Key result
Intra-arterial administration of the arginase inhibitor Nv-hydroxy-nor-L-arginine prevented the decrease in flow-mediated dilatation induced by ischemia-reperfusion in patients with coronary artery disease compared to saline (P<0.01).
Why the study?
Does arginase inhibition prevent endothelial dysfunction induced by ischemia-reperfusion in male patients with coronary artery disease with or without type 2 diabetes?
RCT (n=24)
Single-blind
Randomized cross-over
No
Does arginase inhibition prevent endothelial dysfunction induced by ischemia-reperfusion in male patients with coronary artery disease with or without type 2 diabetes?
Arginase inhibition protects against endothelial dysfunction caused by ischemia-reperfusion in patients with coronary artery disease, suggesting a potential therapeutic strategy for ischemia-reperfusion injury.
Answers are grounded in this paper and cite their sources.
Arginase inhibition prevents ischemia-reperfusion endothelial dysfunction in CAD; extends animal protection to humans and supports outcome trials.
BACKGROUND: Arginase competes with nitric oxide synthase for their common substrate L-arginine. Up-regulation of arginase in coronary artery disease (CAD) and diabetes mellitus may reduce nitric oxide bioavailability contributing to endothelial dysfunction and ischemia-reperfusion injury. Arginase inhibition reduces infarct size in animal models. Therefore the aim of the current study was to investigate if arginase inhibition protects from endothelial dysfunction induced by ischemia-reperfusion in patients with CAD with or without type 2 diabetes ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02009527). METHODS: Male patients with CAD (n = 12) or CAD + type 2 diabetes (n = 12), were included in this cross-over study with blinded evaluation. Endothelium-dependent vasodilatation was assessed by flow-mediated dilatation (FMD) of the radial artery before and after 20 min ischemia-reperfusion during intra-arterial infusion of the arginase inhibitor (Nω-hydroxy-nor-L-arginine, 0.1 mg/min) or saline. RESULTS: The forearm ischemia-reperfusion was well tolerated. Endothelium-independent vasodilatation was assessed by sublingual nitroglycerin. Ischemia-reperfusion decreased FMD in patients with CAD from 12.7±5.2% to 7.9±4.0% during saline administration (P<0.05). Nω-hydroxy-nor-L-arginine administration prevented the decrease in FMD in the CAD group (10.3±4.3% at baseline vs. 11.5±3.6% at reperfusion). Ischemia-reperfusion did not significantly reduce FMD in patients with CAD + type 2 diabetes. However, FMD at reperfusion was higher following nor-NOHA than following saline administration in both groups (P<0.01). Endothelium-independent vasodilatation did not differ between the occasions. CONCLUSIONS: Inhibition of arginase protects against endothelial dysfunction caused by ischemia-reperfusion in patients with CAD. Arginase inhibition may thereby be a promising therapeutic strategy in the treatment of ischemia-reperfusion injury.
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Kövamees et al. (2014) conducted an RCT in Coronary Artery Disease with and without Type 2 Diabetes Mellitus (n=24). Nv-hydroxy-nor-L-arginine vs. Saline was evaluated on Flow-mediated dilatation (FMD) at reperfusion in CAD patients (MD 3.6%, p=<0.01). Intra-arterial administration of the arginase inhibitor Nv-hydroxy-nor-L-arginine prevented the decrease in flow-mediated dilatation induced by ischemia-reperfusion in patients with coronary artery disease compared to saline (P<0.01).
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