Author + information
- Received July 8, 2011
- Revision received August 29, 2011
- Accepted September 2, 2011
- Published online December 1, 2011.
- Karl H. Schuleri, MD⁎,⁎ (, )
- Marco Centola, MD⁎,†,
- Seong Hoon Choi, MD, PhD⁎,‡,
- Kristine S. Evers, BS⁎,
- Fady Dawoud, PhD⁎,
- Richard T. George, MD⁎,
- João A.C. Lima, MD⁎ and
- Albert C. Lardo, PhD⁎,§,⁎ ()
- ↵⁎Reprint requests and correspondence:
Drs. Karl H. Schuleri and Albert C. Lardo, Image Guided Cardiotherapy Laboratory, Johns Hopkins School of Medicine, Division of Cardiology, 1042 Ross Building, Baltimore, Maryland 21205
Objectives The aim of this study was to use multidetector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies.
Background Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).
Methods Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.
Results MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001).
Conclusions This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.
- delayed contrast enhancement
- Göttingen minipig
- heart failure
- mesenchymal stem cell
- myocardial infarction
All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 8, 2011.
- Revision received August 29, 2011.
- Accepted September 2, 2011.
- American College of Cardiology Foundation