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Unlabelled: Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens., Implications: Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Since bupivacaine and epinephrine may both precipitate dysrhythmias, circulating bupivacaine during regional anesthesia could potentiate dysrhythmogenic effects of epinephrine. We therefore examined whether bupivacaine alters the dysrhythmogenicity of subsequent administration of epinephrine in conscious, healthy dogs and in anesthetized dogs with myocardial infarction. Forty-one conscious dogs received 10 micrograms.kg-1.min-1 epinephrine. Seventeen animals responded with ventricular tachycardia (VT) within 3 min. After 3 h, these responders randomly received 1 or 2 mg/kg bupivacaine or saline over 5 min, followed by 10 micrograms.kg-1.min-1 epinephrine. In the bupivacaine groups, epinephrine caused fewer prodysrhythmic effects than without bupivacaine. VT appeared in fewer dogs and at a later time, and there were more sinoatrial beats and less ectopies. Epinephrine shortened QT less after bupivacaine than in control animals. One day after experimental myocardial infarction, six additional halothane-anesthetized dogs received 4 micrograms.kg-1.min-1 epinephrine until VT appeared. After 45 min, 1 mg/kg bupivacaine was injected over 5 min, again followed by 4 micrograms.kg-1.min-1 epinephrine. In these dogs, the prodysrhythmic response to epinephrine was also mitigated by preceding bupivacaine. Bupivacaine antagonizes epinephrine dysrhythmogenicity in conscious dogs susceptible to VT and in anesthetized dogs with spontaneous postinfarct dysrhythmias. There is no evidence that systemic subtoxic bupivacaine administration enhances the dysrhythmogenicity of subsequent epinephrine.

Conventional therapies with recombinant human erythropoietin (rHuEPO) to sustain preoperative autologous blood collection entail high doses of the drug at short intervals. To evaluate the efficacy of a single weekly dose of rHuEPO for autologous blood collection, we randomly assigned 24 male patients scheduled for coronary artery bypass surgery to receive 400 IU/kg rHuEPO subcutaneously once a week or iron only. Patients were examined weekly and a total of up to 4 units of autologous blood were obtained if the hemoglobin level exceeded 12 g/dL. Patients receiving rHuEPO had consistently higher hemoglobin values than those receiving iron only (P < 0.001). Consequently, more autologous red cells were obtained from this group (776 +/- 49 mL vs 682 +/- 91 mL; P < 0.05). One patient receiving rHuEPO and eight in the control group required homologous blood at surgery (P < 0.01). These results suggest that 400 IU/kg rHuEPO administered subcutaneously once a week efficiently stimulates erythropoiesis and compensates the hemoglobin decrease after autologous blood donation.