Effects of autologous bone marrow stem cell transplantation on beta-adrenoceptor density and electrical activation pattern in a rabbit model of non-ischemic heart failure.
BACKGROUND
Since only little is known on stem cell therapy in non-ischemic heart failure we wanted to know whether a long-term improvement of cardiac function in non-ischemic heart failure can be achieved by stem cell transplantation.


METHODS
White male New Zealand rabbits were treated with doxorubicin (3 mg/kg/week; 6 weeks) to induce dilative non-ischemic cardiomyopathy. Thereafter, we obtained autologous bone marrow stem cells (BMSC) and injected 1.5-2.0 Mio cells in 1 ml medium by infiltrating the myocardium via a left anterolateral thoracotomy in comparison to sham-operated rabbits. 4 weeks later intracardiac contractility was determined in-vivo using a Millar catheter. Thereafter, the heart was excised and processed for radioligand binding assays to detect beta1- and beta2-adrenoceptor density. In addition, catecholamine plasma levels were determined via HPLC. In a subgroup we investigated cardiac electrophysiology by use of 256 channel mapping.


RESULTS
In doxorubicin-treated animals beta-adrenoceptor density was significantly down-regulated in left ventricle and septum, but not in right ventricle, thereby indicating a typical left ventricular heart failure. Sham-operated rabbits exhibited the same down-regulation. In contrast, BMSC transplantation led to significantly less beta-adrenoceptor down-regulation in septum and left ventricle. Cardiac contractility was significantly decreased in heart failure and sham-operated rabbits, but was significantly higher in BMSC-transplanted hearts. Norepinephrine and epinephrine plasma levels were enhanced in heart failure and sham-operated animals, while these were not different from normal in BMSC-transplanted animals. Electrophysiological mapping revealed unaltered electrophysiology and did not show signs of arrhythmogeneity.


CONCLUSIONS
BMSC transplantation improves sympathoadrenal dysregulation in non-ischemic heart failure.
Dhein
Stefan
S
Clinic for Cardiac Surgery, Heart Centre Leipzig, University of Leipzig, Germany. dhes@medizin.uni-leipzig.de
Garbade
Jens
J
Rouabah
Djazia
D
Abraham
Getu
G
Ungemach
Fritz-Rupert
FR
Schneider
Katja
K
Ullmann
Cris
C
Aupperle
Heike
H
Gummert
Jan Fritz
JF
Mohr
Friedrich-Wilhelm
FW
D000818:Animals; D001853:Bone Marrow; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D033581:Stem Cell Transplantation
D011943:Receptors, Adrenergic, beta