Myocardial blood flow (MBF) is regulated by the coronary resistive vessels which continuously adapt the coronary blood flow
he myocardial metabolic requirements, modulated by neural and humoral mechanisms, and this adaptation can compensate for
increased resistance of an epicardial stenosis to a considerable extent. In patients with coronary artery disease, we postulate
t dysfunction of the coronary resistive vessels may cause or contribute to myocardial ischaemia. Thus, impaired myocardial
fusion maybe due to the abnormal behaviour of collateral and resistive vessels rather than to epicardial disease alone. We
ipose that this alteration in resistive vessel function occurs, not only in regions subtended by epicardial disease, but is present in
rote myocardium and may be altered by coronary intervention such as coronary angioplasty (PTCA) and after myocardial
irction (MI). To investigate coronary resistive vessel function, positron emission tomography (PET) may be used to evaluate
ional MBF using the flow tracer lsO-labelled water. Using vasodilator (or vasoconstrictor) stimuli, the coronary vasodilator
ponse (CVR=maximal/basal coronary [myocardial] blood flow), an index of coronary resistive vessel function, may be measured
1 compared in regions of interest and in remote myocardium.
Recovery of Resistive Vessel Dysfunction After Successful PTCA. To investigate the frequency and the time course of abnormal
onary resistive vessel function after successful PTCA, patients with single vessel coronary disease and normal left ventricular
ction underwent intracoronary (IC) Doppler measurement of coronary flow velocity, before and after successful PTCA, at basal
I after intravenous (IV) dipyridamole. PET was performed on 3 occasions after PTCA. There was no change in CVR at Doppler
;r PTCA. In patients without restenosis, the CVR was reduced in the PTCA region for >7 days, but returned to normal at 3
nths, due to increased basal MBF for >7 days in the PTCA region, with a reduction in the dipyridamole-induced maximal MBF
> 24 hours.
Altered Nitric Oxide Synthesis/Release and Resistive Vessel Dysfunction After PTCA. Impaired production or release of nitric
de (NO) in the from resistive vessel endothelium may cause this alteration in the CVR after PTCA. As the CVR to exogenous
rates is enhanced by the endothelial dysfunction, large doses of IC sodium nitroprusside, an NO donor, were infused at the peak
?ct of IV dipyridamole to test this hypothesis using Doppler catheterisation in patients with single vessel disease,
roprusside in doses sufficient to cause ultimately a fall in blood pressure did not augment the dipyridamole-induced increase in
onary blood flow velocity.
Altered Flow and Metabolism in Regions Subtended by Angiographically Normal Arteries in Coronary Artery Disease. The
ional CVR was measured using PET in patients with stable single vessel disease. In a second group of patients and controls,
[ultaneous arterial and great cardiac vein catheterisation was done at rest and during atrial pacing to measure myocardial
tabolism in regions subtended by a diseased artery or by an angiographically normal artery with epicardial disease elsewhere.
; CVR was reduced in remote regions compared to controls. In the second group, at maximal pacing, there was net lactate
duction in the diseased region compared to net extraction in both the remote and control.
Resistive Vessel Dysfunction in Infarcted and Remote Myocardium After MI. To investigate acute resistive vessel dysfunction,
ients were studied after thrombolysis for MI. Regional MBF and the CVR in infarct and remote regions was assessed, after a
an of 8 days and 6 months after MI by PET. At early scanning^ the CVR was markedly reduced in the infarct region, and was
tted to the amount of residual viable tissue. There was no correlation between the CVR and residual stenosis area. The remote
R was less than that in remote regions, subtended by a normal artery, in controls with stable single vessel disease without MI.
late scanning, the CVR improved in the infarct region, but the CVR in the remote region still remained lower than in controls.
Impaired Flow Response to Cold Pressor in Collateral-Dependent Myocardium. To investigate the response of collateralpendent
myocardium to reflex sympathetic stimulation (cold pressor stress), patients with stable angina and normal left
itricular function were studied, in whom one coronary artery was occluded (without previous MI), and the other arteries were
;iographically normal supplying collaterals. Regional MBF and glucose uptake (using 18F-deoxyglucose) was measured using
r at basal and at cold pressor. With cold pressor, no patients developed ECG changes. The cold pressor response (cold
ssor/basal MBF) was low in the collateralised region, compared to remote regions, due to vasoconstriction in the majority, but in
absence of demonstrable ischaemia.
In summary, there is coronary resistive vessel dysfunction after PTCA which recovers over 3 months due to acute impairment of
response to dipyridamole and a longer increase in basal flow, possibly due to the previous stenosis. This impairment is not due
iltered production or release of NO in the microcirculation. In stable disease, there is both an impaired CVR and altered
tabolism during pacing in regions subtended by a normal artery. This remote alteration is impaired acutely by myocardial
irction elsewhere, with only incomplete recovery over at least 6 months. In addition to reduced vasodilator function, resistive
sels in patients with atherosclerosis, have an increased tendency to vasoconstrict to a sympathetic stimulus. Thus, the
erosclerotic process and the sympathetic nervous system may both play a role in determining the degree of resistive vessel
function, which may cause or contribute to myocardial ischaemia in patients with coronary artery disease.