Effect of vasoactive drug MJ12880 [1-(4-(1-methyl-ethylothio)phenoxyl-3-Octylamino)-2-propanol hydrochloride] on in vitro blood viscosity of patients suffering from cancer or cardiovascular disorders

2016 ◽  
Vol 1 (2) ◽  
pp. 153-165 ◽  
Author(s):  
L. Dintenfass
Keyword(s):  
Blood Viscosity ◽  
Vasoactive Drug ◽  
Cardiovascular Disorders

Abstract 372: The Endothelial Glycocalyx Promotes Homogenous Blood Flow Distribution within the Microvasculature

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
P Mason McClatchey
Keyword(s):  
Fluid Dynamics ◽  
Blood Flow ◽  
Blood Viscosity ◽  
Tissue Perfusion ◽  
Microvascular Perfusion ◽  
Endothelial Glycocalyx ◽  
Heterogeneous Distribution ◽  
Disease States

Introduction: Impaired tissue oxygenation is observed in many disease states including congestive heart failure, diabetes, cancer and aging. Decreased tissue perfusion and heterogeneous distribution of blood flow in the microvasculature contributes to this pathology. The physiological mechanisms regulating homogeneity/heterogeneity of microvascular perfusion are presently unknown. We hypothesized that microfluidic properties of the glycocalyx would promote perfusion homogeneity. Methods: To test our hypothesis, we used established empirical formulations for modelling blood viscosity in vivo (blood vessels) and in vitro (glass tubes). We first assess distribution of blood flow in idealized arteriolar networks. We next simulated distribution of blood flow at an idealized capillary bifurcation. Finally, we simulated velocity profiles and pressure gradients within the vessel lumen with varying glycocalyx properties using a computational fluid dynamics approach. Results: We found that transit time heterogeneity (as assessed by STD to mean ratio) was increased approximately 9x (6.9x-10.6x) using in vitro formulations of blood viscosity relative to in vivo formulations. This effect was mathematically accounted for by increased effective blood viscosity in smaller arterioles. We also found that distribution of blood flow at an idealized microvascular bifurcation was more symmetric using the in vivo formulation than the in vitro formulation (approximately 2x greater disparity between flow in downstream vessels). This effect was mathematically accounted for by an increased hematocrit dependence of blood viscosity. Both the diameter- and hematocrit-based changes in blood viscosity were entirely predictable from fluid dynamics simulations incorporating a space-filling, semi-permeable glycocalyx layer. Summary: Our simulations indicate that the mechanical properties of the endothelial glycocalyx promote homogeneous microvascular perfusion. Conclusions: The literature provides evidence of both glycocalyx degradation and impaired tissue perfusion in the same disease states. Preservation or restoration of normal glycocalyx properties may be a viable strategy for improving tissue perfusion in a wide variety of diseases.

Angiogenetic transcriptional profiling reveals potential targets modulated in blood of patients with cardiovascular disorders

Vascular ◽  
2021 ◽  
pp. 170853812110523
Author(s):  
Joerg Ukkat ◽  
Artur Rebelo ◽  
Bogusz Trojanowicz
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Pathological Condition ◽  
Transcriptional Profiling ◽  
Platelet Derived Growth Factor ◽  
Vascular Pathology ◽  
Cardiovascular Disorders ◽  
Factor Alpha

Objectives Based on the angiogenetic, transcriptional profile of non-diseased and arteriosclerotic vessels, we aim to identify the leucocytic markers as a potential, minimal invasive tool supporting diagnosis of vascular pathology. Methods Transcriptional profiling was performed with Angiogenesis RT2 Profiler PCR (Polymerase Chain Reaction) array on three non-pathological and three arteriosclerotic vessels, followed by immunohistochemical staining. Based on these screening results, selected transcripts were employed for qPCR with specific primers and investigated on the blood RNA (RiboNucleic Acid) obtained from nine healthy controls and 29 patients with cardiovascular disorders. Thereafter, expression of these transcripts was investigated in vitro in human monocytes under calcification-mimicking conditions. Results and Conclusions Transcriptional profiling on the vessels revealed that out of 84 targets investigated two were up-regulated more than 100-fold, 18 more than 30 and 15 more than 10, while the most noticeable down-regulation was observed by ephrin-A3 and platelet-derived growth factor alpha (PDGFA) genes. Based on the vessel results, investigations of the selected blood transcripts revealed that thrombospondin 1 (THBS1), thrombospondin 3 (THBS3), transforming growth factor, beta receptor 1 (TGFBR1), platelet-derived growth factor alpha, plasminogen activator, urokinase (PLAU) and platelet/endothelial cell adhesion molecule 1 (PECAM-1) were significantly elevated in cardiovascular blood as compared to corresponding controls. Induction of calcification-related conditions in vitro to human THP-1 monocytes led to noticeable modulation of these transcripts. Taken together, these data demonstrate that leucocytic THBS1, THBS3, TGFBR1, platelet-derived growth factor alpha, PLAU and PECAM-1 have a correlation with cardiovascular disorders and could be used as a supportive tool predicting development of this pathological condition.

Denbufylline, pentoxifylline and Zy 16075 decrease rat arterial and venous blood viscosity, but not human venous blood viscosity in vitro

2016 ◽  
Vol 10 (2) ◽  
pp. 215-223
Author(s):  
Marie-Lise Bezençon ◽  
Jacques Roux ◽  
Etienne M. Grandjean ◽  
Toshiko Imamura
Keyword(s):  
Blood Viscosity ◽  
Venous Blood

The effect of propranolol on blood viscosity changes induced by experimental coronary occlusion

1984 ◽  
Vol 62 (10) ◽  
pp. 1333-1337 ◽  
Author(s):  
G. P. Biro ◽  
Diana Beresford-Kroeger
Keyword(s):  
Coronary Artery ◽  
Blood Viscosity ◽  
Coronary Occlusion ◽  
Blood Samples ◽  
Coronary Ligation ◽  
Anesthetized Dogs ◽  
Propranolol Treatment ◽  
Viscosity Changes ◽  
Low Shear

The effect of propranolol treatment was investigated in the myocardial ischemia-induced hyperviscosity state in anesthetized dogs. In untreated control dogs, low shear blood viscosity rose progressively, following an acute occlusion of the left anterior descending coronary artery; this effect was partially but significantly reduced by intravenously administered propranolol (0.2 mg/kg). The effect of the in vitro addition of propranolol was also determined upon viscosity of blood samples obtained at hourly intervals from dogs subjected to similar coronary ligation. The in vitro addition of propranolol did not produce a similar reversal of the hyperviscosity state observed in the blood obtained from dogs after coronary ligation.

Serial Blood Water Estimations and in-Line Blood Viscometry: The Continuous Measurement of Blood Volume during Dialysis Procedures

1984 ◽  
Vol 66 (5) ◽  
pp. 575-583 ◽  
Author(s):  
R. N. Greenwood ◽  
C. Aldridge ◽  
W. R. Cattell
Keyword(s):  
Blood Volume ◽  
Blood Viscosity ◽  
Packed Cell Volume ◽  
Continuous Measurement ◽  
Quantitative Measure ◽  
Capillary Viscometer ◽  
Extracorporeal Circuit ◽  
Volume Changes ◽  
Serial Measurements

1. It has been shown in vitro that serial measurements of blood water during ultrafiltration accurately reflect changing blood volume. 2. It has been shown that minute changes in blood hydration produce detectable changes in blood viscosity. 3. An ‘in-line’ capillary viscometer has been constructed which can be placed in parallel with an extracorporeal circuit to give a continuous semi-quantitative measure of blood viscosity during ultrafiltration or haemodialysis. By making serial measurements of blood water each ‘viscometer curve’ can be corrected to permit calculation of blood volume provided that the starting blood volume is known. 4. Blood volume changes of less than 1% can be detected in vitro and provided that blood volume changes solely as a result of the removal or influx of water it can be measured continuously to within an accuracy of 4% for volume changes up to 30% irrespective of starting packed cell volume or blood water.

Endothelium-dependent arterial wall tone elasticity modulated by blood viscosity

2002 ◽  
Vol 282 (2) ◽  
pp. H389-H394 ◽  
Author(s):  
Edmundo I. Cabrera Fischer ◽  
Ricardo L. Armentano ◽  
Franco M. Pessana ◽  
Sebastián Graf ◽  
Luis Romero ◽  
...  
Keyword(s):  
Blood Viscosity ◽  
Muscle Activation ◽  
Arterial Wall ◽  
Mock Circulation ◽  
Significant Difference ◽  
Before And After ◽  
Strain Relationship ◽  
Instantaneous Pressure

The role of blood viscosity on arterial wall elasticity before and after deendothelization (DE) was studied. Seven ovine brachiocephalic arteries were studied in vitro under physiological pulsatile flow conditions achieved by a mock circulation loop. Instantaneous pressure and diameter signals were assessed in each arterial segment. Incremental elastic modulus ( E inc) was calculated using the slope of the pure elastic stress-strain relationship. There was no significant difference between E inc values before and after DE (3.11 vs. 3.16 107 dyn/cm2) at a blood viscosity of 2.00 mPa · s. Increases in blood viscosity (2.50, 3.00, 3.50, and 4.00 mPa · s) always resulted in decreases of E inc before DE; inversely, increases in blood viscosity resulted in increases of E inc after DE. These values of E inc, for identical levels of blood viscosity, were always significantly lower ( P< 0.05) before DE than those obtained after DE. Arterial wall elasticity assessed through E inc was strongly influenced by blood viscosity, probably due to presence or absence of endothelium relaxing factors or to direct shear smooth muscle activation when endothelial cells are removed.

In vitro comparison of two changeover methods for vasoactive drug infusion pumps: quick-change versus automated relay

2015 ◽  
Vol 60 (4) ◽  
Author(s):  
Stéphanie Genay ◽  
Bertrand Décaudin ◽  
Sébastien Lédé ◽  
Frédéric Feutry ◽  
Christine Barthélémy ◽  
...  
Keyword(s):  
Vasoactive Drug ◽  
Drug Infusion ◽  
Infusion Pumps ◽  
In Vitro Comparison

AbstractThis study aimed to compare

scholarly journals Rheological Effects of L-Glutamine in Patients with Sickle Cell Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3567-3567
Author(s):  
Celeste K. Kanne ◽  
Varun Reddy ◽  
Vivien A. Sheehan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Blood Cells ◽  
Cell Disease ◽  
Phase 3 ◽  
Whole Blood Viscosity

Background: ENDARITM (oral pharmaceutical L-glutamine powder) received FDA approval in 2017 as a treatment for sickle cell disease (SCD). A pivotal phase 3 clinical study conducted by Emmaus Medical, Inc. showed that L-glutamine resulted in a lower incidence of vaso-occlusive crises (VOC) as well as a lower rate of hospitalizations and shorter hospital stays. No changes in standard clinical laboratory values were noted. The clinical improvements associated with sickle cell complications are believed to be due to an increase in the proportion of the reduced form of nicotinamide adenine dinucleotides in the red blood cells (RBC) of patients with SCD, reducing the oxidative stress. While the endpoints in the phase 3 study are clinically important, it is essential that we identify biomarkers or measurable laboratory changes that can serve as endpoints for future clinical trials assessing dose optimization and the efficacy and safety of L-glutamine in SCD individuals, including those with hepatic and renal dysfunction. RBC rheology is markedly abnormal in SCD; blood is more viscous for a given hematocrit than normal individuals, dense red blood cells (DRBC) are packed with HbS, potentiating sickling, and RBCs are less deformable than those of HbAA or HbAS individuals. High whole blood viscosity, high DRBCs, and poor RBC deformability are associated with higher rates of VOC. Given the demonstrated reduction in pain events, we hypothesized that L-glutamine might improve RBC rheology and sought to test this in vitro and in vivo using a battery of rheological tests. Methods: For the in vitro study, 6 mL of whole blood was drawn into an EDTA vacutainer from ten pediatric patients with sickle cell anemia (HbSS or HbSβ0) during routine clinical checkups under an IRB approved protocol. The cohort included 3 female and 7 male patients, ages 2-19 years old. All patients were on a steady dose of hydroxyurea and did not receive a transfusion within the 3 months prior to sample collection. A 200 mM stock solution of L-glutamine and water was mixed and filtered under light-protected conditions. Aliquots were stored at -20°C to avoid multiple freeze/thaw cycles. L-glutamine was added to 3 mL of whole blood for a final concentration of 1 mM (average in vivo L-glutamine plasma concentration in patients with SCD treated with L-glutamine); 3 mL of the same patient sample with water added served as a control. After a 24-hour incubation period at 4°C, whole blood viscosity was measured using a cone and plate viscometer at 37°C (DV3T Rheometer, AMETEK Brookfield, USA), %DRBCs were measured on an ADVIA 120 Hematology System (Siemens Healthcare Diagnostics, Inc., USA), and deformability measured using a Laser Optical Rotational Red Cell Analyzer (Lorrca®) (RR Mechatronics, the Netherlands) with the Oxygenscan module. The Oxygenscan measures RBC deformability at normoxia (Elmax), deformability upon deoxygenation (EImin), and point of sickling (PoS), the oxygen tension at which deformability begins to decline, reflecting the patient-specific pO2 at which sickling begins. Paired samples (with and without added L-glutamine) were analyzed using Student's t-test. For the in vivo study, rheological tests were performed on peripheral blood from one patient (18-year-old male on hydroxyurea) at baseline and treated with L-glutamine as part of his routine clinical care. Results and conclusions: Addition of L-glutamine in vitro significantly reduced the PoS, meaning RBCs incubated with L-glutamine could tolerate a lower pO2 before sickling compared to the control. RBCs incubated with L-glutamine also had significantly higher EImin, meaning deoxygenated RBCs were more flexible and deformable. Whole blood viscosity at 45s-1 and 225s-1 did not change significantly following incubation with L-glutamine; %DRBCs also did not change significantly (Table 1). The in vivo patient sample tested exhibited a similar improvement in PoS and EImin (Figure 1). We therefore propose to further test the performance of the PoS and EImin as possible biomarkers of response to L-glutamine in vivo. If validated, these biomarkers may also help further elucidate the mechanisms of action of L-glutamine in SCD. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document