Effect of Arginase Inhibition on Ischemia-Reperfusion Injury in Patients with Coronary Artery Disease with and without Diabetes MellitusReportar como inadecuado




Effect of Arginase Inhibition on Ischemia-Reperfusion Injury in Patients with Coronary Artery Disease with and without Diabetes Mellitus - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Oskar Kövamees , Alexey Shemyakin, John Pernow

Fuente: http://plos.srce.hr/



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