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Impaired collateral recruitment and outward remodeling in experimental diabetes.

van Golde JM, Ruiter MS, Schaper NC, Vöö S, Waltenberger J, Backes WH, Post MJ, Huijberts MS - Diabetes (2008)

Bottom Line: Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals.The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands. jmcg.vangolde@intmed.unimaas.nl

ABSTRACT

Objective: In this study, the effect of chronic hyperglycemia on acute ligation-induced collateral vasodilation, on monocyte chemotaxis, and on structural outward remodeling of collaterals was investigated.

Research design and methods: Femoral artery ligation was performed 8 weeks after alloxan or saline treatment in New Zealand White rabbits. Angiography was performed directly, 1 and 3 weeks after ligation. These angiographic recordings were used to quantify number of collaterals, lumen, and blood volume index. Reactive hyperemia response was tested by intramuscular laser Doppler measurements. Subsequently, blood was sampled from the aorta for monocyte chemotaxis.

Results: Ligation resulted in markedly lower acute collateral vasodilation in diabetic compared with control rabbits. Also, hyperemic vasodilatory response to local ischemia was impaired in diabetic rabbits. This difference persisted at 1 and 3 weeks after ligation, with a lower number of visible collaterals. In addition, the collateral lumen was markedly lower in diabetic rabbits after the maturation phase. Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals. The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.

Conclusions: This study demonstrates that chronic hyperglycemia negatively affects the different phases of arteriogenesis: 1) impaired shear induced vasodilatation; 2) impaired outward collateral growth, reflected in the number of collaterals and blood volume index; and 3) inhibition of monocyte chemotaxis. Impairments were most evident in the acute phase of arteriogenesis. Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

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Related in: MedlinePlus

Example of an X-ray angiogram and the region of interest (circle) in the ligated limb (A) and post-subtraction angiograms (B) 3 weeks after ligation.
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f1: Example of an X-ray angiogram and the region of interest (circle) in the ligated limb (A) and post-subtraction angiograms (B) 3 weeks after ligation.

Mentions: To address the importance of the luminal volume of collateral arteries, we developed and applied quantitative subtraction angiography. This method enables automated and observer-independent collateral artery growth quantification. To this end, computational software was developed in MATLAB (The Math Works, Natick, MA). Early precontrast frames of the angiographic time series, frame numbers 3–12 before contrast injection, were averaged to provide a noise-suppressed precontrast mask image (Ipre) on which all anatomic structures were depicted except the blood vessels. The frame with maximal contrast intensity of the collateral arteries was defined. Five frames above and below this maximal intensity frame were averaged to provide a noise-suppressed maximal contrast image (Imax). For signal analysis, the quantitative description by Bushberg et al. (30) was used. On the pertaining logarithmic subtraction images (Isub), the region of interest was manually drawn based on predefined landmarks in the adductor magnus muscle of the ligated limb in the direct surrounding of the occlusion. This is the site of collateral anastomoses derived from the deep femoral artery and the internal iliac artery, as depicted in Fig. 1. In this region of interest, the number of enhanced pixels (above noise level) due to collateral filling were quantified directly, 1 and 3 weeks after ligation. In addition, the signal intensities of the pixels in the subtraction angiogram were normalized to the maximal absolute signal intensity in the aorta to provide a measure of the blood volume as function of signal intensity relative to the aorta enhancement. The blood volume index is then defined as the sum of pixel intensities (Isub above noise level), normalized to the maximal aortic signal intensity in the subtraction images in the region of collateral growth.


Impaired collateral recruitment and outward remodeling in experimental diabetes.

van Golde JM, Ruiter MS, Schaper NC, Vöö S, Waltenberger J, Backes WH, Post MJ, Huijberts MS - Diabetes (2008)

Example of an X-ray angiogram and the region of interest (circle) in the ligated limb (A) and post-subtraction angiograms (B) 3 weeks after ligation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551694&req=5

f1: Example of an X-ray angiogram and the region of interest (circle) in the ligated limb (A) and post-subtraction angiograms (B) 3 weeks after ligation.
Mentions: To address the importance of the luminal volume of collateral arteries, we developed and applied quantitative subtraction angiography. This method enables automated and observer-independent collateral artery growth quantification. To this end, computational software was developed in MATLAB (The Math Works, Natick, MA). Early precontrast frames of the angiographic time series, frame numbers 3–12 before contrast injection, were averaged to provide a noise-suppressed precontrast mask image (Ipre) on which all anatomic structures were depicted except the blood vessels. The frame with maximal contrast intensity of the collateral arteries was defined. Five frames above and below this maximal intensity frame were averaged to provide a noise-suppressed maximal contrast image (Imax). For signal analysis, the quantitative description by Bushberg et al. (30) was used. On the pertaining logarithmic subtraction images (Isub), the region of interest was manually drawn based on predefined landmarks in the adductor magnus muscle of the ligated limb in the direct surrounding of the occlusion. This is the site of collateral anastomoses derived from the deep femoral artery and the internal iliac artery, as depicted in Fig. 1. In this region of interest, the number of enhanced pixels (above noise level) due to collateral filling were quantified directly, 1 and 3 weeks after ligation. In addition, the signal intensities of the pixels in the subtraction angiogram were normalized to the maximal absolute signal intensity in the aorta to provide a measure of the blood volume as function of signal intensity relative to the aorta enhancement. The blood volume index is then defined as the sum of pixel intensities (Isub above noise level), normalized to the maximal aortic signal intensity in the subtraction images in the region of collateral growth.

Bottom Line: Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals.The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands. jmcg.vangolde@intmed.unimaas.nl

ABSTRACT

Objective: In this study, the effect of chronic hyperglycemia on acute ligation-induced collateral vasodilation, on monocyte chemotaxis, and on structural outward remodeling of collaterals was investigated.

Research design and methods: Femoral artery ligation was performed 8 weeks after alloxan or saline treatment in New Zealand White rabbits. Angiography was performed directly, 1 and 3 weeks after ligation. These angiographic recordings were used to quantify number of collaterals, lumen, and blood volume index. Reactive hyperemia response was tested by intramuscular laser Doppler measurements. Subsequently, blood was sampled from the aorta for monocyte chemotaxis.

Results: Ligation resulted in markedly lower acute collateral vasodilation in diabetic compared with control rabbits. Also, hyperemic vasodilatory response to local ischemia was impaired in diabetic rabbits. This difference persisted at 1 and 3 weeks after ligation, with a lower number of visible collaterals. In addition, the collateral lumen was markedly lower in diabetic rabbits after the maturation phase. Likewise, a reduced blood volume index in the region of growing collaterals was observed in diabetic animals. The monocyte migration toward vascular endothelial growth factor-A and monocyte chemotactic protein-1 was strongly reduced in diabetic rabbits.

Conclusions: This study demonstrates that chronic hyperglycemia negatively affects the different phases of arteriogenesis: 1) impaired shear induced vasodilatation; 2) impaired outward collateral growth, reflected in the number of collaterals and blood volume index; and 3) inhibition of monocyte chemotaxis. Impairments were most evident in the acute phase of arteriogenesis. Therapies aimed at restoring acute collateral recruitment, such as vasodilators, may be of interest to improve collateral function in diabetes.

Show MeSH
Related in: MedlinePlus