Previous angina alters in-hospital outcome in TIMI 4. A clinical correlate to preconditioning?

BACKGROUND: Ischemic preconditioning has been shown to reduce myocardial infarct size in experimental models, but its role in patients remains unclear. Angina before myocardial infarction reflects brief episodes of ischemia and may be a marker of preconditioning. As part of the Thrombolysis in Myocardial Infarction (TIMI) 4 study, we performed an analysis on the effect of a history of previous angina on in-hospital outcomes for patients with acute myocardial infarction. METHODS AND RESULTS: Patients eligible for thrombolytic therapy were enrolled into the study. Data were collected from case report forms regarding previous history of angina, in-hospital outcome and 6-week follow-up. Two hundred eighteen patients had a history of previous angina at any time before acute myocardial infarction, and 198 patients did not have previous angina. Patients with any previous history of angina were less likely than with those without angina to experience in-hospital death (3% versus 8%) (P = .03), severe congestive heart failure (CHF) or shock (1% versus 7%, P = .006), or the combined end point of in-hospital death, severe CHF, or shock (4% versus 12%, P = .004). Moreover, patients with any history of angina were more likely to have a smaller creatine kinase (CK)-determined infarct size (119 versus 154 CK integrated units; P = .01) and were less likely to have Q waves on their ECG (57% versus 69%; P = .01). In the subset of patients who experienced angina within the 48 hours before infarction (compared with those who did not), there was a trend toward less likely in-hospital death (3% versus 6%; P = .09), a lower incidence of severe CHF or shock (1% versus 6% P = .008), a lower combined end point of death, CHF, or shock (3% versus 10%; P = .006), smaller infarct size assessed by CK (115 versus 151 CK units; P = .03), and a trend toward fewer Q-wave infarcts. However, patients with a history of previous angina did have a trend toward more recurrent ischemic pain. Of importance is that the beneficial in-hospital effects of previous angina were not dependent on angiographically visible coronary collaterals. CONCLUSIONS: Previous angina confers a beneficial effect on in-hospital outcome after acute myocardial infarction. The reasons for this benefit are uncertain, but one potential mechanism for this observation may be ischemic preconditioning.

HeLa cell invasion by a strain of enteropathogenic Escherichia coli that lacks the O-antigenic polysaccharide.

The interaction with HeLa cells of an enteropathogenic Escherichia coli (EPEC) strain and its plasmid-cured derivative strain was examined. An O111:NM EPEC strain B171 harbours a 54 megadalton plasmid (pYR111) necessary for the expression of both localized adherence (LA) to HeLa cells and the O-repeating side chain of the lipopolysaccharide. Under light microscopy, the plasmid-cured derivative strain B171-4 was observed to interact with HeLa cells in a pattern distinct from LA. Transmission electron microscopy showed that the bacteria were internalized by HeLa cells. In contrast, strain B171 induced pedestal-like projections and invaginations of the plasma membrane, but was never completely internalized. A quantitative assay to determine the number of internalized bacteria revealed that strain B171-4 was internalized at levels 30-70-fold higher than those of avirulent E. coli strains. Cytochalasin B reduced the levels of internalization of both strain B171-4 and an enteroinvasive E. coli strain (E11), but did not affect LA by strain B171. These results suggest that EPEC strain B171 may carry a specific chromosomally determined surface factor needed to initiate internalization by HeLa cells. However, a plasmid-determined factor alters the nature of this interaction; the combined effects of the chromosomal and plasmid determinants lead to the characteristic attachment of the bacteria in clusters on the surface of the eukaryotic cell.

Plasmid-encoded expression of lipopolysaccharide O-antigenic polysaccharide in enteropathogenic Escherichia coli.

The role of a plasmid in the virulence activity of an enteropathogenic Escherichia coli (EPEC) strain belonging to serotype 0111:NM was examined. EPEC strain B171, which is resistant to chloramphenicol, streptomycin, sulfathiazole, and tetracycline, harbors a 54-megadalton plasmid, pYR111, and exhibits localized adherence (LA) with HeLa cells. Curing the plasmid yielded strain B171-4, which had lost the ability to exhibit LA, resistance to the antibiotics, and the lipopolysaccharide (LPS) O-antigenic polysaccharide. To confirm that these phenotypic characteristics were specified by pYR111, the plasmid was transferred by conjugation into a nalidixic acid-resistant strain of E. coli HB101. LA and antimicrobial resistance were expressed in most of the transconjugants examined. The O-polysaccharide side chains, antigenically reactive with O111-specific antiserum, were also expressed by the transconjugants. Although EPEC plasmids coding for both drug resistance and LA have been described, an EPEC plasmid encoding the expression of an LPS O antigen has not been previously reported. Similar findings described for some Shigella and Salmonella strains suggest that plasmid-encoded modification of the LPS in some enteric bacterial species may be more common than previously recognized and may contribute to the characteristic virulence activity of the organism.