Supine sleep and positional sleep apnea after acute ischemic stroke and intracerebral hemorrhage

OBJECTIVE: Obstructive sleep apnea is frequent during the acute phase of stroke, and it is associated with poorer outcomes. A well-established relationship between supine sleep and obstructive sleep apnea severity exists in non-stroke patients. This study investigated the frequency of supine sleep and positional obstructive sleep apnea in patients with ischemic or hemorrhagic stroke. METHODS: Patients who suffered their first acute stroke, either ischemic or hemorrhagic, were subjected to a full polysomnography, including the continuous monitoring of sleep positions, during the first night after symptom onset. Obstructive sleep apnea severity was measured using the apnea-hypopnea index, and the NIHSS measured stroke severity. RESULTS: We prospectively studied 66 stroke patients. The mean age was 57.6+/-11.5 years, and the mean body mass index was 26.5+/-4.9. Obstructive sleep apnea (apnea-hypopnea index >= 5) was present in 78.8% of patients, and the mean apnea-hypopnea index was 29.7+/-26.6. The majority of subjects (66.7%) spent the entire sleep time in a supine position, and positional obstructive sleep apnea was clearly present in the other 23.1% of cases. A positive correlation was observed between the NIHSS and sleep time in the supine position (r(s) = 0.5; p<0.001). CONCLUSIONS: Prolonged supine positioning during sleep was highly frequent after stroke, and it was related to stroke severity. Positional sleep apnea was observed in one quarter of stroke patients, which was likely underestimated during the acute phase of stroke. The adequate positioning of patients during sleep during the acute phase of stroke may decrease obstructive respiratory events, regardless of the stroke subtype.

Suppression of Hypoxia-Inducible Factor-1 alpha Contributes to the Antiangiogenic Activity of Red Propolis Polyphenols in Human Endothelial Cells

Polyphenol-enriched fractions from natural sources have been proposed to interfere with angiogenesis in pathological conditions. We recently reported that red propolis polyphenols (RPP) exert antiangiogenic activity. However, molecular mechanisms of this activity remain unclear. Here, we aimed at characterizing molecular mechanisms to explain the impact of RPP on endothelial cells' (EC) physiology. We used in vitro and ex and in vivo models to test the hypothesis that RPP inhibit angiogenesis by affecting hypoxia-inducible factor-1 alpha (HIF1 alpha) stabilization in EC. RPP (10 mg/L) affected angiogenesis by reducing migration and sprouting of EC, attenuated the formation of new blood vessels, and decreased the differentiation of embryonic stem cells into CD31-positive cells. Moreover, RPP (10 mg/L) inhibited hypoxia- or dimethyloxallylglycine-induced mRNA and protein expression of the crucial angiogenesis promoter vascular endothelial growth factor (VEGF) in a time-dependent mariner. Under hypoxic conditions, RPP at 10 mg/L, supplied for 1-4 h, decreased HIF1 alpha protein accumulation, which in turn attenuated VEGF gene expression. In addition, RPP reduced the HIF1 alpha protein half-life from similar to 58 min to 38 min under hypoxic conditions. The reduced HIF1 alpha protein half-life was associated with an increase in the von Hippel-Lindau (pVHL)-dependent proteasomal degradation of HIF1 alpha. RPP (10 mg/L, 4 h) downregulated Cdc42 protein expression. This caused a corresponding increase in pVHL protein levels and a subsequent degradation of HIF1 alpha. In summary, we have elucidated the underlying mechanism for the antiangiogenic action of RPP, which attenuates HIF1 alpha protein accumulation and signaling. J. Nutr. 142: 441-447, 2012.