Coronary vasoregulation in patients with various risk factors in response to cold pressor testing: contrasting myocardial blood flow responses to short- and long-term vitamin C administration.
OBJECTIVE
We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants.


BACKGROUND
There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors.


METHODS
Fifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily.


RESULTS
In hypertensive patients, the change in MBF (DeltaMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 +/- 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 +/- 0.27 and 0.63 +/- 0.17 vs. 0.14 +/- 0.18 ml/g/min; both p < or = 0.001). In smokers, DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 +/- 0.10, 0.54 +/- 0.13, 0.50 +/- 0.07 vs. -0.08 +/- 0.10 ml/g/min; all p < or = 0.001). In hypercholesterolemic patients, no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 +/- 0.14, 0.08 +/- 0.18, 0.02 +/- 0.19 vs. 0.08 +/- 0.16 ml/g/min; p = NS). The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p < or = 0.001).


CONCLUSIONS
The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion.
Schindler
Thomas H
TH
Division of Cardiology and Nuclear Medicine, Medical Clinic III, University Hospital of the Albert Ludwig University, Freiburg, Germany. tschindler@mednet.ucla.edu
Nitzsche
Egbert U
EU
Munzel
Thomas
T
Olschewski
Manfred
M
Brink
Ingo
I
Jeserich
Michael
M
Mix
Michael
M
Buser
Peter T
PT
Pfisterer
Matthias
M
Solzbach
Ulrich
U
Just
Hanjörg
H
D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000209:etiology / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000009:adverse effects / Q000378:metabolism; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D001205:Ascorbic Acid