Response of serum proteome in patients undergoing infrarenal aortic aneurysm repair.
BACKGROUND
Postoperative organ dysfunction in conventional surgery for abdominal aortic aneurysm (AAA) is associated with a complex inflammatory reaction, with activation of coagulation and fibrinolysis. A prospective,observational study was performed to define the complex plasma proteomic changes after AAA repair and to identify factor(s) that may affect myocardial function in uncomplicated procedures.


METHODS
Ten patients undergoing infrarenal AAA repair were investigated. Eight subjects subjected to major abdominal surgery served as controls. Hemodynamic changes were continuously monitored by using the pressure recording analytical method technique. The time course of plasma proteins was investigated after induction of anesthesia and at different times after surgery (6 h, 12 h, 24 h, 36 h) by using two-dimensional difference gel electrophoresis, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and Western blot. The effects of plasma on the functional properties of isolated rat ventricular myocytes were also investigated.


RESULTS
In AAA patients alone, 18 spots were found to change more than two-fold in expression level, spot identification revealing an increased thrombin generation 6 h after surgery. At the same time cardiac cycle efficiency significantly reduced versus baseline (-0.5 +/- 0.9 vs. 0.18 +/- 0.3 in AAA patients, P < 0.01; 0.4 +/- 0.1 vs. 0.2 +/- 0.3 in control surgery, not significant; P < 0.01 group x time interaction at ANOVA). Plasma obtained 6 h after AAA surgery dose-dependently inhibited contractile function of control rat myocytes (percent shortening fell by 51% with 10% of AAA plasma and was abolished with 20% of AAA plasma, P < 0.001 for both). The inhibitory response was abolished by thrombin antagonism.


CONCLUSIONS
These findings show for the first time the possible role of thrombin generation within the complex activation of inflammatory response in causing hemodynamic instability in the early postoperative period after AAA surgery.
Modesti
Pietro Amedeo
PA
Department of Critical Care Medicine and Don C. Gnocchi Foundation, University of Florence, Viale Morgagni 85, Florence, Italy. pamodesti@unifi.it
Gamberi
Tania
T
Bazzini
Cristina
C
Borro
Marina
M
Romano
Salvatore Mario
SM
Cambi
Giulia Elisa
GE
Corvi
Andrea
A
Dorigo
Walter
W
Paparella
Laura
L
Pratesi
Carlo
C
Carini
Marco
M
Gensini
GianFranco
G
Modesti
Alessandra
A
D000368:Aged; D000818:Animals; D001014:Aortic Aneurysm / Q000097:blood* / Q000601:surgery*; D001798:Blood Proteins / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology; D010449:Peptide Mapping; D020543:Proteome / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013917:Thrombin / Q000737:chemistry / Q000235:genetics; D014656:Vascular Surgical Procedures
D001798:Blood Proteins; D020543:Proteome; D013917:Thrombin