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(Circulation. 2004;110:II-225 – II-230.)
© 2004 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Targeted Cell Delivery Into Infarcted Rat Hearts by Retrograde Intracoronary Infusion: Distribution, Dynamics, and Influence on Cardiac Function

Ken Suzuki, MD PhD; Bari Murtuza, MD PhD; Satsuki Fukushima, MD; Ryszard T. Smolenski, MD PhD; Anabel Varela-Carver, PhD; Steven R. Coppen, PhD; Magdi H. Yacoub, FRS

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

Correspondence to Dr Ken Suzuki, Cell and Gene Therapy Group, Harefield Heart Science Centre, Harefield, Middlesex, UB9 6JH, UK. E-mail k.suzuki{at}ic.ac.uk

Background— Intracoronary infusion for cell transplantation has potential advantages in disseminating cells globally into the myocardium with less injury over direct intramuscular injection. Arterial route, however, has a risk of coronary embolism and a limitation in cell delivery into ischemic or infarcted areas. We assessed the efficiency of retrograde intracoronary cell implantation into infarcted hearts using a novel rat model.

Methods and Results— After left coronary artery ligation in rat, a catheter was inserted into the left cardiac vein, which drains the left ventricular free wall. Through this, 1x10⁶ skeletal muscle precursor cells expressing nuclear ß-galactosidase were infused retrogradely into the vein. In situ staining demonstrated that ß-galactosidase–expressing donor cells had disseminated throughout the left ventricular free wall, including both infarcted and surrounding border areas, at 10 minutes after infusion. At 28 days, in contrast, positively stained multinuclear myotubes were found in border zones, whereas no positive cells were seen in infarcted areas. Measurement of ß-galactosidase enzyme activity estimated that 29.8±6.9% of total infused cells were retained within the myocardium at 10 minutes and that this number decreased to 23.7±8.1% at 3 days but rapidly increased thereafter, reaching a plateau at 90.2±17.1% by 14 days. Echocardiography and Langendorff perfusion demonstrated that cell implantation improved cardiac function and dimensions by 28 days, compared with both sham-treated and phosphate-buffered saline-infused infarcted hearts, and this was associated with decreased collagen deposition.

Conclusion— Retrograde intracoronary cell transplantation could provide an effective cell delivery into infarcted hearts and could be a useful strategy for treating myocardial infarction.

Key Words: cell transplantation • coronary vein • intracoronary infusion • myocardial infarction • skeletal myoblast