alloimmunized patients, compatible and incompatible donor platelets were demonstrated by PA-IgG crossmatching and were confirmed by platelet survival studies. With the other 3 alloimmunized patients, only studies with 5 of these incompatible donor platelets showed markedly reduced survival times on 4 occasions. PA-Igg compatible donor platelets survived 3.5- 8.7 days, while PA-IgG incompatible platelets showed survival times of 0.1–2.4 days. Overall, PA-IgG testing correctly indicated survival results on 15/17 occasions (88%), whereas platelet aggregation, serotonin release, and lymphocytotoxicity testing showed correct predictions for only 41%-59% of the survival studies. PA-IgG testing predicted which times, thus indication patients with platelet-specific alloantibodies. the PA-IgG assay provides a sensitive method to detect platelet alloantibodies and to perform platelet crossmatching, which can complement HLA typing in the selection of donor platelets for alloimmunized patients.

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