(Circulation. 1995;91:635-640.)
© 1995 American Heart Association, Inc.
Articles |
Maximal Coronary Flow Reserve and Metabolic Coronary Vasodilation in Patients With Diabetes Mellitus
From the Cardiovascular Division and the Cardiovascular Center, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, and the Veterans Affairs Medical Center, Iowa City, Iowa.
Correspondence to James D. Rossen, MD, Department of Internal Medicine, 4212 RCP, The University of Iowa, Iowa City, IA 52242.
Background Structural and functional abnormalities of the coronary microcirculation have been reported in experimental diabetes mellitus. The purpose of this study was to evaluate coronary microvascular function in human diabetes.
Methods and Results Twenty-four diabetic and 31 nondiabetic patients were studied during cardiac catheterization. A Doppler catheter or guidewire was used to measure changes in coronary blood flow velocity in a nonstenotic artery. Maximal coronary blood flow reserve was determined by using intracoronary adenosine or papaverine. Coronary dilation in response to an increase in myocardial metabolic demand was assessed by using rapid atrial pacing. Maximal vasodilator responses to papaverine and adenosine were compared in 12 diabetic patients. Maximal pharmacologic coronary flow reserve was depressed in diabetic (2.8±0.2, n=19) compared with nondiabetic (3.7±0.2, n=21, P<.001) patients. During atrial pacing, the decrease in coronary vascular resistance was attenuated in the diabetic (-14±3%) compared with the nondiabetic (-24±2%, P<.05) patients. Differences in coronary microvascular function between diabetic and nondiabetic patients were not attributable to differences in drug therapy, resting hemodynamics, or incidence of hypertension. In 12 diabetic patients the maximal coronary vasodilator responses to papaverine and adenosine were similar.
Conclusions This study demonstrates both reduced maximal coronary vasodilation and impairment in the regulation of coronary flow in response to submaximal increases in myocardial demand in patients with diabetes mellitus. These microvascular abnormalities may lead to myocardial ischemia in the absence of epicardial coronary atherosclerosis in some circumstances, and thus contribute to adverse cardiovascular events in diabetic patients.
Key Words: diabetes mellitus • microcirculation • vasodilation • blood flow
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|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 R. F. Ammar Jr., D. D. Gutterman, L. A. Brooks, and K. C. Dellsperger Impaired dilation of coronary arterioles during increases in myocardial O2 consumption with hyperglycemia Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E868 - E874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
H. Laine, P. Nuutila, M. Luotolahti, C. Meyer, T. Elomaa, P. Koskinen, T. Rönnemaa, and J. Knuuti Insulin-Induced Increment of Coronary Flow Reserve Is Not Abolished by Dexamethasone in Healthy Young Men J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1868 - 1873. [Abstract] [Full Text]
|
|
|
|
|
|
R. A. M. van Liebergen, J. J. Piek, K. T. Koch, R. J. G. Peters, R. J. de Winter, C. E. Schotborgh, and K. I. Lie Hyperemic coronary flow after optimized intravascular ultrasound-guided balloon angioplasty and stent implantation J. Am. Coll. Cardiol., December 1, 1999; 34(7): 1899 - 1906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 J. A. MILLER Impact of Hyperglycemia on the Renin Angiotensin System in Early Human Type 1 Diabetes Mellitus J. Am. Soc. Nephrol., August 1, 1999; 10(8): 1778 - 1785. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 V. H. Thourani, W. S. Weintraub, B. Stein, S. S.P. Gebhart, J. M. Craver, E. L. Jones, and R. A. Guyton Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting Ann. Thorac. Surg., April 1, 1999; 67(4): 1045 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
N. S Dhalla, X. Liu, V. Panagia, and N. Takeda Subcellular remodeling and heart dysfunction in chronic diabetes Cardiovasc Res, November 1, 1998; 40(2): 239 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Bache Vasodilator Reserve : A Functional Assessment of Coronary Health Circulation, September 29, 1998; 98(13): 1257 - 1260. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
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