Coagulant stability and sterility of thawed S/D-treated plasma

BACKGROUND: Units of frozen S/D-treated plasma (SDP) must be transfused within 24 hours after thawing. To avoid waste, an attempt was made to determine how long SDP could be therapeutically effective after thawing and storing it at 20 degrees C. STUDY DESIGN AND METHODS: The microbiologic safety and the activity of labile coagulation factors were evaluated in units stored at 20 degrees C of thawed SDP units and FFP within 24 hours of collection (FFP24). Five SDP and FFP24 samples of each ABO blood group were cultured and assayed for coagulation factors daily over 5 days. Assays included FV, FVII, FVIIa, FVIII, F IX, FXI, protein S, antiplasmin, fibrinogen, prothrombin times (PTs), and activated partial thromboplastin times (aPTTs). RESULTS: None of the 80 bacterial cultures demonstrated growth under either aerobic or anaerobic conditions. FV, FVIII, F IX, FXI, fibrinogen, and the aPTT appeared to be stable in both thawed FFP24 and SDP. The PT increased slightly in thawed FFP24 and insignificantly in SDP. FVII decreased slightly in FFP24 but remained in the normal range, and FVIIa was low and constant. FVII was increased in SDP and FVIIa was markedly increased. Protein S decreased from initial normal values in FFP24 to very low values. Protein S was very low immediately after thawing in the SDP and continued to decline. Antiplasmin was normal and stable in thawed FFP24 but was low in SDP and remained constant after thawing. CONCLUSION: Sterile SDP that is stored at 20 degrees C provides sufficient coagulant activity of labile FV and FVIII to transfuse it for up to 5 days after thaw. Caution is warranted by decreases in Protein S and antiplasmin, clinical evidence of coagulopathy in some recipients of SDP, and a recent manufacturer's warning.     

Effect of histamine H3 receptor blockade on venous return and splanchnic hemodynamics in experimental bacteremia

OBJECTIVE: In the heart, histamine H3 receptors may function as inhibitory presynaptic receptors that decrease adrenergic neural norepinephrine release in conditions of enhanced sympathetic tone. In a previous study, we found that H3 receptor blockade improved cardiac contractility and systemic hemodynamics in experimental bacteremia in dogs. Because histamine H3 receptors have been found in the splanchnic circulation in other animal models, it was not clear the extent to which H3 receptor blockade may have altered splanchnic hemodynamics, and variables of venous return, that in turn contributed to the overall improvement in systemic hemodynamics observed in the previous experiment. In the present study, we examined splanchnic hemodynamics in the presence of H3 receptor blockade in a canine model of Escherichia coli bacteremia. DESIGN: Bacteremia was produced by intravenous infusion of live E. coli administered throughout the experiment. Variables of venous return included mean systemic pressure, resistance to venous return, and mean right atrial pressure. Splanchnic measurements included hepatic and portal pressures and flows. Measurements were obtained before and after H3 receptor blockade with thioperamide maleate. The animals were studied while ventilated and anesthetized. RESULTS: H3 receptor blockade caused a decrease in mean right atrial pressure from 5.9 mm Hg pretreatment to 3.5 mm Hg posttreatment (p < .05), although it did not affect mean systemic pressure or resistance to venous return. There were no changes in portal or hepatic flows after H3 receptor blockade. The cardiac function curve after H3 receptor blockade was shifted upward and to the left compared with the pretreatment curve. CONCLUSIONS: The results showed that the primary effect of H3 receptor blockade in experimental bacteremia was attributable to an increase in inotropy. There was no evidence to indicate that H3 receptor activation contributed to altered splanchnic hemodynamics in this model.     

Feasibility study of real-time three-dimensional intracardiac echocardiography for guidance of interventional electrophysiology

The authors tested the feasibility of real-time three-dimensional intracardiac echocardiography for guidance of interventional electrophysiological studies. The three-dimensional scanner uses a matrix array ultrasound transducer of 64 channels operating at 5 MHz in a 12 Fr catheter. The system features real-time three-dimensional image rendering and produces up to 60 volumetric scans per second. Using an open-chest sheep model, real-time three-dimensional images of anatomic landmarks were obtained, including the pulmonary veins and coronary sinus, which are of value in electrophysiological procedures. In vivo radio frequency ablation procedures in the right ventricle were also monitored, which yielded lesions of high image contrast.     

Sympathoadrenergic mechanisms in reduced hemodynamic stress responses after exercise

PURPOSE: This study examines the acute effects of moderate aerobic exercise on 1) hemodynamic and sympathetic activity during behavioral stress and 2) beta-adrenergic receptor responsivity in a biracial sample of 24 sedentary adults. METHODS: Before and after exercise, blood pressure (BP), impedance-derived cardiovascular measures, and plasma norepinephrine (NE) and epinephrine (EPI) were assessed during mental arithmetic and active speech tasks, and beta-adrenergic receptor responsivity was assessed using a standard isoproterenol challenge procedure. RESULTS: After exercise, BP, NE, and EPI responses to stress were reduced (0.0001 < P < 0.08), preejection period (PEP) was elongated (P < 0.0001), and beta(1)- and beta(2)-receptor responsivity (P < 0.02) was enhanced. Approximately 65% of the prepost exercise mean arterial pressure response difference could be accounted for by changes in sympathetic factors, with change in NE and PEP being the single best predictors. CONCLUSIONS: Reduced BP responses to stress after acute exercise are strongly linked to a decrease in sympathetic drive, as evidenced by reduced NE responses and elongation of the PEP. Coincident with this overall dampening of the hemodynamic response to stress, increases in cardiac and vascular beta-adrenergic receptor responsivity occur. These findings may have important implications for future translational studies that seek to articulate the mechanisms through which regular aerobic exercise reduces the risks of hypertensive and coronary heart disease.     

Drinking to extremes: theoretical and empiricalanalyses of peak drinking levels among college students

OBJECTIVE: Heavy drinking among college students continues to be a substantial problem on campuses across the United States. Attempts to predict these drinking events have been restricted to assessments of the correlates of heavy drinking (measured at 4 or 5 drinks) and have not examined the peak drinking levels that can be fatal to students. This article presents a theoretical analysis of college drinking patterns that provides a basis for estimating peak drinking levels and predicts future risks related to peak drinking events. METHOD: Survey data were collected on sociodemographics and drinking patterns of 2,102 college students from two college campuses in California. A mathematical model of drinking patterns was used to characterize the stochastic distribution of drinking events among 1,273 students who drank five or more times and consumed more than one drink on some occasion since the beginning of the school year. An application of extreme value theory enabled the estimation of peak drinking levels for every college drinker. These estimates were related to self-reported maximum drinking levels and sociodemographic characteristics of respondents. RESULTS: Among these drinkers, the distribution of self-reported maximum drinking levels ranged from 2 to 43 drinks per occasion. Estimated peak drinking levels ranged from 3 to 49. Maximum drinking levels were well characterized by peak drinking estimates (R2 = 0.503). Variations in peak drinking levels were large and specifically related to particular sociodemographic groups (i.e., white male freshmen). CONCLUSIONS: The theoretical model of peak drinking events effectively characterizes maximum drinking levels among college students. High levels of peak drinking are to be expected among specific sociodemographic subgroups. These risks can be assessed on an individual basis. At the population level, risks for harm related to peak drinking events are predictable.     

Human factor Xa bound amidine inhibitor conformation by double rotational-echo double resonance nuclear magnetic resonance and molecular dynamics simulations

Double rotational-echo double resonance (double REDOR) NMR was used to investigate the conformation of a (13)C-, (15)N-, and (19)F-labeled inhibitor (Berlex Biosciences compound no. ZK-806299) bound to human factor Xa. Conformationally dependent carbon-fluorine dipolar couplings were measured by (13)C[(19)F] REDOR. Natural abundance carbon signals in the full-echo spectra were removed by (13)C[(15)N] REDOR. Major and minor binding modes were suggested by the NMR data, but only the former had adequate signal to noise for distance determinations. Molecular dynamics simulations restrained by double-REDOR-determined intramolecular (13)C-(19)F distances revealed two models for the dominant binding mode that are consistent with the NMR data. We conclude that ZK-806299 binds similarly to both FXa. Moreover, it appears to bind to FXa in a fashion previously demonstrated for ZK-807834, a more selective FXa inhibitor.     

Variations in pleural fluid WBC count and differential counts with different sample containers and different methods

OBJECTIVE: To compare the results of pleural fluid analysis for WBC counts and differential cell counts as follows: (1) counting performed manually vs that performed by an automated cell counter; (2) cells collected in different types of specimen containers; and (3) cell counts performed at 4 and 24 h postthoracentesis. METHODS: Twenty-eight pleural fluid samples were each collected in five different containers (ie, ethylenediaminetetraacetic acid (EDTA)-treated glass, citrate-treated glass, heparinized glass, plain glass, and plain plastic tubes). The WBC counts and differential cell counts were obtained manually (on the EDTA tube) and with an automated counter on all tubes within 4 h of collection, and again after 24 h of refrigeration. RESULTS: There was a close correlation between the WBC counts obtained manually and those obtained with the automated counter from the pleural fluid samples collected in the EDTA tubes (r = 0.92). With the automated counter, the pleural fluid WBC counts were similar among the three tubes containing anticoagulants, but the counts obtained from the tubes without anticoagulants were significantly lower. The differential cell counts obtained manually and those obtained with the automated cell counter differed substantially. Although the percentage of lymphocytes was similar, the automated counter was inaccurate in differentiating neutrophils from large monocytes or mesothelial cells. The WBC counts obtained within 4 h of collection and 24 h after collection were virtually identical. CONCLUSIONS: The WBC counts obtained manually and with the automated counter from pleural fluid samples in EDTA tubes correlated very closely. The pleural fluid WBC count was lower if the pleural fluids had been collected in tubes without an anticoagulant. Automated WBC counts from pleural fluid specimens were inaccurate, possibly due to difficulty in separating neutrophils from monocyte/mesothelial cells. Refrigerated storage for up to 24 h had no significant effect on the total WBC count or on the WBC count differential regardless of the tube utilized.