Effect Of Novel PGEl Analogue (OP-1206) On The Platelet Functions

PGEl is one of prostaglandins which inhibit platelet functions and has vasodilating activity similar to PGI2. Newly developed PGEi analogue (OP-1206) was supplied for the clinical evaluations on oral administration. This research was performed to analyze the effect of orally administrated PGE1 analogue on platelet functions and to evaluate the usefulness on the thromboembolic disorders. Comparing with PGI2, this analogue demonstrated the similar inhibitory activity on the platelet aggregation in vitro study. Oral administration of OP-1206 on the patients with thromboembolic disorders showed the dose-dependent inhibition on platelet aggregation and adhesiveness. This activity continued for l80 min (max at 120 min). Daily oral administration (20μg and 30μg t.i.d.) was continued for two weeks and its effect on blood pressure, heart rate, ADP induced platelet aggregation, platelet adhesiveness and platelet c-AMP level were evaluated. Both of administration doses caused remarkable depression of platelet aggregation, increment of c-AMP level in the platelet and mild suppression on the platelet adhesiveness. Blood pressure was decreased, but heart rate remained unchanged. Clinical improvement of symptoms were observed in the patients with deep vein thrombosis or angina pectoris. These results emphasize the effectiveness and usefulness of this orally administrated PGE1 analogue against the prevention and treatment of thromboembolic disorders.

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Effect Of The Stable Prostacy Clin-nilic, 7-OXO-PGI2 On Some Haemostatic Parameters

10.1055/s-0038-1653376 ◽

1981 ◽

Author(s):

Gy Blaskó ◽

P Körmöczy ◽

I Stadler ◽

V Simonidesz ◽

I Tömösközy

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Platelet Aggregation ◽

Natural Compound ◽

Antithrombin Iii ◽

Inhibitory Effect ◽

Relative Potency ◽

Pharmacological Profile ◽

Haemodynamic Parameters

7-oxo-PGI2 sodium salt produced by the Chinoin was investigated regarding some haemostatic and haemodynamic parameters. According to our results, 7-oxo-PGI2 is a powerful inhibitor of platelet aggregation induced by ADP and collagen (IC50: 10-15 ng/ml and 60-80 ng/ml respectively). It is stable in solution and the duration of its inhibitory effect on platelet aggregation in vitro is more than 3 hours (for PGI2 it is only 1,5 h ). Investigating the effect of this substance on the activities of the key-enzymes of blood coagulation (thrombin, Factor Xs and plasmin), we could neither demonstrate any effect on these enzyme activities nor on the inactivation of these enzymes by antithrombin-III and/or heparin at a concentration as high as 200 μg/ral.The relative potency of 7-oxo-PGI2 on isolated bovine coronary artery is one tenth, as compared to PGI2. It decreases the systolic and diastolic blood pressure with a relative potency of 1:20 to PGI2 without effecting the heart rate. Comparing its stimulatory effect on platelet adenylate cyclase to that of PGI2, we have found, that 1 μM of 7-o xo-PGI2 activates this enzyme to 246%, while 1 μM of PGI2 causes a 370% activation. The platelet disaggregating activity of this compound -tested on cat Achilles tendon - is comparable to the effect of the natural compound.The pharmacological profile of 7-oxo-PGI2 is similar to that of PGI , just even as another well known leading representativerGI -analogue - carboprostacyclin - , furthermore it is slightly preferred in certain conditions.

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Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648052 ◽

1976 ◽

Vol 36 (02) ◽

pp. 376-387 ◽

Cited By ~ 3

Author(s):

Teruhiko Umetsu ◽

Kazuko Sanai ◽

Tadakatsu Kato

Keyword(s):

Platelet Aggregation ◽

Platelet Adhesion ◽

Human Platelets ◽

Rabbit Platelet ◽

Rabbit Platelets ◽

Β Blocker ◽

Platelet Aggregates ◽

Induced Aggregation ◽

Platelet Functions

SummaryThe effects of bupranolol, a new β-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known β-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased.Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4–3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the β-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8–3.3 times as effectively as propranolol.From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.

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The Involvement of Platelets and the Coronary Vasculature in Collagen-Induced Sudden Death in Rabbits

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661239 ◽

1985 ◽

Vol 53 (01) ◽

pp. 070-074 ◽

Cited By ~ 4

Author(s):

G Mallarkey ◽

G M Smith

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Platelet Count ◽

Sudden Death ◽

Myocardial Ischaemia ◽

Plasma Levels ◽

Sodium Citrate ◽

Plasma Samples ◽

Calcium Entry Blockers

SummaryThe mechanism of collagen-induced sudden death in rabbits was studied by measuring blood pressure (BP), heart rate, ECG, the continuous platelet count and the plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin Fia (6-keto PGF1α). Death was preceded by myocardial ischaemia and a sharp fall in BP which occurred before any fall in platelet count was observed. The calcium entry blockers (CEBs), verapamil, nifedipine and PY 108-068 protected the rabbits from sudden death without any significant effect on the decrease in the platelet count or increase in plasma TxB2 levels. 6-keto PGF1α could not be detected in any plasma samples. Indomethacin and tri-sodium citrate also protected the rabbits but significantly reduced the fall in platelet count and plasma TxB2. In vitro studies on isolated aortae indicated that verapamil non-specifically inhibited vasoconstriction induced by KC1, adrenaline and U46619 (a thromboxane agonist). It is concluded that CEBs physiologically antagonize the vasoconstricting actions of platelet-derived substances and that it is coronary vasoconstriction that is primarily the cause of death.

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Disturbance Of Platelet Function In The Nephrotic Syndrome

10.1055/s-0038-1653301 ◽

1981 ◽

Author(s):

E Walter ◽

D Deppermann ◽

K Andrassy ◽

E Weber

Keyword(s):

Nephrotic Syndrome ◽

Platelet Count ◽

Platelet Aggregation ◽

Kidney Function ◽

Platelet Function ◽

Platelet Adhesiveness ◽

Spontaneous Aggregation ◽

Spontaneous Platelet Aggregation ◽

Platelet Functions

Thromboembolic phenomena often (30 %) complicate the nephrotic syndrome. It was therefor investigated, wether disturbed platelet functions play a role in this disease.28 normals, 34 patients with nephrotic syndrome and 18 of them with impaired kidney function were tested. In 20 patients the measurements were repeated after administration of aspirin plus dipyridamo1e.Patients with nephrotic syndrome showed in comparison to normals the following changes: 1. increased platelet count (p < 0.01), 2. enhanced platelet adhesiveness (Wright-test: p < 0.001), 3. increased spontaneous aggregation (PAT I: p < 0.001; PAT III: p < 0.01), 4. enhanced PF 4-activity (heparin neutralisation: p < 0.001), 5. elevated β TG-levels only in impaired kidney function. There was no difference in the reaction of platelets against ADP as well as collagen. The changes in platelet function correlated with the severity of the nephrotic syndrome (proteinurea, hypalbuminaemia, hyperlipo- proteinaemia). After aspirin plus dipyridamole administration spontaneous platelet aggregation and adhesiveness were normalized.There is a disturbance of platelet function in patients with nephrotic syndrome, which can be reversed with antiaggregating agents.

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Potential and Limitations of the New P2Y12 Inhibitor, Cangrelor, in Preventing Heparin-Induced Platelet Aggregation During Cardiac Surgery: An In Vitro Study

Anesthesia & Analgesia ◽

10.1213/ane.0000000000004700 ◽

2020 ◽

Vol 131 (2) ◽

pp. 622-630 ◽

Cited By ~ 2

Author(s):

Emmanuelle Scala ◽

Christiane Gerschheimer ◽

Francisco J. Gomez ◽

Lorenzo Alberio ◽

Carlo Marcucci

Keyword(s):

Cardiac Surgery ◽

Platelet Aggregation ◽

In Vitro Study ◽

Vitro Study ◽

P2y12 Inhibitor

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Predictors of the development of cardiac arrhythmias in women after induction of superovulation in vitro fertilization

Pediatrician (St Petersburg) ◽

10.17816/ped10557-65 ◽

2020 ◽

Vol 10 (5) ◽

pp. 57-65

Author(s):

Victoria V. Vakareva ◽

Marina V. Avdeeva ◽

Larisa V. Scheglova ◽

Sergey A. Bondarev ◽

Pavel B. Voronkov

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cardiovascular System ◽

Functional State ◽

Blood Pressure Monitoring ◽

Myocardial Oxygen Demand ◽

Heart Rate Variability Analysis ◽

Supraventricular Arrhythmias ◽

Rate Profile

The article presents the results of a clinical and instrumental examination of 80 healthy women (average age 32,313,57 years) in order to assess the heart rhythm disturbances after induction of superovulation duringin vitrofertilization. All women were examined twice before and after induction of superovulation during extracorporeal fertilization. Clinical and instrumental examination included: electrocardiography at rest; echocardiography; 24-hour ECG monitoring with heart rate variability analysis; 24-hour blood pressure monitoring. Induction of superovulation is associated with a significant increase in mean daily HR max (р0,01), and consequently with an increase in myocardial oxygen demand. It has been established that induction of superovulation contributes to the development of supraventricular arrhythmias (р0,01) and an increase in episodes of apnea/hypnea (р0,01). Regression analysis revealed predictors of supraventricular arrhythmias after induction of superovulation, including adverse circadian heart rate profile, adverse circadian blood pressure profile, impaired autonomic regulation of heart activity (р0,01). It was shown that the appearance of rhythm disturbances is associated with both the initial functional state of the cardiovascular system and its response to the induction of superovulation. It was established a correlation between the estradiol concentration and the increase of daily average heart rate after induction of superovulation (r=0,30,р0,05), apnea/hypnea index after induction of superovulation (r=0,34,р0,05). Conclusion. Superovulation induction may exacerbate existing chronic cardiovascular diseases. Due to the adverse effect of superovulation induction on the daily heart rate profile, women need to evaluate the functional state of the cardiovascular system duringinvitrofertilization planning. This will prepare the woman for the upcoming procedure and avoid adverse reactions from the cardiovascular system in response to stimulation of superovulationin vitrofertilization.

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Ponatinib and Risk of Thrombotic Events: In Vitro Study on Platelet Functions

10.17303/jcvm.2021.7.203 ◽

2021 ◽

Vol 7 (2) ◽

pp. 1-8

Author(s):

Elisabetta Straface

Keyword(s):

In Vitro Study ◽

Vitro Study ◽

Platelet Functions

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Blocking properties of terguride at the 5-HT2 receptor subtypes mediating cardiovascular responses in the rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0591 ◽

2020 ◽

Vol 98 (8) ◽

pp. 511-521

Author(s):

Oscar Alcántara-Vázquez ◽

Ma. Trinidad Villamil-Hernández ◽

Araceli Sánchez-López ◽

Heinz H. Pertz ◽

Carlos M. Villalón ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Diastolic Blood Pressure ◽

Receptor Agonist ◽

Cardiovascular Responses ◽

Receptor Subtypes ◽

Pithed Rats ◽

Anaesthetized Rats ◽

Dose Dependent

In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT2A/2B receptors. This study has now investigated terguride’s blocking properties on central/peripheral 5-HT2 receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.v. administration of several compounds. In both groups of rats, i.v. bolus injections of 5-HT or (±)-DOI (a 5-HT2 receptor agonist; 1–1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and heart rate. These responses were dose-dependently antagonized by terguride (10–3000 μg/kg). In anaesthetized rats, i.v. bolus injections of BW723C86 (a 5-HT2B receptor agonist; 1–1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and not dose-dependent increases in heart rate, while in pithed rats, these responses were attenuated. The vasopressor responses elicited by BW723C86 in anaesthetized rats were dose-dependently blocked by terguride (10–300 μg/kg), whereas its the tachycardic responses were dose-independently blocked. These results, taken together, suggest that terguride behaved as an antagonist at the 5-HT2 receptors located in the central nervous system and (or) the systemic vasculature. This is the first evidence demonstrating that terguride can block central/peripheral 5-HT2 receptors mediating cardiovascular responses in anaesthetized or pithed rats.

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Effect of Heparin on Aggregation, Release Reaction and Thromboxane A2synthesis in Human Platelets

10.1055/s-0039-1684468 ◽

1979 ◽

Author(s):

H.Y.K. Chuang ◽

S.F. Mohammad ◽

R.G. Mason

Keyword(s):

Platelet Aggregation ◽

Platelet Rich Plasma ◽

Thromboxane A2 ◽

Rabbit Aorta ◽

Human Platelets ◽

Appreciable Effect ◽

Layer Chromatography ◽

Aggregation Of Platelets ◽

Platelet Functions

Studies on the effect of heparin on platelet functions have resulted in conflicting observations: heparin has been reported to cause aggregation of platelets, potentiate aggregation induced by various aggregating agents, or cause inhibition of aggregation. Using paritally purified heparin (beef lung or porcine mucosa) we observed that addition of heparin to citrated platelet rich plasma(C-PRP)potentiated the aggregation of platelets induced by ADP, epinephrine, or arachidonic acid. Presence of heparin in C-PRP results in complete inhibition of thrombin induced effects and partial inhibition of platelet aggregation induced by collagen. Presence of heparin in C-PRP also resulted in release of significantly higher concentrations of 14C-serotonin when platelets were challenged by appropriate aggregating agents. Those concentrations of heparin that resulted in potentiation of aggregation had no appreciable effect on c-AiMP or c-GMP levels of platelets. However, the presence of heparin results in a significant elevation of thromboxane A2 as determined by contraction of rabbit aorta or after conversion to thromboxane B2 by thin layer chromatography. These observations are of interest since increased production of thromboxane A2 in the presence of heparin may explain in part, the potentiation of platelet aggregation in vitro or thrombocytopenia observed frequently in patients receiving heparin intravenously Supported in part by grants HL22583 & 20679 from NHLBI of NIH.

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