May 25, 2007

The fibrin-derived peptide Bbeta15-42 is cardioprotective in a pig model of myocardial ischemia-reperfusion injury

Critical Care Medicine
Jan P RoesnerKai Zacharowski

Abstract

The fibrin-derived peptide Bbeta15-42 has been shown to reduce infarct size in rodent models of ischemia-reperfusion injury. To increase its potential for translation into the clinic, we studied the effects of Bbeta15-42 in pigs, whose coronary anatomy is similar to that of humans. In addition, we evaluated the pharmacokinetics and safety of Bbeta15-42 in several species, including humans. Animal study and phase I trial. University hospital and contract research laboratories. Pigs/healthy volunteers. Male farm-bred Landrace pigs were subjected to 1 hr of left anterior descending coronary artery occlusion followed by 3 hrs of reperfusion. At the time of reperfusion, Bbeta15-42 (2.4 mg/kg, n = 6) or random peptide (control; 2.4 mg/kg, n = 6) was administered as an intravenous bolus. As a positive control, pigs were subjected to ischemic preconditioning (n = 6). Cardiac damage and hemodynamics were recorded. Biodistribution and pharmacokinetics of Bbeta15-42 were determined in rats and dogs. In a phase I trial involving 30 male healthy volunteers, pharmacokinetics and safety were tested in a randomized, double-blinded, placebo-controlled, parallel-group, single ascending dose study. Bbeta15-42 and ischemic preconditioning signific...Continue Reading

Mentioned in this Paper

Ischemia
Reperfusion Injury
Fibrin Measurement
Derivatives
Pathogenic Organism
Anti-Inflammatory Agents
Intravenous Bolus
Myocardial Infarction
Myocardial Ischemia
Adverse Effects

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