Endothelial Dysfunction of the Peripheral Vascular Bed in the Acute Phase after Ischemic Stroke

Abstract

Background: Endothelial dysfunction (ED) is relevant for the development of cerebrovascular and cardiovascular diseases. Asymmetric dimethylarginine (ADMA) competes with L-arginine and has been implicated in the development of ED. Increased levels of ADMA have been found in chronic heart failure (CHF). We hypothesized that peripheral ED in acute ischemic stroke is associated with increased ADMA levels. Methods: We evaluated 60 patients with acute stroke in the territory of the middle cerebral artery. Stroke patients were classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. We compared these patients with patients of similar age without known cardiovascular disease (negative controls, n = 23) and patients with stable, ambulatorily treated CHF (n = 46, left ventricular ejection fraction = 33.8 ± 10.9) with known ED (positive controls). Peripheral endothelial function was assessed by EndoPAT2000 technology using the reactive hyperemia index (RHI). Results: RHI was significantly decreased in stroke and in CHF compared to controls (1.8 ± 0.3 vs. 1.8 ± 0.4 vs. 2.2 ± 0.4, respectively, ANOVA p = 0.01). A decreased RHI was observed in cardioembolic and lacunar infarcts and stroke of undetermined etiology (1.7 ± 0.4, 1.8 ± 0.5 and 1.7 ± 0.3, p < 0.0001). The L-arginine/ADMA ratio was significantly decreased in stroke and in CHF (147.6 ± 31.7 and 126.1 ± 37.9 vs. controls: 161.5 ± 26.1, p < 0.0001) and was lowest in stroke patients in the cardioembolic group (133.0 ± 29.4, p < 0.0001). A lower L-arginine/ADMA ratio was associated with ED in cardioembolic stroke and CHF (r = 0.324, p < 0.05 and r = 0.429, p < 0.0001). Conclusion: Peripheral ED occurs to a similar degree in acute ischemic stroke and CHF. The impaired vasodilator capacity of peripheral arteries reflects the TOAST classification. ADMA may play a role in ED in both acute ischemic stroke and CHF.

Catabolic Signaling and Muscle Wasting After Acute Ischemic Stroke in Mice

“…Along with muscle atrophy, 8 these changes include reduced capillarization and impaired glucose use, 25 proinflammatory cytokine activation, 26 fiber type changes, 8 and endothelium dysfunction. 27 Stroke-induced local damage of inhibitory preganglionic pathways of the sympathetic nervous system may result in massive sympathetic overflow, particularly in the target tissues, with subsequent metabolic and inflammatory overagitation. 28 Atrophic changes in muscle tissue in hemiplegic patients are well known.…”

Benefit of Cilostazol in Patients with High Risk of Bleeding: Subanalysis of Cilostazol Stroke Prevention Study 2

“…Endothelial dysfunction rather than chronic platelet activation is reported to play a central role in the pathophysiology of lacunar stroke [15], and also, acute ischemic stroke is considered associated with endothelial dysfunction of the peripheral vascular beds [16], suggesting that treatment which can improve endothelial dysfunction might be necessary for the prevention of lacunar stroke and hemorrhagic stroke. Aspirin therapy is known to be associated with increased hemorrhagic risk, and dual antiplatelet therapy with clopidogrel and aspirin was reported to add no benefit, but increased the bleeding risk in patients with lacunar stroke for long-time treatment [17,18].…”

Endothelial Function In Stroke Subtypes Using EndoPAT Technology.

“…Endothelial function is characterized by the vasodilator capacity of blood vessel smooth muscle cells mediated by nitric oxide [1]. In recent years, a number of experimental and clinical studies have established the role of endothelial dysfunction (ED) in the development of cerebrovascular diseases [2].…”