Bbeta15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion.
OBJECTIVE
The fibrin-derived peptide Bbeta15-42 (also called FX06) has been shown to reduce myocardial infarct size following ischemia/reperfusion. Hemorrhagic shock (HS) followed by volume resuscitation represents a similar scenario, whereby a whole organism is vulnerable to reperfusion injury.


METHODS
We subjected male farm-bred landrace pigs ( approximately 30 kg) to HS by withdrawing blood to a mean arterial pressure of 40 mm Hg for 60 minutes. Pigs were then resuscitated with shed blood and crystalloids for 60 minutes, and at this time, FX06 (2.4 mg/kg, n = 8) or vehicle control (phosphate buffered saline; 2.4 mg/kg, n = 7) was injected as an intravenous bolus.


METHODS
University hospital laboratory.


METHODS
Anesthetized male farm-bred landrace pigs.


RESULTS
Data are presented as mean +/- sd. Five hours after resuscitation, controls presented acute lung injury (Pao2/Fio2-ratio <300 mm Hg; extra-vascular lung water index (marker for lung injury): 9.0 +/- 1.8 mL/kg) and myocardial dysfunction/damage (cardiac index: 4.3 +/- 0.25 L/min/m; stroke volume index: 30 +/- 6 mL/m; cardiac TnT levels: 0.58 +/- 0.25 ng/mL). In contrast, FX06-treated animals showed significantly improved pulmonary and circulatory function (Pao2/Fio2-ratio >*400 mm Hg; extra-vascular lung water index: *5.2 +/- 2.1 mL/kg, cardiac index: *6.3 +/- 1.4 L/min/m; stroke volume index: *51 +/- 11 mL/m; cardiac TnT levels: *0.11 +/- 0.09 ng/mL; *p < 0.05). Also, tissue oxygenation (tpO2; mm Hg) was significantly improved during reperfusion in FX06-treated pigs when compared with controls (liver 51 +/- 4 vs. *65 +/- 4; serosa 44 +/- 5 vs. *55 +/- 7; mucosa 14 +/- 4 vs. *26 +/- 4). Finally, FX06 reduced accumulation of myeloperoxidase-positive cells (mainly neutrophils) in myocardium, liver, and small intestine and reduced interleukin-6 plasma levels (*p < 0.05; compared with controls).


CONCLUSIONS
We conclude that in a pig model of HS and reperfusion, administration of FX06 during reperfusion protects shock- susceptible organs such as heart, lung, liver, and small intestine.
Roesner
Jan P
JP
Department of Anaesthesia and Intensive Care Medicine, University Hospital Rostock, Germany.
Petzelbauer
Peter
P
Koch
Alexander
A
Tran
Nguyen
N
Iber
Thomas
T
Vagts
Dierk A
DA
Scheeren
Thomas W L
TW
Vollmar
Brigitte
B
Nöldge-Schomburg
Gabriele E F
GE
Zacharowski
Kai
K
D000818:Animals; D005338:Fibrin Fibrinogen Degradation Products / Q000627:therapeutic use*; D006335:Heart Injuries / Q000517:prevention & control*; D006801:Humans; D007421:Intestine, Small / Q000293:injuries*; D008099:Liver / Q000293:injuries*; D055370:Lung Injury / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D023421:Models, Animal; D010446:Peptide Fragments / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine
D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42)