Mucous Fistula Refeeding Promotes Earlier Enteral Autonomy in Infants With Small Bowel Resection.

OBJECTIVE: Infants requiring intestinal resection because of necrotizing enterocolitis (NEC) or small bowel atresia (SBA) may benefit from mucous fistula refeeding (MFR) of enterostomy output to improve nutrition and bowel adaptation before reanastomosis. Previous series demonstrated improved outcomes with MFR but did not account for varied patient characteristics as potential sources of bias. We performed a cohort analysis using multivariable adjusted models to compare outcomes of patients with and without MFR. METHODS: Retrospective chart review was performed for patients with NEC or SBA and small bowel resection with enterostomy and MF. Demographic and outcome data was compared between MFR and non-MFR groups using adjusted multivariable analysis for potential confounding variables. RESULTS: MFR was performed in 65 of 101 patients (64%), including 45 of 75 patients with NEC and 20 of 26 patients with SBA. Reasons for not receiving MFR included bowel stricture, technical limitation, or not otherwise specified. NEC patients receiving MFR had 14 fewer days to achieve full enteral feeds after intestinal reconnection, 22 fewer days of parenteral nutrition, lower peak direct bilirubin by 2.4 mg/dL, and 77% less odds of ursodiol use (all P < 0.01). SBA patients had similar trends not reaching statistical significance. Growth parameters were improved in MFR groups. There were no complications or increased infections from MFR. CONCLUSIONS: This study suggests that MFR safely improves nutritional outcomes in infants with intestinal resection, related to decreased total parenteral nutrition (TPN) dependence and earlier enteral autonomy.

Three variations in rabbit angiographic stroke models.

PURPOSE: To develop angiographic models of embolic stroke in the rabbit using pre-formed clot or microspheres to model clinical situations ranging from transient ischemic events to severe ischemic stroke. MATERIALS AND METHODS: New Zealand White rabbits (N=151) received angiographic access to the internal carotid artery (ICA) from a femoral approach. Variations of emboli type and quantity of emboli were tested by injection into the ICA. These included fresh clots (1.0-mm length, 3-6h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble microspheres (700-900 µm). Neurological assessment scores (NAS) were based on motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or 24h after embolization, and infarct volume was measured as a percent of total brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). RESULTS: Infarct volume percent at 24 h after stroke was lower for rabbits embolized with fresh clot (0.45±0.14%), compared with aged clot (3.52±1.31%) and insoluble microspheres (3.39±1.04%). Overall NAS (including posterior vessel occlusions) were positively correlated to infarct volume percent measurements in the fresh clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001). CONCLUSION: The three basic angiographic stroke models may be similar to human transient ischemic attacks (TIA) (fresh clot), major strokes that can be thrombolysed (aged clot), or major strokes with insoluble emboli such as atheromata (microspheres). Model selection can be tailored to specific research needs.

Dodecafluoropentane emulsion decreases infarct volume in a rabbit ischemic stroke model.

PURPOSE: To assess the efficacy of dodecafluoropentane emulsion (DDFPe), a nanodroplet emulsion with significant oxygen transport potential, in decreasing infarct volume in an insoluble-emboli rabbit stroke model. MATERIALS AND METHODS: New Zealand White rabbits (N = 64; weight, 5.1 ± 0.50 kg) underwent angiography and received embolic spheres in occluded internal carotid artery branches. Rabbits were randomly assigned to groups in 4-hour and 7-hour studies. Four-hour groups included control (n = 7, embolized without treatment) and DDFPe treatment 30 minutes before stroke (n = 7), at stroke onset (n = 8), and 30 minutes (n = 5), 1 hour (n = 7), 2 hours (n = 5), or 3 hours after stroke (n = 6). Seven-hour groups included control (n = 6) and DDFPe at 1 hour (n = 8) and 6 hours after stroke (n = 5). DDFPe dose was a 2% weight/volume intravenous injection (0.6 mL/kg) repeated every 90 minutes as time allowed. After euthanasia, infarct volume was determined by vital stains on brain sections. RESULTS: At 4 hours, median infarct volume decreased for all DDFPe treatment times (pretreatment, 0.30% [P = .004]; onset, 0.20% [P = .004]; 30 min, 0.35% [P = .009]; 1 h, 0.30% [P = .01]; 2 h, 0.40% [P = .009]; and 3 h, 0.25% [P = .003]) compared with controls (3.20%). At 7 hours, median infarct volume decreased with treatment at 1 hour (0.25%; P = .007) but not at 6 hours (1.4%; P = .49) compared with controls (2.2%). CONCLUSIONS: Intravenous DDFPe in an animal model decreases infarct volumes and protects brain tissue from ischemia, justifying further investigation.

Decreased Serum Levels of S-100B Protein Reflect Successful Treatment Effects in a Rabbit Model of Acute Ischemic Stroke.

Serum levels of S-100B were investigated as a marker for infarct volume and response to treatment following acute ischemic stroke in rabbits. Following subselective angiography, rabbits (n=31) were embolized by injection of a 3-day-old blood clot (0.6x4.0-mm) into the internal carotid artery. Treatment began 1-hr post-embolization, groups included: Control (n=8, embolization only), tissue plasminogen activator (tPA, n=12, 0.9mg/kg), and perflutren lipid microbubbles with transcranial ultrasound (MB+US, n=11, MB at 0.16mg/kg, US at 1-MHz pulsed-wave, 0.8 W/cm(2) for 1-hr). Serum S-100B levels were significantly increased (P<0.01) 24-hours following embolization in control (3.1-fold over baseline) and tPA (2.9-fold) groups, while treatment with MB+US resulted in an attenuated, non-significant (P=0.221) increase (1.6-fold). Twenty-four hour infarct volumes averaged 4.76%±1.16% for controls, 2.25%±0.95% for rabbits treated with tPA (P=0.32 vs. control), and 0.79%±0.99% for rabbits treated with MB+US (P=0.04 vs. control). Twenty-four hour concentrations of S-100B were positively correlated with infarct volume (r=0.59, P=0.0004).

Successful microbubble sonothrombolysis without tissue-type plasminogen activator in a rabbit model of acute ischemic stroke.

BACKGROUND AND PURPOSE: Microbubbles (MB) combined with ultrasound (US) have been shown to lyse clots without tissue-type plasminogen activator (tPA) both in vitro and in vivo. We evaluated sonothrombolysis with 3 types of MB using a rabbit embolic stroke model. METHODS: New Zealand White rabbits (n=74) received internal carotid angiographic embolization of single 3-day-old cylindrical clots (0.6 × 4.0 mm). Groups included: (1) control (n=11) embolized without treatment; (2) tPA (n=20); (3) tPA+US (n=10); (4) perflutren lipid MB+US (n=16); (5) albumin 3 µm MB+US (n=8); and (6) tagged albumin 3 µm MB+US (n=9). Treatment began 1 hour postembolization. Ultrasound was pulsed-wave (1 MHz; 0.8 W/cm²) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Lipid MB dose was intravenous (0.16 mg/kg) over 30 minutes. Dosage of 3 µm MB was 5 × 109 MB intravenously alone or tagged with eptifibatide and fibrin antibody over 30 minutes. Rabbits were euthanized at 24 hours. Infarct volume was determined using vital stains on brain sections. Hemorrhage was evaluated on hematoxylin and eosin sections. RESULTS: Infarct volume percent was lower for rabbits treated with lipid MB+US (1.0%± 0.6%; P=0.013), 3 µm MB+US (0.7% ± 0.9%; P=0.018), and tagged 3 µm MB+US (0.8% ± 0.8%; P=0.019) compared with controls (3.5%± 0.8%). The 3 MB types collectively had lower infarct volumes (P=0.0043) than controls. Infarct volume averaged 2.2% ± 0.6% and 1.7%± 0.8% for rabbits treated with tPA alone and tPA+US, respectively (P=nonsignificant). CONCLUSIONS: Sonothrombolysis without tPA using these MB is effective in decreasing infarct volumes. Study of human application and further MB technique development are justified.