2.1 Patients and control subjects: selection
The investigation compared patients with known CAS, either due to
underlying large vessel spasm (PA; n = 39) or to the CSFP (n = 24). In
all cases this diagnosis was made at coronary angiography, which showed
the absence of haemodynamically significant stenoses in epicardial
coronary arteries plus either:-
(a) Inducible coronary artery spasm with intracoronary injection of 25
to 100 µg of ACh, with a positive test being defined on the basis of a
> 75% reduction in luminal diameter (either focal or
diffuse) together with onset of chest pain
(Ong et al. , 2012)
or (b) Presence of CSFP, defined as TIMI-2 flow in at least one major
epicardial vessel (Beltrame et al. ,
2002; Beltrame et al. , 2003).
All patients (n = 63) were subjected to elective peripheral venous blood
sampling during chronic treatment of their angina. However, in 16 cases,
sampling was also performed during presentation to hospital with
prolonged pain, implying the onset of an acute exacerbation. In such
cases, blood samples were taken before initiation of emergency treatment
measures, 2-12 hours thereafter, and 2 -6 weeks post resolution of
symptoms, in order to compare these 3 phases of the disease process.
Treatment during the acute phase of the disease consisted of the
intravenous infusion of GTN at the low rate of 2.5µg/min, utilizing
non-adsorptive tubing, together with N-acetylcysteine (NAC, 10 g per 24
hours), which has been shown to potentiate the vasodilator
(Horowitz et al. , 1983) and
anti-aggregatory (Loscalzo, 1985) effects
of NTG, and which has been shown to suppress cyclical coronary
vasoconstriction and associated phasic platelet aggregation in a canine
model of coronary artery spasm (Foltset al. , 1991).
Healthy control subjects (n= 31) were recruited by advertisement.
Clinical characteristics of patients and control subjects are summarized
in the Table.
In patients undergoing coronary angiography, blood sample collection was
carried out at least 20 minutes post contrast injection. Blood was taken
by venesection into plastic tubes containing1:10 volume of citrate
anticoagulant (2 parts of 0.1 M citric acid to 3 parts of 0.1 M
trisodium citrate, pH 5) for platelet aggregation studies, and into EDTA
Vacutainer tubes for plasma syndecan-1 and tryptase assays.
All human studies were performed in accordance with the Declaration of
Helsinki. The study was approved by the Institutional Human Research and
Ethics Committee, and informed consent was obtained from all subjects.