Periventricular white matter (PVWM) injury is the leading cause of neurologic disability in survivors of prematurity. To address the role of ischemia in PVWM and cerebral cortical injury, we hypothesized that immaturity of spatially distal vascular 'end zones' or 'border zones' predisposes PVWM to greater decreases in cerebral blood flow (CBF) than more proximal structures. We quantified regional CBF with fluorescently labeled microspheres in 0.65 gestation fetal sheep in histopathologically defined three-dimensional regions by post hoc digital dissection and coregistration algorithms. Basal flow in PVWM was significantly lower than in gyral white matter and cortex, but was equivalent in superficial, middle, and deep PVWM. Absolute and relative CBF (expressed as percentage of basal) did not differ significantly during ischemia or reperfusion between PVWM, gyral white matter, or cortex. Moreover, CBF during ischemia-reperfusion was equivalent in three adjacent PVWM levels and was not consistent with the magnitude of severity of PVWM injury, defined by TUNEL (terminal deoxynucleotidyltransferase-mediated dUPT nick end labeling) staining. However, the magnitude of ischemia was predicted by the severity of discrete cortical lesions. Hence, unlike cerebral cortex, unique CBF disturbances did not account for the distribution of PVWM injury. Previously defined cellular maturational factors, thus, appear to have a greater influence on PVWM vulnerability to ischemic injury than the presence of immature vascular boundary zones.

Introduction Pulmonary oedema and impairment of oxygenation are reported as common consequences of haemorrhagic shock and resuscitation (HSR). Surprisingly, there is little information in the literature examining differences in crystalloid type during the early phase of HSR regarding the development of pulmonary oedema, the impact on oxygenation and the haemodynamic response. These experiments were designed to determine if differences exist because of crystalloid fluid type in the development of oedema, the impact on oxygenation and the haemodynamic response to fluid administration in early HSR.

The PDAS provides a reliable tool to record physiologic signals and associated clinical events on a second-to-second basis and may serve as an important adjunctive research tool in designing and performing clinical physiologic studies in critical illness and injury.

Objective: Traumatic brain injury (TBI) frequently results in poor outcome, suggesting that new approaches are needed. We hypothesized that a patient-specific in silico computer model of ICP dynamics may predict the ICP response to therapy. Design: In silico model analysis of prospective data. Stetting: 16-bed pediatric intensive care unit in a tertiary care academic hospital. Patients: 9 subjects with severe TBI undergoing ICP monitoring (7M/2F, age range 3-17 years). Interventions: Random changes in head-of-bed (HOB)(0 0 , 10 0 , 20 0 , 30 0 , 40 0) elevation and respiratory rate (to achieve a ∆ETCO2 = ±3-4 mmHg) daily as long as an ICP monitor was in place. Methods and Main Outcome Measures: A 6-compartment dynamic ICP model was constructed based on data from the interventions and session-specific model parameters were estimated. The accuracy of session-specific model-calculated ICP was compared to the accuracy ICP calculated using non-session specific parameter values. To assess the prediction accuracy of the model, two analyses were performed: a "within" session analysis of Segment A for model estimation and Segment B for prediction, and a "between" session analysis to predict later session ICP using parameters from > 1 earlier sessions. A mean absolute error to mean absolute deviation ratio (MAE/MAD) of < 1 was considered favorable. Results: For non-session specific parameters, MAE/MAD was <1 in 2/24 (8%) sessions. For session-specific parameter values MAE/MAD was <1 in 21/24 (88%) sessions, and <0.5 in 9/24 (38%) sessions. Sessions with low (<12 mm Hg) (N=8; 33%) or high (>18 mm Hg) (N=6; 25%) ICP had lower error than moderate ICP (12-18 mmHg) (N=10; 42%). MAE/MAD was <1 for 6/22 (27%) for within-session predictions and 3/31 (10%) for between-session predictions. 3 Conclusions: The protocol for collecting physiologic data in subjects with severe TBI was feasible and without undue risk. The in silico ICP model with session-specific parameters accurately reproduced actual ICP response to changes in HOB and RR. We demonstrated modest success at predicting future ICP within a session and to a lesser extent between sessions.