Inhibition of platelet function by organic nitrate vasodilators

Blood ◽  
1980 ◽  
Vol 55 (4) ◽  
pp. 649-654
Author(s):  
AI Schafer ◽  
RW Alexander ◽  
RI Handin
Keyword(s):  
Myocardial Ischemia ◽  
Platelet Function ◽  
Coronary Circulation ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Organic Nitrate ◽  
Artery Disease ◽  
In Vitro Effects ◽  
External Calcium

There is evidence that platelet activation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Since organic nitrate vasodilators are commonly used in coronary artery disease, we have studied the in vitro effects of these drugs on platelet function. Nitroglycerin, isosorbide dinitrate, and their biotransformation product, inorganic nitrite, inhibited platelet aggregation with collagen, epinephrine, arachidonate, and ionophore, and blocked both primary and secondary aggregation in response to ADP. Nitroglycerin was studied in more detail. Its inhibitory effect was reversible and not dependent on external calcium concentration. It inhibited arachidonic acid oxygenation as measured by the arachidonate- induced oxygen burst and malonaldehyde production. These effects were not due to an increase in intracellular cyclic AMP. This unusual generalized inhibition of platelet function by nitroglycerin possibly contributes to its beneficial effect in myocardial ischemia in part by attenuating platelet reactivity in the coronary circulation.

scholarly journals Inhibition of platelet function by organic nitrate vasodilators

Blood ◽  
1980 ◽  
Vol 55 (4) ◽  
pp. 649-654 ◽  
Author(s):  
AI Schafer ◽  
RW Alexander ◽  
RI Handin
Keyword(s):  
Myocardial Ischemia ◽  
Platelet Function ◽  
Coronary Circulation ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Organic Nitrate ◽  
Artery Disease ◽  
In Vitro Effects ◽  
External Calcium

Abstract There is evidence that platelet activation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Since organic nitrate vasodilators are commonly used in coronary artery disease, we have studied the in vitro effects of these drugs on platelet function. Nitroglycerin, isosorbide dinitrate, and their biotransformation product, inorganic nitrite, inhibited platelet aggregation with collagen, epinephrine, arachidonate, and ionophore, and blocked both primary and secondary aggregation in response to ADP. Nitroglycerin was studied in more detail. Its inhibitory effect was reversible and not dependent on external calcium concentration. It inhibited arachidonic acid oxygenation as measured by the arachidonate- induced oxygen burst and malonaldehyde production. These effects were not due to an increase in intracellular cyclic AMP. This unusual generalized inhibition of platelet function by nitroglycerin possibly contributes to its beneficial effect in myocardial ischemia in part by attenuating platelet reactivity in the coronary circulation.

Inhibition of Platelet Function by Antiarrhythmic Drugs, Verapamil and Disopyramide

1982 ◽  
Vol 47 (02) ◽  
pp. 150-153 ◽  
Author(s):  
P Han ◽  
C Boatwright ◽  
N G Ardlie
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Antiarrhythmic Drugs ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Second Phase ◽  
Ionophore A23187 ◽  
High Concentrations ◽  
Artery Disease

SummaryVarious cardiovascular drugs such as nitrates and propranolol, used in the treatment of coronary artery disease have been shown to have an antiplatelet effect. We have studied the in vitro effects of two antiarrhythmic drugs, verapamil and disopyramide, and have shown their inhibitory effect on platelet function. Verapamil, a calcium channel blocker, inhibited the second phase of platelet aggregation induced by adenosine diphosphate (ADP) and inhibited aggregation induced by collagen. Disopyramide similarly inhibited the second phase of platelet aggregation caused by ADP and aggregation induced by collagen. Either drug in synergism with propranolol inhibited ADP or collagen-induced platelet aggregation. Disopyramide at high concentrations inhibited arachidonic add whereas verapamil was without effect. Verapamil, but not disopyramide, inhibited aggregation induced by the ionophore A23187.

Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

1985 ◽  
Vol 54 (04) ◽  
pp. 808-812 ◽  
Author(s):  
Ulf Berglund ◽  
Henning von Schenck ◽  
Lars Wallentin
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Plasma Levels ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Controlled Study ◽  
Double Blind ◽  
Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

PLATELET FUNCTION AND PLASMA FIBRINOGEN IN YOUNG SURVIVORS OF MYOCARDIAL INFARCTION

1987 ◽  
Author(s):  
U Berglund ◽  
H von Schenk ◽  
L Wallentin
Keyword(s):  
Myocardial Infarction ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Plasma Fibrinogen ◽  
Women Patients ◽  
Platelet Factor ◽  
Young Survivors

An increased liability for thrombosis might be of pathogenetic importance in young survivors of myocardial infarction (MI). In 73 (58 men and 15 women) patients with MI below 45 years of age and 73 matched healthy controls plasma fibrinogen and platelet function tests were studied 3-6 months after the MI. At the time of the MI 77% of the patients were smokers but at the time of the investigation 27% of the patients smoked compared to 37% of the controls. Platelet aggregabi1ity was measured in vitro in platelet-rich plasma (PRP) as maximal aggregation to ADP and collagen. The platelet sensitivity to the inhibitory effect of prostacyclin (PG12) was tested by preincubation of PRP with PG12 before inducing aggregation with ADP 5 μM. Plasma levels of beta-thrombog1obuIin (BTG) and platelet factor 4 (PF4) were measured by RIA methods and plasma fibrinogen by heat precipitation. The table presents the results (means ± SE). * is p<0.04, ** is D<0.02 and ns is non significant.Severe emotional stress preceeding the MI occured in 7 patients - these cases had an increased platelet reactivity to ADP. The fibrinogen level was also elevated by smoking and obesity (multivariate analysis). Conclusion: young MI patients have elevated levels ol fibrinogen and reduced platelet sensitivity to PGI2. This might cause an increased thrombotic tendency.

Enhancing Effect of Collagen Receptor Polymorphisms on In Vitro Platelet Reactivity to Aspirin in Healthy Subjects.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1099-1099 ◽  
Author(s):  
Miho Ushida ◽  
Yumiko Matsubara ◽  
Shinichi Takahashi ◽  
Hiroaki Ishihara ◽  
Toshiro Shibano ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Repeated Measures ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Antiplatelet Drug ◽  
Platelet Response ◽  
Individual Variations ◽  
Collagen Receptor

Abstract [Background] Aspirin (ASA) is widely used as an antiplatelet drug, and a large number of clinical trials with ASA demonstrated significant efficacies for prevention and treatment of athrothrombosis. Recently, accumulating evidences indicated that there are inter-individual variations in the platelet response to ASA. The subpopulation, called ASA resistance, has the inability of response to ASA on ex vivo or in vitro platelet function tests and the poor clinical outcomes, although the mechanism underlying the variability is largely unknown. To date, genetic factors were showed to have an impact on platelet reactivity to ASA, and the inter-individual variations in platelet response to ASA was also reported to be associated with platelet sensitivity to collagen. In this study, the association between collagen-induced platelet aggregation (CIPA) and genetic polymorphisms of collagen receptors, glycoprotein (GP) Ia and GPVI, was analyzed using platelets treated by ASA (ASA +/−). We also investigated the effect of these polymorphisms on platelet thromboxane (TXB2) levels, closely related to the final stages of the arachidonate pathway inhibited by ASA. [Methods] We recruited genetically unrelated Japanese males (n=172) at their regular checkups. The mean age was 46.7±5.1 years. The subjects had no apparent hematologic or vascular disease and were not taking any medications that affect platelet function. Written informed consent was obtained from all study subjects. Platelet-rich plasma (PRP) sample was incubated with ASA [final concentration (fc) 10μM] or vehicle for 30 min at 24 degree Centigrade, and CIPA (fc 2μg/ml) test was performed on each PRP sample. Subsequently, platelet TXB2 levels were measured in the supernatant after centrifugation of each sample of CIPA test. Genotypes of the 807TC, Glu534Lys, Asn927Ser polymorphisms of GPIa and the Ser219Pro, Lys237Glu, Thr249Ala, Gln317Leu, His322Asn polymorphisms of GPVI were determined using the single-nucleotide primer extension-based method. [Results] To examine the sensitivity of platelets to ASA in vitro, we analyzed CIPA and platelet TXB2 levels in ASA(+/−). The maximum platelet aggregation and TXB2 levels in ASA(+) were significantly lower than those in ASA(−) (paired t-test, p&lt;0.0001 and p&lt;0.0001, respectively). Next, we investigated the association between the collagen receptor polymorphisms and the maximum platelet aggregation in ASA (+/−). For ASA(−), all genotypes of GPIa and GPVI were not associated with the maximum platelet aggregation. For ASA(+), subjects with 807TT/TC of GPIa had higher aggregation compared to those with 807CC(P=0.0135) whereas no association was observed between other polymorphisms and the maximum platelet aggregation. Moreover, repeated measures ANOVA showed that the difference in this inhibitory effect of ASA was significant between the 807TT/TC and 807CC genotypes (p=0.0253); the 807CC genotype has higher inhibitory effect of ASA. There was no association between platelet TXB2 levels and the GPIa and GPVI polymorphisms both in ASA(+) and ASA(−). [Conclusion] The 807CC genotype of GPIa polymorphism is associated with higher sensitivity to ASA in CIPA.

scholarly journals Platelet-Derived PCSK9 Is Associated with LDL Metabolism and Modulates Atherothrombotic Mechanisms in Coronary Artery Disease

2021 ◽  
Vol 22 (20) ◽  
pp. 11179
Author(s):  
Álvaro Petersen-Uribe ◽  
Marcel Kremser ◽  
Anne-Katrin Rohlfing ◽  
Tatsiana Castor ◽  
Kyra Kolb ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Platelet Count ◽  
Coronary Artery ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Clinical Effects ◽  
Monocyte Migration ◽  
Artery Disease ◽  
Pcsk9 Inhibition

Platelets play a significant role in atherothrombosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is critically involved in the regulation of LDL metabolism and interacts with platelet function. The effect of PCSK9 in platelet function is poorly understood. The authors of this article sought to characterize platelets as a major source of PCSK9 and PCSK9’s role in atherothrombosis. In a large cohort of patients with coronary artery disease (CAD), platelet count, platelet reactivity, and platelet-derived PCSK9 release were analyzed. The role of platelet PCSK9 on platelet and monocyte function was investigated in vitro. Platelet count and hyper-reactivity correlated with plasma LDL in CAD. The circulating platelets express on their surface and release substantial amounts of PCSK9. Release of PCSK9 augmented platelet-dependent thrombosis, monocyte migration, and differentiation into macrophages/foam cells. Platelets and PCSK9 accumulated in tissue derived from atherosclerotic carotid arteries in areas of macrophages. PCSK9 inhibition reduced platelet activation and platelet-dependent thrombo-inflammation. The authors identified platelets as a source of PCSK9 in CAD, which may have an impact on LDL metabolism. Furthermore, platelet-derived PCSK9 contributes to atherothrombosis, and inhibition of PCSK9 attenuates thrombo-inflammation, which may contribute to the reported beneficial clinical effects.

HEPARIN AND ACETYLSALICYLIC ACID (ASA) 75 MG/DAY IN UNSTABLE CORONARY ARTERY DISEASE - EFFECTS ON PLATELET REACTIVITY

1987 ◽  
Author(s):  
Lars Wallentin ◽  
Ingyar Nyman ◽  
ULF Berglund ◽  
Eva Swahn
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Unstable Coronary Artery Disease ◽  
Long Term Treatment ◽  
Artery Disease ◽  
One Year

In unstable coronary artery disease (UCAD), i.e. unstable angina pectoris (UAP) or non-Q-myocardial infarction (NMI), treatment with heparin or ASA have given encouraging results. The present study attempts to verify the effects of i.v. heparin (5 days) and to evaluate the utility of ASA 75 mg/day (one year). Patients, admitted because of chest pain, who either develops NMI or signs of ischemia in resting or exercise ECG.s are included. Within 72 hours patients are randomized to obtain Heparin+ASA, Heparin+Placebo, Placebo + ASA or Placebo+Placebo . Platelet reactivity is studied in vitro in platelet rich plasma (PRP) in a subgroup of patients.The aggregation response is studied after addition of collagen and ADP and after preincubation with prostacyclin before aggregation with ADP. The figures present results from 85 randomized patients tested before, 5 days, one month and one year after start of therapy.Conclusion: In patients with unstable CAD long term treatment with ASA 75 mg/day inhibits collagen induced platelet aggregation and hampers the ADP response. I.v. heparin tends to raise platelet reactivity and reduce the inhibitory effect of prostacyclin. Heparin induced platelet activation is reduced by simultaneous ASA therapy.

Comparison of in Vivo and in Vitro Effects of Platelet Function Suppressing Drugs

1975 ◽  
Author(s):  
M. Buchanan ◽  
J. Hirsh
Keyword(s):  
Platelet Function ◽  
Prosthetic Heart Valve ◽  
Inhibitory Effect ◽  
Potent Effect ◽  
Platelet Survival ◽  
In Vitro Effects ◽  
Antithrombotic Efficacy ◽  
Induced Aggregation

Comparison of in vivo and in vitro platelet function tests to assess the antithrombotic efficacy of drugs which suppress platelet function have been contradictory. For example, aspirin (ASA) has a potent effect in vitro but little effect when tested on platelet survival in prosthetic heart valve replacements whereas dipyridamole (DIP) has little or no effect in vitro but a marked effect on platelet survival. We have compared in parallel the in vivo and in vitro effects of a number of drugs which suppress platelet function in an animal model. Rabbits were infused with homologous 51Cr-labelled platelets and then given either ASA (10-200 mg/kg), DIP (1-20 mg/kg) or sulfinpyrazone (SUF) (30-200 mg/kg) intravenously. One hour later PRP from each rabbit was tested by ADP and collagen-induced aggregation. Then each rabbit was infused with an identical final concentration of collagen and the subsequent recovery of 51Cr platelet radioactivity was monitored. In untreated rabbits collagen infusion produced 30% reduction of 51Cr platelets which returned to within 85% of a procollagen level by 5 min. ASA (⪖ 10 mg/kg) inhibited in vitro collagen-induced aggregation while a dose of 100 mg/kg of ASA was necessary to achieve the same inhibitory effect in vivo. On the other hand, DIP (1-20 mg/kg) had no inhibitory effect on in vitro platelet aggregation whereas it inhibited aggregation in vivo. The results of SUF were similar in vitro and in vivo. These results suggest that the effectiveness of drugs on platelet function may be affected by centrifugation, addition of anticoagulant or removal of red cells. This may explain the discrepancies reported between the in vivo and in vitro effectiveness of such drugs.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

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