Myocardial injection of skeletal myoblasts impairs contractility of host cardiomyocytes.
BACKGROUND
Mechanisms underlying improvement of myocardial contractile function after cell therapy as well as arrhythmic side effect remain poorly understood. We hypothesised that cell therapy might affect the mechanical properties of isolated host cardiomyocytes.


METHODS
Two weeks after myocardial infarction (MI), rats were treated by intramyocardial myoblast injection (SkM, n=8), intramyocardial vehicle injection (Medium, n=6), or sham operation (Sham, n=7). Cardiac function was assessed by echocardiography. Cardiomyocytes were isolated in a modified Langendorff perfusion system, their contraction was measured by video-based inter-sarcomeric analysis. Data were compared with a control-group without myocardial infarction (Control, n=5).


RESULTS
Three weeks post-treatment, ejection fraction (EF) further deteriorated in vehicle-injected and non-injected rats (respectively 40.7+/-11.4% to 33+/-5.5% and 41.8+/-8% to 33.5+/-8.3%), but was stabilised in SkM group (35.9+/-6% to 36.4+/-9.7%). Significant cell hypertrophy induced by MI was maintained after cell therapy. Single cell contraction (dL/dt(max)) decreased in SkM and vehicle groups compared to non-injected group as well as cell shortening and relaxation (dL/dt(min)) in vehicle group. A significantly increased predisposition for alternation of strong and weak contractions was observed in isolated cardiomyocytes of the SkM group.


CONCLUSIONS
Our study provides the first evidence that injection of materials into the myocardium alters host cardiomyocytes contractile function independently of the global beneficial effect of the heart function. These findings may be important in understanding possible adverse effects.
Giraud
Marie-Noëlle
MN
Department of Cardiovascular Surgery, Inselspital, Berne, Switzerland.
Liechti
Emanuel F
EF
Tchantchaleishvili
Vakhtang
V
Siepe
Matthias
M
Cook
Stéphane
S
Carrel
Thierry P
TP
Tevaearai
Hendrik T
HT
D000818:Animals; D002450:Cell Communication; D004195:Disease Models, Animal; D004452:Echocardiography; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D012044:Regression Analysis; D019737:Transplants / Q000009:adverse effects*; D016277:Ventricular Function, Left / Q000502:physiology