Con respecto al objetivo específico “2”

7.50 7.25 7.00 6.75

O

1)

/

If

Solid bars= medians

Final concentrations of mixtures:

citrate=0

citrate+ASA=0

2.4 DISCUSSION

A simple and highly reproducible method of stud y i n g PSC has been described. This method allows the effect of agonists to be examined by measuring the increase in M e P V and is a m e n a b l e to serial measurements for the g e n e r a t i o n of dose responses. From a methodological point of view, it is important to sample for M e P V at specific times after the a d d i t i o n of agonists. For example, the increase in M e P V is latent in the case of collagen and Cal and the reversal of PSC occurs over a period of time that varies with each agonist.

A d r e n a l i n e ' s lack of effect on M e P V requires clarification. There are other peculiarities w h e n c o n s i d e r i n g this agonist. Platelets from neonates and from some adults do not a g g r e g a t e in response to this agonist (Barradas et al., 1986) and adrenaline-induced aggregation cannot be m e a s u r e d in w h o l e blood by the impedance method despite the fact t hat this a g o n i s t reduces the free platelet count (Mackie et al., 1984; B a r r a d a s et al., 1992b). Furthermore, n o r a d r e n a l i n e is a w e a k e r agonist than adrenaline, vis-a-vis, p l a t e l e t a g g r e g a t i o n (O'Brien, 1964) whereas the reverse is true for PSC. T h e lack of increase in MePV following the a d d i t i o n of a d r e n a l i n e has previously been reported although this issue is c o n t r o v e r s i a l (Gear, 1981; Milton and Frojmovic, 1984; K e r a l y et al., 1988; Erne et al., 1988). This i n consistency m a y be a t t r i b u t e d to turbidometric and impedance v o lume m e a s u r e m e n t s p r i m a r i l y r e f lecting increases in "spheration" rather than " p s e u d o p o d formation". Adrenaline, however, does activ a t e p l a t e l e t s and enhances PSC w hen added in combi n a t i o n w i t h 5-HT

(Table 2.9).

Evidence that synergism/additive effects occur between agon i s t s was also presented. Which of these latter effects is observed, p robably depends on whether a maximal (Table 2.8) or subma x i m a l (Table 2.7) response is induced by each individual agonist. These findings suggest that, in vivo, low c o n c e n t r a t i o n s of agonists, which are present in blood, may c o m b i n e to increase the MePV. It is, therefore, of interest that sign i f i c a n t l y higher MePVs have been reported in patients w i t h MI (Cameron et al., 1983; Martin et al., 1983; Sewell et al., 1984; Trowbridge and Martin, 1987). A l t h o u g h in MI "big" p l a t e l e t s m a y be produced as a result of a l t e rations in t h r o m b o p o i e s i s (Martin and Trowbridge, 1990), acute increases in M e P V following direct activatory effects on platelets s h o u l d not be ruled out. We have documented increases in M e P V in v a r i o u s settings, e.g. following the intravenous injection of t h e r a p e u t i c doses of heparin (Mikhailidis et al., 1990); e x p o s u r e to hypothermia (Escalda et al., 1993) or after the a d d i t i o n (in vitro) of bacterial lipopolysaccharide (Whitworth et al., 1989) or to N-formyl-methionine p h e n y l a l a n i n e (a b a c t e r i a l chemotactic peptide; Nystrom et al., 1993).

Part 2