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Introduction Most people with coronary artery disease are treated with angioplasty and stenting or coronary bypass surgery and medications to improve blood flow to the heart muscle. The objective of each of these approaches is to increase blood flow through the coronary arteries to the heart. When these treatment options are exhausted, the patient is left with no viable surgical alternative other than, in limited cases, heart transplantation. Without a viable surgical alternative, the patient is generally managed with drug therapy, often with significant lifestyle limitations. TMR, or transmyocardial laser revascularization, is a newer treatment aimed at improving blood flow to areas of the heart that were not treated by angioplasty or surgery. Patients with chronic severe angina refractory to medical therapy who cannot be completely revascularized with either percutaneous catheter intervention or coronary artery bypass graft surgery present clinical challenges. Transmyocardial laser revascularization, either as sole therapy or as an adjunct to coronary artery bypass graft surgery, may be appropriate for some of these patients. Although transmyocardial revascularization has consistently been demonstrated as an efficacious means of relieving angina, the mechanism of its effects are still debated, and criteria for the selection of patients for this novel therapy have not been adequately defined. Background The nature of the connections between the lumina of the ventricles and the coronary arteries has been debated at least since the description by Vieussens in 1706 of “fleshy vessels” thought to represent direct communications between left ventricular myocardium and the left cardiac chambers. This debate was reignited by Wearn and colleagues with their classic description of myocardial sinusoids in 1933. The description of myocardial microanatomy by Wearn and associates  stimulated several investigators to develop new techniques for delivering oxygenated blood to the myocardium. More than two decades ago, Mirhoseini and Cayton used a 450-W industrial carbon dioxide laser in a canine model of acute ischemia. Mirhoseini and associates were the first to use the technique clinically as an adjunct to CABG. The major limitation of their approach was that the 80-W CO2 laser available for clinical use required a stationary heart during channel creation, requiring ischemic arrest or ventricular fibrillation. Although the original rationale for TMR was the hypothesis that direct channels from the left ventricular lumen could supply the myocardium with oxygenated blood, most have rejected this hypothesis as most experimental and clinical autopsy studies do not demonstrate patent channels. Thus, a variety of newer hypotheses of the mechanism of action of TMR have emerged. Lasers Used for Transmyocardial Revascularization Currently, the only US Food and Drug Administration– approved lasers for TMR are the CO2 laser (PLC Systems) and the holmium:YAG laser-yttrium-aluminum-garnet (Cardiogenesis Sunnyvale, CA). The CO2 laser energy (wavelength, 10.6 micro m) is more efficiently absorbed by water molecules than the holmium: YAG laser energy (wavelength, 2.1micro m). The energy per pulse of the CO2 system is 20 J to 80 J, and only one pulse is required to create a transmural channel. In contrast, the pulse energy of the holmium: YAG laser used clinically is typically 2 J to 5 J, and multiple pulses during several cardiac cycles are required to generate a transmural channel. Current Hypotheses for Transmyocardial Revascularization (Mechanism of Action) Clinical studies of TMR using a CO2 laser or holmium: YAG laser have consistently demonstrated a reduction in angina symptoms and, in several cases, an improvement in exercise tolerance and quality of life [34–51]. In general, however, these studies are not placebo-controlled, and the degree of angina improvement has varied significantly. The two leading proposed mechanisms of TMR effect include laser-induced angiogenesis with improvement in regional myocardial blood flow and laser induced denervation of the myocardium resulting in an improvement in angina symptoms without the requirement for any improvement in oxygen delivery. 1.	Angiogenesis - A variety of experimental studies in normal and ischemic canine, porcine, and ovine models have demonstrated that myocardial laser injury leads to an increase in the density of arterial vessels. In a chronically ischemic porcine model, Chiu and associates demonstrated that sufficient needle injury of the myocardium and TMR lead to similar degrees of stimulation of vascular endothelium growth factor expressions and angiogenesis. Horvath and colleagues [55] showed that TMR leads to an induction of vascular endothelium growth factor gene expression and elevated tissue levels of vascular endothelium growth factor mRNA. Thus, the bulk of the available evidence demonstrates that there is indeed, a molecular basis for laser-induced TMR angiogenesis. Several investigators have used mechanical means other than laser to create transmural myocardial channels. The techniques used experimentally have included needle puncture, a mechanical drill a non energized laser fiber [, and ultrasound.Although some of these mechanical techniques may have theoretical merit, the results have been variable and no mechanical technique is approved by the US Food and Drug Administration.

2.	Denervation Kwong and associates found evidence that holmium: YAG TMR interrupted subepicardial visceral afferent neural signals. In contrast, Hirsch and colleagues did not find evidence of a reduction in ventricular contractile responses to direct electrical or chemical activation of sympathetic or parasympathetic efferent neurons after holmium:YAG TMR. Al-Sheik and colleagues in a clinical study of 8 patients after holmium:YAG TMR found no increase in resting or stress myocardial perfusion using positron emission tomography imaging with ammonia but found that most patients had an increase in sympathetic denervation as assessed by positron emission tomography imaging with hydroxyephedrine. They concluded that the angina relief was caused, at least in part, by cardiac sympathetic denervation. Performing the procedure In Transmyocardial Revascularization the surgeon creates new perfusion channels in the heart muscle to supplement the diseased coronary arteries In TMLR the surgeon makes use of a laser to create blood perfusion channels in the heart muscle to supplement the function of the coronary arteries. The heart then feeds itself by taking blood from within its chambers, just like in reptiles, whose hearts have no coronary arteries. During the TMLR procedure the surgeon makes an incision in the patient's left chest. With the heart exposed, the surgeon uses a laser to create multiple narrow channels through the wall of the left ventricle into the ventricular cavity in the area of the heart suffering form ischemia (lack of oxygenated blood). The inside surface of the channels develop a smooth, permeable membrane that allows blood to perfuse to heart muscle. The exterior surface opening of the channel is sealed off as blood coagulates and scar tissue closes the hole. When the surgeon has covered the ischemic areas of the heart with sufficient revascularization channels and verified that there is no bleeding from them, the access incision is closed. Recovery is usually rapid, requiring only three to four days in hospital. When the condition of the patient is so serious that even this procedure would not be tolerated easily, surgeons can use heart assist devices as bridges to this procedure. By implanting the assist device and permitting the heart to rest, the damaged heart cells may return to normal. The assist device can then be removed, and a TMLR can be performed. Thus far, the results have been promising.

1.	http://www.youtube.com/watch?v=Fq4m0ajqcd0 2.	http://www.youtube.com/watch?v=Uzn57VLrSmg&feature=related 3.