Gelatin Use Impairs Platelet Adhesion during Cardiac Surgery

1995 ◽  
Vol 74 (06) ◽  
pp. 1447-1451 ◽  
Author(s):  
Norlyuki Tabuchi ◽  
Jacob de Haan ◽  
Rolf C G Gallandat Huet ◽  
Plet W Boonstra ◽  
Willem van Oeveren
Keyword(s):  
Cardiac Surgery ◽  
Platelet Adhesion ◽  
Randomized Study ◽  
High Dose ◽  
Negative Effects ◽  
Retrospective Clinical Study ◽  
Heart Lung Machine ◽  
Plug Formation

SummaryArtificial colloids based on gelatin are used as plasma expander to replace donor blood products. In laboratory experiments, gelatin reduced both the velocity and extend of platelet agglutination by ristocetin, and only the agglutination velocity by polybrene (p <0.05). Furthermore, gelatin delayed the in-vitro platelet plug formation under shear-stress in the absence of ADP (p <0.05), whereas gelatin induced no delay in the presence of ADP. Thus, after induction of vWF release from platelets by polybrene or ADP, platelet function was normal. These results indicate that gelatin affects in particular the functionality of plasma-vWF and partly inhibits platelet adhesion.These negative effects of gelatin on hemostasis were demonstrated in two clinical studies during cardiac surgery. In a randomized study of sixty patients undergoing cardiac surgery, gelatin as prime in the heart-lung machine appeared to result in diminished efficacy of aprotinin on hemostasis, whereas it did not affect hemostasis in non-aprotinin patients. An additional retrospective clinical study showed that only high dose of gelatin affected hemostasis. This suggests a limited role of plasma-vWF and a strong back-up mechanism of platelet-vWF in achieving hemostasis.

Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation

1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
In Vitro Test ◽  
Pharmacological Agents ◽  
Vitro Test ◽  
Releasing Effect ◽  
Plug Formation

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.

scholarly journals High-dose Aprotinin in Cardiac Surgery—A Prospective, Randomized Study

1994 ◽  
Vol 22 (5) ◽  
pp. 529-533 ◽  
Author(s):  
M. J. Swart ◽  
P. C. Gordon ◽  
P. B. Hayse-Gregson ◽  
R. A. Dyer ◽  
A. L. Swanepoel ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Placebo Group ◽  
Blood Loss ◽  
Artery Bypass ◽  
Randomized Study ◽  
Postoperative Blood Loss ◽  
High Dose ◽  
Maintenance Infusion ◽  
Transfusion Requirements ◽  
High Dose Aprotinin

Fifty patients undergoing primary coronary artery bypass surgery and 50 patients undergoing valve surgery received either high-dose aprotinin (2 million units loading dose, 2 million units added to the CPB prime, and 500,000 units/hr maintenance infusion) or placebo. Mean postoperative blood loss in the first six hours was reduced from 321 ml in the placebo group to 172 ml in the aprotinin group (95% confidence interval (CI) for difference = 95 to 189 ml). Seven patients in the placebo group and 16 patients in the aprotinin group did not require transfusion with homologous blood. This study adds to the growing body of evidence that the administration of high-dose aprotinin reduces blood loss and blood transfusion requirements associated with primary cardiac surgery.

scholarly journals Dose dependence of efficacy but not of safety in sublingual immunotherapy

2016 ◽  
Vol 65 (1) ◽  
Author(s):  
F. Frati ◽  
C. Incorvaia ◽  
F. Marcucci ◽  
L. Sensi ◽  
G. Di Cara ◽  
...  
Keyword(s):  
Sublingual Immunotherapy ◽  
Clinical Symptoms ◽  
Meta Analysis ◽  
Dose Dependence ◽  
Subcutaneous Immunotherapy ◽  
High Dose ◽  
Systemic Reactions ◽  
Significant Difference

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies.

Arachidonic acid mediates dual effect of TNF-α on Ca2+ transients and contraction of adult rat cardiomyocytes

2002 ◽  
Vol 282 (6) ◽  
pp. C1339-C1347 ◽  
Author(s):  
Aïssata Amadou ◽  
Artur Nawrocki ◽  
Martin Best-Belpomme ◽  
Catherine Pavoine ◽  
Françoise Pecker
Keyword(s):  
Arachidonic Acid ◽  
Cyclooxygenase Inhibitors ◽  
High Dose ◽  
Negative Effects ◽  
Dual Effect ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Tnf Α ◽  
Biphasic Effect

Tumor necrosis factor (TNF)-α has a biphasic effect on heart contractility and stimulates phospholipase A2 (PLA2) in cardiomyocytes. Because arachidonic acid (AA) exerts a dual effect on intracellular Ca2+ concentration ([Ca2+]i) transients, we investigated the possible role of AA as a mediator of TNF-α on [Ca2+]i transients and contraction with electrically stimulated adult rat cardiac myocytes. At a low concentration (10 ng/ml) TNF-α produced a 40% increase in the amplitude of both [Ca2+]i transients and contraction within 40 min. At a high concentration (50 ng/ml) TNF-α evoked a biphasic effect comprising an initial positive effect peaking at 5 min, followed by a sustained negative effect leading to 50–40% decreases in [Ca2+]i transients and contraction after 30 min. Both the positive and negative effects of TNF-α were reproduced by AA and blocked by arachidonyltrifluoromethyl ketone (AACOCF3), an inhibitor of cytosolic PLA2. Lipoxygenase and cyclooxygenase inhibitors reproduced the high-dose effects of TNF-α and AA. The negative effects of TNF-α and AA were also reproduced by sphingosine and were abrogated by the ceramidase inhibitor n-oleoylethanolamine. These results point out the key role of the cytosolic PLA2/AA pathway in mediating the contractile effects of TNF-α.

Surgical setup for cardiopulmonary bypass through central cannulation

2021 ◽  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Surgical Care ◽  
Heart Lung Machine ◽  
American College Of Surgeons ◽  
History Of ◽  
Central Cannulation ◽  
First John ◽  
Clinical Advances

The introduction of cardiopulmonary bypass was one of the most important clinical advances of 1952. In that year, John Gibbon performed the first successful cardiac surgery using cardiopulmonary bypass. The procedure has been described as “One of the most impressive evidences of the role of investigative surgery in the history of medicine in the persevering efforts of Dr. Gibbon for more than 20 years, which finally culminated in a practical heart-lung machine”, at the first John H. Gibbon, Jr. Lecture at the annual meeting of the American College of Surgeons. Due to on-going advancements in cardiopulmonary bypass, many patients with complex heart disease requiring surgical care undergo cardiac surgery while the other organs remain adequately oxygenated and perfused. This tutorial discusses the access, surgical technique, and initiation of cardiopulmonary bypass through central cannulation and describes the safeguards and pitfalls.

scholarly journals The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1894
Author(s):  
Marcelo Villagran ◽  
Jorge Ferreira ◽  
Miquel Martorell ◽  
Lorena Mardones
Keyword(s):  
Clinical Trials ◽  
Vitamin C ◽  
Cancer Prevention ◽  
Randomized Study ◽  
Regulation Of Gene Expression ◽  
Water Soluble ◽  
In Vitro Assays ◽  
High Concentration

Vitamin C is a water-soluble antioxidant associated with the prevention of the common cold and is also a cofactor of hydrolases that participate in the synthesis of collagen and catecholamines, and in the regulation of gene expression. In cancer, vitamin C is associated with prevention, progression, and treatment, due to its general properties or its role as a pro-oxidant at high concentration. This review explores the role of vitamin C in cancer clinical trials and the aspects to consider in future studies, such as plasmatic vitamin C and metabolite excretion recording, and metabolism and transport of vitamin C into cancer cells. The reviewed studies show that vitamin C intake from natural sources can prevent the development of pulmonary and breast cancer, and that vitamin C synergizes with gemcitabine and erlotinib in pancreatic cancer. In vitro assays reveal that vitamin C synergizes with DNA-methyl transferase inhibitors. However, vitamin C was not associated with cancer prevention in a Mendelian randomized study. In conclusion, the role of vitamin C in the prevention and treatment of cancer is still an ongoing area of research. It is necessary that new phase II and III clinical trials be performed to collect stronger evidence of the therapeutic role of vitamin C in cancer.

scholarly journals Talin is required for integrin-mediated platelet function in hemostasis and thrombosis

2007 ◽  
Vol 204 (13) ◽  
pp. 3103-3111 ◽  
Author(s):  
Brian G. Petrich ◽  
Patrizia Marchese ◽  
Zaverio M. Ruggeri ◽  
Saskia Spiess ◽  
Rachel A.M. Weichert ◽  
...  
Keyword(s):  
Platelet Adhesion ◽  
Ex Vivo ◽  
Focal Adhesions ◽  
Β1 Integrin ◽  
Normal Morphology ◽  
And Function ◽  
Specific Deletion

Integrins are critical for hemostasis and thrombosis because they mediate both platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic adaptor that is a central organizer of focal adhesions, and loss of talin phenocopies integrin deletion in Drosophila. Here, we have examined the role of talin in mammalian integrin function in vivo by selectively disrupting the talin1 gene in mouse platelet precursor megakaryocytes. Talin null megakaryocytes produced circulating platelets that exhibited normal morphology yet manifested profoundly impaired hemostatic function. Specifically, platelet-specific deletion of talin1 led to spontaneous hemorrhage and pathological bleeding. Ex vivo and in vitro studies revealed that loss of talin1 resulted in dramatically impaired integrin αIIbβ3-mediated platelet aggregation and β1 integrin–mediated platelet adhesion. Furthermore, loss of talin1 strongly inhibited the activation of platelet β1 and β3 integrins in response to platelet agonists. These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian α2β1 and αIIbβ3 integrins in vivo.

Microfibrils (MF) Platelet Interaction: Requirement Of Von Willebrand Factor In Platelet Adhesion To A Placenta Microfibrillar Component (PMC)

1981 ◽  
Author(s):  
F Fauvel ◽  
Y J Legrand ◽  
N Gutman ◽  
J P Muh ◽  
G Tobelem ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Human Platelets ◽  
Human Artery ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Adhesion Of Platelets ◽  
Aggregation Of Platelets

It has been shown that collagenase resistant arterial microfibrils (MF) are able to interact with platelets and therefore represents, besides collagen, a second thrombogenic structure in the vessel wall. In vitro observation using a PMC purified from the villosities of human placenta by a mechanical non denaturing procedure confirm this interaction between platelets and MF. PMC was homogenous under electron microscope (feltwork of MF with a mean diameter of 120 – 130 A) and was glycoproteic in nature. PMC were able to induce an aggregation of human platelets only if the platelets were in plasma. The role of Von Willebrand factor (F VIII/WF) as a cofactor of the aggregation of platelets by MF has been postulated from the fact that twice washed platelets from normal subject resuspended in PPP obtained from a severe Von Willebrand deficient patient were not aggregated by the PMC. Furthermore, aggregation was restored after resuspension of the same platelets in the PPP of the same patient 30 and 120 minutes after perfusion of cryoprecipitate (40 units F VIII/RA per kg).F VIII/WF mediates platelet adhesion after binding to subendothelium of human artery. Our observation strongly supports the idea that MF are the subendothelial components to which F VIII/WF binds, thus promoting an adhesion of platelets.

scholarly journals Radiotherapy Planning and Molecular Imaging in Lung Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 204-217
Author(s):  
Angelina Filice ◽  
Massimiliano Casali ◽  
Patrizia Ciammella ◽  
Marco Galaverni ◽  
Federica Fioroni ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Case Reports ◽  
Locally Advanced ◽  
Inflammatory Cells ◽  
High Rate ◽  
Radiotherapy Planning ◽  
High Dose ◽  
18F Fdg

Introduction: In patients suitable for radical chemoradiotherapy for lung cancer, 18F-FDGPET/ CT is a proposed management to improve the accuracy of high dose radiotherapy. However, there is a high rate of locoregional failure in patients with locally advanced non-small cell lung cancer (NSCLC), probably due to the fact that standard dosing may not be effective in all patients. The aim of the present review was to address some criticisms associated with the radiotherapy image-guided in NSCLC. Materials and Methods: A systematic literature search was conducted. Only published articles that met the following criteria were included: articles, only original papers, radiopharmaceutical ([18F]FDG and any tracer other than [18F]FDG), target, only specific for lung cancer radiotherapy planning, and experimental design (eventually “in vitro” studies were excluded). Peer-reviewed indexed journals, regardless of publication status (published, ahead of print, in press, etc.) were included. Reviews, case reports, abstracts, editorials, poster presentations, and publications in languages other than English were excluded. The decision to include or exclude an article was made by consensus and any disagreement was resolved through discussion. Results: Hundred eligible full-text articles were assessed. Diverse information is now available in the literature about the role of FDG and new alternative radiopharmaceuticals for the planning of radiotherapy in NSCLC. In particular, the role of alternative technologies for the segmentation of FDG uptake is essential, although indeterminate for RT planning. The pros and cons of the available techniques have been extensively reported. : Conclusion: PET/CT has a central place in the planning of radiotherapy for lung cancer and, in particular, for NSCLC assuming a substantial role in the delineation of tumor volume. The development of new radiopharmaceuticals can help overcome the problems related to the disadvantage of FDG to accumulate also in activated inflammatory cells, thus improving tumor characterization and providing new prognostic biomarkers.

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