Ann Thorac Surg 2003;75:773-774
© 2003 The Society of Thoracic Surgeons
Invited commentary
Frank W. Sellke, MD
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St, No. LMOB Suite 2A, Boston, MA 02215, USA
e-mail: fsellke{at}caregroup.harvard.edu
The study by Nishida and colleagues complements other studies published by this group and that of other groups which have examined the effects of implantation of bone marrow cells into the ischemic myocardium or ischemic hind limb of rats. The distinguishing aspect of the present study is that a novel method was used to create ischemic but not infarcted tissue. The authors used a thin copper wire as a guide to place a ligature around the left anterior descending coronary artery. The authors contend that this produced a stenotic but open vessel.
Most prior studies in rodent models of ischemia have simply ligated the left anterior descending coronary artery with a suture and the authors have acknowledged the limitation of having an acute MI versus chronically ischemic tissue. Larger animal models of chronic myocardial ischemia used to investigate angiogenesis, improved myocardial performance, or basic physiology of the collateralized myocardium have significant advantages. The two more popular of these methods are the ameroid occluder model and the repetitive embolization model of chronic ischemia, often adapted in the pig, dog, or pony. The ameroid occluder is a hydrophilic casein plastic (ameroid) encased into a stainless steel or hard plastic ring. As the center portion collects water, it occludes the vessel, usually over 10–20 days. The repetitive embolization model uses an injection of microspheres or similar small particles into the coronary artery. Both models have advantages and disadvantages. However, the use of large animal models is very expensive and time consuming.
If the authors have, in fact, developed a new rodent model of chronic myocardial ischemia, this could have a major impact on the progress of future work. However, the authors have not directly assessed whether the artery remains open after the ligature is placed or on the state of the artery after 60 days when flow measurements are made. Whereas, the anterior wall of the hearts was hypokinetic and not dyskinetic according to the authors, my impression is that many or most of these arteries had occluded within days after placement of the ligature. Further studies will be required to verify the model.
The use of bone marrow, skeletal myocytes, and other transplanted cells to improve vascular density and myocardial perfusion and function is still somewhat novel in practice but not novel in concept. In deed, Philippe Menasche has even transplanted skeletal myoblasts into the hearts of patients. This is a long jump from rat research. However, to date, the results have been modest and many obstacles must be overcome before cell-based therapy will be in widespread clinical practice. Despite these issues, the authors have nicely demonstrated increased end-systolic dimension and improved factional shortening, increased vascular density, blood flow, and left ventricular thickness in rats having received the bone marrow implantation. They should be congratulated on their work. However, before dramatic conclusions can be drawn from animal experiments, they need to be repeated in a large animal model of chronic myocardial ischemia. Better yet, positive results need to be demonstrated in patients before cell-based therapy is expanded to patient care.
