Skip to main content
Top
Published in: Cardiovascular Ultrasound 1/2012

Open Access 01-12-2012 | Research

Brachial Artery Flow-mediated Dilation Following Exercise with Augmented Oscillatory and Retrograde Shear Rate

Authors: Blair D Johnson, Kieren J Mather, Sean C Newcomer, Timothy D Mickleborough, Janet P Wallace

Published in: Cardiovascular Ultrasound | Issue 1/2012

Login to get access

Abstract

Background

Acute doses of elevated retrograde shear rate (SR) appear to be detrimental to endothelial function in resting humans. However, retrograde shear increases during moderate intensity exercise which also enhances post-exercise endothelial function. Since SR patterns differ with the modality of exercise, it is important to determine if augmented retrograde SR during exercise influences post-exercise endothelial function. This study tested the hypothesis that (1) increased doses of retrograde SR in the brachial artery during lower body supine cycle ergometer exercise would attenuate post-exercise flow-mediated dilation (FMD) in a dose-dependent manner, and (2) antioxidant vitamin C supplementation would prevent the attenuated post-exercise FMD response.

Methods

Twelve men participated in four randomized exercise sessions (90 W for 20 minutes) on separate days. During three of the sessions, one arm was subjected to increased oscillatory and retrograde SR using three different forearm cuff pressures (20, 40, 60 mmHg) (contralateral arm served as the control) and subjects ingested placebo capsules prior to exercise. A fourth session with 60 mmHg cuff pressure was performed with 1 g of vitamin C ingested prior to the session.

Results

Post-exercise FMD following the placebo conditions were lower in the cuffed arm versus the control arm (arm main effect: P < 0.05) and without differences between cuff pressures (20 mmHg: 5.7 ± 2.2%; 40 mmHg: 4.7 ± 1.3%; 60 mmHg: 5.4 ± 2.4%) (P > 0.05). Following vitamin C treatment, post-exercise FMD in the cuffed and control arm increased from baseline (P < 0.05) but were not different (control: 7.1 ± 3.5% vs. cuffed: 6.6 ± 3.3%) (P > 0.05).

Conclusions

These results indicate that augmented oscillatory and retrograde SR in non-working limbs during lower body exercise attenuates post-exercise FMD without an evident dose–response in the range of cuff pressures evaluated. Vitamin C supplementation prevented the attenuation of FMD following exercise with augmented oscillatory and retrograde SR suggesting that oxidative stress contributes to the adverse effects of oscillatory and retrograde shear during exercise on FMD.
Appendix
Available only for authorised users
Literature
1.
go back to reference Mora S, Cook N, Buring JE, Ridker PM, Lee I-M: Physical Activity and Reduced Risk of Cardiovascular Events: Potential Mediating Mechanisms. Circulation. 2007, 116 (19): 2110-2118.CrossRefPubMedPubMedCentral Mora S, Cook N, Buring JE, Ridker PM, Lee I-M: Physical Activity and Reduced Risk of Cardiovascular Events: Potential Mediating Mechanisms. Circulation. 2007, 116 (19): 2110-2118.CrossRefPubMedPubMedCentral
2.
go back to reference Green DJ: Exercise Training as Vascular Medicine: Direct Impacts on the Vasculature in Humans. Exerc Sport Sci Rev. 2009, 37 (4): 196-202.PubMed Green DJ: Exercise Training as Vascular Medicine: Direct Impacts on the Vasculature in Humans. Exerc Sport Sci Rev. 2009, 37 (4): 196-202.PubMed
3.
go back to reference Rush JWE, Turk JR, Laughlin MH: Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. Am J Physiol Heart Circ Physiol. 2003, 284 (4): H1378-H1387.CrossRefPubMed Rush JWE, Turk JR, Laughlin MH: Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. Am J Physiol Heart Circ Physiol. 2003, 284 (4): H1378-H1387.CrossRefPubMed
4.
go back to reference Laughlin MH, Newcomer SC, Bender SB: Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. J Appl Physiol. 2008, 104 (3): 588-600.CrossRefPubMed Laughlin MH, Newcomer SC, Bender SB: Importance of hemodynamic forces as signals for exercise-induced changes in endothelial cell phenotype. J Appl Physiol. 2008, 104 (3): 588-600.CrossRefPubMed
5.
go back to reference Hambrecht R, Adams V, Erbs S, Linke A, Krankel N, Shu Y, Baither Y, Gielen S, Thiele H, Gummert J: Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation. 2003, 107 (25): 3152-3158.CrossRefPubMed Hambrecht R, Adams V, Erbs S, Linke A, Krankel N, Shu Y, Baither Y, Gielen S, Thiele H, Gummert J: Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation. 2003, 107 (25): 3152-3158.CrossRefPubMed
6.
go back to reference Adams V, Linke A, Krankel N, Erbs S, Gielen S, Mobius-Winkler S, Gummert J, Mohr F, Schuler G, Hambrecht R: Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation. 2005, 111 (5): 555.CrossRefPubMed Adams V, Linke A, Krankel N, Erbs S, Gielen S, Mobius-Winkler S, Gummert J, Mohr F, Schuler G, Hambrecht R: Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation. 2005, 111 (5): 555.CrossRefPubMed
7.
go back to reference Tinken TM, Thijssen DHJ, Hopkins N, Dawson EA, Cable NT, Green DJ: Shear Stress Mediates Endothelial Adaptations to Exercise Training in Humans. Hypertension. 2010, 55 (2): 312-318.CrossRefPubMed Tinken TM, Thijssen DHJ, Hopkins N, Dawson EA, Cable NT, Green DJ: Shear Stress Mediates Endothelial Adaptations to Exercise Training in Humans. Hypertension. 2010, 55 (2): 312-318.CrossRefPubMed
8.
go back to reference Chappell DC, Varner SE, Nerem RM, Medford RM, Alexander RW: Oscillatory Shear Stress Stimulates Adhesion Molecule Expression in Cultured Human Endothelium. Circ Res. 1998, 82 (5): 532-539.CrossRefPubMed Chappell DC, Varner SE, Nerem RM, Medford RM, Alexander RW: Oscillatory Shear Stress Stimulates Adhesion Molecule Expression in Cultured Human Endothelium. Circ Res. 1998, 82 (5): 532-539.CrossRefPubMed
9.
go back to reference Hsiai TK, Cho SK, Wong PAKK, Ing M, Salazar A, Sevanian A, Navab M, Demer LL, Ho CM: Monocyte recruitment to endothelial cells in response to oscillatory shear stress. FASEB J. 2003, 17 (12): 1648.CrossRefPubMedPubMedCentral Hsiai TK, Cho SK, Wong PAKK, Ing M, Salazar A, Sevanian A, Navab M, Demer LL, Ho CM: Monocyte recruitment to endothelial cells in response to oscillatory shear stress. FASEB J. 2003, 17 (12): 1648.CrossRefPubMedPubMedCentral
10.
go back to reference Ziegler T, Bouzourene K, Harrison VJ, Brunner HR, Hayoz D: Influence of Oscillatory and Unidirectional Flow Environments on the Expression of Endothelin and Nitric Oxide Synthase in Cultured Endothelial Cells. Arterioscler Thromb Vasc Biol. 1998, 18 (5): 686-692.CrossRefPubMed Ziegler T, Bouzourene K, Harrison VJ, Brunner HR, Hayoz D: Influence of Oscillatory and Unidirectional Flow Environments on the Expression of Endothelin and Nitric Oxide Synthase in Cultured Endothelial Cells. Arterioscler Thromb Vasc Biol. 1998, 18 (5): 686-692.CrossRefPubMed
11.
go back to reference Hwang J, Ing MH, Salazar A, Lassegue B, Griendling K, Navab M, Sevanian A, Hsiai TK: Pulsatile Versus Oscillatory Shear Stress Regulates NADPH Oxidase Subunit Expression: Implication for Native LDL Oxidation. Circ Res. 2003, 93 (12): 1225-1232.CrossRefPubMedPubMedCentral Hwang J, Ing MH, Salazar A, Lassegue B, Griendling K, Navab M, Sevanian A, Hsiai TK: Pulsatile Versus Oscillatory Shear Stress Regulates NADPH Oxidase Subunit Expression: Implication for Native LDL Oxidation. Circ Res. 2003, 93 (12): 1225-1232.CrossRefPubMedPubMedCentral
12.
go back to reference De Keulenaer GW, Chappell DC, Ishizaka N, Nerem RM, Alexander RW, Griendling KK: Oscillatory and Steady Laminar Shear Stress Differentially Affect Human Endothelial Redox State: Role of a Superoxide-Producing NADH Oxidase. Circ Res. 1998, 82 (10): 1094-1101.CrossRefPubMed De Keulenaer GW, Chappell DC, Ishizaka N, Nerem RM, Alexander RW, Griendling KK: Oscillatory and Steady Laminar Shear Stress Differentially Affect Human Endothelial Redox State: Role of a Superoxide-Producing NADH Oxidase. Circ Res. 1998, 82 (10): 1094-1101.CrossRefPubMed
13.
go back to reference Takabe W, Jen N, Ai L, Hamilton R, Wang S, Holmes K, Darbandi F, Khalsa B, Bressler S, Barr M: Oscillatory Shear Stress Induces Mitochondrial Superoxide Production: Implication of NADPH Oxidase and c-Jun NH 2-terminal Kinase Signaling. Antioxid Redox Signal. 2011, 15 (5): 1379-1388.CrossRefPubMedPubMedCentral Takabe W, Jen N, Ai L, Hamilton R, Wang S, Holmes K, Darbandi F, Khalsa B, Bressler S, Barr M: Oscillatory Shear Stress Induces Mitochondrial Superoxide Production: Implication of NADPH Oxidase and c-Jun NH 2-terminal Kinase Signaling. Antioxid Redox Signal. 2011, 15 (5): 1379-1388.CrossRefPubMedPubMedCentral
14.
go back to reference Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, Tarpey M, Fukai T, Harrison DG: Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation. 2001, 103 (9): 1282.CrossRefPubMed Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, Tarpey M, Fukai T, Harrison DG: Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation. 2001, 103 (9): 1282.CrossRefPubMed
15.
go back to reference Förstermann U: Nitric oxide and oxidative stress in vascular disease. Pflügers Archiv Eur J Physiol. 2010, 459 (6): 923-939.CrossRef Förstermann U: Nitric oxide and oxidative stress in vascular disease. Pflügers Archiv Eur J Physiol. 2010, 459 (6): 923-939.CrossRef
16.
go back to reference May JM, Qu Z-c, Li X: Ascorbic acid blunts oxidant stress due to menadione in endothelial cells. Arch Biochem Biophys. 2003, 411 (1): 136-144.CrossRefPubMed May JM, Qu Z-c, Li X: Ascorbic acid blunts oxidant stress due to menadione in endothelial cells. Arch Biochem Biophys. 2003, 411 (1): 136-144.CrossRefPubMed
17.
go back to reference Smith AR, Visioli F, Hagen TM: Vitamin C matters: increased oxidative stress in cultured human aortic endothelial cells without supplemental ascorbic acid. The FASEB Journal. 2002. Smith AR, Visioli F, Hagen TM: Vitamin C matters: increased oxidative stress in cultured human aortic endothelial cells without supplemental ascorbic acid. The FASEB Journal. 2002.
18.
go back to reference Thijssen DHJ, Dawson EA, Tinken TM, Cable NT, Green DJ: Retrograde Flow and Shear Rate Acutely Impair Endothelial Function in Humans. Hypertension. 2009, 53 (6): 986-992.CrossRefPubMed Thijssen DHJ, Dawson EA, Tinken TM, Cable NT, Green DJ: Retrograde Flow and Shear Rate Acutely Impair Endothelial Function in Humans. Hypertension. 2009, 53 (6): 986-992.CrossRefPubMed
19.
go back to reference Thijssen DHJ, Dawson EA, Black MA, Hopman MTE, Cable NT, Green DJ: Brachial Artery Blood Flow Responses to Different Modalities of Lower Limb Exercise. Med Sci Sports Exer. 2009, 41 (5): 1072-1079.CrossRef Thijssen DHJ, Dawson EA, Black MA, Hopman MTE, Cable NT, Green DJ: Brachial Artery Blood Flow Responses to Different Modalities of Lower Limb Exercise. Med Sci Sports Exer. 2009, 41 (5): 1072-1079.CrossRef
20.
go back to reference Green D, Cheetham C, Reed C, Dembo L, O'Driscoll G: Assessment of brachial artery blood flow across the cardiac cycle: retrograde flows during cycle ergometry. J Appl Physiol. 2002, 93 (1): 361-368.CrossRefPubMed Green D, Cheetham C, Reed C, Dembo L, O'Driscoll G: Assessment of brachial artery blood flow across the cardiac cycle: retrograde flows during cycle ergometry. J Appl Physiol. 2002, 93 (1): 361-368.CrossRefPubMed
21.
go back to reference Simmons GH, Padilla J, Young CN, Wong BJ, Lang JA, Davis MJ, Laughlin MH, Fadel PJ: Increased brachial artery retrograde shear rate at exercise onset is abolished during prolonged cycling: role of thermoregulatory vasodilation. J Appl Physiol. 2011, 110 (2): 389.CrossRefPubMed Simmons GH, Padilla J, Young CN, Wong BJ, Lang JA, Davis MJ, Laughlin MH, Fadel PJ: Increased brachial artery retrograde shear rate at exercise onset is abolished during prolonged cycling: role of thermoregulatory vasodilation. J Appl Physiol. 2011, 110 (2): 389.CrossRefPubMed
22.
go back to reference Tanaka H, Shimizu S, Ohmori F, Muraoka Y, Kumagai M, Yoshizawa M, Kagaya A: Increases in blood flow and shear stress to nonworking limbs during incremental exercise. Med Sci Sports Exerc. 2006, 38: 81-85.CrossRefPubMed Tanaka H, Shimizu S, Ohmori F, Muraoka Y, Kumagai M, Yoshizawa M, Kagaya A: Increases in blood flow and shear stress to nonworking limbs during incremental exercise. Med Sci Sports Exerc. 2006, 38: 81-85.CrossRefPubMed
23.
go back to reference Tinken TM, Thijssen DHJ, Hopkins N, Black MA, Dawson EA, Minson CT, Newcomer SC, Laughlin MH, Cable NT, Green DJ: Impact of Shear Rate Modulation on Vascular Function in Humans. Hypertension. 2009, 54 (2): 278-285.CrossRefPubMedPubMedCentral Tinken TM, Thijssen DHJ, Hopkins N, Black MA, Dawson EA, Minson CT, Newcomer SC, Laughlin MH, Cable NT, Green DJ: Impact of Shear Rate Modulation on Vascular Function in Humans. Hypertension. 2009, 54 (2): 278-285.CrossRefPubMedPubMedCentral
24.
go back to reference Johnson BD, Padilla J, Wallace JP: The exercise dose affects oxidative stress and brachial artery flow-mediated dilation in trained men. Eur J Appl Physiol. 2012, 112 (1): 33-42.CrossRefPubMed Johnson BD, Padilla J, Wallace JP: The exercise dose affects oxidative stress and brachial artery flow-mediated dilation in trained men. Eur J Appl Physiol. 2012, 112 (1): 33-42.CrossRefPubMed
25.
go back to reference American College of Sports Medicine: ACSM's Guidelines for Exercise Testing and Prescription. Lippencott, Williams & Wilkins, Philadelphia, Seventh, 2006. American College of Sports Medicine: ACSM's Guidelines for Exercise Testing and Prescription. Lippencott, Williams & Wilkins, Philadelphia, Seventh, 2006.
26.
go back to reference Thijssen DHJ, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker BA, Widlansky ME, Tschakovsky ME, Green DJ: Assessment of flow mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011, 300 (1): H2-H12.CrossRefPubMed Thijssen DHJ, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, Parker BA, Widlansky ME, Tschakovsky ME, Green DJ: Assessment of flow mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011, 300 (1): H2-H12.CrossRefPubMed
27.
go back to reference Potter K, Reed C, Green D, Hankey G, Arnolda L: Ultrasound settings significantly alter arterial lumen and wall thickness measurements. Cardiovasc Ultrasound. 2008, 6 (1): 6.CrossRefPubMedPubMedCentral Potter K, Reed C, Green D, Hankey G, Arnolda L: Ultrasound settings significantly alter arterial lumen and wall thickness measurements. Cardiovasc Ultrasound. 2008, 6 (1): 6.CrossRefPubMedPubMedCentral
28.
go back to reference Newcomer SC, Sauder CL, Kuipers NT, Laughlin MH, Ray CA: Effects of posture on shear rates in human brachial and superficial femoral arteries. Am J Physiol Heart Circ Physiol. 2008, 294 (4): H1833-H1839.CrossRefPubMedPubMedCentral Newcomer SC, Sauder CL, Kuipers NT, Laughlin MH, Ray CA: Effects of posture on shear rates in human brachial and superficial femoral arteries. Am J Physiol Heart Circ Physiol. 2008, 294 (4): H1833-H1839.CrossRefPubMedPubMedCentral
29.
go back to reference Pyke KE, Tschakovsky ME: Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation?. J Appl Physiol. 2007, 102: 1510-1519.CrossRefPubMed Pyke KE, Tschakovsky ME: Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation?. J Appl Physiol. 2007, 102: 1510-1519.CrossRefPubMed
30.
go back to reference Kizhakekuttu TJ, Gutterman DD, Phillips SA, Jurva JW, Arthur EIL, Das E, Widlansky ME: Measuring FMD in the brachial artery: how important is QRS gating?. J Appl Physiol. 2010, 109 (4): 959-965.CrossRefPubMedPubMedCentral Kizhakekuttu TJ, Gutterman DD, Phillips SA, Jurva JW, Arthur EIL, Das E, Widlansky ME: Measuring FMD in the brachial artery: how important is QRS gating?. J Appl Physiol. 2010, 109 (4): 959-965.CrossRefPubMedPubMedCentral
31.
go back to reference McNally JS, Davis ME, Giddens DP, Saha A, Hwang J, Dikalov S, Jo H, Harrison DG: Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. Am J Physiol Heart Circ Physiol. 2003, 285 (6): H2290-H2297.CrossRefPubMed McNally JS, Davis ME, Giddens DP, Saha A, Hwang J, Dikalov S, Jo H, Harrison DG: Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress. Am J Physiol Heart Circ Physiol. 2003, 285 (6): H2290-H2297.CrossRefPubMed
32.
go back to reference Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, Mitch WE, Harrison DG: Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest. 2003, 111 (8): 1201-1209.CrossRefPubMedPubMedCentral Landmesser U, Dikalov S, Price SR, McCann L, Fukai T, Holland SM, Mitch WE, Harrison DG: Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension. J Clin Invest. 2003, 111 (8): 1201-1209.CrossRefPubMedPubMedCentral
33.
go back to reference Förstermann U: Endothelial NO synthase as a source of NO and superoxide. Eur J Clin Pharmacol. 2006, 62: 5-12.CrossRef Förstermann U: Endothelial NO synthase as a source of NO and superoxide. Eur J Clin Pharmacol. 2006, 62: 5-12.CrossRef
34.
go back to reference Kuzkaya N, Weissmann N, Harrison DG, Dikalov S: Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols. J Biol Chem. 2003, 278 (25): 22546.CrossRefPubMed Kuzkaya N, Weissmann N, Harrison DG, Dikalov S: Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols. J Biol Chem. 2003, 278 (25): 22546.CrossRefPubMed
35.
go back to reference Higashi Y, Sasaki S, Nakagawa K, Fukuda Y, Matsuura H, Oshima T, Chayama K: Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals. Am J Hypertens. 2002, 15 (4): 326-332.CrossRefPubMed Higashi Y, Sasaki S, Nakagawa K, Fukuda Y, Matsuura H, Oshima T, Chayama K: Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals. Am J Hypertens. 2002, 15 (4): 326-332.CrossRefPubMed
36.
go back to reference Padilla J, Harris RA, Wallace JP: Can the measurement of brachial artery flow-mediated dilation be applied to the acute exercise model?. Cardiovasc Ultrasound. 2007, 5: 45-52.CrossRefPubMedPubMedCentral Padilla J, Harris RA, Wallace JP: Can the measurement of brachial artery flow-mediated dilation be applied to the acute exercise model?. Cardiovasc Ultrasound. 2007, 5: 45-52.CrossRefPubMedPubMedCentral
37.
go back to reference Anderson RA, Evans LM, Ellis GR, Kahn N, Morris K, Jackson SK, Rees A, Lewis MJ, Frenneaux MP: Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in type 2 diabetes. Diabet Med. 2006, 23: 258-264.CrossRefPubMed Anderson RA, Evans LM, Ellis GR, Kahn N, Morris K, Jackson SK, Rees A, Lewis MJ, Frenneaux MP: Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in type 2 diabetes. Diabet Med. 2006, 23: 258-264.CrossRefPubMed
38.
go back to reference Valkonen M, Kuusi T: Vitamin C prevents the acute atherogenic effects of passive smoking. Free Radic Biol Med. 2000, 28 (3): 428-436.CrossRefPubMed Valkonen M, Kuusi T: Vitamin C prevents the acute atherogenic effects of passive smoking. Free Radic Biol Med. 2000, 28 (3): 428-436.CrossRefPubMed
39.
go back to reference Silvestro A, Scopacasa F, Oliva G, de Cristofaro T, Iuliano L, Brevetti G: Vitamin C prevents endothelial dysfunction induced by acute exercise in patients with intermittent claudication. Atherosclerosis. 2002, 165 (2): 277-283.CrossRefPubMed Silvestro A, Scopacasa F, Oliva G, de Cristofaro T, Iuliano L, Brevetti G: Vitamin C prevents endothelial dysfunction induced by acute exercise in patients with intermittent claudication. Atherosclerosis. 2002, 165 (2): 277-283.CrossRefPubMed
Metadata
Title
Brachial Artery Flow-mediated Dilation Following Exercise with Augmented Oscillatory and Retrograde Shear Rate
Authors
Blair D Johnson
Kieren J Mather
Sean C Newcomer
Timothy D Mickleborough
Janet P Wallace
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cardiovascular Ultrasound / Issue 1/2012
Electronic ISSN: 1476-7120
DOI
https://doi.org/10.1186/1476-7120-10-34

Other articles of this Issue 1/2012

Cardiovascular Ultrasound 1/2012 Go to the issue