Advanced Cardiac Models: Considerations for the Bioengineering of Advanced Cardiac In Vitro Models of Myocardial Infarction (Small 15/2021)

SummaryPharmacokinetics and systemic effects of recombinant tissue type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean ±SD) of 3310±950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of. 2210±470 nglml and 930±200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380±74 ml/min, t,½α was 3.6±0.9 min and t,½β was 16±5.4 min.After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, α2-antiplasmin to 25%, α2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 μg/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.

Download Full-text

Clinical Trials in Thrombosis: Secondary Prevention of Myocardial Infarction

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647910 ◽

1976 ◽

Vol 35 (01) ◽

pp. 049-056 ◽

Cited By ~ 4

Author(s):

Christian R Klimt ◽

P. H Doub ◽

Nancy H Doub

Keyword(s):

Myocardial Infarction ◽

Secondary Prevention ◽

Case Control ◽

Therapeutic Effects ◽

Case Control Studies ◽

Definitive Answer ◽

Inhibition Of Platelet Aggregation ◽

Prospective Trials

SummaryNumerous in vivo and in vitro experiments, investigating the inhibition of platelet aggregation and the prevention of experimentally-induced thrombosis, suggest that anti-platelet drugs, such as aspirin or the combination of aspirin and dipyridamole or sulfinpyrazone, may be effective anti-thrombotic agents in man. Since 1971, seven randomized prospective trials and two case-control studies have been referenced in the literature or are currently being conducted, which evaluate the effects of aspirin, sulfinpyrazone, or dipyridamole in combination with aspirin in the secondary prevention of myocardial infarction. A critical review of these trials indicates a range of evidence from no difference to a favorable trend that antiplatelet drugs may serve as anti-thrombotic agents in man. To date, a definitive answer concerning the therapeutic effects of these drugs in the secondary prevention of coronary heart disease is not available.

Download Full-text

Plasminogen Depletion during Streptokinase Treatment or Two-Chain Urokinase Incubation Correlates with Decreased Clot Lysability Ex Vivo and In Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649714 ◽

1993 ◽

Vol 70 (06) ◽

pp. 0998-1004 ◽

Cited By ~ 13

Author(s):

Páll T Önundarson ◽

H Magnús Haraldsson ◽

Lena Bergmann ◽

Charles W Francis ◽

Victor J Marder

Keyword(s):

Myocardial Infarction ◽

Ex Vivo ◽

Time Dependent ◽

State Variables ◽

Thrombolytic Treatment ◽

Direct Proportion ◽

Plasmin Activity ◽

Plasma Exposure ◽

The Relationship

SummaryThe relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/1. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 ± 8% after 5 min to 21 ± 8% at 10 min and was significantly lower (8 ± 9%, p <0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p <0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.

Download Full-text

Faculty Opinions recommendation of Assessment of the psoriatic transcriptome in a large sample: additional regulated genes and comparisons with in vitro models.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3402956.3097056 ◽

2010 ◽

Author(s):

Michelle Lowes ◽

Kristine Nograles

Keyword(s):

In Vitro Models ◽

Large Sample

Download Full-text

Faculty Opinions recommendation of Defining GM-CSF- and macrophage-CSF-dependent macrophage responses by in vitro models.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.716398013.791803076 ◽

2012 ◽

Author(s):

Peter Murray

Keyword(s):

In Vitro Models ◽

Gm Csf

Download Full-text

Effect of carbon source on Phenobarbital metabolism by Rhizopus stolonifer

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2010.3.2.17 ◽

2010 ◽

Vol 3 (2) ◽

pp. 1022-1027

Author(s):

Kavitha K ◽

Asha S ◽

Hima Bindu T.V.L ◽

Vidyavathi M

Keyword(s):

Carbon Source ◽

High Performance ◽

Carbon Sources ◽

In Vitro Models ◽

Rhizopus Stolonifer ◽

Safety And Efficacy ◽

Alternative Systems ◽

Toxicological Studies ◽

Microbial Model

The safety and efficacy of a drug is based on its metabolism or metabolite formed. The metabolism of drugs can be studied by different in vitro models, among which microbial model became popular. In the present study, eight microbes were screened for their ability to metabolize phenobarbital in a manner comparable to humans with a model to develop alternative systems to study human drug metabolism. Among the different microbes screened, a filamentous fungi Rhizopus stolonifer metabolized phenobarbital to its metabolite which is used for further pharmacological and toxicological studies. The transformation of phenobarbital was identified by high- performance liquid chromatography (HPLC). Interestingly, Rhizopus stolonifer sample showed an extra metabolite peak at 3.11min. compared to its controls. The influence of different carbon sources in media used for growth of fungus, on metabolite production was studied, to find its effect in production of metabolite as the carbon source may influence the growth of the cell.

Download Full-text

3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas

Current Medicinal Chemistry ◽

10.2174/0929867326666191212162102 ◽

2020 ◽

Vol 27 (29) ◽

pp. 4778-4788 ◽

Cited By ~ 1

Author(s):

Victoria Heredia-Soto ◽

Andrés Redondo ◽

José Juan Pozo Kreilinger ◽

Virginia Martínez-Marín ◽

Alberto Berjón ◽

...

Keyword(s):

High Throughput Screening ◽

Cancer Biology ◽

Soft Tissues ◽

Three Dimensional ◽

3D Culture ◽

Resistance Mechanisms ◽

In Vitro Models ◽

Tumour Spheroids ◽

Current Therapies

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.

Download Full-text