JTCS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Drossos, G. E.
Right arrow Articles by Anagnostopoulos, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Drossos, G. E.
Right arrow Articles by Anagnostopoulos, C. E.
Related Collections
Right arrow Cardiac - pharmacology
Right arrow Cardiac - other
Right arrow Coronary disease

J Thorac Cardiovasc Surg 2003;125:330-335
© 2003 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease (ACD)

Is vitamin C superior to diltiazem for radial artery vasodilation in patients awaiting coronary artery bypass grafting?

George E. Drossos, MDa, Ioannis K. Toumpoulis, MDa, Demosthenes G. Katritsis, MDb, John P. A. Ioannidis, MDa,c, Persephone Kontogiorgi, MDa, Eugenia Svarna, MDa, Constantine E. Anagnostopoulos, MDa,b,d

From the Departments of Cardiothoracic Surgery, Cardiology, Radiology and Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greecea; the Department of Cardiology, Athens Euroclinic, Athens, Greeceb; the Division of Clinical Care Research, Department of Medicine, Tufts-New England Medical Center, Boston, Massc; and the Division of Cardiothoracic Surgery, St Luke's/Roosevelt Hospital Center at Columbia University, New York, NY.d

Received for publication Dec 12, 2001. Revisions requested May 16, 2002; revisions received May 28, 2002. Accepted for publication July 1, 2002. Address for reprints: Constantine E. Anagnostopoulos, MD, Department of Cardiothoracic Surgery, University of Ioannina School of Medicine, Ioannina 45110, Greece (E-mail: cea8{at}columbia.edu).


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 References
 
Objectives: We aimed to measure the vasodilating effects of vitamin C on the radial arteries of healthy subjects and to assess whether vitamin C is superior in this regard to diltiazem, a commonly used vasodilator in coronary artery bypass using radial conduits.
Methods: In a case-control study (study 1) oral single-dose vitamin C (2 g) was given to 15 healthy nonsmokers and 15 matched otherwise healthy smokers. In a randomized double-blind study (study 2) oral single-dose vitamin C (2 g, n = 15) and diltiazem (180 mg, n = 15) were compared in preoperative patients with coronary artery disease. We examined the dilation of the radial artery with high-resolution ultrasonography and measurement of the lumen surface and color Doppler images of the nondominant radial artery just before and 2 hours after drug administration.
Results: In study 1 both smokers and nonsmokers showed a significant increase in the lumen surface at 2 hours compared with at baseline (P < .001 and P = .013, respectively). The increase was larger in smokers (median, 37.5% vs 14.3%; P = .004). In study 2 both groups showed statistically significant increases in the lumen surface at 2 hours compared with at baseline (P < .001 and P = .008 for vitamin C and diltiazem, respectively). Vitamin C achieved a larger increase than diltiazem (median, 33.3% vs 18.2%; P = .016). In multivariate modeling the increase in lumen surface was independently predicted by use of vitamin C over diltiazem (+21.2%, P = .007), diabetes mellitus (+14.5%, P = .085), increased cholesterol (+26.2%, P = .001), and smoking history (+20.8%, P = .017).
Conclusions: Vitamin C is a potent acute vasodilator in both smokers and nonsmokers and is superior to diltiazem in preoperative coronary patients who need protection from vasospasm of the radial conduit.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 References
 
The radial artery is increasingly used as a conduit for coronary artery bypass grafting because of reports of long-term patency, accessibility, and encouraging midterm results.Go Go 1-3 Calcium-channel antagonists, in particular diltiazem, or other vasodilators are used to prevent perioperative spasm of the graft.Go Go 4-6 The choice of a potent vasodilator with minimal side effects appears to be an important parameter in ensuring the success of radial artery conduits.

Human coronary and peripheral arteries display abnormal endothelial function and loss of endothelium-dependent vasodilation in the presence of overt coronary artery disease or coronary risk factors.Go Go 7-9 Ascorbic acid, or vitamin C, the main water-soluble antioxidant in human plasmaGo 10 has been shown to reverse endothelial dysfunction in patients with ischemic heart disease.Go Go 11,12 It has also been shown to improve endothelial dysfunction in smokersGo Go 13-15 and patients with diabetes,Go 16 hypercholesterolemia,Go 17 and hypertension,Go 18 although not in a consistent manner.Go Go 19,20 It is not known whether, given these observations, vitamin C could be used instead of calcium-channel blockers as a vasodilator in coronary surgery patients receiving radial artery conduits.

Vitamin C was studied in 2 groups of healthy volunteers with and without a history of smoking. Subsequently, in a randomized double-blind study vitamin C was compared with diltiazem in patients with coronary artery disease, as measured by using Doppler imaging 2 hours after administration.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 References
 
Subjects
A total of 30 healthy subjects were enrolled in a case-control study evaluating the effects of vitamin C in smokers (n = 15) versus nonsmokers (n = 15, study 1). Exclusion criteria included known cardiovascular disease or the presence of any known coronary risk factors (other than smoking and family history). Subjects in the 2 groups were frequency matched for age. Subjects in both groups received vitamin C orally (2 g), and the effect on the radial artery was assessed 2 hours later by an evaluator who was blinded to the smoking status of the subject. The vitamin C dose was selected because it has been used in previous studiesGo 21 and is known to achieve 2.5-fold increases of plasma ascorbic acid in 2 hours.Go 12

A total of 30 preoperative subjects with coronary artery disease who had been admitted to the Department of Cardiothoracic Surgery of the University of Ioannina were enrolled in a randomized, double-blind, parallel-arm trial comparing single-dose oral vitamin C (2 g) with oral diltiazem (180 mg, study 2). The effect of each drug on the radial artery was similarly assessed 2 hours after drug administration by a blinded evaluator. The randomization was performed by using a computer-generated code, and allocation concealment was ensured.

For both studies, all subjects had to refrain from smoking for at least 3 hours before the study to minimize any relevant effect of acute smoking. In addition, all subjects were instructed to refrain from the intake of caffeine-containing beverages within 24 hours before administration of the drug. No patients were receiving any vitamins. The collected information on each subject included demographics, as well as data on potential cardiovascular risk factors for the subjects enrolled in the randomized trial. Both studies received approval, and all subjects were enrolled after providing informed consent according to the hospital's ethics committee. No patients withdrew after providing informed consent.

Radial artery measurements
High-resolution ultrasound measurements and color Doppler images were taken by using an ultrasound device (color Doppler Acuson 128 XP/10 with 7-MHz linear transducer), and records of the lumen surface of the radial artery (nondominant) before the drug administration were followed by using a measurement 2 hours later (Figure 1). All lumen surface areas (derived from the estimated lumen diameter) are expressed in square millimeters. The measurements were performed by 2 independent observers who were blinded as to the group to which the individual belonged. For each patient, optimal radial artery images were obtained between 2 and 5 cm above the radial styloid. This location was marked, and all subsequent images were obtained at the same location. In our study, the interobserver variability for the repeated measurements of resting radial artery diameter was 0.04 ± 0.02 mm. The intraobserver variability for the repeated measurements of resting radial artery diameter was 0.03 ± 0.02 mm.



View larger version (96K):
[in this window]
[in a new window]
  		Fig. 1. High-resolution ultrasound and color Doppler images in a preoperative patient with coronary artery disease before (right images, lumen surface of the radial artery, 10 mm2) and 2 hours after the oral administration of 2 g of vitamin C (left images, lumen surface of the radial artery, 14 mm2).

 
Statistical methods
Both the case-control and randomized studies were designed to have 80% power (ß = .20) to detect a difference of 20% between the compared groups at an {alpha} value of .05, assuming that the SD of the percentage changes in the artery lumen surface seen at 2 hours would be approximately 15%. With these assumptions, we estimated that 15 subjects per group would be needed.

Comparisons of groups were performed with the t test and nonparametric Mann-Whitney U test for continuous variables and the Fisher exact test for discrete variables, as appropriate. Pre-post comparisons with paired observations were analyzed by using the Wilcoxon test. Linear regression models were built with least-squares methods by using all variables and also with a backward elimination approach, starting with all variables that were significant (P < .05) in univariate relationships and eliminating variables with P values of greater than .05 in a stepwise fashion. Given the limited sample size, multivariate models should be viewed cautiously, but they are useful in further validating the unadjusted results. All analyses were conducted with SPSS 10.0 software (SPSS Inc, Chicago, Ill), and all P values are 2-tailed.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 References
 
Characteristics of subjects
Tables 1 and 2 summarize key characteristics of the subjects in the case-control study and of the patients in the randomized controlled trial. As shown, there were no significant differences between the compared groups for either of the 2 comparisons. High cholesterol, diabetes, and hypertension were relatively common among the preoperative patients with coronary artery disease who were enrolled in the randomized trial. Left ventricular ejection fractions were similar, and the use of ß-blockade was not different in the 2 groups.


View this table:
[in this window]
[in a new window]
  		Table 1. Summary of the key characteristics of the subjects in the case-control study
 

View this table:
[in this window]
[in a new window]
  		Table 2. Summary of the key characteristics of the patients in the randomized controlled study
 
Case-control study: Evaluation of vitamin C in smokers versus nonsmokers
Both smokers and nonsmokers showed a statistically significant increase in the radial artery lumen surface at 2 hours compared with at baseline (P < .001 and P = .013, respectively, Wilcoxon test). Nonsmokers showed a median increase of 14.3% (interquartile range [IQR], 0%-28.6%; mean, 16.0%), whereas the respective increase in smokers was 37.5% (IQR, 25.0%-57.1%; mean, 42.4%). The increase in the lumen surface was significantly larger in the group of smokers (Figure 2). After adjusting for age in a mutlivariate model, smokers still had a larger increase (+30.4%, P = .0016), whereas age had a marginal influence, with decreasing response in older subjects (-0.60% per year, P = .092).



View larger version (14K):
[in this window]
[in a new window]
  		Fig. 2. Baseline and 2-hour values of radial artery surface area in smokers and nonsmokers. Given a similar baseline value, smokers typically achieve larger vasodilatation at 2 hours (P = .005 by t test and P = .004, Mann-Whitney U test). Not shown is one outlier in the nonsmoker group. The regression lines are fit separately to each group (2-hour value = 2.9 + 0.86 x baseline value for the nonsmokers and 7.9 + 0.50 x baseline value for smokers).

 
Randomized study of vitamin C versus diltiazem
Both patients in the vitamin C group and patients in the diltiazem group showed statistically significant increases of the radial artery lumen surface at 2 hours compared with baseline values (P < .001 and P = .008, respectively, Wilcoxon test). Patients receiving vitamin C showed a median increase of 33.3% (IQR, 14.3%-45.5%; mean, 35.4%), whereas the respective median increase in the diltiazem group was only 18.2% (IQR, 0%-22.2%; mean, 16.9%). The difference was statistically significant (Figure 3).



View larger version (15K):
[in this window]
[in a new window]
  		Fig. 3. Baseline and 2-hour values of radial artery surface area in the diltiazem and vitamin C groups. Given a similar baseline value, patients receiving vitamin C typically achieve larger vasodilatation at 2 hours (P = .043 by t test and P = .016, Mann-Whitney U test). The regression lines are fit separately to each group (2-hour value = 1.0 + 1.25 x baseline value for the vitamin C group and 3.7 + 0.78 x baseline value for the diltiazem group).

 
In an adjusted analysis considering age, sex, systolic and diastolic pressure, the presence of diabetes mellitus, high cholesterol levels, and history of smoking, vitamin C still resulted in a statistically better response than diltiazem (+22.4%, P = .009). A backward elimination model starting from these variables showed that the percentage response was independently predicted by the use of vitamin C over diltiazem (+21.2%, P = .007), diabetes mellitus (+14.5%, P = .085), high cholesterol levels (+26.2%, P = .001), and a history of smoking (+20.8%, P = .017). Age, sex, and blood pressure were not retained as independent predictors in this multivariate model. There was no strong evidence of interaction effects between the retained independent predictors.

Safety
There were 2 patients with asymptomatic modest decreases in blood pressure and heart rate in the diltiazem group. No other side effects were observed.


   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
References
 
The vasodilator of choice in radial conduits is still a matter of controversy.Go Go 22-25 Neurohormonal activation during coronary revascularization stimulates the release of bioactive peptides and catecholamines, both of which might contribute to early radial artery vasospasm.Go 22 Endothelin and norepinephrine cause vascular smooth muscle contraction through the activation of calcium channels.Go 22 This engages the contractile apparatus, resulting in vasoconstriction.

Calcium-channel antagonists are selective vasodilators that inhibit the voltage-dependent calcium channel in human arteries;Go 23 they are less effective at inhibiting vascular contraction mediated by receptor mechanisms.Go 23

Diltiazem is a 1,5-benzothiazepine that binds to the a1c subunit of the L-type calcium channel, the main pore-forming unit of the channel.Go 25 Blockage of L-type calcium channels in vascular tissues results in relaxation of vascular smooth muscle and vasodilation.Go 25 L-Type blockade in the heart, however, results in negative inotropic and chronotropic effect that induces bradycardia, particularly when used in combination with ß-blockers,Go 23 a cornerstone in the management of ischemic heart failure. It is also notorious for the frequent need to modify its dosage or discontinue its administration because of hypotension perioperatively. Moreover, use of diltiazem does not completely eliminate spasm and has been reported to be less effective than other vasodilators, such as nitroglycerin.Go Go 24,25

Vitamin C (ascorbate), an antioxidant factor, improves defective endothelial function. This has been attributed to an enhancement of the synthesis or prevention of the breakdown of nitric oxide.Go 21 Vitamin C-induced decreases in low-density lipoprotein oxidation, scavenging of intracellular superoxide, release of nitric oxide from circulating or tissue S-nitrosothiols, direct reduction of nitride to nitric oxide, and activation of either endothelial nitric oxide synthetase or smooth muscle guanylate cyclase might all be implicated in the ability of ascorbate to preserve nitric oxide.Go Go Go 21,26,27

Smoking has a direct toxic effect on human endothelial cells.Go 14 The gas phase of cigarette smoke contains free radicals and pro-oxidants, and the particulate phase contains high concentrations of lipophilic quinones, which can form the highly reactive OH radical.Go 14 In addition, superoxide anion, which directly originates from smoke, results in the formation of peroxynitrite anion (ONOO-), which reduces the vasoactivate level of nitric oxide.Go 14 In our case-control study vitamin C was able to achieve substantial vasodilation of the radial artery among healthy young adults, and the effect was more prominent among smokers. This suggests that vitamin C might be even more useful among smokers, in whom the underlying vasoconstrictive effects might be more prominent, and the mechanism of action of vitamin C might share a common pathway counterbalancing the biologic effects of chronic smoking. Interestingly, smokers are known to have lower plasmaGo 28 and tissueGo 15 vitamin C levels than nonsmokers.

Vitamin C has a potent acute vasodilating effect on the radial artery, and the effect is more prominent among smokers. On the basis of this (first to our knowledge) double-blind randomized comparison, we demonstrated that a single oral dose of vitamin C achieves better vasodilation of the radial artery than diltiazem in preoperative coronary patients. In the multivariate analysis of the data from the randomized trial, vitamin C was superior to diltiazem in achieving radial artery vasodilation, even when all the other key risk factors that seem to affect endothelial dysfunction (including smoking, hypertension, diabetes, and hypercholesterolemia) were taken into account.

Study limitations
The beneficial effects of vitamin C might not necessarily translate into efficacy during the perioperative manipulations after an acute surgical, metabolic, and pharmacologic assault. Furthermore, in healthy young smokers vitamin C has been shown not to have sustainable, long-term effects on endothelial function, despite sustained increase of plasma ascorbate levels,Go 20 and although vitamin C improves endothelial dysfunction, there is no proved relationship between baseline ascorbic acid concentration and baseline endothelial function.Go 12 Our results, however, suggest a potential role for this substance in the management of patients receiving radial artery grafts. This role would have to be further delineated against other available vasodilation options in this setting. For example, in addition to calcium-channel blockers, nitroglycerin has also shown significant efficacy for preventing coronary bypass conduit spasm,Go Go 24,25 and a combination of calcium-channel blockers with nitroglycerinGo 29 might be even more potent. However, recent evidence of unchanged coronary vascular resistance during postoperative nitroglycerin administration casts doubt on such use.Go 30 Future studies should compare vitamin C against such combinations.

Conclusion
The results of the present study provide evidence that vitamin C is a potent vasodilator in healthy subjects, particularly smokers. In addition, it is a superior acute vasodilating agent in vivo compared with diltiazem in ischemic patients awaiting cardiac surgery. This pilot study should justify a perioperative trial to evaluate the vasodilating effect of vitamin C on radial artery conduits during coronary revascularization.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

  1. Parolari A, Rubini P, Alamanni F, Cannata A, Xin W, Gherli T, et al. The radial artery: Which place in coronary operation? Ann Thorac Surg. 2000;69:1288-94.[Abstract/Free Full Text]
  2. Tatoulis J, Buxton BF, Fuller JA. Bilateral radial artery grafts in coronary reconstruction: technique and early results in 261 patients. Ann Thorac Surg. 1998;66:714-9.[Abstract/Free Full Text]
  3. Weinschelbaum EE, Macchia A, Caramutti VM, Machain HA, Raffaelli HA, Favaloro MR, et al. Myocardial revascularization with radial and mammary arteries: initial and mid-term results. Ann Thorac Surg. 2000;70:1378-83.[Abstract/Free Full Text]
  4. Acar C, Jebara VA, Portoghese M, Beyssen B, Pagny JY, Grare P, et al. Revival of the radial artery for coronary artery bypass grafting. Ann Thorac Surg. 1992;54:652-9.[Abstract/Free Full Text]
  5. Brodman RF, Frame R, Camacho M, Hu E, Chen A, Hollinger I. Routine use of unilateral and bilateral radial arteries for coronary artery bypass graft surgery. J Am Coll Cardiol. 1996;28:959-63.[Medline]
  6. Chen AH, Nakao T, Brodman RF, Greenberg M, Charney R, Menegus M, et al. Early postoperative angiographic assessment of radial grafts used for coronary artery bypass grafting. J Thorac Cardiovasc Surg. 1996;111:1208-12.[Abstract/Free Full Text]
  7. Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24:1468-74.[Medline]
  8. Cox DA, Vita JA, Treasure CB, Fish RD, Alexander RW, Ganz P, et al. Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation. 1989;80:458-65.[Abstract/Free Full Text]
  9. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987;84:9265-9.[Abstract/Free Full Text]
  10. Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A. 1989;86:6377-81.[Abstract/Free Full Text]
  11. Hamabe A, Takase B, Uehata A, Kurita A, Ohsuzu F, Tamai S. Impaired endothelium-dependent vasodilation in the brachial artery in variant angina pectoris and the effect of intravenous administration of vitamin C. Am J Cardiol. 2001;87:1154-9.[Medline]
  12. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JF Jr, Vita JA. Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation. 1996;93:1107-13.[Abstract/Free Full Text]
  13. Heitzer T, Just H, Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation. 1996;94:6-9.[Abstract/Free Full Text]
  14. Kaufmann PA, Gnecchi-Ruscone T, di Terlizzi M, Schafers KP, Luscher TF, Camici PG. Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function. Circulation. 2000;102:1233-8.[Abstract/Free Full Text]
  15. Mezzetti A, Lapenna D, Pierdomenico SD, Calafiore AM, Costantini F, Riario-Sforza G, et al. Vitamins E, C and lipid peroxidation in plasma and arterial tissue of smokers and non-smokers. Atherosclerosis. 1995;112:91-9.[Medline]
  16. Beckman JA, Goldfine AB, Gordon MB, Creager MA. Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation. 2001;103:1618-23.[Abstract/Free Full Text]
  17. Ting HH, Timimi FK, Haley EA, Roddy MA, Ganz P, Creager MA. Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation. 1997;95:2617-22.[Abstract/Free Full Text]
  18. Solzbach U, Hornig B, Jeserich M, Just H. Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation. 1997;96:1513-9.[Abstract/Free Full Text]
  19. Duffy SJ, Gokce N, Holbrook M, Hunter LM, Biegelsen ES, Huang A, et al. Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension. Am J Physiol Heart Circ Physiol. 2001;280:H528-34.[Abstract/Free Full Text]
  20. Raitakari OT, Adams MR, McCredie RJ, Griffiths KA, Stocker R, Celermajer DS. Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect. J Am Coll Cardiol. 2000;35:1616-21.[Medline]
  21. Gokce N, Keaney JF Jr, Frei B, Holbrook M, Olesiak M, Zachariah BJ, et al. Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation. 1999;99:3234-40.[Abstract/Free Full Text]
  22. Bond BR, Zellner JL, Dorman BH, Multani MM, Kratz JM, Crumbley AJ III, et al. Differential effects of calcium channel antagonists in the amelioration of radial artery vasospasm. Ann Thorac Surg. 2000;69:1035-40.[Abstract/Free Full Text]
  23. He GW, Yang CQ. Comparative study on calcium channel antagonists in the human radial artery: clinical implications. J Thorac Cardiovasc Surg. 2000;119:94-100.[Abstract/Free Full Text]
  24. Shapira OM, Xu A, Vita JA, Aldea GS, Shah N, Shemin RJ, et al. Nitroglycerin is superior to diltiazem as a coronary bypass conduit vasodilator. J Thorac Cardiovasc Surg. 1999;117:906-11.[Abstract/Free Full Text]
  25. Shapira OM, Alkon JD, Macron DS, Keaney JF Jr, Vita JA, Aldea GS, et al. Nitroglycerin is preferable to diltiazem for prevention of coronary bypass conduit spasm. Ann Thorac Surg. 2000;70:883-8.[Abstract/Free Full Text]
  26. May JM. How does ascorbic acid prevent endothelial dysfunction? Free Radic Biol Med. 2000;28:1421-9.[Medline]
  27. Vita JA, Frei B, Holbrook M, Gokce N, Leaf C, Keaney JF Jr. L-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease. J Clin Invest. 1998;101:1408-14.[Medline]
  28. Schectman G, Byrd JC, Gruchow HW. The influence of smoking on vitamin C status in adults. Am J Public Health. 1989;79:158-62.[Medline]
  29. Chanda J, Brichkov I, Canver CC. Prevention of radial artery graft vasospasm after coronary bypass. Ann Thorac Surg. 2000;70:2070-4.[Abstract/Free Full Text]
  30. Walpoth BH, Springe D, Kipfer B, Berdat P, Neidhart P, Robe J, et al. Adverse effect of nitroglycerin on coronary artery bypass flow early after mycardial revascularisation. In: American Association for Thoracic Surgery, 82nd Annual Meeting, Program book, May 7th, 2002. Abstract 40.



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
C. J. Kelsall, A. H. Chester, M. Amrani, and D. R.J. Singer
C-Type Natriuretic Peptide Relaxes Human Coronary Artery Bypass Grafts Preconstricted by Endothelin-1
Ann. Thorac. Surg., October 1, 2005; 80(4): 1347 - 1351.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
A. Madhavan and J. Goodfellow
Lack of evidence for vitamin C as acute vasodilator
J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1671 - 1672.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Drossos, G. E.
Right arrow Articles by Anagnostopoulos, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Drossos, G. E.
Right arrow Articles by Anagnostopoulos, C. E.
Related Collections
Right arrow Cardiac - pharmacology
Right arrow Cardiac - other
Right arrow Coronary disease

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS