Impaired microvascular response to graded coronary occlusion in diabetic and hyperglycemic dogs

J. R. Kersten, L. A. Brooks, K. C. Dellsperger

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The hypothesis that coronary microvascular responses to ischemia are impaired in diabetes was tested in 9 alloxan-treated (60 mg/kg iv), 8 hyperglycemic, and 16 control dogs. Arteriolar diameters were measured in intact beating left ventricle by use of stroboscopic epi-illumination and intravital microscopy with fluorescence microangiography. Coronary arterial diameters were measured during graded reductions in mean coronary perfusion pressure to 60 ± 1 (SE) mmHg (mild stenosis), 39 ± 1 mmHg (severe stenosis), and 26 ± 1 mmHg (coronary artery occlusion). Blood glucose levels were 95 ± 5, 264 ± 17, and 277 ± 15 mg/dl in control, diabetic, and hyperglycemic animals, respectively. In control dogs, arteriolar microvessels (< 100 μm) dilated (24 ± 5, 31 ± 5, and 26 ± 6% change in diameter from baseline during mild stenosis, severe stenosis, and coronary occlusion, respectively). Diabetes or hyperglycemia prevented the normal dilatory response and resulted in decreases in microvascular diameter during decreases in perfusion pressure (-2 ± 3, -4 ± 3, and 15 ± 4% change in diameter in diabetic animals and -11 ± 2, -9 ± 4, and -8 ± 5% change in diameter in hyperglycemic animals). Large-vessel (> 100 μm) dilation was also significantly impaired in diabetic and hyperglycemic animals. Myocardial perfusion was significantly lower in the epicardium during a severe stenosis in diabetic and hyperglycemic than in control dogs. Because the ATP- sensitive K+ (K(ATP)) channel mediates this response in normal animals, we tested the hypothesis that K(ATP) channel responsiveness is impaired in diabetes and hyperglycemia. The response to aprikalim (0.1-1.0 μM), a K(ATP) channel agonist, was enhanced in < 100-μm coronary microvessels in diabetic and hyperglycemic animals. Thus diabetes and hyperglycemia impair coronary microvascular responses to hypoperfusion but not to K(ATP) channel impairment.

Original languageEnglish (US)
Pages (from-to)H1667-H1674
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume268
Issue number4 37-4
StatePublished - May 9 1995

Keywords

  • ATP-sensitive potassium channels
  • aprikalim
  • autoregulation
  • coronary microcirculation
  • diabetes mellitus
  • intravital microscopy
  • microspheres

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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