The role of prehospital electrocardiograms in the recognition of ST-segment elevation myocardial infarctions and reperfusion times.

BACKGROUND: Clinical outcomes in ST-segment elevation myocardial infarction (STEMI) are related to reperfusion times. Given the benefit of early recognition of STEMI and resulting ability to decrease reperfusion times and improve mortality, current prehospital recommendations are to obtain electrocardiograms (ECGs) in patients with concern for acute coronary syndrome. OBJECTIVES: We sought to determine the effect of wireless transmission of prehospital ECGs on STEMI recognition and reperfusion times. We hypothesized decreased reperfusion times in patients in whom prehospital ECGs were obtained. METHODS: We conducted a retrospective, observational study of patients who presented to our suburban, tertiary care, teaching hospital emergency department with STEMI on a prehospital ECG. RESULTS: Ninety-nine patients underwent reperfusion therapy. Patients with prehospital ECGs had a mean time to angioplasty suite of 43 min (95% confidence interval [CI] 31-54). Compared to patients with no prehospital ECG, mean time to angioplasty suite was 49 min (95% CI 41-57), p = 0.035. Patients with prehospital STEMI identification and catheterization laboratory activation had a mean time to angioplasty suite of 33 min (95% CI 25-41), p = 0.007. Patients with prehospital ECGs had a mean door-to-balloon time of 66 min (95% CI 53-79), whereas the control group had a mean door-to-balloon time of 79 min (95% CI 67-90), p = 0.024. Patients with prehospital STEMI identification and catheterization laboratory activation had a mean door-to-balloon time of 58 min (95% CI 48-68), p = 0.018. CONCLUSIONS: Prehospital STEMI identification allows for prompt catheterization laboratory activation, leading to decreased reperfusion times.

Severe feto-placental abnormalities precede the onset of hypertension and proteinuria in a mouse model of preeclampsia.

Preeclampsia is a prevalent and potentially devastating disorder of pregnancy. Characterized by a sudden spike in blood pressure and urinary protein levels, it is associated with significant obstetric complications. BPH/5 is an inbred mouse model of preeclampsia with borderline hypertension before pregnancy. BPH/5 mice develop hypertension, proteinuria, and endothelial dysfunction during late gestation (after E14.5). We hypothesized that BPH/5 mice might exhibit early feto-placental abnormalities before the onset of maternal disease. All placental cell lineages were present in BPH/5 mice. However, the fetal and placental weights were reduced, with abnormalities in all the placental zones observed starting early in gestation (E9.5-E12.5). The fractional area occupied by the junctional zone was significantly reduced at all gestational timepoints. Markedly fewer CDKN1C-stained trophoblasts were seen invading the proximal decidual zone, and this was accompanied by reductions in Cdkn1c gene expression. Trophoblast giant cell morphology and cytokeratin staining were not altered, although the mRNA levels of several giant cell-specific markers were significantly downregulated. The labyrinth layer displayed decreased branching morphogenesis of endothelial cells, with electron microscopy evidence of attenuated trophoblast layers. The maternal decidual arteries showed increased wall-to-lumen ratios with persistence of actin-positive smooth muscle cells. These changes translated into dramatically increased vascular resistance in the uterine arteries, as measured by pulse-wave Doppler. Collectively, these results support the hypothesis that defects at the maternal-fetal interface are primary causal events in preeclampsia, and further suggest the BPH/5 model is important for investigations of the underlying pathogenic mechanisms in preeclampsia.

Biochemical and functional characterization of membrane blebs purified from Neisseria meningitidis serogroup B.

Studies with purified aggregates of endotoxin have revealed the importance of lipopolysaccharide-binding protein (LBP)-dependent extraction and transfer of individual endotoxin molecules to CD14 in Toll-like receptor 4 (TLR4)-dependent cell activation. Endotoxin is normally embedded in the outer membrane of intact Gram-negative bacteria and shed membrane vesicles ("blebs"). However, the ability of LBP and CD14 to efficiently promote TLR4-dependent cell activation by membrane-associated endotoxin has not been studied extensively. In this study, we used an acetate auxotroph of Neisseria meningitidis serogroup B to facilitate metabolic labeling of bacterial endotoxin and compared interactions of purified endotoxin aggregates and of membrane-associated endotoxin with LBP, CD14, and endotoxin-responsive cells. The endotoxin, phospholipid, and protein composition of the recovered blebs indicate that the blebs derive from the bacterial outer membrane. Proteomic analysis revealed an unusual enrichment in highly cationic (pI > 9) proteins. Both purified endotoxin aggregates and blebs activate monocytes and endothelial cells in a LBP-, CD14-, and TLR4/MD-2-dependent fashion, but the blebs were 3-10-fold less potent when normalized for the amount of endotoxin added. Differences in potency correlated with differences in efficiency of LBP-dependent delivery to and extraction of endotoxin by CD14. Both membrane phospholipids and endotoxin are extracted by LBP/soluble CD14 (sCD14) treatment, but only endotoxin.sCD14 reacts with MD-2 and activates cells. These findings indicate that the proinflammatory potency of endotoxin may be regulated not only by the intrinsic structural properties of endotoxin but also by its association with neighboring molecules in the outer membrane.

Role of FcRgamma and factor XIIIA in coated platelet formation.

Platelet activation in response to dual stimulation with collagen and thrombin results in the formation of a subpopulation of activated platelets known as coated platelets. Coated platelets are characterized by high surface levels of alpha-granule proteins and phosphatidylserine, which support the assembly of procoagulant protein complexes. Using murine models, we tested the hypothesis that the collagen receptor-associated molecule FcRgamma and the transglutaminase factor XIIIA are required for the formation of coated platelets. Following dual stimulation with the collagen receptor agonist convulxin and thrombin, 68% of platelets from C57BL/6 mice acquired the coated platelet phenotype, defined by high surface levels of fibrinogen and von Willebrand factor and decreased binding of the alphaIIbbeta3 activation-dependent antibody PE-JON/A. In FcRgamma-/- mice, only 10% of platelets became "coated" after dual stimulation with convulxin plus thrombin (P < .05 vs C57BL/6 platelets). Decreased coated platelet formation in FcRgamma-/- platelets was accompanied by decreased annexin V binding (P < .01) and decreased platelet procoagulant activity (P < .05). Platelets from FXIIIA-/- mice did not differ from control platelets in coated platelet formation or annexin V binding. We conclude that FcRgamma, but not factor XIIIA, is essential for formation of highly procoagulant coated platelets following dual stimulation with collagen and thrombin.