Skip Navigation

European Heart Journal 2000 21(1):39-44; doi:10.1053/euhj.1999.1695
Copyright © 2000 by the European Society of Cardiology.
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Leyva, F
Right arrow Articles by Stevenson, J.C
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leyva, F
Right arrow Articles by Stevenson, J.C
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Non-invasive assessment of vascular function. Paradoxical vascular response to intravenous glucose in coronary heart disease

F Leyvaa,b,f1, M Rauchhausa, S.D Ankera, A.J Proudlerb, I.F Godslandb, P Stiefelc, A.J.S Coatsa, P.A Poole-Wilsona and J.C Stevensonb

a Department of Cardiac Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, U.K.
b Rosen Laboratories of the Wynn Institute, Endocrinology and Metabolism, Imperial College School of Medicine, St Mary's Campus, London, U.K.
c Hypertension and Lipids Unit, Hospital Vírgen del Rocio, Sevilla, Spain

revised May 4, 1999; accepted May 5, 1999

Abstract

Background In healthy individuals, insulin administration causes an increase in forearm blood flow which is dependent on the effects of insulin on the vascular endothelium. Glucose, administered as an intravenous bolus, produces a transient hyperinsulinaemic response. We hypothesized that the insulin response to an intravenous glucose challenge during the intravenous glucose tolerance test might lead to increases in forearm blood flow in healthy individuals, and that such a response might be altered in patients with coronary heart disease.

Methods and Results Healthy individuals (n=10, aged 41·6±3·0 years, mean±SEM) and patients with angiographically proven coronary heart disease (n=13, aged 65·5±2·4 years) underwent an intravenous glucose tolerance test with simultaneous measurement of right forearm blood flow at 28 time points, using mercury-in-silastic venous occlusion plethysmography. In controls, forearm blood flow increased to a mean of 31·7% above baseline values at 7min and remained above baseline up to 180min after intravenous glucose. In contrast, patients with coronary heart disease exhibited an opposite response, with forearm blood flow decreasing to a mean of –16·2% below baseline values at 7min and –25·8% at 180min. Marked group differences emerged in net changes from baseline in forearm blood flow throughout the intravenous glucose tolerance test, expressed as incremental areas under the forearm blood flow profiles (controls: +351·3±121·7; coronary heart disease patients: –244·3±72·4minml–1.100ml–1,P =0·001).

Conclusions We have demonstrated for the first time that in healthy individuals forearm blood flow increases after an intravenous bolus of glucose, and that paradoxically, this response is reduced below baseline forearm blood flow in patients with coronary heart disease. Further studies are needed to determine whether plethysmographic measurement of forearm blood flow after an intravenous bolus of glucose could provide a clinically useful non-invasive test for the diagnosis of occult coronary heart disease.

Key Words: Endothelium, insulin, atherosclerosis

f1 Correspondence: Dr Francisco Leyva, Department of Cardiology, Royal Brompton Hospital, Sydney Street, London SW3 6NP, U.K. e-mail:leyvaleon@hotmail.com

References

  1. Healy B. Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease. J Am Coll Cardiol. 1990;16:357–358[Web of Science][Medline]
  2. Sanz G, Castaner A, Betriu A. Determinants of prognosis in survivors of myocardial infarction. A prospective clinical and angiographic study. N Engl J Med. 1982;306:1065–1070[Abstract]
  3. El-Tamimi H, Mansour M, Wargovich TJ. Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Endothelial function revisited. Circulation. 1994;12:56–62
  4. Reddy KG, Nair RN, Sheehan HM, Hodgson JMcB. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. J Am Coll Cardiol. 1994;23:833–843[Abstract]
  5. Ludmer PL, Selwyn AP, Shook TL. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046–1051[Abstract]
  6. Folkow B, Grimby G, Thulesius O. Adaptive structural changes of the vascular walls in hypertension and their relation to the control of peripheral resistance. Acta Physiol Scand. 1958;44:255–272[Web of Science][Medline]
  7. Nabel EL, Selwyn AP, Ganz P. Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. J Am Coll Cardiol. 1990;16:349–356[Abstract]
  8. Wendelhag I, Gustavsson T, Suurkula M, Berglund G, Wikstrand U. Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of computerised analysing system. Clin Physiol. 1991;11:565–577[Web of Science][Medline]
  9. Pohl U, Holtz J, Busse R, Bassenge E. Crucial role of the endothelium in the vasodilator response to increased blood flow. Hypertension. 1996;8:37–44
  10. Baron AD. Hemodynamic actions of insulin. Am J Physiol. 1994;267:E187–E202
  11. Vollenweider P, Tappy L, Randin D. Differential effects of hyperinsulinaemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. J Clin Invest. 1993;92:147–154[Web of Science][Medline]
  12. Mäkimattila S, Virkamäki A, Malmström R. Insulin resistance in type 1 diabetes: a major role for reduced glucose extraction. J Clin Endocrinol Metab. 1996;81:707–712[Abstract]
  13. McNulty PH, Pfau S. Insulin stimulates myocardial blood flow in humans by a direct effect within the coronary circulation. Circulation. 1997;96:I-379
  14. Wu H-Y, Jeng Y-Y, Yue C-J, Chyu K-Y, Hsueh WA, Chan TM. Endothelial dependent vascular effects of insulin and insulin-like growth factor 1 in the perfused rat mesenteric artery and aortic ring. Diabetes. 1994;43:1027–1032[Abstract]
  15. Utrianen T, Mäkimattila S, Virkamäki A, Lindholm H, Sovijärvi A, Yri-Järvinen H. Physical fitness and endothelial function (nitric oxide synthesis) are independent determinants of insulin-stimulated blood flow in normal subjects. J Clin Endocrinol Metab. 1996;81:4258–4263[Abstract]
  16. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle stimulation of limb blood flow in normal subjects. J Clin Invest. 1994;94:1172–1179[Web of Science][Medline]
  17. Scherrer YU, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin's vascular effects in humans. J Clin Invest. 1994;94:2511–2515[Web of Science][Medline]
  18. Steinberg HO, Brechtel G, Johnson A, Baron AD. Insulin modulates endothelium derived relaxing factor/nitric oxide dependent vasodilation in skeletal muscle. Hypertension Dallas. 1993;22:74–76[Abstract/Free Full Text]
  19. Cardillo C, Kilcoyne CM, Quyyumi AA, Cannon RO, Panza JA. Nitric oxide-dependent vasodilator response to systemic but not to local hyperinsulinemia in the human forearm (Abstr). Circulation. 1997;96:I-101
  20. Baron AD, Laakso M, Brechtel G, Hoit B, Edelman SV. Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity. J Clin Endocrinol Metab. 1990;70:1525–1533[Abstract/Free Full Text]
  21. Swan JW, Walton C, Godsland IF. Assessment of insulin sensitivity in man: a comparison of minimal model and euglycaemic clamp derived measures in health and heart failure. Clin Sci. 1994;86:317–322[Medline]
  22. Bennett WM, Connacher AA, Scrimgeour RT, Jung RT, Rennie MJ. Euglycemic hyperinsulinemia augments amni acid uptake by human leg tissues during hyperaminoacidemia. Am J Physiol (Endocrinol Metab 22). 1990;259:E185–E194[Abstract/Free Full Text]
  23. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. J Clin Invest. 1990;85:1844–1852[Web of Science][Medline]
  24. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. 1994;94:1172–1179[Web of Science][Medline]
  25. Vita JA, Treasure CB, Nabel EG. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990;81:491–497[Abstract/Free Full Text]
  26. Panza JA, Quyyumy A, Brush JE, Epstein SE. Abnormal endothelium dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323:22–27[Abstract]
  27. McVeigh GE, Brennan GM, Johnston GD. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1992;35:771–776[Web of Science][Medline]
  28. Calver A, Collier J, Vallance P. Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin dependent diabetes. J Clin Invest. 1992;90:2548–2554[Web of Science][Medline]
  29. Schini VB, Catovsky S, Schray-Utz B, Busse R, Vanhoutte PM. Insulin-like growth factor I inhibits induction of nitric oxide synthase in vascular smooth muscle cells. Circ Res. 1994;74:24–32[Abstract/Free Full Text]
  30. Tesfamariam B, Brown ML, Deykin D, Cohen RA. Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. J Clin Invest. 1990;85:929–932[Web of Science][Medline]
  31. Bohlen HG, Lash JM. Topial hyperglycemia rapidly supresses EDRF-mediated vasodilation of normal rat arterioles. Am J Physiol. 1993;265:H219–225
  32. Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy M-A, Simonson DC, Creager MA. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation. 1998;97:1695–1701[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. G. Clark, M. G. Wallis, E. J. Barrett, M. A. Vincent, S. M. Richards, L. H. Clerk, and S. Rattigan
Blood flow and muscle metabolism: a focus on insulin action
Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E241 - E258.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
C. Basso, F. Calabrese, D. Corrado, and G. Thiene
Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings
Cardiovasc Res, May 1, 2001; 50(2): 290 - 300.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
W. Doehner, I. F. Godsland, and S. D. Anker
Vascular effect of insulin in endothelial dysfunction
J. Am. Coll. Cardiol., February 1, 2001; 37(2): 689 - 689.
[Full Text] [PDF]

Home page
 Eur Heart JHome page
W. Bagg, G.D. Braatvedt, and N. Sharpe
A complex relationship: glucose, insulin and coronary artery disease
Eur. Heart J., January 1, 2000; 21(1): 8 - 9.
[PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Leyva, F
Right arrow Articles by Stevenson, J.C
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leyva, F
Right arrow Articles by Stevenson, J.C
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?