期刊
TRANSPLANTATION
卷 89, 期 7, 页码 824-829出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181ccd822
关键词
Fibrin-derived peptide B beta(15-42); Vascular endothelial cadherin; Inflammatory response; Ischemia-reperfusion; Heart transplantation
资金
- Department of Cardiac Surgery, Innsbruck Medical University, Austria
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 beta(15-42) (also called FX06) reduces infarct size in coronary artery occlusion/reperfusion models by inhibition of leukocyte migration. Further, beta(15-42) preserves endothelial barrier function. The purpose of this study was to investigate whether beta(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. beta(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 beta(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. beta(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 beta(15-42) may play a useful role in organ preservation, but clinical evaluation is warranted.
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