OBJECTIVES: We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function. BACKGROUND:Hyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary circulation is not known. METHODS:Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA) (0.3 mg/kg/min intravenously). RESULTS:Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 +/- 1.00 ml/min/g vs. 0.58 +/- 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 +/- 2.6% vs. 2.6 +/- 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of l-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of l-NMMA (2.08 +/- 1.34 ml/min/g vs. 1.48 +/- 1.32 ml/min/g, placebo vs. l-NMMA, p < 0.05). CONCLUSION: The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability.
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OBJECTIVES: We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function. BACKGROUND:Hyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary circulation is not known. METHODS: Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA) (0.3 mg/kg/min intravenously). RESULTS:Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 +/- 1.00 ml/min/g vs. 0.58 +/- 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 +/- 2.6% vs. 2.6 +/- 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of l-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of l-NMMA (2.08 +/- 1.34 ml/min/g vs. 1.48 +/- 1.32 ml/min/g, placebo vs. l-NMMA, p < 0.05). CONCLUSION: The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability.
Authors: Thomas H Schindler; Alvaro D Facta; John O Prior; Roxana Campisi; Masayuki Inubushi; Michael C Kreissl; Xiao-Li Zhang; James Sayre; Magnus Dahlbom; Heinrich R Schelbert Journal: Eur J Nucl Med Mol Imaging Date: 2006-04-26 Impact factor: 9.236
Authors: Thomas H Schindler; Xiao-Li Zhang; Gabriella Vincenti; Leila Mhiri; René Lerch; Heinrich R Schelbert Journal: J Nucl Cardiol Date: 2007-07 Impact factor: 5.952
Authors: Micaela Iantorno; Allison G Hays; Michael Schär; Rupa Krishnaswamy; Sahar Soleimanifard; Angela Steinberg; Matthias Stuber; Gary Gerstenblith; Robert G Weiss Journal: Circ Cardiovasc Imaging Date: 2016-03 Impact factor: 7.792