Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function.

Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Bohm M, Quaini F, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P. Proc Natl Acad Sci USA. 2005 Jun 21;102(25):8966-71. Epub 2005 Jun 10.

Reviewer: Theodore A. Alston, MD, PhD
Assistant Professor
Harvard Medical School

Abstract: The ability of myocardium to re-grow in large mammals is demonstrated. About one cardiac stem cell is present for each 18,000 myocytes in the adult dog heart. The stem cells carry surface antigens that facilitate cell isolation. For instance, cells can be tagged with fluorescent antibodies for cell sorting. The cells can also be collected with antibodies attached to magnetic microbeads. The stem cells lack cardiac actomyosin but can be stimulated to grow in vitro into multicellular clones of cardiomyocytes, endothelial cells, and vascular smooth muscle cells. Stimulants included the so-called hepatocyte growth factor as well as insulin-like growth factor one. These test tube tricks prompted an exciting experi-ment in vivo.

The two growth factors achieved tissue regeneration in experimental myocardial infarction. Dogs underwent implantation of sonomicrometric crystals into the left ventricle in order to facilitate serial measurements of regional cardiac performance. Four hours after a left anterior descending artery occlusion, the growth factors were injected into the border zone of the infarct. After another 4 hours, without the growth factors, there were no stem cells in the infarcted tissue. Stem cells and myocytes alike had undergone apoptosis. With the growth factors, stem cells were found within the infarct. After 28 days, the growth factors had caused marked recovery of contractile force, and the treated hearts contained clusters of new myocytes, arterioles, and capillaries.

Comments: This paper offers a promise that regeneration of human myocardium can occur and be deliberately stimulated. Regeneration requires stem cells, but the stem cells will not necessarily need to be harvested from the patient, nor from a donor. In the large, mature mammals now studied (dogs), the cells are already present, and they can restore significant function, but they have to be pharmacologically supported. The experimenters above and their colleagues also have already reported some intriguing human studies (Urbanek K, Torella D, Sheikh F, De An-gelis A, Nurzynska D, Silvestri F, Beltrami CA, Bussani R, Beltrami AP, Quaini F, Bolli R, Leri A, Kajstura J, Anversa P. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8692-7. Epub 2005 Jun 2). Hearts have been examined from transplant recipients and from victims of acutely fatal infarctions. The bad news is that cardiac stem cells seem to be reduced in chronic ischemic cardiomyopathy. The good news is that some are still there. Also promising, 7 out of 20 acutely infarcted human hearts containedclusters of highly proliferating small developing myocytes within the infarct. Foci of regeneration were up to 5 square millimeters in area and included small blood vessels. This novel observation in human hearts coupled with impressive healing of dog hearts almost certainly indicates that deliberate and significant human heart regeneration will be effected. It will be interesting to see how cardiovascular anesthesiologists will prove to participate in the novel therapies.

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• Literature Reviews
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  • Secondary tricuspid regurgitation or dilatation: Which should be the criteria for surgical repair?
  • Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function.
  • Overexpression of mitochondrial transcription factor A ameliorates mito­chondrial deficiencies and cardiac failure after myocardial infarction.
  • An essential role for mitochondrial aldehyde dehydrogenase in nitroglyc­erin bioactivation.


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  • Child-Pugh and MELD classifications and the mortality following cardiac surgery.
  • Anesthetic preconditioning and perioperative myocardial protection


• PRO/CON: Conscious Neuraxial Anesthesia is a Viable Alternative to General Anesthesia in Cardiac Surgery.
• Pro - Paul Kessler, MD
• Con - Peggy T. Y. Li, MBChB & Anthony M. H. Ho, MD, FRCPC, FCCP

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