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 |
|
This article has been cited by other articles:

|
 |

|
 |
 
E. Raichlin, A. Prasad, W. K. Kremers, B. S. Edwards, C. S. Rihal, A. Lerman, and S. S. Kushwaha
Sirolimus as primary immunosuppression is associated with improved coronary vasomotor function compared with calcineurin inhibitors in stable cardiac transplant recipients
Eur. Heart J.,
June 1, 2009;
30(11):
1356 - 1363.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Zhong, Y. Bai, B. Yang, K. Ju, K. Shin, M. Lee, K.-M. Jan, and K. H. Chon
Autonomic nervous nonlinear interactions lead to frequency modulation between low- and high-frequency bands of the heart rate variability spectrum
Am J Physiol Regulatory Integrative Comp Physiol,
November 1, 2007;
293(5):
R1961 - R1968.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Naya, T. Tsukamoto, K. Morita, C. Katoh, T. Furumoto, S. Fujii, N. Tamaki, and H. Tsutsui
Olmesartan, But Not Amlodipine, Improves Endothelium-Dependent Coronary Dilation in Hypertensive Patients
J. Am. Coll. Cardiol.,
September 18, 2007;
50(12):
1144 - 1149.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Morita, T. Tsukamoto, M. Naya, K. Noriyasu, M. Inubushi, T. Shiga, C. Katoh, Y. Kuge, H. Tsutsui, and N. Tamaki
Smoking Cessation Normalizes Coronary Endothelial Vasomotor Response Assessed with 15O-Water and PET in Healthy Young Smokers
J. Nucl. Med.,
December 1, 2006;
47(12):
1914 - 1920.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. T. Siegrist, O. Gaemperli, P. Koepfli, T. Schepis, M. Namdar, I. Valenta, F. Aiello, S. Fleischmann, H. Alkadhi, and P. A. Kaufmann
Repeatability of Cold Pressor Test-Induced Flow Increase Assessed with H215O and PET
J. Nucl. Med.,
September 1, 2006;
47(9):
1420 - 1426.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. H. Schindler, J. Cardenas, J. O. Prior, A. D. Facta, M. C. Kreissl, X.-L. Zhang, J. Sayre, M. Dahlbom, J. Licinio, and H. R. Schelbert
Relationship Between Increasing Body Weight, Insulin Resistance, Inflammation, Adipocytokine Leptin, and Coronary Circulatory Function
J. Am. Coll. Cardiol.,
March 21, 2006;
47(6):
1188 - 1195.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. H. Schindler, E. U. Nitzsche, H. R. Schelbert, M. Olschewski, J. Sayre, M. Mix, I. Brink, X.-L. Zhang, M. Kreissl, N. Magosaki, et al.
Positron Emission Tomography-Measured Abnormal Responses of Myocardial Blood Flow to Sympathetic Stimulation Are Associated With the Risk of Developing Cardiovascular Events
J. Am. Coll. Cardiol.,
May 3, 2005;
45(9):
1505 - 1512.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. H. Schindler, E. U. Nitzsche, M. Olschewski, N. Magosaki, M. Mix, J. O. Prior, A. D. Facta, U. Solzbach, H. Just, and H. R. Schelbert
Chronic Inflammation and Impaired Coronary Vasoreactivity in Patients With Coronary Risk Factors
Circulation,
August 31, 2004;
110(9):
1069 - 1075.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. H. Endemann and E. L. Schiffrin
Endothelial Dysfunction
J. Am. Soc. Nephrol.,
August 1, 2004;
15(8):
1983 - 1992.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Duvernoy, J. Martin, K. Briesmiester, A. Bargardi, O. Muzik, and L. Mosca
Myocardial Blood Flow and Flow Reserve in Response to Hormone Therapy in Postmenopausal Women with Risk Factors for Coronary Disease
J. Clin. Endocrinol. Metab.,
June 1, 2004;
89(6):
2783 - 2788.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. H. Schindler, E. U. Nitzsche, M. Olschewski, I. Brink, M. Mix, J. Prior, A. Facta, M. Inubushi, H. Just, and H. R. Schelbert
PET-Measured Responses of MBF to Cold Pressor Testing Correlate with Indices of Coronary Vasomotion on Quantitative Coronary Angiography
J. Nucl. Med.,
March 1, 2004;
45(3):
419 - 428.
[Abstract]
[Full Text]
|
 |
|
|