Possible role of the erythrocyte in causing prolonged cerebral vasospasm

1979 ◽  
Vol 51 (6) ◽  
pp. 773-778 ◽  
Author(s):  
Nobuyuki Ozaki ◽  
Sean Mullan
Keyword(s):  
Cerebral Vasospasm ◽  
Contractile Activity ◽  
Platelet Rich Plasma ◽  
Red Cells ◽  
Significant Activity ◽  
Sephadex Column ◽  
Content Type ◽  
Canine Basilar Artery

✓ Contractile activity of the various fractions of fresh and incubated blood was studied in vitro using the isolated canine basilar artery. Of the various fractions of fresh blood, significant contraction was induced by serum, but moderate contraction was induced by platelet-rich plasma and lysed red cells, while intact red cells and platelet-poor plasma had no significant activity. The contractions induced by serum and platelet-rich plasma were blocked by phenoxybenzamine, while those induced by lysed red cells were not. Whereas serum and platelet-rich plasma lost their contractile activity after 24 hours of incubation, lysed red cells retained activity up to 7 days after incubation. Biochemical analysis of the hemolysate by means of Sephadex column chromatography revealed that the contractile substance(s) possessed a molecular weight above 5000. These results suggest the possibility that the above substance(s) may play a role in prolonged cerebral vasospasm.

Evidence of the role of hemolysis in experimental cerebral vasospasm

1990 ◽  
Vol 72 (5) ◽  
pp. 775-781 ◽  
Author(s):  
John W. Peterson ◽  
Lawrence Roussos ◽  
Byung-Duk Kwun ◽  
John D. Hackett ◽  
Christopher J. Owen ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Canine Model ◽  
Initial Reaction ◽  
Basal Cistern ◽  
Content Type ◽  
Vascular Reaction ◽  
Erythrocyte Lysis

✓ The short-term (≤ 72-hour) reaction to subarachnoid injections of various blood components was determined in a canine model of cerebral vasospasm. Platelet-rich plasma (PRP) formed durable clots in the basal cistern surrounding the basilar artery and provoked no vascular reaction in 72 hours or more. Freshly isolated autologous erythrocytes resuspended in PRP likewise provoked no vasoconstriction in 72 hours, although a second injection of fresh erythrocytes in PRP induced significant reaction, as in the conventional “double subarachnoid hemorrhage (SAH)” canine model. Hemolysate of fresh erythrocytes led to a severe immediate vascular reaction after introduction into the basal cistern using PRP as the carrier/clotting medium, as did the injection of intact erythrocytes incubated ex vivo for 72 hours. Resolution of the initial reaction was rapid for hemolysate, but slow and (depending on hematocrit) incomplete for intact “aged” erythrocytes. In vitro measurements of erythrocyte lysis in these media and histological examination indicate that the production of erythrocyte lysate was responsible for the vascular reaction observed, suggesting that the rate of lysis of erythrocytes in the subarachnoid clot is a major factor in the genesis of vasospasm after SAH.

Cerebral arterial spasm

1974 ◽  
Vol 40 (4) ◽  
pp. 442-450 ◽  
Author(s):  
George S. Allen ◽  
Lavell M. Henderson ◽  
Shelley N. Chou ◽  
Lyle A. French
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Human Serum ◽  
Basilar Artery ◽  
Contractile Activity ◽  
Arterial Spasm ◽  
Content Type ◽  
Canine Basilar Artery ◽  
Fine Print

✓ In vitro experiments were performed to determine the contractile activity of human serum and cerebrospinal fluid on the canine basilar artery. The majority of contractile activity in these CSF samples, which were collected 2 to 7 days following a subarachnoid hemorrhage, was proven to be due to serotonin. Serotonin was capable of producing a prolonged contraction of the artery depending on its activity. Methylsergide reversibly blocked the artery's response to serotonin and caused a contraction of the basilar artery. Phenoxybenzamine irreversibly blocked the basilar artery's response to serotonin, serum, and CSF.

Prolonged vasospasm produced by the breakdown products of erythrocytes

1977 ◽  
Vol 47 (3) ◽  
pp. 403-411 ◽  
Author(s):  
Kunihiko Osaka
Keyword(s):  
Cerebral Vasospasm ◽  
Arterial Wall ◽  
Platelet Rich Plasma ◽  
Prolonged Incubation ◽  
Content Type ◽  
Fresh Serum ◽  
Fresh State ◽  
Basilar Arteries ◽  
Fine Print

✓ The cause of cerebral vasospasm has been generally attributed to the vasoconstrictive substances released from platelets. The role of extravasated erythrocytes in vasospasm has never been well analyzed. To elucidate this point, the basilar arteries of cats were exposed and subjected to topical application of various blood fractions in their fresh state and after prolonged incubation for 1 to 7 days. Incubation was done to test stability of the vasoconstrictors. Severe vasospasm was induced by application of fresh and incubated fractions of lysed erythrocytes. Fresh, intact erythrocytes had no vasoactivity, but by incubation they lysed and gained vasoconstrictors. Vasospasm induced by lysed erythrocytes both in their fresh state and after prolonged incubation never relaxed, and tended to increase in severity during observation up to 24 hours. Fresh serum and platelet-rich plasma had vasoconstrictors, but they were lost after incubation. Apparently platelet-induced vasoconstriction is of short duration and contributes only to the early phase of vasospasm. Later, 12 to 24 hours after hemorrhage, iron pigments released by lysis of extravasated erythrocytes (oxyhemoglobin or methemoglobin) irritate the arterial wall and induce prolonged vasospasm. It is emphasized that the study of cerebral vasospasm should be focused on the role of the breakdown products of extravasated erythrocytes.

scholarly journals Identification, Characterization, and Functional Role of Phosphodiesterase Type IV in Cerebral Vessels: Effects of Selective Phosphodiesterase Inhibitors

1997 ◽  
Vol 17 (2) ◽  
pp. 210-219 ◽  
Author(s):  
Robert N. Willette ◽  
Aaron O. Shiloh ◽  
Charles F. Sauermelch ◽  
Anthony Sulpizio ◽  
Marcus P. Michell ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Cerebral Vessels ◽  
Type Iv ◽  
Canine Basilar Artery ◽  
Camp Hydrolysis ◽  
Phosphodiesterase Type ◽  
Chronic Cerebral Vasospasm

The role of the phosphodiesterase type IV isozyme (PDE IV) in the regulation of cerebrovascular tone was investigated in the canine basilar artery in vitro and in vivo. The PDE isozymes extracted from the canine basilar artery were isolated by diethylaminoethanol (DEAE)-Sepharose affinity chromatography and identified based on sensitivity to tsozyme-selective PDE inhibitors. [3H]cAMP hydrolysis was observed in one major and one minor peak of activity. The predominant peak was inhibited by the addition of cGMP (25%), siguazodan (26%), rolipram (39%), and the combination of siguazodan and rolipram (95%). Selective PDE IV inhibitors BRL 61063, rolipram, and denbufylline were equieffective inhibitors of [3H]-ccAMP hydrolysis mediated by PDE IV isolated from the canine basilar artery [concentrations producing 50% inhibition (IC50s) = 0.21 ± 0.05 μM, 0.67 ± 0.23 μM, and 0.73 ±0.16 μM, respectively]. In precontracted isolated ring segments of the canine basilar artery, selective PDE IV inhibitors produced potent and complete relaxation (IC50s <150 nM). In contrast, zaprinast (a selective PDE V inhibitor) and siguazodan (a selective PDE III inhibitor) produced only weak relaxation of the basilar artery (IC50s = 4.5 μM and >10 μM, respectively). Vasorelaxation produced by PDE IV inhibitors was not altered by removing the endothelium, l-NAME, or adenosine receptor antagonism. In a canine model of acute cerebral vasospasm, all three selective PDE IV inhibitors reversed basilar artery spasm produced by autologous blood without altering mean arterial blood pressure. In contrast, prolonged treatment with BRL 61063 failed to alter the development of basilar spasm in the two hemorrhage canine models of chronic cerebral vasospasm. Denbufylline-induced relaxation in vitro was also significantly impaired in basilar arteries obtained from the model of chronic vasospasm. In conclusion, PDE IV appears to be the predominant isozyme regulating vascular tone mediated by cAMP hydrolysis in cerebral vessels. In addition, vasorelaxation modulated by PDE IV is compromised in chronic cerebral vasospasm associated with subarachnoid hemorrhage.

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.

Tridegin, a Novel Peptidic Inhibitor of Factor XIIIa from the Leech, Haementeria ghilianii, Enhances Fibrinolysis In Vitro

1997 ◽  
Vol 77 (05) ◽  
pp. 0959-0963 ◽  
Author(s):  
Lisa Seale ◽  
Sarah Finney ◽  
Roy T Sawyer ◽  
Robert B Wallis
Keyword(s):  
Potent Inhibitor ◽  
Platelet Rich Plasma ◽  
Factor Xiiia ◽  
Cross Linking ◽  
Fibrinolytic Enzymes ◽  
Small Polypeptide ◽  
Tissue Plasminogen ◽  
Protein Cross Linking

SummaryTridegin is a potent inhibitor of factor Xllla from the leech, Haementeria ghilianii, which inhibits protein cross-linking. It modifies plasmin-mediated fibrin degradation as shown by the absence of D-dimer and approximately halves the time for fibrinolysis. Plasma clots formed in the presence of Tridegin lyse more rapidly when either streptokinase, tissue plasminogen activator or hementin is added 2 h after clot formation. The effect of Tridegin is markedly increased if clots are formed from platelet-rich plasma. Platelet-rich plasma clots are lysed much more slowly by the fibrinolytic enzymes used and if Tridegin is present, the rate of lysis returns almost to that of platelet- free clots. These studies indicate the important role of platelets in conferring resistance to commonly used fibrinolytic enzymes and suggest that protein cross-linking is an important step in this effect. Moreover they indicate that Tridegin, a small polypeptide, may have potential as an adjunct to thrombolytic therapy.

Myocardial CO2 buffering: role of transmembrane transport of H+ or HCO3-ions

1976 ◽  
Vol 230 (4) ◽  
pp. 1037-1041 ◽  
Author(s):  
DR Strome ◽  
RL Clancy ◽  
NC Gonzalez
Keyword(s):  
Small Volume ◽  
Coronary Circulation ◽  
Myocardial Cell ◽  
Ringer Solution ◽  
Red Cells ◽  
Transmembrane Transport ◽  
High Degree

Isolated rabbit hearts were perfused with rabbit red cells suspended in Ringer solution. A small volume of perfusate was recirculated for 10 min at Pco2 of 33.4 +/- 0.9 or 150.8 +/- 7.5 mmHg. Hypercapnia resulted in an increase in perfusate HCO3- concentration that was smaller than that observed when isolated perfusate was equilibrated in vitro with the same CO2 tensions (delta HCO-3e = 1.6 mM, P less than 0.01). This difference is consistent with a net movement of HCO3- into or H+ out of the mycardial cell, and cannot be accounted for by dilution of HCO3- in the myocardial interstitium. Recirculation of perfusate through the coronary circulation at normal Pco2 for two consecutive 10-min periods was not followed by changes in perfusate HCO3- concentration. A high degree of correlation (r = 0.81) was observed between intracellular HCO-3e concentration and the corresponding delta HCO-3e in individual experiments. The results suggest that transmembrane exchange of H+ or HCO3- is a buffer mechanism for CO2 in the myocardial cell.

scholarly journals Application of the 1-µsec pulsed-dye laser to the treatment of experimental cerebral vasospasm

1991 ◽  
Vol 75 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Atsushi Teramura ◽  
Robert Macfarlane ◽  
Christopher J. Owen ◽  
Ralph de la Torre ◽  
Kenton W. Gregory ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Laser Energy ◽  
Autologous Blood ◽  
Preliminary Investigation ◽  
Dye Laser ◽  
Pulsed Dye Laser ◽  
Content Type

✓ Laser energy of 480 nm was applied in 1-µsec pulses varying between 2.2 and 10 mJ to in vitro and in vivo models of cerebral vasospasm. First, the pulsed-dye laser was applied intravascularly via a 320-µm fiber to basilar artery segments from six dogs. The segments were mounted in a vessel-perfusion apparatus and constricted to, on average, 70% of resting diameter by superfusion with dog hemolysate. Immediate increase in basilar artery diameter occurred to a mean of 83% of control. In a second model, the basilar artery was exposed transclivally in the rabbit. In three normal animals, superfusion of the artery with rabbit hemolysate resulted in a reduction of mean vessel diameter to 81% of control. Following extravascular application of the laser, vessels returned to an average of 106% of the resting state. In six rabbits, the basilar artery was constricted by two intracisternal injections of autologous blood, 3 days apart. Two to 4 days after the second injection, the basilar artery was exposed. Extravascular laser treatment from a quartz fiber placed perpendicular to the vessel adventitia resulted in an immediate 53% average increase in caliber to an estimated 107% of control. No reconstriction was observed over a period of up to 5 hours. Morphologically, damage to the arterial wall was slight. This preliminary investigation suggests that the 1-µsec pulsed-dye laser may be of benefit in the treatment of cerebral vasospasm.

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

scholarly journals Haemodynamic flow conditions at the initiation of high-shear platelet aggregation: a combined in vitro and cellular in silico study

2020 ◽  
Vol 11 (1) ◽  
pp. 20190126 ◽  
Author(s):  
B. J. M. van Rooij ◽  
G. Závodszky ◽  
A. G. Hoekstra ◽  
D. N. Ku
Keyword(s):  
Platelet Aggregation ◽  
In Silico ◽  
Platelet Rich Plasma ◽  
High Shear ◽  
Shear Rates ◽  
Flow Simulations ◽  
In Silico Study ◽  
Platelet Aggregates

The influence of the flow environment on platelet aggregation is not fully understood in high-shear thrombosis. The objective of this study is to investigate the role of a high shear rate in initial platelet aggregation. The haemodynamic conditions in a microfluidic device are studied using cell-based blood flow simulations. The results are compared with in vitro platelet aggregation experiments performed with porcine whole blood (WB) and platelet-rich-plasma (PRP). We studied whether the cell-depleted layer in combination with high shear and high platelet flux can account for the distribution of platelet aggregates. High platelet fluxes at the wall were found in silico . In WB, the platelet flux was about twice as high as in PRP. Additionally, initial platelet aggregation and occlusion were observed in vitro in the stenotic region. In PRP, the position of the occlusive thrombus was located more downstream than in WB. Furthermore, the shear rates and stresses in cell-based and continuum simulations were studied. We found that a continuum simulation is a good approximation for PRP. For WB, it cannot predict the correct values near the wall.

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