Effect of recombinant aprotinin on postoperative blood loss and coronary vascular function in a canine model of cardiopulmonary bypass.
OBJECTIVE
Aprotinin is a widely used serine protease inhibitor during cardiopulmonary bypass to reduce blood loss and preserve platelet function. However, the bovine-derived aprotinin can induce hypersensitivity reaction with fatal complications. Furthermore, vascular effects of aprotinin are not completely elucidated. The current study is designed to investigate the effects of recently developed recombinant aprotinin on blood loss and coronary vascular function in a clinically relevant canine model of cardiopulmonary bypass without aortic cross-clamping and cardioplegia.


METHODS
Twenty-four dogs underwent cardiopulmonary bypass without aortic cross-clamping and cardioplegia. Dogs were divided into three groups in a blinded fashion: control animals (n=8) received placebo, aprotinin treatment groups received bovine (n=8) or recombinant aprotinin (n=8) according to the Hammersmith method. The doses of bovine and recombinant aprotinin were the same. Coagulation parameters and blood loss were measured regularly at different time points. Endothelium-dependent and -independent vasorelaxation were investigated in isolated left anterior descendent coronary arterial rings by using acetylcholine and bradykinin or sodium nitroprusside and adenosine, respectively.


RESULTS
Postoperative blood loss was significantly reduced in the aprotinin-treated groups in comparison to control and there was no significant difference between the two aprotinin-treated groups. Endothelium-dependent relaxation of coronary arteries to acetylcholine and bradykinin was unaffected in the aprotinin treatment groups. Both types of aprotinin significantly increased vasorelaxation to adenosine when compared with controls, but did not affect that to sodium nitroprusside.


CONCLUSIONS
The effectiveness of recombinant aprotinin on blood loss was equivalent to bovine-derived aprotinin. Neither types of aprotinin impaired endothelium-dependent relaxation in a canine model of cardiopulmonary bypass.
Veres
Gábor
G
Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
Radovits
Tamás
T
Schultz
Holger
H
Lin
Li-ni
LN
Hütter
Joachim
J
Weigang
Ernst
E
Szabolcs
Zoltán
Z
Szabó
Gábor
G
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D002315:Cardiopulmonary Bypass / Q000379:methods*; D002417:Cattle; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004285:Dogs; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000008:administration & dosage; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D011994:Recombinant Proteins; D015842:Serine Proteinase Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D007611:Aprotinin; D000109:Acetylcholine; D001920:Bradykinin