Published Online
on April 16, 2007

A more recent version of this article appeared on May 1, 2007

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Submitted on September 11, 2006
Accepted on February 20, 2007

Direct Intramyocardial But Not Intracoronary Injection of Bone Marrow Cells Induces Ventricular Arrhythmias in a Rat Chronic Ischemic Heart Failure Model

Satsuki Fukushima MD, Anabel Varela-Carver PhD, Steven R. Coppen PhD, Kenichi Yamahara MD, PhD, Leanne E. Felkin BSc, Joon Lee MRCS, Paul J.R. Barton PhD, Cesare M.N. Terracciano MD, PhD, Magdi H. Yacoub FRS, and Ken Suzuki MD, PhD^*

From the Harefield Heart Science Centre, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, UK.

^* To whom correspondence should be addressed. E-mail: k.suzuki{at}ic.ac.uk.

Background--Therapeutic efficacy of bone marrow (BM) cell injection for treating ischemic chronic heart failure has not been established. In addition, experimental data are lacking on arrhythmia occurrence after BM cell injection. We hypothesized that therapeutic efficacy and arrhythmia occurrence induced by BM cell injection may be affected by the cell delivery route.

Methods and Results--Three weeks after left coronary artery ligation, wild-type female rats were injected with 1x10⁷ mononuclear BM cells derived from green fluorescent protein-transgenic male rats through either a direct intramyocardial or a retrograde intracoronary route. Both intramyocardial and intracoronary injection of BM cells demonstrated similar improvement in left ventricular ejection fraction measured by echocardiography and a similar graft size analyzed by real-time polymerase chain reaction for the Y chromosome-specific Sry gene. Noticeably, intramyocardial injection of BM cells induced frequent ventricular premature contractions (108±73 per hour at 7 days after BM cell injection), including multiform, consecutive ventricular premature contractions and ventricular tachycardia for the initial 14 days; intracoronary injection of BM cells and intramyocardial injection of phosphate-buffered saline rarely induced arrhythmias. Immunohistochemistry demonstrated that intramyocardial BM cell injection formed distinct cell clusters containing donor-derived cells and accumulated host-derived inflammatory cells in the infarct border zone, whereas intracoronary BM cell injection provided more homogeneous donor cell dissemination with less inflammation and without disrupting the native myocardial structure.

Conclusions--BM cell injection is able to improve cardiac function in ischemic chronic heart failure but has a risk of arrhythmia occurrence when the intramyocardial route is used. Such arrhythmias may be prevented by using the intracoronary route.

Key words: arrhythmia • cell therapy • heart failure

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