Platelet aggregation rate

Figure 30.2. A. The effect of X-aerogel on platelet aggregation rate towards TRAPs and ADP (Data presented as mean + standard error of the mean). B. The effect of X-aerogel on platelet participation within the coagulation cascade, as measured by thrombin generation (Data presented as mean standard error of the mean). Different platelet concentrations were used to determine if enhanced platelet-platelet contact affects the biocompatibility.

Radomski et al. [113] demonstrated that the CNTs were efficient in causing platelet aggregation both in vitro and in vivo, accelerating significantly the rate of development of carotid artery thrombosis in rats. Platelet aggregation was likely to result from MMP-dependent activation of GPIIb/IIa receptor. 

B-NOD is a new NO donor compound. It has a chemical NO-releasing group similar to that of NTG, however, it releases NO in vitro and in vivo. After administration of B-NOD in vivo its activity persists for more than 7 h. In vitro, the release of NO from B-NOD was augmented by the presence ofliving cells (blood platelets). B-NOD increased cGMP levels and prevented thrombin-induced platelet aggregation in vitro in the same manner as SNP. In vivo, administration of B-NOD in rabbits did not cause a fall in blood pressure or an increase in heart rate [97]. 

As shown in double-blind, placebo-controlled, randomized studies with healthy subjects, both infused [145] and oral [146] L-arg significantly inhibited (by =40%) ADP-induced platelet aggregation in vitro and potentiated platelet cGMP content. The effect, though, was weak the plasma concentration of L-arg required to produce an anti-platelet effect was some 2-fold above normal, steady-state levels, and the oral anti-aggregatory L-arg dose was 4-fold greater than the usual daily L-arg intake in humans. The infused L-arg dose that effectively inhibited platelet activity (30 g total) was hypotensive and increased heart rate, whereas the oral anti-platelet dose (7 g per day over 3 days) did not affect blood pressure, suggestive of oral L-arg platelet selectivity. 

Cilostazol is a selective cAMP phosphodiesterase inhibitor. It inhibits platelet aggregation and is a direct arterial vasodilator. It is used for the symptoms of intermittent claudication in individuals with peripheral vascular disease. Side-effects of cilostazol include headache, diarrhea, increased heart rate, and palpitations. Drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure. 

Prostacyclin, a potent inhibitor of platelet aggregation, is derived from metabo-lisation of arachidonic acid by endothelial cells, and shear stress increases its production rate [12]. It is postulated that this effect is due to perturbations of the permeability of the plasma membrane changing the cytosolic Ca + content and leading to an increase in phospholipase C activity (through the by-passing of the receptor requirement), which contributes to a higher production of arachidonic metabolites. 

CN125 Vas Dias, F. W., M. J. Gibney, and T. G. Taylor. The effect of polyunsatu-rated fatty acids on the n-3 and n-6 series on platelet aggregation and platelet and aortic fatty acid composi-tion in rabbits. Atherosclerosis 1982 43(2-3) 245-257. 

Enzymatic kinetic resolution is a key step in the synthesis of the platelet aggregation inhibitor Lotrafiban (Figure 10.11). A disclosed process involves CaLB in tert-butyl alcohol/water (88 12) at 50 °C the substrate concentration was only r> g I 1 owing to its low solubility in this medium [122]. By exploiting the higher solubility in 88% [BMIm][PF6] and the better thermal stability of the biocatalyst in this medium, a higher rate was observed, the reaction was performed at 40 54 1. 1 at 75 °C, and the biocatalyst (Novozym 435) could be recycled 10 times. 

C) Inhibition of cyclic nucleotide PDEs. Elevation in cellular cyclic nucleotides induces vascular smooth muscle relaxation [132]. The cellular accumulation of cAMP and cGMP depends upon the rate of their synthesis and their breakdown. The latter is achieved by cyclic nucleotide PDEs that have been classified into seven families [133]. Some flavonoids (apigenin, kaempferol, fisetin and quercetin) produce an inhibitory action on cyclic nucleotide PDEs [134,135] which may collaborate in the inhibitory effect on platelet aggregation [93] and vascular smooth muscle relaxation... 

Induction of abortion and labor Prostaglandin I series Reduced platelet aggregation Reduced mean arterial pressure Reduced total peripheral and pulmonary resistances Increased heart rate... 

As indicated above, there are many possible oxidation products of the different polyenoic acids. It is probably naive to ascribe the effects of dietary intervention reported thus far to such metabolites. Carefully controlled clinical studies will be needed before these questions can be satisfactorily answered. However, subjects on diets containing highly saturated fatty acids clearly show increased platelet aggregation when compared with other study groups. Such diets (eg, in Finland and the USA) are associated with higher rates of myocardial infarction than are more polyunsaturated diets (eg, in Italy). 

Cilostazol is a phosphodiesterase inhibitor that reduces platelet aggregation, vascular smooth muscle proliferation and also has vasodilatory effects. Earlier studies comparing cilostazol and aspirin to ticlodipine and aspirin identified no significant increase in the subacute stent thrombosis rate (21-23). Indeed, the latter has been supported by comparison of this combination to clopidogrel and aspirin (24). Two recent trials, however, have demonstrated that a much higher proportion of patients develop subacute stent thrombosis when taking cilostazol as compared with ticlodipine (25,26). The data from these trials are summarized in Table I. 

Blocks sodium channels. Produces euphoria, mood elevation, energy, tremors, chest pain, agitation, paranoia and convulsions It t heart rate, BP and cardiac output, as well as enhancing platelet aggregation ... 

PUFAs suppress HMG-CoA reductase and ACE activities, inhibit platelet aggregation, enhance parasympathetic activity and, thus, enhance heart rate variabihty (and thus, have actions similar to that of fS-blockers), and possess diuretic properties either by themselves and/or by increasing the formation of PGAs and PGEs that have been shown to increase renal blood flow and augment diuresis. These actions of PUFAs are similar to that of the polypill that is a combination of aspirin, fS-blockers, statins, and ACE inhibitors, which is expected to reduce cardiovascular diseases by over 70-80% (92). This suggests that PUFAs could function as an endogenous polypill the evidence for this is detailed below. 

---