Addition of aprotinin to organ preservation solutions decreases lung reperfusion injury.
BACKGROUND
Organ preservation injury is associated with endothelial cell damage, destabilization of mitochondrial and cell membranes, and the release of proteolytic enzymes. In addition to its well-known clinical effect of reducing perioperative blood loss, aprotinin has antiproteolytic and membrane-stabilizing properties. We hypothesized that adding aprotinin to Euro-Collins (EC) and University of Wisconsin (UW) solutions would decrease preservation injury in cultured endothelial cells and a whole organ rat lung model.


METHODS
Bovine aortic endothelial cells were cultured and stored in the respective solution at 4 degrees C for 12 or 48 hours. Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. In the whole organ model, rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were ventilated with 100% O2 and reperfused with fresh blood. Alveolar-arterial O2 difference, O2 tension, capillary filtration coefficient, and compliance were determined.


RESULTS
Endothelial cell viability was optimized with the addition of aprotinin to EC and UW at a dose of 150 KIU/mL (0.02 mg/mL). In the isolated perfused lung model, after 6 hours of ischemic storage, aprotinin-enhanced (100 KIU/mL [0.014 mg/mL]) EC and UW decreased alveolar-arterial O2 difference, increased O2 tension, and decreased capillary filtration coefficient compared with EC and UW alone. After 12 hours of ischemic storage, aprotinin-enhanced EC and UW decreased alveolar-arterial O2 difference, increased O2 tension, decreased capillary filtration coefficient, and increased compliance compared with EC and UW alone.


CONCLUSIONS
The addition of aprotinin to EC and UW solutions increases endothelial cell viability in hypoxic cold storage conditions. In terms of whole organ function, aprotinin improves lung preservation as demonstrated by increased oxygenation and compliance, and decreased capillary permeability. This study is clinically applicable as there is already extensive experience with the use of aprotinin in heart and lung transplant recipients, in addition to its routine use in conventional cardiac operations.
Roberts
R F
RF
Department of Surgery, University of Southern California School of Medicine and Childrens Hospital Los Angele, 90033, USA.
Nishanian
G P
GP
Carey
J N
JN
Darbinian
S H
SH
Kim
J D
JD
Sakamaki
Y
Y
Chang
J Y
JY
Starnes
V A
VA
Barr
M L
ML
D000241:Adenosine / Q000627:therapeutic use; D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D002196:Capillaries / Q000502:physiology; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival; D002478:Cells, Cultured; D015925:Cryopreservation; D010450:Endopeptidases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D005978:Glutathione / Q000627:therapeutic use; D006490:Hemostatics / Q000627:therapeutic use*; D006982:Hypertonic Solutions / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008170:Lung Compliance; D008171:Lung Diseases / Q000517:prevention & control*; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000648:ultrastructure; D019188:Organ Preservation Solutions / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D011480:Protease Inhibitors / Q000627:therapeutic use; D011887:Raffinose / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D014692:Ventilation-Perfusion Ratio
C037096:Euro-Collins' solution; D006490:Hemostatics; D006982:Hypertonic Solutions; D007328:Insulin; D019188:Organ Preservation Solutions; D011480:Protease Inhibitors; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D007611:Aprotinin; D010450:Endopeptidases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen