The stimulation of myocardial angiogenesis may be an important method to diminsh ischemia and improve the quality of patients' lives. Transmyocardial laser revascularization (TMR)is one such method that employs the use of a high powered laser to create a controlled injury and engender the natural angiogenic response. While clinical results with two different wavelengths of laser light are reportedly similar there are vast differences between the laser tissue interactions. We investigated whether this difference led to a myocardial functional change and whether the mechanisms whereby each laser achieves its clinical success is different.? Employing a porcine model of chronic myocardial ischemia; cine MRI, hyperenhancement MRI, rest and stress echocardiography and histology were performed after TMR. There were significant improvements in myocardial function after treatment by a carbon dioxide that were not seen when a holmium:YAG device was used. Histology and MRI confirmed more scarrring and less angiogenesis with the Ho:YAG device at 6 weeks post treatment.? Building on these results we have embarked on the addition of cellular therapy to further enhance the angiogenic response engendered by the laser. Using autologous bone marrow which has been allowed to differentiate and expand, mesenchymal stem cells are injected into the ischemic zone of the aforementioned large animal model. MRI, echo and histologic endpoints are being gathered to determine if a synergistic response is possible.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL005071-02
Application #
7594428
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2007
Total Cost
$677,796
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Horvath, Keith A (2008) Transmyocardial laser revascularization. J Card Surg 23:266-76
Horvath, Keith A (2006) Light and ice cream. Ann Thorac Surg 82:771; author reply 771-2
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Horvath, Keith A (2006) Percutaneous laser revascularization does not equal transmyocardial laser revascularization. J Am Coll Cardiol 48:2354; author reply 2355
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Horvath, Keith A; Ferguson Jr, T Bruce; Guyton, Robert A et al. (2005) Impact of unstable angina on outcomes of transmyocardial laser revascularization combined with coronary artery bypass grafting. Ann Thorac Surg 80:2082-5
Horvath, Keith A; Lu, Chia Yang J; Robert, Emmanuel et al. (2005) Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach. J Thorac Cardiovasc Surg 129:1071-7