The influence of sunitinib on contractility of human atrial trabeculae

Recently, sunitinib (a tyrosine kinase inhibitor that is used for treatment of
metastasic renal carcinoma and gastrointestinal stroma tumors) has been
associated with development of heart failure, possibly by off-target inhibition
of AMP-protein kinase. We hypothesize that sunitinib reduces the contractile
ability of myocardium and the tolerance against ischemia-reperfusion and that
activators of AMP-protein kinase such as atorvastatin and AICAR reverse this
unwanted effect of sunitinib.

The primary objective of the study is to investigate the effect of sunitinib
on ex-vivo atrial contractile force in absence and presence of
ischemia-reperfusion.
A secondary objective is to explore if atorvastatin or AICAR prevent
sunitinib-induced deterioration of contractile function of human atrial
trabecels

In vitro study on human tissue

The use of human atrial tissue derived from patients undergoing heart surgery
is an unique way of studying human tissue with minimal effort or risks for the
patient.
At our department of cardiothoracic surgery all relevant clinical data at
baseline and follow up (including the involved surgeon, postoperative plasma
troponin levels and occurrence of supraventricular tachycardias) are stored in
a prospective observational database. Since one of the surgeons routinely
amputates the atrial auricle when he introduces the extracorporal circulation,
we have the opportunity to compare plasma troponins and incidence of
supraventricular tachycardia between patients in whom their auricles were
excised (n=209) with those patients in whom this procedure was not performed
(n=1401). Average 8-hour plasma troponin concentrations were 6.1 +/- 13.9 and
5.8 +/- 12.6 microgram/l respectively (not significant). In 24% of the 209
patients in whom the auricle was amputated, and in 23.7 % of the 1401 patients
in whom the auricles remained in situ, a supraventricular tachycardia developed
(Dr. L. Noyez, personal communication). Based on these data, we conclude that
sampling of atrial (auricular) tissue at the time of introduction of
extracorporal circulation does not pose the patient at significant additional
risk.