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normal angiogenesis induced by cells producing high levels of hVEGF was not due to a rapid loss of
expression in vivo.
Conclusion: Human VEGF165 displayed a radically different dose-effect relationship compared to
murine VEGF164 in a highly controlled in vivo model, inducing only normal angiogenesis despite much
higher microenvironmental expression levels. These data suggest that the therapeutic window of human
VEGF may be different than indicated by preclinical studies with murine VEGF, highlighting the
need for rigorous safety testing in Stage I clinical trials.
44.9
Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo
D. Roulin, Y. Cerantola, A. Dormond-Meuwly, N. Demartines, O. Dormond (Lausanne)
Objective: The mammalian target of rapamycin (mTOR), which exists in two functionally distinct complexes,
mTORC1 and mTORC2, plays an important role in tumor growth. Whereas the role of mTORC1
has been well characterized in this process, little is known about the functions of mTORC2 in cancer
progression. This present study aims at exploring the specific role of mTORC2 in colon cancer progression.
Methods: A short hairpin RNA expression system was used to silence the mTORC2-associated protein
rictor.
Results: We observed that downregulation of rictor in HT29 and LS174T colon cancer cells significantly
reduced cell proliferation. Knockdown of rictor also resulted in a G1 arrest as observed by cell cycle
analysis. We further observed that LS174T cells deficient for rictor failed to form tumors in a nude mice
xenograft model.
Conclusion: Taken together, these results show that the inhibition of mTORC2 reduces colon cancer
cell proliferation in vitro and tumor xenograft formation in vivo. They also suggest that specifically targeting
mTORC2 may provide a novel treatment strategy for colorectal cancer.
Cardiac Surgery 45
45.1
Aortic-valve sparing or aortic root replacement: experience over 48 consecutive patients
P. Matt, B. Winkler, F. Rüter, M. Grapow, O. Reuthebuch, F. Eckstein (Basel)
Objective: Controversy exists on how often aortic-valve sparing can be performed in case of aortic
root surgery.
Methods: We report our experience over 48 consecutive patients operated for aortic root disease from
July 2008 to December 2009.
Results: 11 (23%) patients underwent aortic-valve sparing (AVS; mean age 59.2 years; 9 males) and
37 (77%) composite-graft replacement (CG; 53.6 years; 33 males; P=0.1, P=0.8). Preoperative logistic
Euroscore was 16.3 (AVS) and 21.4 (CG; P=0.4). There were 11 redo-procedures and 2 homografts
(CG), no such in the AVS group. Emergent procedures were performed in 3 (AVS) and 6 (CG; P=0.7).
Aortic valve regurgitation was moderate or severe in 9 (AVS) and 23 (CG; P=0.4). Aortic valve stenosis
had 10 patients in the CG group, none in the AVS. Deep hypothermic circulatory arrest (DHCA) was
performed in 8 (AVS) and 30 (CG; P=0.8). Hemiarch and arch replacement was done in 5 and 3 AVS
patients, respectively, and in 23 and 0 of those with CG. DHCA time was 17.6 min (AVS) and 24 min
(CG; P=0.0). Ischemic and perfusion time was 134.8 min and 158.8 min (AVS), and 119 min and
168 min (CG; P=0.2, P=0.7). Deepest temperature was 26 degree (AVS) and 23 degree (CG; P=0.3).
Intensive care unit time was 2.7 days (AVS) and 3.4 days (CG; P=0.6). Stroke occurred in 2 (AVS) and
3 (CG; P=0.6). Pneumonia or pulmonary embolism showed 1 (AVS) and 3 (CG) patients (P=1). At
discharge, AVS patients showed no (n=10) or mild (n=1) aortic valve insufficiency. 30-day mortality
was 0% in AVS patients, and 8% in CG patients (3 of 37, one patient died due to intestinal ischemia, two
patients due to multi-organ failure).
Conclusion: AVS was performed in 23% of consecutive aortic root procedures with excellent results.
Operative risk of AVS and CG is low, even if combined with hemiarch or arch surgery.
45.2
Aortic root replacement with cryopreserved homografts in prosthetic valve endocarditis
F. Rüter, B. Winkler, M. T. Grapow, P. Matt, O. Reuthebuch, F. Eckstein (Basel)
Objective: Prosthetic valve endocarditis remains a serious disorder after aortic valve replacement
(AVR) despite novel antibiotic regimens. In case of extensive abscess formation, rhythm disorders or
non responding to drug therapy, surgical intervention remains as only curative treatment. For these
patients, cryopreserved homografts are increasingly used for aortic root and valve replacement.
Methods: We report five consecutive patients who required reoperation after AVR due to severe endocarditis.
In cooperation with the European Homograft Bank (Brussels, Belgium) the homograft program
has been set up according to National Health Comission standards. Infrastructure, training of
staff and follow-up guidelines were established at our institute.
Results: All operations were performed in full root technique, a partial replacement of the anterior mitral
valve leaflet was additionally necessary in one case. All patients were included in a retrospective
survey with echocardiographic and clinical checkups before discharge and 6 months postoperatively.
No patient has evidence for persistent infection or required reoperation. All patients recovered to full
extend.
Conclusion: In prosthetic aortic valve endocarditis with annulus destruction or involvement of the an-
terior mitral valve leaflet, homograft aortic root replacement appears to show the best outcome and
combines avoidance of anticoagulation, best hemodynamic function and resistance to infection.
45.3
Fluid dynamics in aortic valve bioprostheses: a novel approach
T. Syburra, A. Landolt, T. Rösgen, D. Obrist, M. Genoni (Zurich)
Objective: Calcification limits the durability of aortic valve bioprostheses. Fluid dynamical phenomena
are involved as well as biochemical and mechanical phenomena.
Methods: We chose an incremental constant-flow configuration (Fig. 1) to study the intrinsic flow characteristics
of several 23mm bioprostheses. An electric pump generates a constant flow (0.5 to 90
l/min) with a 36.6% glycerine-water solution. The pressure drop over the valve is recorded and the
cusps’ positions are captured with a high-speed camera (Fig. 2).
Results: In Figure 3 pressure loss and opening area for the valves is plotted as a function of the flow
rates. Figure 4 shows the pressure drop against maximum bulk flow velocity u, given by u=Q/A of flow
rate Q and opening area A. The curves for bovine pericardial valves collapse to a single curve. For these
valves, the pressure drop p is only a function of the bulk velocity u=Q/A: Δp = f(u).
Conclusion: There appears to be a general relation between the pressure drop and the maximum bulk
flow velocity for certain bovine pericardial bioprostheses. It suggests that the transvalvular pressure
drop is mainly a function of the maximum bulk flow velocity and not of the flow rate. Valves should
be designed to yield large opening areas already at low flow rates minimizing the bulk flow velocity.
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Figure 2. Camera image of the partially (right) open Edwards Magna
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