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Stroke and myocardial infarction are major causes of death in Western countries. Hypoxia and its associated tissue hypoperfusion are among the factors that cause or contribute to cellular ischemia, a state that is characterized by a disturbed oxygen balance. Because early treatment with erythropoietin (EPO) has been shown to be effective in ischemic tissues, we decided to investigate whether the neurohumoral action of EPO could improve cardiac function in a heart failure model. Hematocrit was decreased to 24-25% in sham-operated or infarcted animals by intravenous administration of darbepoetin alfa, a recombinant human EPO. The effect of EPO on cardiac function was examined in a left anterior descending coronary artery occlusion model of rat myocardial infarction. Administration of darbepoetin alfa at doses of 150, 300, or 450 U/kg significantly elevated hematocrit to 31% to 37%. These increases in hematocrit were not accompanied by significant changes in blood pressure. Heart rate, aortic pressure, left ventricular developed pressure, and its first derivative (dP/dt) were unchanged. However, erythrocyte-restricted EPO at doses of 150, 300, or 450 U/kg significantly decreased infarct size to 10 +/- 5%, 7 +/- 3%, and 7 +/- 4%, respectively, compared with 23 +/- 8% in saline-treated controls (P THE RUMOURS OF DANGER: The Cast of the Dark Knight Returns

(Photo: Warner Bros. Home Entertainment)

I recently spent the better part of the afternoon reading an almost impossibly interesting script online by Chris Sims, which is called The Rumours of Danger: The Cast of the Dark Knight Returns. As you might guess from the title


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