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Figure 4. Pressure loss aigainst the maximum bulk flow velocity
45.4
Electroporation-mediated delivery of functional genes - a promising approach for nonviral-based gene
therapy of the failing heart
S. Eigeldinger-Berthou 1 , P. Buntschu 1 , A. Frobert 1 , M. Flück 2 , M.-N. Giraud-Flück 1 , R. A. Schmid 1 ,
T. Carrel 1 , H. Tevaearai 1 , A. Kadner 1 ( 1 Berne, 2 Manchester/UK)
Objective: Alterations of alpha-adrenergic receptor signaling is a hallmark of heart failure (HF). Gene
therapy may represent a promising therapeutic strategy. Here, we aim to establish and to utilize an
electroporation-based viral-free system to transfect the alpha-adrenergic receptor kinase inhibitor
alpha-ARKct) in myocardial muscles in vivo to restore alpha-adrenergic receptor normal function.
Methods: Electroporation (EP) was performed with the reporter plasmid (pCMV GFP), as control, and
the gene of interest (pUB & ß-ARKct). The genes were electroporated in vitro in neonatal rat cardiomyocyts,
and in vivo, on the beating heart of anesthetized Lewis rats. In vitro, EP efficiency was quantified by
FACS and quantitative RT-PCR. Expression of the proteins was also assessed by Western blot. In vivo,
gene expression was assessed seven days and three weeks post-intramyocardial EP by fluorescence,
immunohistology and Western blot.
Results: Electroporation was technically easy to apply and safe. Serial assessments of gene expression
demonstrated cellular and intramyocardial expression of the reporter gene and ß-ARKct. Expression
pattern showed in vivo strongest expression areas around electrode placement zones.
Conclusion: Electroporation is a promising therapeutic approach for non-viral-based gene therapy for
HF. It is easy to apply and without harmful side-effects. However further functional analyses are necessary
to demonstrate ß-ARKct expression up to three weeks and to confirm the positive effects of restoring
the long-term ß-adrenergic signaling for improvement of HF.
45.5
High incidence of severely prolonged QT interval after cardiac surgery
U. Schurr, M. Biry, S. Ritter, H. Loeblein, T. Syburra, A. Zollinger, M. Genoni (Zurich)
Objective: Prolonged QT-interval may be associated with torsades-de-pointes and lead to sudden
cardiac death. Aim of this study was to determine the frequency and administration of QT-prolonging
drugs perioperatively in cardiac-surgery.
Methods: This prospective observational study included 82 patients undergoing elective cardiacsurgery
(coronary-bypass-grafting 37, valve-surgery 29, combination 16). QT-interval was manually
measured in a 12-lead electrocardiogram-(ECG) and corrected for heart rate (corrected QT-interval,
QTc, (Bazett’s-formula) on the day before surgery, immediately after surgery, daily until day five and
before hospital discharge. QTc-interval >440msec in men and >460msec in women was defined as
moderately prolonged. QTc-interval >500msec was considered to be moderately prolonged in patients
showing complete left-or right-bundle-block, and severely prolonged in patients without complete
bundle-block. All administered drugs that may prolong the QT-interval were identified and classified according
to the QT-drugs.org Advisory-Board: drugs with a definite risk of torsades-de-pointes (class-1,
e.g. amiodarone, sotalol, haloperidol) or with a possible risk (class-2, e.g. granisetron, risperidone).
Results: 489-ECG were analyzed. QTc-interval was moderately prolonged in 40/82 patients before surgery
(48.8%). 5/40-patients (12.5%) had received drugs from class-1 preoperatively and 1/40(2.5%)
from class-2. The QTc-interval was severely prolonged in 3/82 patients before surgery (3.7%), of
which none had received QT prolonging drugs preoperatively. 38/82 patients(46.3%) moderate QTcprolongation
was newly discovered in at least one postoperative ECG. 17/38-patients(44.7%) received
drugs from class-1, and 3/38(7.9%) from class-2 perioperatively. In 16/82 patients (19.5%) severe
QTc-prolongation newly appeared in at least one postoperative ECG. 7/16- patients (43.8%) received
drugs from class-1 and 1/16(6.3%) from class-2 perioperatively.
Conclusion: Severe QT-interval prolongation >500msec occurs in a quarter of cardiac-surgical patients
in the perioperative period while moderate prolongation occurs in most of them. In nearly half of
these cases, QT-prolonging drugs like amiodarone and haloperidol may be involved. Before and during
administration of such drugs in cardiac-surgical patients perioperatively, assessment of QT-interval
from routine-ECG is recommended.
42 swiss knife 2010; 7: special edition
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Visceral Surgery – General Surgery 52
52.1
A clinico-radiological score for predicting the risk of strangulated small bowel obstruction
P. Gervaz, F. Schwenter, P.-A. Poletti, A. Platon, Ph. Morel (Geneva)
Objective: Successful management of small bowel obstruction (SBO) relies on sound clinical judgment,
but CT scan has emerged as a robust imaging modality to provide additional prognostic information.
We elaborated a score to predict the risk of intestinal ischemia in patients with SBO.
Methods: A prospective assessment of patients who presented with SBO was performed. A logistic
regression model helped to identify determinant variables and to construct a predictive clinical score
according to the risk for the patient to undergo small bowel resection.
Results: Among 233 successive patients with SBO, 138 required a laparotomy, and 45 underwent
small bowel resection. In multivariate analysis, 6 variables correlated with small bowel resection and
were given 1 point each for the score: 1) history of pain >4 days; 2) guarding; 3)C-reactive Protein
>75 mg/l; 4) leukocytes count >10 G/l; 5) CT scan ascites fluid >500 ml; 6) reduction of small bowel
wall contrast enhancement. The risk of intestinal ischemia was 6.2% in patients with a score 3 underwent small bowel resection (sensitivity 68%; specificity 91%;
area under the curve: AUC=0.87 [95% CI 0.79-0.95]).
Conclusion: By combining 2 clinical, 2 biological and 2 radiological parameters, our score allows for
early identification of strangulated SBO, and underlines the prognostic information provided by CT scan
imaging in this setting.
52.2
Long-term persistence of non-specific abdominal pain is associated with decreased quality of life
V. Banz, K. Paul, D. Candinas, A. K. Exadaktylos, H. Zimmermann (Berne)
Objective: Patients suffering from chronic pain have a high prevalence of depression, resulting in a
significant impact on overall quality of life as well as general functioning and well-being. Our aim was
to investigate how many patients admitted to our emergency department (ED) with acute non-specific
abdominal pain (NSAP) suffered from persistent NSAP some 12 months after ED discharge and how
this affected overall physical and mental well-being.
Methods: All patients discharged from our ED with NSAP between 06/2007 and 06/2008 were included
for follow-up. NSAP was defined as any acute abdominal pain less than 7 days in duration prior
to ED admission without underlying somatic cause. Current health and well-being was evaluated using
the SF-36 ® health questionnaire. Ordinal linear regression models were chosen to separately assess
variables influencing SF-36 ® outcome with adjustment for age and gender. Results were expressed as
regression coefficients with corresponding 95% confidence intervals and p-values.
Results: Of the 200 patients reached 57% were women, average age at ED admission was 33 years,
60% of all patients (N=122) were of Swiss nationality. Mean follow-up was 12.5months at which time
point 53 (26.5%) of all patients still suffered from NSAP. Overall prevalence of chronic pain syndromes
in the study population was 10%, with 15 patients known to have psychiatric comorbidities. Patients
with persistent NSAP suffered more often from chronic pain (26.4%) or a known psychiatric illness
(15.1%) than patients without NSAP (p