Short-term Statin Treatment Does Not Prevent Ischemia and Reperfusion-induced Endothelial Dysfunction in Humans

Wouters, Carine; Wever, Kimberley E.; Bronckers, Inge M G J; Hopman, Maria T. E.; Smits, P.; Thijssen, Dick H. J.; Rongen, Gerard A.

doi:10.1097/fjc.0b013e318232b1a4

Cited by 10 publications

(9 citation statements)

References 53 publications

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“…We found a significant decrease in FMD after the IR protocol, which agrees with the observations from other groups (Kharbanda et al 2001;Loukogeorgakis et al 2006). The average decrease in FMD in our study was somewhat lower than typically observed by others (Kharbanda et al 2001;Loukogeorgakis et al 2006), but in agreement with previous observations from our laboratory (Wouters et al 2012). Differences in the magnitude of decline in FMD may relate to between study differences in the protocol to induce IR injury (i.e., longer period of ischaemia is associated with larger decline in FMD (Devan et al 2011)) or to the inclusion of different groups (Devan et al 2011).…”

Section: Discussionsupporting

confidence: 94%

Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia–reperfusion in humans

Schreuder

Eijsvogels

Greyling

et al. 2014

Appl. Physiol. Nutr. Metab.

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Tea consumption is associated with reduced cardiovascular risk. Previous studies found that tea flavonoids work through direct effects on the vasculature, leading to dose-dependent improvements in endothelial function. Cardioprotective effects of regular tea consumption may relate to the prevention of endothelial ischaemia-reperfusion (IR) injury. Therefore, we examined the effect of black tea consumption on endothelial function and the ability of tea to prevent IR injury. In a randomized, crossover study, 20 healthy subjects underwent 7 days of tea consumption (3 cups per day) or abstinence from tea. We examined brachial artery (BA) endothelial function via flow-mediated dilation (FMD), using high resolution echo-Doppler, before and 90 min after tea or hot water consumption. Subsequently, we followed a 20-min ischaemia and 20-min reperfusion protocol of the BA after which we measured FMD to examine the potential of tea consumption to protect against IR injury. Tea consumption resulted in an immediate increase in FMD% (pre-consumption: 5.8 ± 2.5; post-consumption: 7.2 ± 3.2; p < 0.01), whilst no such change occurred after ingestion of hot water. The IR protocol resulted in a significant decrease in FMD (p < 0.005), which was also present after tea consumption (p < 0.001). This decline was accompanied by an increase in the post-IR baseline diameter. In conclusion, these data indicate that tea ingestion improves BA FMD. However, the impact of the IR protocol on FMD was not influenced by tea consumption. Therefore, the cardioprotective association of tea ingestion relates to a direct effect of tea on the endothelium in humans in vivo.

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Section: Discussionsupporting

confidence: 94%

Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia–reperfusion in humans

Schreuder

Eijsvogels

Greyling

et al. 2014

Appl. Physiol. Nutr. Metab.

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“…23 However, it has been demonstrated that the administration of either lipo-or hydrophilic statins does not modulate the effect of ischaemia reperfusion injury on brachial artery FMD in healthy volunteers. 24 Of additional note, a reduction in infarct size may well be associated with short-term use and these protective effects may be lost in chronic use. 25 According to Suvorava and Kojda, repeated shortterms bouts of oxidative stress may cause the up-regulation of anti-oxidant protein expression in the vascular wall, eventually increasing its antioxidant capacity.…”

Section: Discussionmentioning

confidence: 99%

Potential identification of a claudicant group vulnerable to acute kidney injury

et al. 2016

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This observational study aimed to investigate the relationship between renal injury, endothelial function and oxidative stress in claudicants undergoing maximal treadmill exercise. Twenty patients with claudication were identified in whom the urinary N-acetyl-β-D-glucosaminidase (β-NAG)/creatinine ratio, plasma oxidative state and endothelial function were tested pre- and post-maximal treadmill walking exercise. Of the 20 participants in this study, the urinary NAG/creatinine (Cr) rose from a pre-exercise level of 8.9, 6.7 to 14.3 (μmol/L/mmol Cr; median, IQR) to 12.9, 9.1 to 17.7 post exercise (p = 0.0003, Mann Whitney U test). Of the 20 participants, eight participants had a rise of the NAG/Cr ratio post exercise whereas 12 did not. Participants with a rise in the NAG/Cr ratio post exercise had a greater ability to increase endothelial reactivity (%; median, IQR; 2.56, 0.1 to 3.7) cf. (0.1, -4.8 to 0.9, p = 0.03); they also walked further (metres; median, IQR; 415, 208 to 908) cf. (170, 100 to 315, p = 0.04), had a lower pre-exercise H2O2 (median, IQR; 1.9, 1.4 to 2.3 cf. 2.7, 2.1 to 3.3; p = 0.04) and a greater rise in H2O2 post exercise (18.8, -1.5 to 129.7 cf., -7.7, -13.9 to -2.0, p = 0.04). The mechanism by which the phenotypically distinct sub-group of patients with intermittent claudication who experience a NAG/Cr rise involves complex interactions between systemic oxidative stress and endothelial function. Implications on cardiovascular risk in this group requires further investigation.

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“…However, most strategies that limit myocardial infarct size in animal models also conferred protection against endothelial IR-injury, although some studies could not observe protection [13], [34], [36], [37].…”

Section: Discussionmentioning

confidence: 99%

Impact of Metformin on Endothelial Ischemia-Reperfusion Injury in Humans In Vivo: A Prospective Randomized Open, Blinded-Endpoint Study

et al. 2014

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IntroductionLarge prospective studies in patients with type 2 diabetes mellitus have demonstrated that metformin treatment improves cardiovascular prognosis, independent of glycemic control. Administration of metformin potently limits infarct size in murine models of myocardial infarction. This study examined, for the first time in humans, whether metformin limits ischemia-reperfusion (IR) injury in vivo using a well-validated forearm model of endothelial IR-injury.MethodsTwenty-eight healthy volunteers (age 41±6 years, 10 male/16 female) were randomized between pretreatment with metformin (500 mg three times a day for 3 days) or no treatment in a Prospective Randomized Open Blinded Endpoint study. Brachial artery flow mediated dilation (FMD) was measured before and after 20 minutes of forearm ischemia and 20 minutes of reperfusion. FMD analysis was performed offline by investigators blinded for the treatment arm.ResultsBaseline FMD did not differ between metformin pretreatment and no pretreatment (6.9±3.6% and 6.1±3.5%, respectively, p = 0.27, n = 26). FMD was significantly lower after forearm IR in both treatment arms (4.4±3.3% and 4.3±2.8%, respectively, P<0.001 in both conditions). A linear mixed model analysis revealed that metformin treatment did not prevent the decrease in FMD by IR.ConclusionA 3 day treatment with metformin in healthy, middle-aged subjects does not protect against endothelial IR-injury, measured with brachial artery FMD after forearm ischemia. Further studies are needed to clarify what mechanism underlies the cardiovascular benefit of metformin treatment.Trial Registration ClinicalTrials.gov NCT01610401

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Short-term Statin Treatment Does Not Prevent Ischemia and Reperfusion-induced Endothelial Dysfunction in Humans

Cited by 10 publications

References 53 publications

Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia–reperfusion in humans

Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia–reperfusion in humans

Potential identification of a claudicant group vulnerable to acute kidney injury

Impact of Metformin on Endothelial Ischemia-Reperfusion Injury in Humans In Vivo: A Prospective Randomized Open, Blinded-Endpoint Study

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