Influence of frequency of atrial contraction on coronary blood flow and ventricular performance in the conscious dog with myocardial infarction.

The effects of alterations in the frequency of contraction on coronary blood flow and ventricular performance were studied in 12 conscious, unsedated dogs with established myocardial infarction. Total and regional coronary blood flow was measured using radioactive microspheres. The peak increase in flow to the right ventricle was 71% to the infarcted area of the left ventricle was 72% to the non-infarcted area of the left ventricle was 90% and to the ventricular septum was 104%. Despite the generalized increases in regional myocardial blood flow, flow tended to decrease to the subendocardial portion of the infarcted area of the left ventricle. The peak increases in coronary flow and the reduction in flow to the subendocardial portion of the infarcted area occurred at a heart rate of approximately 200/min provided by atrial pacing. Myocardial contractility, as evidenced by peak increases of 16% in maximum LV dP/dt and 12% in dP/dtP, was only enhanced with abrupt incremental changes in heart rate and not with continuous atrial pacing over 15-min periods. Despite the generalized increases in coronary perfusion coronary sinus oxygen content decreased with a widening of the coronary arteriovenous oxygen difference indicating increased myocardial oxygen usage. Thus increasing frequency of contraction in myocardial infarction results in a slight initial but not sustained inotropic effect, a moderate and generalized increase in regional myocardial blood flow, increased myocardial oxygen consumption, and the potential for subendocardial extension of the area of myocardial damage within the infarcted area.     

Heterogeneity in the response of vascular smooth muscle to heparin: altered signaling in heparin-resistant cells

OBJECTIVE: Vascular smooth muscle cells show phenotypic heterogeneity in vivo that affects the extent to which they respond to the antimitogenic effects of heparin. In vitro, heparin-resistant cells are readily selected. This study was undertaken to determine whether differences in the antiproliferative response to heparin involve differences in activity of heparin-sensitive signal transduction pathways. METHODS: Rat thoracic aorta smooth muscle cells (ASMC) at early passage together with two established vascular smooth muscle lines, PAC-1 and A10, were examined before and after selection for growth in the presence of heparin (10 micrograms/ml). Cells were rendered quiescent and then stimulated with serum. RESULTS: The three cell types showed different sensitivities to the antimitogenic effects of heparin. With respect to [3H]thymidine incorporation, A10 cells were insensitive to 1 microgram/ml heparin whereas PAC-1 cells responded down to 0.05 microgram/ml and ASMC were of intermediate sensitivity. ASMC and PAC-1 cells but not A10 showed a decrease in c-fos mRNA in response to 1 microgram/ml heparin, and a decrease in the c-Fos content of AP-1 DNA binding activity. None of the cells had decreased c-jun mRNA in the presence of heparin. Although induction of c-fos by serum is thought to signal through the Erk mitogen activated protein kinase family, Erk activity was decreased more by 1 microgram/ml heparin in A10 cells than in PAC-1 or ASMC. When cells were selected by growth in the presence of 10 micrograms/ml heparin, A10 cells were unaffected but PAC-1 and ASMC showed a blunted effect of heparin on serum stimulation. In contrast to A10 and their controls not exposed to continuous heparin, heparin-selected PAC-1 and ASMC showed a diminished ability to induce c-fos in response to serum. CONCLUSIONS: Smooth muscle cell lines show different responses to the antimitogenic effects of heparin that correlate with the heparin sensitivity of c-Fos/c-Jun expression. Although Erk is implicated in c-fos induction, cells comparatively resistant to heparin still show heparin-dependent inhibition of Erk activation, suggesting that other pathways may be more important for heparin resistance. Furthermore, cells selected for heparin resistance may develop c-fos-independent pathways for proliferation.     

Systematic review of enhanced recovery after gastro-oesophageal cancer surgery

Introduction

Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery.

Methods

A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria.

Results

From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re-establishing oral intake in the first three postoperative days and early removal of nasogastric tubes.In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies.

Conclusions

The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay.     

Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor

The extracellular matrix (ECM) of cultured bovine aortic endothelial cells (BAEs) was analyzed by immunoblotting and reverse fibrin autography and shown to contain type 1 plasminogen activator inhibitor (PAI-1). Most PAI-1 in the ECM formed complexes with exogenously added tissue-type plasminogen activator (tPA), demonstrating that this PAI-1 was functionally active. The resulting tPA/PAI-1 complexes were recovered in the reaction solution, indicating that the PAI-1 in such complexes no longer bound to ECM. The PAI-1 could not be removed by incubating ECM in high salt (2 mol/L NaCl), sugars (1 mol/L galactose, 1 mol/L mannose), glycosaminoglycans (10 mmol/L heparin, 10 mmol/L dermatan sulfate), or epsilon-aminocaproic acid (0.1 mol/L). However, PAI-1 could be extracted from ECM by treatment with either arginine (0.5 mol/L) or potassium thiocyanate (2 mol/L), or by incubation under acidic conditions (pH 2.5). ECM depleted of PAI-1 by acid extraction was able to bind both the active and latent forms of PAI-1. In this instance, most of the bound PAI-1 did not form complexes with tPA, indicating that the latent form was not activated as a consequence of binding to ECM. Although the PAI-1 activity in conditioned medium decayed with a half-life (t 1/2) of less than 3 hours, the t 1/2 of ECM- associated PAI-1 was greater than 24 hours. These data suggest that PAI- 1 is produced by cultured BAEs in an active form and is then either released into the medium where it is rapidly inactivated or into the subendothelium where it binds to ECM. The specific binding of PAI-1 to ECM protects it from this inactivation.     

Eosinophils stimulate fibroblast DNA synthesis

Fibrosis complicates a number of chronic inflammatory diseases and occurs in some conditions following chronic hypereosinophilic syndromes. We assessed whether eosinophils might be a source of fibrogenic factors. Extracts of human and guinea pig cell populations enriched for eosinophils contained substances that stimulated tritiated thymidine incorporation by human fibroblasts. Supernatants derived from resting eosinophils and extracts prepared from eosinophil granules also contained fibrogenic factors. Our findings demonstrate a new potential role for eosinophils and suggest a causal relationship between tissue eosinophilia and scar formation in certain parasitic conditions.     

Urban legends series: Sjögren’s syndrome

Oral Diseases (2012) 19 , 46–58 Sjögren’s syndrome (SjS) is one of the most common autoimmune rheumatic diseases, clinically characterized by xerostomia and keratoconjunctivitis sicca. We investigated the following controversial topics: (i) Do we have reliable ways of assessing saliva production? (ii) How important are the quantity and quality of saliva? (iii) Are only anti‐SSA/Ro and anti‐SSB/La relevant for the diagnosis of SjS? (iv) Are the American‐European Consensus criteria (AECC) the best way to diagnose SjS? Results from literature searches suggested the following: (i) Despite the fact that numerous tests are available to assess salivation rates, direct comparisons among them are scarce with little evidence to suggest one best test. (ii) Recent developments highlight the importance of investigating the composition of saliva. However, more research is needed to standardize the methods of analysis and collection and refine the quality of the accumulating data. (iii) In addition to anti‐Ro/La autoantibodies, anti α‐fodrin IgA and anti‐MR3 autoantibodies seem to be promising diagnostic markers of SjS, but more studies are warranted to test their sensitivity and specificity. (iv) AECC are classification, not diagnostic criteria. Moreover, recent innovations have not been incorporated into these criteria. Consequently, treatment directed to patients diagnosed using the AECC might exclude a significant proportion of patients with SjS.