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EXPERIMENTAL STUDY

A comparison of mechanical and laser transmyocardial revascularization for induction of angiogenesis and arteriogenesis in chronically ischemic myocardium

G. Chad Hughes, MD^*,*, Shankha S. Biswas, MD^*, Bangliang Yin, MD^*, Dmitri V. Baklanov, MD^*, Brian H. Annex, MD, R. Edward Coleman, MD, Timothy R. DeGrado, PhD, Carolyn K. Landolfo, MD, FACC, Kevin P. Landolfo, MD^* and James E. Lowe, MD, FACC^*

^* Departments of Surgery and Medicine, Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, North Carolina, USA
Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA
Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA

Manuscript received September 18, 2001; revised manuscript received December 27, 2001, accepted January 10, 2002.

^* Reprint requests and correspondence: Dr. G. Chad Hughes, Duke University Medical Center, Box 3954, Durham, North Carolina, USA
chadh{at}duke.edu

OBJECTIVES: The purpose of the present study was to compare the use of a mechanical transmyocardial implant (TMI) device with transmyocardial laser revascularization (TMR) for induction of therapeutic angiogenesis and arteriogenesis in the chronically ischemic heart.

BACKGROUND: Prior experimental studies have demonstrated evidence for neovascularization after both mechanical and laser transmyocardial revascularization, although a long-term comparison of the two techniques has not been performed.

METHODS: Using an established model of chronic hibernating myocardium, mini-swine underwent 90% proximal left circumflex (LCx) coronary artery stenosis. One month later, baseline positron emission tomography (PET) and dobutamine stress echocardiography (DSE) were performed to quantitate regional myocardial blood flow (MBF) and function. Animals then underwent TMR with a holmium:yttrium-aluminum-garnet (holmium:YAG) laser (n = 5), TMI (n = 5), or sham redo-thoracotomy (n = 5). In the TMR group, the entire LCx region was treated with transmural laser channels at a density of 1/cm². Transmyocardial implants were placed transmurally at a similar density in the LCx region of the TMI group. Six months later, the PET and DSE studies were repeated, and the animals were euthanized.

RESULTS: Six months after TMR, there was a significant increase over baseline in resting MBF to the lased LCx region (68.9 ± 4.6% vs. 89.3 ± 3.0% reference non-ischemic septal segments; p < 0.001). This increased MBF was accompanied by a significant improvement in LCx regional wall motion during peak dobutamine stress (p = 0.04). Compared with baseline, there was no change in LCx region MBF six months after either TMI (72.9 ± 4.8% vs. 85.7 ± 3.4%; p = 0.10) or sham redo-thoracotomy (75.6 ± 4.6% vs. 80.1 ± 5.0%; p > 0.2). Likewise, there was no significant change in rest or stress wall motion by DSE six months postoperatively in either group. Overall vascular density was increased only in the TMR-treated regions six months postoperatively. The difference between groups was most notable for a twofold increase in the number of small arterioles seen in the lased (4.4 ± 0.3 arterioles per high power field; p < 0.001 vs. both TMI and sham) compared with TMI (2.2 ± 0.2) and sham (1.9 ± 0.2)-treated regions.

CONCLUSIONS: Mechanical transmyocardial revascularization with a TMI device does not appear to promote physiologically significant angiogenesis or arteriogenesis in the chronically ischemic porcine heart and cannot be recommended for clinical trials at this time. Infrared laser-mediated injury mechanisms may be important for inducing therapeutic neovascularization with direct myocardial revascularization techniques.

Abbreviations and Acronyms   CAD   coronary artery disease   DSE   dobutamine stress echocardiography   FDG   fluorodeoxyglucose   holmium:YAG   holmium:yttrium-aluminum-garnet   LCx   left circumflex coronary artery   LV   left ventricle/ventricular   MBF   myocardial blood flow   PET   positron emission tomography   TMI   transmyocardial implant   TMR   transmyocardial laser revascularization   VEGF   vascular endothelial growth factor   WMSI   wall motion score index

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