TY - JOUR
T1 - Deferoxamine improves coronary vascular responses to sympathetic stimulation in patients with type 1 diabetes mellitus
AU - Hattori, Naoya
AU - Schnell, Oliver
AU - Bengel, Frank Michael
AU - Rihl, Julian
AU - Nekolla, Stephan G.
AU - Drzezga, Alexander E.
AU - Standl, Eberhard
AU - Schwaiger, Markus
PY - 2002
Y1 - 2002
N2 - Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1±17.5 vs 63.2±14.9 mg 100 g-1 min-1, P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28±0.35; controls, 1.55±0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81±17 ml 100 g-1 min-1; saline, 75±19 ml 100 g-1 min-1, P=NS) or MVR (deferoxamine, 1.0±0.5 mmHg ml-1 100 g-1 min-1; saline, 1.2±0.6 mmHg ml-1 100 g-1 min-1, P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary microvasculature to sympathetic stimulation. Hydroxyl radicals may play a role in the pathogenesis of flow abnormalities in type 1 diabetes.
AB - Effects of oxygen-derived free radicals are suggested to be a potential pathogenic factor for endothelial dysfunction. In this study we sought to evaluate the effect of hydroxyl radicals on the human coronary vascular bed in type I diabetes mellitus using positron emission tomography (PET). Thirteen patients with type 1 diabetes underwent PET using nitrogen-13 ammonia at rest and during sympathetic stimulation with the cold pressor test (CPT). The rest-stress study protocol was repeated twice (on different days) using pre-stress infusion of either saline as placebo or deferoxamine, an iron chelator which inhibits generation of hydroxyl radicals. At rest, global MBF was higher in diabetics than in normal controls (78.1±17.5 vs 63.2±14.9 mg 100 g-1 min-1, P<0.05) and myocardial vascular resistance (MVR) showed a trend towards lower values (patients, 1.28±0.35; controls, 1.55±0.32, P=NS). CPT increased MBF in all controls while 7/13 diabetics responded normally. CPT decreased MVR in 10/13 controls but in only 4/13 diabetics. There was no significant difference in the duration of diabetes, HbA1c, daily insulin dose, body mass index, or lipid profiles between patients with and patients without abnormal MBF or MVR responses. Pre-stress infusion of deferoxamine normalized MBF response in all six patients, and MVR response in six of the nine patients. Another group consisting of seven patients underwent a rest-rest protocol after infusion of deferoxamine and saline to investigate the effect of deferoxamine on resting MBF. Deferoxamine did not change the resting MBF (deferoxamine, 81±17 ml 100 g-1 min-1; saline, 75±19 ml 100 g-1 min-1, P=NS) or MVR (deferoxamine, 1.0±0.5 mmHg ml-1 100 g-1 min-1; saline, 1.2±0.6 mmHg ml-1 100 g-1 min-1, P=NS). In conclusion, inhibition of hydroxyl radical formation using deferoxamine significantly improved the responses of coronary microvasculature to sympathetic stimulation. Hydroxyl radicals may play a role in the pathogenesis of flow abnormalities in type 1 diabetes.
KW - Endothelium
KW - Free radicals
KW - Positron emission tomography
KW - Type 1 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=0036092655&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036092655&partnerID=8YFLogxK
U2 - 10.1007/s00259-002-0799-0
DO - 10.1007/s00259-002-0799-0
M3 - Article
C2 - 12111129
AN - SCOPUS:0036092655
SN - 0340-6997
VL - 29
SP - 891
EP - 898
JO - European Journal of Nuclear Medicine
JF - European Journal of Nuclear Medicine
IS - 7
ER -