Cryptic cardiac alteration in uncomplicated patients undergoing aortic aneurysm repair. Role of trombin

Objective: Hypertension is a relevant risk factor for Abdominal Aortic Aneurysm (AAA) which recognize surgery as the main treatment. Ischemia-reperfusion during AAA repair often result in the release of proinflammatory cytokines that alter the plasma composition and may be followed by cardiovascular complications that contribute to increase of the mortality rate in the postoperative phase. However, whether a relationship exists between the systemic inflammatory response and the occurrence of cryptic hemodynamic alterations in uncomplicated procedures is still unknown. The objective was to investigate 1) the time course of plasma proteoma changes involved in ischemia-reperfusion injury, 2) the effects of plasma obtained at different times after AAA and general surgery on isolated rat cardiomyocyte contractility, and 3) the specific effects of heparin on myocyte contractility. Design and Method: Ten patients (aged 68±6 years) undergoing infrarenal AAA repair were investigated. Eight age and sex matched subjects undergoing major abdominal surgery (AS) served as controls. Hemodynamic changes were continuously monitored using a system based upon online, real-time, digital processing of intraarterial radial pressure waveform analysis. Plasma samples obtained after induction of anesthesia were compared with those obtained at different times after surgery (30 min and 6h, 12h, 24h, 36h). Plasma proteoma changes were investigated by using two-dimensional difference gel electrophoresis. The effects of plasma on the contractility of myocytes obtained from Wistar rats by enzymatic dissociation (collagenase type II), were investigated by using a IonOptix system (IonOptix, Milton, MA) and an inverted microscope (Olympus, IX-70). Results: Only in AAA patients we detected 30 spots which changed more than two-fold in expression level and 16 spots were identified. Among these, thrombin generation increased 6h and 12h after surgery. Likewise a significant reduction (P-value<0,05) of the contractility parameters was observed only in the presence of plasma taken from AAA patients at 6h, and 12h after surgery. The effects were dependent on the concentration of plasma added (from 5 to 20%). The effects of plasma were abolished when heparin (0,5 U/ml) was added to freshly isolated myocytes Conclusions: These findings show for the first time the relationship between the activation of inflammatory response and cryptic hemodynamic changes following infrarenal AAA repair.