Did Clinical Trials in Which Erythropoietin Failed to Reduce Acute Myocardial Infarct Size Miss a Narrow Therapeutic Window?

Background: To test a hypothesis that in negative clinical trials of erythropoietin in patients with acute myocardial infarction (MI) the erythropoietin (rhEPO) could be administered outside narrow therapeutic window. Despite overwhelming evidence of cardioprotective properties of rhEPO in animal studies, the outcomes of recently concluded phase II clinical trials have failed to demonstrate the efficacy of rhEPO in patients with acute MI. However, the time between symptoms onset and rhEPO administration in negative clinical trials was much longer that in successful animal experiments. Methodology/Principal Findings: MI was induced in rats either by a permanent ligation of a descending coronary artery or by a 2-hr occlusion followed by a reperfusion. rhEPO, 3000 IU/kg, was administered intraperitoneally at the time of reperfusion, 4 hrs after beginning of reperfusion, or 6 hrs after permanent occlusion. MI size was measured histologically 24 hrs after coronary occlusion. The area of myocardium at risk was similar among groups. The MI size in untreated rats averaged,42 % of area at risk, or,24 % of left ventricle, and was reduced by more than 50 % (p,0.001) in rats treated with rhEPO at the time of reperfusion. The MI size was not affected by treatment administered 4 hrs after reperfusion or 6 hrs after permanent coronary occlusion. Therefore, our study in a rat experimental model of MI demonstrates that rhEPO administered within 2 hrs of a coronary occlusion effectively reduces MI size, but when rhEPO was administered following a delay similar to that encountered in clinical trials, it had no effect on MI size

Diseases and Causes of Death in European Bats: Dynamics in Disease Susceptibility and Infection Rates

Bats receive increasing attention in infectious disease studies, because of their well recognized status as reservoir species for various infectious agents. This is even more important, as bats with their capability of long distance dispersal and complex social structures are unique in the way microbes could be spread by these mammalian species. Nevertheless, infection studies in bats are predominantly limited to the identification of specific pathogens presenting a potential health threat to humans. But the impact of infectious agents on the individual host and their importance on bat mortality is largely unknown and has been neglected in most studies published to date.) were collected in different geographic regions in Germany. Most animals represented individual cases that have been incidentally found close to roosting sites or near human habitation in urban and urban-like environments. The bat carcasses were subjected to a post-mortem examination and investigated histo-pathologically, bacteriologically and virologically. Trauma and disease represented the most important causes of death in these bats. Comparative analysis of pathological findings and microbiological results show that microbial agents indeed have an impact on bats succumbing to infectious diseases, with fatal bacterial, viral and parasitic infections found in at least 12% of the bats investigated.Our data demonstrate the importance of diseases and infectious agents as cause of death in European bat species. The clear seasonal and individual variations in disease prevalence and infection rates indicate that maternity colonies are more susceptible to infectious agents, underlining the possible important role of host physiology, immunity and roosting behavior as risk factors for infection of bats

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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