- Email: [email protected]
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Abstracts / Nitric Oxide 31 (2013) S13–S48
P50 Cocoa flavanols reverse age-related vascular dysfunction Roberto Sansone University Hospital Düsseldorf, Düsseldorf, Germany Background: Aging is associated with progressive vascular dysfunction. Cocoa flavanols were shown to improve endothelial vasodilator function and decrease blood pressure.Objectives: The aim of the study was to investigate the effect of a flavanol intervention on circulatory function in healthy elderly subjects. Methods: We recruited 22 young (<35 yrs) and 20 elderly (50–80 yrs) male non-smoking subjects that had no history or symptoms of vascular disease. In a double masked controlled trial subjects were randomly assigned to either a flavanol-rich intervention (820 mg/ day) or a matched flavanol-free control drink each consumed twice per day over 14 days. Measurements were taken after overnight fasting before and 1 h after the first drink on day 0 and day 14. The primary endpoint was conduit artery endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints tested the changes in cardiac output, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Plasma flavanol metabolites were determined with HPLC. Results: Flavanols ‘‘acutely’’ increase FMD at 1 h after ingestion in both young (6.1 ± 0.7% vs. 7.4 ± 0.8%, p < 0.001) and elderly (4.9 ± 0.6% vs. 5.9 ± 0.8%, p < 0.001); at day 14, FMD remained ‘‘chronically’’ increased even after overnight fasting in elderly (4.9 ± 0.6% vs. 6.3 ± 0.9%, p < 0.001) and young (6.1 ± 0.7% vs. 7.6 ± 0.7%, p < 0.001), respectively. Additional ‘‘acute-on-chronic’’ ingestion did not further improve FMD. Secondary endpoint analysis showed that cardiac function was not affected by flavanols. However, the flavanol intervention decreased pulse wave velocity (PWV) and total peripheral resistance, increased arteriolar and microvascular vasodilator capacity and red cell deformability resulting in a significant decrease in diastolic blood pressure in both groups. In elderly subjects baseline central systolic blood pressure was elevated and driven by a stiffness-related augmentation of the forward wave. Only in elderly subjects, the flavanols decrease central systolic blood pressure and thus aortic augmentation index. (Clinicaltrials.gov: NCT01639781). Conclusion: Cocoa flavanols improve endothelial function in conduit arteries, conductance of resistance arteries and cutaneous microcirculation. They selectively reverse age-related increases in systolic blood pressure and vascular stiffness. These findings highlight the potential of flavanols to counteract vascular aging. Disclosure: Nothing to disclose.
S35
Methods: We recruited 50 patients, 59 ± 10 years, undergoing TCA with a transradial access (5-F) that were current smokers (n = 21) or ex-smokers that had quit smoking >1 year prior to TCA (n = 29). In a first series (n = 10), we confirmed the time course of endothelial functional recovery up to 72 h following TCA by flow-mediated vasodilation (FMD) of the radial artery. In a second series (n = 40), we investigated long term arterial remodeling at the site of TCA injury by intima-media thickness (IMT), luminal and external arterial diameter, and fractional diameter change (FDC) along with FMD at 9–12 months after TCA. The contralateral radial artery served as a control. Results: Current smokers exhibited significantly lower radial artery FMD at baseline (8.0 ± 0.9% vs. 9.5 ± 0.7%, p = 0.016) and decreased to similar values at 6 h after TCA (4.1 ± 1.6% vs. 4.8 ± 1.6%, p = 0.479). Whereas in former smokers’ radial artery FMD had returned to baseline at 24 h, smokers’ FMD remained impaired at 24 h and only recovered at 48 h (7.8 ± 1.1% vs. 9.8 ± 0.8%, p = 0.009); at a mean follow-up of 9.7 ± 2.9 months, FMD was not different from baseline values. However, significant structural changes were detectable at the vascular access site with IMT in the intervention arm thicker (0.40 ± 0.07 mm vs. 0.31 ± 0.06 mm, p < 0.01) and FDC (6.7 ± 4.6% vs. 2.8 ± 3.5% p < 0.01) lower as compared to the control arm. Subgroup analysis revealed that smokers’ IMT thickening was significantly greater as compared to former smokers (0.45 ± 0.06 mm vs. 0.37 ± 0.05 mm, p = 0.001), the outside diameter was significantly greater (2.95 ± 0.32 mm vs. 2.71 ± 0.33 mm, p = 0.048), at similar luminal diameters (2.02 ± 0.34 mm vs. 2.12 ± 0.36 mm, p = 0.072), and the FDC was significantly lower(5.4 ± 3.7% vs. 2.3 ± 1.2%, p = 0.029) indicating more pronounced arterial stiffening and positive remodeling in current smokers. Values for IMT correlated with cigarette consumption within 24 h of TCA (r = 0.62, p < 0.001). Control arm measurements were not different between groups. Conclusion: Our data suggest that current smoking status strongly impacts on the recovery of endothelial function and structural maintenance of arteries following arterial injury potentially interfering with vascular repair mechanisms. Therefore, enforcement of periinterventional smoking abstinence may be necessary to allow optimal regeneration. Disclosure: Nothing to disclose.
http://dx.doi.org/10.1016/j.niox.2013.02.053
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http://dx.doi.org/10.1016/j.niox.2013.02.052
( )-Epicatechin increases angiogenesis after hindlimb ischemia
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Dominik Schuler University Hospital Düsseldorf, Düsseldorf, Germany
Current smoking aggravates intimal hyperplasia after arterial injury following transradial catheterization Roberto Sansone University Hospital Düsseldorf, Düsseldorf, Germany Objectives: The aim of the study was to investigate the effect of current smoking on long term arterial structural remodeling processes after arterial injury induced by transradial coronary angiography (TCA). Background: Cigarette smoking is the most important modifiable cardiovascular risk factor, leading to endothelial dysfunction, and delayed recovery of endothelial function after arterial injury.
Background: Clinical studies have shown that regular consumption of flavanols can lead to a sustained improvement in vascular function. The mechanisms are not well studied. Objective: To investigate whether dietary flavanols can improve peripheral vascular regeneration in vivo. Methods: Male 10-week-old C57/Bl6 mice (n = 6 per group) were subjected to hindlimb ischemia and recovery of perfusion monitored with laser Doppler perfusion imaging. Values are presented in relation to the contralateral, non-operated hindlimb. After baseline perfusion measurements, induction of hindlimb ischemia was conducted through two ligations (proximal and distal to the deep femoral artery). In order to test the impact of flavanols on vascular regeneration, animals were fed vehicle or increasing daily doses of
P50 Cocoa flavanols reverse age-related vascular dysfunction Roberto Sansone University Hospital Düsseldorf, Düsseldorf, Germany Background: Aging is associated with progressive vascular dysfunction. Cocoa flavanols were shown to improve endothelial vasodilator function and decrease blood pressure.Objectives: The aim of the study was to investigate the effect of a flavanol intervention on circulatory function in healthy elderly subjects. Methods: We recruited 22 young (<35 yrs) and 20 elderly (50–80 yrs) male non-smoking subjects that had no history or symptoms of vascular disease. In a double masked controlled trial subjects were randomly assigned to either a flavanol-rich intervention (820 mg/ day) or a matched flavanol-free control drink each consumed twice per day over 14 days. Measurements were taken after overnight fasting before and 1 h after the first drink on day 0 and day 14. The primary endpoint was conduit artery endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints tested the changes in cardiac output, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Plasma flavanol metabolites were determined with HPLC. Results: Flavanols ‘‘acutely’’ increase FMD at 1 h after ingestion in both young (6.1 ± 0.7% vs. 7.4 ± 0.8%, p < 0.001) and elderly (4.9 ± 0.6% vs. 5.9 ± 0.8%, p < 0.001); at day 14, FMD remained ‘‘chronically’’ increased even after overnight fasting in elderly (4.9 ± 0.6% vs. 6.3 ± 0.9%, p < 0.001) and young (6.1 ± 0.7% vs. 7.6 ± 0.7%, p < 0.001), respectively. Additional ‘‘acute-on-chronic’’ ingestion did not further improve FMD. Secondary endpoint analysis showed that cardiac function was not affected by flavanols. However, the flavanol intervention decreased pulse wave velocity (PWV) and total peripheral resistance, increased arteriolar and microvascular vasodilator capacity and red cell deformability resulting in a significant decrease in diastolic blood pressure in both groups. In elderly subjects baseline central systolic blood pressure was elevated and driven by a stiffness-related augmentation of the forward wave. Only in elderly subjects, the flavanols decrease central systolic blood pressure and thus aortic augmentation index. (Clinicaltrials.gov: NCT01639781). Conclusion: Cocoa flavanols improve endothelial function in conduit arteries, conductance of resistance arteries and cutaneous microcirculation. They selectively reverse age-related increases in systolic blood pressure and vascular stiffness. These findings highlight the potential of flavanols to counteract vascular aging. Disclosure: Nothing to disclose.
S35
Methods: We recruited 50 patients, 59 ± 10 years, undergoing TCA with a transradial access (5-F) that were current smokers (n = 21) or ex-smokers that had quit smoking >1 year prior to TCA (n = 29). In a first series (n = 10), we confirmed the time course of endothelial functional recovery up to 72 h following TCA by flow-mediated vasodilation (FMD) of the radial artery. In a second series (n = 40), we investigated long term arterial remodeling at the site of TCA injury by intima-media thickness (IMT), luminal and external arterial diameter, and fractional diameter change (FDC) along with FMD at 9–12 months after TCA. The contralateral radial artery served as a control. Results: Current smokers exhibited significantly lower radial artery FMD at baseline (8.0 ± 0.9% vs. 9.5 ± 0.7%, p = 0.016) and decreased to similar values at 6 h after TCA (4.1 ± 1.6% vs. 4.8 ± 1.6%, p = 0.479). Whereas in former smokers’ radial artery FMD had returned to baseline at 24 h, smokers’ FMD remained impaired at 24 h and only recovered at 48 h (7.8 ± 1.1% vs. 9.8 ± 0.8%, p = 0.009); at a mean follow-up of 9.7 ± 2.9 months, FMD was not different from baseline values. However, significant structural changes were detectable at the vascular access site with IMT in the intervention arm thicker (0.40 ± 0.07 mm vs. 0.31 ± 0.06 mm, p < 0.01) and FDC (6.7 ± 4.6% vs. 2.8 ± 3.5% p < 0.01) lower as compared to the control arm. Subgroup analysis revealed that smokers’ IMT thickening was significantly greater as compared to former smokers (0.45 ± 0.06 mm vs. 0.37 ± 0.05 mm, p = 0.001), the outside diameter was significantly greater (2.95 ± 0.32 mm vs. 2.71 ± 0.33 mm, p = 0.048), at similar luminal diameters (2.02 ± 0.34 mm vs. 2.12 ± 0.36 mm, p = 0.072), and the FDC was significantly lower(5.4 ± 3.7% vs. 2.3 ± 1.2%, p = 0.029) indicating more pronounced arterial stiffening and positive remodeling in current smokers. Values for IMT correlated with cigarette consumption within 24 h of TCA (r = 0.62, p < 0.001). Control arm measurements were not different between groups. Conclusion: Our data suggest that current smoking status strongly impacts on the recovery of endothelial function and structural maintenance of arteries following arterial injury potentially interfering with vascular repair mechanisms. Therefore, enforcement of periinterventional smoking abstinence may be necessary to allow optimal regeneration. Disclosure: Nothing to disclose.
http://dx.doi.org/10.1016/j.niox.2013.02.053
P52
http://dx.doi.org/10.1016/j.niox.2013.02.052
( )-Epicatechin increases angiogenesis after hindlimb ischemia
P51
Dominik Schuler University Hospital Düsseldorf, Düsseldorf, Germany
Current smoking aggravates intimal hyperplasia after arterial injury following transradial catheterization Roberto Sansone University Hospital Düsseldorf, Düsseldorf, Germany Objectives: The aim of the study was to investigate the effect of current smoking on long term arterial structural remodeling processes after arterial injury induced by transradial coronary angiography (TCA). Background: Cigarette smoking is the most important modifiable cardiovascular risk factor, leading to endothelial dysfunction, and delayed recovery of endothelial function after arterial injury.
Background: Clinical studies have shown that regular consumption of flavanols can lead to a sustained improvement in vascular function. The mechanisms are not well studied. Objective: To investigate whether dietary flavanols can improve peripheral vascular regeneration in vivo. Methods: Male 10-week-old C57/Bl6 mice (n = 6 per group) were subjected to hindlimb ischemia and recovery of perfusion monitored with laser Doppler perfusion imaging. Values are presented in relation to the contralateral, non-operated hindlimb. After baseline perfusion measurements, induction of hindlimb ischemia was conducted through two ligations (proximal and distal to the deep femoral artery). In order to test the impact of flavanols on vascular regeneration, animals were fed vehicle or increasing daily doses of