Timeliness of intravenous thrombolysis via telestroke in Georgia.

BACKGROUND AND PURPOSE: Through 2-way live video and audio communication, telestroke enhances urgent treatment of patients with acute stroke in emergency departments (EDs) without immediate access to on-site specialists. To assess for opportunities to shorten the door to thrombolysis time, we measured multiple time intervals in a telestroke system. METHODS: We retrospectively analyzed 115 records of consecutive acute stroke patients treated with intravenous thrombolysis during a 20-month period via a statewide telestroke system in 17 EDs in Georgia. On the basis of times documented in the telestroke system, we calculated the time elapsed between the following events: ED arrival, telestroke patient registration, start of specialist consultation, head computed tomography, thrombolysis recommendation, and thrombolysis initiation. RESULTS: The most conspicuous delay was from ED arrival to telestroke patient registration (median, 39 minutes; interquartile range, 21-56). Median time from ED arrival to thrombolysis initiation was 88 minutes, interquartile range 75 to 105. Thrombolysis was initiated within 60 minutes from ED arrival in 13% of patients. CONCLUSIONS: The greatest opportunity to expedite acute thrombolysis via telestroke is by shortening the time from ED arrival to telestroke patient registration.

Dynamic association of nitric oxide downstream signaling molecules with endothelial caveolin-1 in rat aorta.

Classically, nitric oxide (NO) formed by endothelial NO synthase (eNOS) freely diffuses from its generation site to smooth muscle cells where it activates soluble guanylyl cyclase (sGC), producing cGMP. Subsequently, cGMP activates both cGMP- and cAMP-dependent protein kinases [cGMP-dependent protein kinase (PKG) and cAMP-dependent protein kinase (PKA), respectively], leading to smooth muscle relaxation. In endothelial cells, eNOS has been localized to caveolae, small invaginations of the plasma membrane rich in cholesterol. Membrane cholesterol depletion impairs acetylcholine (ACh)-induced relaxation due to alteration in caveolar structure. Given the nature of NO to be more soluble in a hydrophobic environment than in water, and assuming that colocalization of components in a signal transduction cascade seems to be a critical determinant of signaling efficiency by eNOS activation, we hypothesize that sGC, PKA, and PKG activation may occur at the plasma membrane caveolae. In endothelium-intact rat aortic rings, the relaxation induced by ACh, by the sGC activator 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1), and by 8-bromo-cGMP was impaired in the presence of methyl-beta-cyclodextrin, a drug that disassembles caveolae by sequestering cholesterol from the membrane. sGC, PKG, and PKA were colocalized with caveolin-1 in aortic endothelium, and this colocalization was abolished by methyl-beta-cyclodextrin. Methyl-beta-cyclodextrin efficiently disassembled caveolae in endothelium. In summary, our results provide evidence of compartmentalization of sGC, PKG, and PKA in endothelial caveolae contributing to NO signaling cascade, giving new insights by which the endothelium mediates vascular smooth muscle relaxation.