The fibrin-derived peptide Bβ _15-42 significantly attenuates ischemia-reperfusion injury in a cardiac transplant model

BACKGROUND.: The inflammatory response after prolonged ischemia and subsequent reperfusion leads to increased risk of primary organ dysfunction after cardiac transplantation. It has been demonstrated that the fibrin-derived peptide Bβ_15-42 (also called FX06) reduces infarct size in coronary artery occlusion/reperfusion models by inhibition of leukocyte migration. Further, Bβ_15-42 preserves endothelial barrier function. The purpose of this study was to investigate whether Bβ_15-42 has a protective effect in cardiac allografts exposed to prolonged global ischemia and subsequent in vivo reperfusion. METHODS.: Hearts of male Lewis rats were flushed and stored in cold Bretschneider preservation solution for 4 or 8 hr. Bβ_15-42 was administered before being transplanted into syngeneic recipients. Serum samples were collected for troponin-T measurements. Hemodynamic performance was evaluated after a reperfusion period of 24 hr. Morphologic quantification of myocardial necrosis was performed in hearts exposed to 24 hr or 10 days of reperfusion. RESULTS.: Allografts from Bβ_15-42 treated animals showed less myocardial necrosis (2.5%±2.5% vs. 18.4%±9.2%, P=0.0019) and decreased values of cardiac troponin-T (1.1±0.6 ng/mL vs. 2.7±2.3 ng/mL, P=0.0045), reduced number of infiltrating leukocytes (7.2±13.6 vs. 49.2±34.9 per high powerfield, P=0.0045), and superior cardiac output (78.1±1.8 mL/min vs. 21.7±4 mL/min, P=0.0034). Hearts exposed to 0 and 4 hr of ischemia showed no severe signs of myocardial damage. CONCLUSION.: Bβ_15-42 ameliorates the ischemia-reperfusion injury in transplanted hearts during extended cold ischemia by reduction of infiltrating leukocytes. This experimental protocol provides evidence that Bβ_15-42 may play a useful role in organ preservation, but clinical evaluation is warranted.