Magnetic Nanoparticle-Mediated Targeting of Cell Therapy Reduces In-Stent Stenosis in Injured Arteries.

Although drug-eluting stents have dramatically reduced the recurrence of restenosis after vascular interventions, the nonselective antiproliferative drugs released from these devices significantly delay reendothelialization and vascular healing, increasing the risk of short- and long-term stent failure. Efficient repopulation of endothelial cells in the vessel wall following injury may limit complications, such as thrombosis, neoatherosclerosis, and restenosis, through reconstitution of a luminal barrier and cellular secretion of paracrine factors. We assessed the potential of magnetically mediated delivery of endothelial cells (ECs) to inhibit in-stent stenosis induced by mechanical injury in a rat carotid artery stent angioplasty model. ECs loaded with biodegradable superparamagnetic nanoparticles (MNPs) were administered at the distal end of the stented artery and localized to the stent using a brief exposure to a uniform magnetic field. After two months, magnetic localization of ECs demonstrated significant protection from stenosis at the distal part of the stent in the cell therapy group compared to both the proximal part of stent in the cell therapy group and the control (stented, nontreated) group: 1.7-fold (p < 0.001) less reduction in lumen diameter as measured by B-mode and color Doppler ultrasound, 2.3-fold (p < 0.001) less reduction in the ratios of peak systolic velocities as measured by pulsed wave Doppler ultrasound, and 2.1-fold (p < 0.001) attenuation of stenosis as determined through end point morphometric analysis. The study thus demonstrates that magnetically assisted delivery of ECs is a promising strategy for prevention of vessel lumen narrowing after stent angioplasty procedure.

Functional behavior and gene expression of magnetic nanoparticle-loaded primary endothelial cells for targeting vascular stents.

AIM: To assess functional competence and gene expression of magnetic nanoparticle (MNP)-loaded primary endothelial cells (ECs) as potential cell-based therapy vectors. MATERIALS & METHODS: A quantitative tube formation, nitric oxide and adhesion assays were conducted to assess functional potency of the MNP-loaded ECs. A quantitative real-time PCR was used to profile genes in both MNP-loaded at static conditions and in vitro targeted ECs. RESULTS: Functional behavior of MNP-loaded and unloaded cells was comparable. MNPs induce expression of genes involved in EC growth and survival, while repress genes involved in coagulation. CONCLUSION: MNPs do not adversely affect cellular function. Gene expression indicates that targeting MNP-loaded ECs to vascular stents may potentially stimulate re-endothelialization of an implant and attenuate neointimal hyperplasia.

Prophylactic glycopyrrolate prevents bradycardia after spinal anesthesia for Cesarean section: a randomized, double-blinded, placebo-controlled prospective trial with heart rate variability correlation.

STUDY OBJECTIVE: To determine if prophylactic glycopyrrolate prevents bradycardia after spinal anesthesia. DESIGN: Prospective, randomized, double-blinded, placebo-controlled study. SETTING: Large university-affiliated community hospital. PATIENTS: 81 consecutive term parturients (not in active labor) who were scheduled for elective Cesarean section. INTERVENTIONS: Parturients received 1.0 to 1.5 L of intravenous Ringer's lactate and either glycopyrrolate 0.4 mg or an equal volume of saline, with caregivers blinded to the immediate sequelae of study drug. Each patient received intrathecal bupivacaine (12 to 14 mg) with morphine sulfate (0.1 to 0.2 mg). MEASUREMENTS: Continuous heart rate (HR) and blood pressure monitoring occurred for 20 minutes, with the minimum HR recorded for each 5-minute epoch. Heart rates < 60 beats per minute defined bradycardia. Heart rate variability (HRV) analysis occurred offline. MAIN RESULTS: None of 34 patients administered glycopyrrolate and 6 of 35 (17%) patients receiving saline experienced bradycardia (P = 0.02476). Time domain, frequency domain, and nonlinear and embedded spectrum entropy analyses all reflected the decrease in HRV accompanying administration of glycopyrrolate. CONCLUSION: Bradycardia after spinal anesthesia occurs commonly. Prophylactic glycopyrrolate may prevent the bradycardia, but not necessarily the hypotension.