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CLINICAL STUDY

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

Thomas H. Schindler, MD^*,*, Egbert U. Nitzsche, MD^*, Thomas Munzel, MD, Manfred Olschewski, MSc, Ingo Brink, MD^*, Michael Jeserich, MD^*, Michael Mix, MSc^*, Peter T. Buser, MD, FACC, FESC, Matthias Pfisterer, MD, FACC, FESC, Ulrich Solzbach, MD^* and Hanjörg Just, MD, FRCP, FESC, FAHA^*

^* Division of Cardiology and Nuclear Medicine, Medical Clinic III, University Hospital of the Albert Ludwig University, Freiburg, Germany
Division of Cardiology and Nuclear Medicine, University Hospital, Basel, Switzerland
Division of Cardiology, Medical Clinic III, University Hospital Eppendorf Hamburg, Hamburg, Germany
Institute for Medical Statistics and Biometry, Albert Ludwigs University, Freiburg, Germany

Manuscript received November 23, 2002; revised manuscript received May 8, 2003, accepted May 13, 2003.

^* Reprint requests and correspondence: Dr. Thomas H. Schindler, Department of Molecular and Medical Pharmacology, Radiological Science, UCLA School of Medicine, B2-045 CHS, Box 956948, Los Angeles, California 90095-6948, USA.
tschindler{at}mednet.ucla.edu

OBJECTIVES: 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 (MBF) 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 0.001). In smokers, MBF 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 0.001). In hypercholesterolemic patients, no improvement in MBF 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 MBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p 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.

Abbreviations and Acronyms   ANOVA = analysis of variance   CPT = cold pressor test(ing)   CVR = coronary vascular resistance   eNOS = endothelial nitric oxide synthase   LAD = left anterior descending coronary artery   LCx = left circumflex artery   LDL = low-density lipoprotein   HDL = high-density lipoprotein   MBF = myocardial blood flow   NO = nitric oxide   PET = positron emission tomography   ROS = reactive oxygen species   RPP = rate-pressure product

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