Filtration of fentanyl is not the cause of the elevation of arterial blood pressure associated with post-bypass ultrafiltration in children

Modified ultrafiltration after cardiopulmonary bypass in children has been shown to be associated with an increase in arterial blood pressure. As part of a series of studies to investigate the possible causes of this blood pressure elevation, the hypothesis that if filtration was removing a significant amount of fentanyl, then the increase in blood pressure might be due to pain was proposed. Ten children, aged between 0.5 and 9.3 years (median 3.8 years), weighing 5.9 to 25..5 kg (median 15.7 kg), underwent corrective cardiac surgery (incorporating modified ultrafiltration). A standard anesthetic protocol was followed, with up to 78 μg/kg of fentanyl given prebypass for analgesia. After completion of cardiopulmonary bypass, modified ultrafiltration was commenced at 100 mL/min until a hematocrit of 35% was reached. Samples were taken of arterial blood (prefiltration, 3, 10, and 20 minutes postfiltration), the venous reservoir blood (prefiltration) and the filtrate (5 and 10 minutes into filtration). Hemodynamic data were recorded both prefiltration and postfiltration. The hemodynamic data showed the expected rise in both systemic arterial pressure and cardiac index after ultrafiltration. The plasma fentanyl concentrations did not significantly change after ultrafiltration: 1.59 to 12.39 ng/mL (median 6.27 ng/mL) prefiltration and 2.05 to 15.59 ng/mL (6.29 ng/mL) at 3 minutes, 2.22 to 12.64 ng/mL (6.87 ng/mL) at 10 minutes, and 1.83 to 11.52 ng/mL (5.85 ng/mL) at 20 minutes postfiltration. The concentration of fentanyl in the venous reservoir, 2.06 to 11.64 ng/mL (7.04 ng/mL), was not significantly different from the plasma levels. The level of fentanyl in the filtrate was significantly less than the plasma levels, 0.243 to 1.87 ng/mL (0.894 ng/mL) at 5 minutes and 0.385 to 1.688 ng / mL (0.952 ng / mL) at 10 minutes into filtration; (P < 0.02 by the Wilcoxon signed-rank method). The data show that the plasma fentanyl concentration was not significantly reduced by modified ultrafiltration. The fentanyl levels found prefiltration were maintained postfiltration, and the observed changes in systemic arterial pressure were not due to an acute fall in the plasma concentration of analgesic drug.     

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.     

Regional left atrial voltage in patients with atrial fibrillation

BACKGROUND: Regional differences in fibrosis, particularly related to the posterior wall and septum, may be important in atrial fibrillation (AF). Using electroanatomic mapping, voltage can be used as a measure of fibrosis. OBJECTIVES: The purpose of this study was to determine if patients with AF have disproportionately lower voltage in the septal and posterior walls of the left atrium. METHODS: Sinus rhythm left atrial electroanatomic maps were used in serial patients presenting for left atrial ablation of AF (8-mm tip). Patients undergoing left atrial mapping for focal atrial tachycardia (AT) were used as a comparison group (4-mm tip). Animal experiments were performed to assess the influence of ablation catheter tip size on voltage amplitude. RESULTS: The posterior and septal walls exhibited the lowest voltages in both groups. Compared with the anterior wall, there was a 3.78-fold greater odds of finding a low-voltage point (<0.5 mV) in the septum (P <.001) and a 3.37-fold greater odds of finding a low-voltage point in the posterior wall (P <.001) in the AF patients; the proportion of low-voltage points by region were not significantly different in the AT group. In the animal model, the mean voltage obtained from an 8-mm ablation catheter was significantly higher (0.30 +/- 0.17 mV) than that obtained from the same points using a 4-mm catheter (0.22 +/- 0.17, P = .05). CONCLUSION: Regional differences in voltage are present in patients with atrial arrhythmias, with AF patients exhibiting significantly more low-voltage areas in the septum and posterior walls.     

Deep dermal burn injury results in scarless wound healing in the ovine fetus

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.     

Extracorporeal membrane oxygenation for postcardiotomy mechanical cardiovascular support in children with congenital heart disease

Extracorporeal membrane oxygenation (ECMO) is increasingly used to support postcardiotomy cardiorespiratory failure in children with congenital heart disease. We report on survival outcomes and factors associated with survival for postcardiotomy ECMO patients.