Con respecto al objetivo específico “3”

T h e r e are notable studies examining p l a t e l e t volume in p a t i e n t s w i t h MI (Cameron et al., 1983; M a r t i n et al., 1983; Sewell et al., 1984; Martin et al., 1991). In contrast, there are v e r y few studies examining PSC phenomena. One study

i nvestigated PSC in patients with coronary artery d i s e a s e and p a t i e n t s w ith congestive heart failure (Erne et al., 1988) . In this study, citrated PRP was diluted (with NaCl but not fixed) b efo r e measurements were carried out w i t h a Coulter ZBI c o u pled to a channelyzer. These workers repor t e d enhanced s e n s i t i v i t y to 5-HT and adrenaline in patients w i t h acute MI and chronic stable angina and a reduced s e n s itivity to both agonists in patients with congestive h eart failure (CHF). S e n s i t i v i t y to adrenaline but not 5-HT, was r e d u c e d in MI p a t i e n t s that were tested 4-7 days after admis s i o n w h e n plasma c a t e c h o l a m i n e concentrations had normalized. T hese results suggest a possible catecholamine-induced r e c e p t o r - d o w n r e g u l a t i o n in the MI phase which is in a g reement w i t h a p r e v i o u s l y documented reduction in Og-receptors f o llowing MI (Sakaguchi et al., 1986). Diminished responses to 5-HT and a d r e n a l i n e in CHF also imply a rece p t o r - d o w n r e gulation p o s s i b l y due to chronically elevated adrenaline, norad r e n a l i n e and 5-HT (the latter bioamine was not measured) . A study by F e t k o v s k a et al., (1990) reported unch a n g e d 5-HT- i n d u c e d PSC in e s sential hypertensives. In DM, an investigation of A D P and v a s o p r e s s i n - i n d u c e d PSC reported normal r e sponses for A D P but no PSC following vasopressin (VP; Vitt e t et al., 1991). In this c o n d i t i o n a decrease in the number of VP rece p t o r s was also documented. Interestingly, DM patients showed the same ex t e n t of plat e l e t aggregation as healthy subjects w h e n high e r c o n c e n t r a t i o n s of VP were used.

In the p r e sent thesis, PSC induced by 5-HT and A D P was e x a m i n e d in patients with PVD and h e a l t h y subjects.

2 .6 METH O D S

A) S election of PVD patients and healthy subjects

The patients selected were PVD patients a t t e n d i n g the v a s c u l a r clinic at The Royal Free Hospital ( RFH). Informed c o n s e n t was obtained from all p atients and h e a l t h y subjects b e f o r e b lood sampling. Twenty PVD patients, of w h i c h 14 were m a l e s and 6 were females volunteered for this study. The m e d i a n age and (range) of the patients was 61 (45-84) years. P a t i e n t s selected were drug-free and in a metabolically/ c l i n i c a l l y stable condition with no history of rece n t cardiac events, strokes, transient ischaemic attacks or changes in th e i r clau d i c a t i o n distance. None of the p a t i e n t s had u n d e r g o n e any recent surgery, a n g i ography or angioplasty. T w e n t y h e a l t h y subjects were selected; 14 w ere m ales and 6 w e r e females. Median age and (range) was 32 (20-58) years. B l o o d w a s collected into citrate (solution A; c o m p o s i t i o n in Appendix) and PRP prepared as p r e v i o u s l y d e s c r i b e d (P art 1 ).

B) P l a t e l e t counting and particle size analvsis

P l a t e l e t counting and platelet size analysis w ere carried out a f t e r agonist addition and sample fixation as desc r i b e d a b o v e (P a r t 1 ). The PRP platelet counts that changed by more t h a n 5-10% of the basal count were d e emed to h a v e aggregated a n d w e r e not analyzed.

2.7 R E S U L T S

M e d i a n platelet counts in PRP of h e a l t h y subjects ( e xpressed per 10^/L) was 312 (range: 224-520) and in PVD

patients: 262 (range: 164-320); this diffe r e n c e was s ign i f i c a n t (P<0.03). Basal MePV was not diff e r e n t in PVD p a t i e n t s when compared to healthy subjects (Table 2.11 and 2.12). PSC following stimulation w i t h 0.1 jitmol/L 5-HT was s i g n i f i c a n t l y increased (Vs. basal) in h e a l t h y subjects but not in PVD patients. At 1.0 /xmol/L 5-HT, PSC achie v e d by PVD p a t i e n t s was significantly (P<0.04) d i m i n i s h e d as c ompared to h e a l t h y subjects. At high concentrations of 5-HT (10 /xmol/L) , PVD plat e l e t s were hyperaggregable. Thus, 4 PVD patients show e d appreciable aggregation and w ere excluded. N one of the h e a l t h y subjects were excluded (Table 2.11). A D P - i n d u c e d PSC r e s p o n s e s w e r e similar in patients and h e a l t h y subjects. H i g h e r concentrations of ADP (0.4 /xmol/L) induced a p p r eciable a g g r e g a t i o n in all PVD patients and, therefore, sizing was not c a r r i e d out (Table 2.12).

TABLE 2.11