ABSTRACT
OBJECTIVE: To test whether the variations of tissue hemoglobin concentration (∆THb) measured by the FORE-SIGHT(TM) cerebral oximeter can accurately detect changes in arterial hemoglobin concentration (∆AHb) before, during, and after cardiopulmonary bypass. DESIGN: A prospective clinical study. SETTING: Cardiac surgery operating room. PARTICIPANTS: Thirty patients scheduled for cardiac surgery. INTERVENTIONS: Tissue hemoglobin concentration (THb) was recorded continuously via 2 sensors applied on the forehead and connected to the cerebral oximeter. Arterial hemoglobin concentration (AHb) was measured in a hematology analyzer laboratory. Hemodynamic and respiratory parameters as well as epidemiologic data also were noted. Data were collected at 3 perioperative times: After induction of anesthesia, 10 minutes after cardioplegia, and at the end of the surgery. MEASUREMENTS AND MAIN RESULTS: Ninety pairs of data were collected. The coefficient of linear regression between ∆THb and ∆AHb was 0.4 (p<0.001). After exclusion of Hb variations<5%, the trending ability of THb to predict ∆AHb was 87%. However, the Bland and Altman plot graph for THb and AHb showed major limits of agreement (2.4 times the standard deviation). Central venous pressure and carbon dioxide tension were linked independently and positively with THb (p = 0.03). CONCLUSIONS: Continuous monitoring of THb cannot accurately track variations of AHb during the transition from pulsatile to continuous flow and vice versa in cardiac surgery. Local hemodynamic factors such as PaCO2 and vasodilation significantly impact THb. In this setting, THb monitoring should not be used to guide eventual blood transfusion management.
Subject(s)
Cardiac Surgical Procedures/methods , Hemoglobinometry/methods , Hemoglobins/metabolism , Oximetry/methods , Adult , Aged , Aged, 80 and over , Blood Gas Analysis , Carbon Dioxide/blood , Central Venous Pressure , Female , Hemoglobins/analysis , Humans , Male , Middle Aged , Monitoring, Intraoperative , Postoperative Period , Prospective StudiesABSTRACT
Accumulation of amyloid-beta (Abeta) is one of the earliest molecular events in Alzheimer disease (AD), whereas tau pathology is thought to be a later downstream event. It is now well established that Abeta exists as monomers, oligomers, and fibrils. To study the temporal profile of Abeta oligomer formation in vivo and to determine their interaction with tau pathology, we used the 3xTg-AD mice, which develop a progressive accumulation of plaques and tangles and cognitive impairments. We show that SDS-resistant Abeta oligomers accumulate in an age-dependent fashion, and we present evidence to show that oligomerization of Abeta appears to first occur intraneuronally. Finally, we show that a single intrahippocampal injection of a specific oligomeric antibody is sufficient to clear Abeta pathology, and more importantly, tau pathology. Therefore, Abeta oligomers may play a role in the induction of tau pathology, making the interference of Abeta oligomerization a valid therapeutic target.
Subject(s)
Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , tau Proteins/metabolism , Aging , Amyloid beta-Peptides/genetics , Animals , Disease Models, Animal , Functional Laterality , Hippocampus/growth & development , Hippocampus/pathology , Humans , Macromolecular Substances/metabolism , Mice , Mice, Transgenic , Neurons/pathology , Recombinant Proteins/metabolismABSTRACT
The association between nicotinic acetylcholine receptor (nAChR) dysfunction and cognitive decline in Alzheimer's disease (AD) has been widely exploited for its therapeutic potential. The effects of chronic nicotine exposure on Abeta accumulation have been studied in both humans and animal models, but its therapeutic efficacy for AD neuropathology is still unresolved. To date, no in vivo studies have addressed the consequences of activating nAChRs on tau pathology. To determine the effects of chronic nicotine administration on Abeta and tau pathology, we chronically administrated nicotine to a transgenic model of AD (3xTg-AD) in their drinking water. Here, we show that chronic nicotine intake causes an up-regulation of nicotinic receptors, which correlated with a marked increase in the aggregation and phosphorylation state of tau. These data show that nicotine exacerbates tau pathology in vivo. The increase in tau phosphorylation appears to be due to the activation of p38-mitogen-activated protein kinase, which is known to phosphorylate tau in vivo and in vitro. We also show that the 3xTg-AD mice have an age-dependent reduction of alpha7nAChRs compared with age-matched nontransgenic mice in specific brain regions. The reduction of alpha7nAChRs is first apparent at 6 months of age and is restricted to brain regions that show intraneuronal Abeta(42) accumulation. Finally, this study highlights the importance of testing compounds designed to ameliorate AD pathology in a model with both neuropathological lesions because of the differential effects it can have on either Abeta or tau.
