Effect of known history of heart disease on survival outcomes after out‐of‐hospital cardiac arrests

Objective

We aimed to investigate the effect of known heart disease on post‐out‐of‐hospital cardiac arrest (OHCA) survival outcomes, and its association with factors influencing survival.

Methods

This was an observational, retrospective study involving an OHCA database from seven Asian countries in 2009–2012. Heart disease was defined as a documented diagnosis of coronary artery disease or congenital heart disease. Patients with non‐traumatic arrests for whom resuscitation was attempted and with known medical histories were included. Differences in demographics, arrest characteristics and survival between patients with and without known heart disease were analysed. Multivariate logistic regression was performed to identify factors influencing survival to discharge.

Results

Of 19 044 eligible patients, 5687 had known heart disease. They were older (77 vs 72 years) and had more comorbidities like diabetes (40.9 vs 21.8%), hypertension (60.6 vs 36.0%) and previous stroke (15.2 vs 10.1%). However, they were not more likely to receive bystander cardiopulmonary resuscitation (P = 0.205) or automated external defibrillation (P = 0.980). On univariate analysis, known heart disease was associated with increased survival (unadjusted odds ratio 1.16, 95% confidence interval 1.03–1.30). However, on multivariate analysis, heart disease predicted poorer survival (adjusted odds ratio 0.76, 95% confidence interval 0.58–1.00). Other factors influencing survival corresponded with previous reports.

Conclusions

Known heart disease independently predicted poorer post‐OHCA survival. This study may provide information to guide future prospective studies specifically looking at family education for patients with heart disease and the effect on OHCA outcomes.     

The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and hemostasis

Essentials

• Heat shock protein 47 (HSP47), a collagen specific chaperone is present on the platelet surface.
• Collagen mediated platelet function was reduced following blockade or deletion of HSP47.
• GPVI receptor regulated signalling was reduced in HSP47 deficient platelets.
• Platelet HSP47 tethers to exposed collagen thus modulating thrombosis and hemostasis.

Summary

Objective

Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering hemostasis and thrombosis, in this study we sought to characterize the role of HSP47 in these cells.

Methods and Results

The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP‐XL), but responses to thrombin were unaltered. In the absence of functional HSP47, the interaction of collagen with platelets was reduced, and this was associated with reduced GPVI‐collagen binding, signalling and platelet activation. Thrombus formation on collagen, under arterial flow conditions, was also decreased following the inhibition or deletion of HSP47, in the presence or absence of eptifibatide, consistent with a role for HSP47 in enhancing platelet adhesion to collagen. Platelet adhesion under flow to von Willebrand factor was unaltered following HSP47 inhibition. Laser‐induced thrombosis in cremaster muscle arterioles was reduced and bleeding time was prolonged in HSP47‐deficient mice or following inhibition of HSP47.

Conclusions

Our study demonstrates the presence of HSP47 on the platelet surface, where it interacts with collagen, stabilizes platelet adhesion and increases collagen‐mediated signalling and therefore thrombus formation and hemostasis.     

Angiostatin diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells

Angiostatin is an endogenous inhibitor of angiogenesis that was isolated from tumor-bearing mice. It has been established that angiostatin inhibits endothelial cell proliferation; however, the underlying mechanisms remain to be elucidated. Here we report that angiostatin reduces transiently the phosphorylation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular cells, but not in human vascular smooth muscle cells or human dermal fibroblasts. We demonstrate that angiostatin diminishes ERK activation by basic fibroblast growth factor and vascular endothelial growth factor. Dephosphorylation of ERK and other tyrosine-phosphorylated proteins was blocked by pretreatment of the cells with sodium meta-vanadate, an inhibitor of protein tyrosine phosphatases, indicating that angiostatin signaling may require the activity of a tyrosine phosphatase. Concentrations of angiostatin that inhibited ERK activation also inhibited basic fibroblast growth factor-stimulated collagen gel invasion by endothelial cells, but did not affect endothelial cell proliferation. We thus show that angiostatin inhibits primarily the invasion of endothelial cells and exerts minimal (if any) effects on their proliferation. Invasion is a process that involves proteolysis, adhesion and migration, all of which have been linked to ERK signaling.     

Microvascular function at the margins of early experimental myocardial infarcts in isolated rabbit hearts

Summary Injection of low-viscosity resin was used to identify in situ functional blood vessels at the margins of developing regional myocardial infarcts. The ventral interventricular branch (VIB) of the left coronary artery was occluded for 0–240 min in 20 isolated perfused rabbit hearts. After perfusion fixation with glutaraldehyde, resin was injected into the coronary arteries—that injected into the VIB contained dispersed lead dioxide and that injected into the remainder of the heart contained Fat Red 7B dye. This allowed macroscopic and microscopic identification of functional blood vessels. Following transmural freeze fracture, left ventricles were examined using back-scattered electron imaging in a scanning electron microscope. Close to 60% of capillaries in nonischemic myocardium allowed the passage of resin. Thirty minutes of ischemia produced a hyperemic increase to 80%–90% in the proportion of filled vessels. After 60 min, however, a severe reperfusion defect corresponding to the no-reflow phenomenon had developed, with virtually all vessels collapsed and <10% functional. Among the structurally normal myocytes adjacent to the infarct margin there was a significant reduction (to 30%–40%) in the proportion of functional capillaries. This was due to groups of dilated vessels which were not accessible to arterial supply. Although these marginal low-flow regions were of small volume at any one point in time, they seem likely to contribute to the progression of ischemic necrosis, and are probably nonfunctional due to the compression of their venous drainage traversing the infarct.This research was supported by grants from the Medical Research Council of New Zealand and the National Heart Foundation of New Zealand.     

Anemia of the Belgrade rat: evidence for defective membrane transport of iron

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.     

Lexical influences in graphemic buffer disorder

Abstract

We report the case of patient BH, who misspelled about half of the words she attempted and showed the characteristic features of “graphemic buffer disorder” (an effect of letter length on spelling accuracy, errors involving the substitution, omission, addition, and movement of letters that affect the middles more than the ends of words). Speech comprehension and production were good. Reading of words was, at most, only mildly impaired, though reading of nonwords was more affected. Words were spelled more accurately than nonwords, and BH's ability to spell words correctly was influenced by their imageability, age of acquisition, frequency, and number of orthographic neighbours (N). The effect of length was much reduced once these factors (especially N) were controlled. BH's spelling pattern is discussed in terms of top-down lexical influences on the graphemic buffer. We argue that such effects may be more widespread than has previously been acknowledged.