Article

Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function.

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
The Journal of thoracic and cardiovascular surgery (Impact Factor: 3.41). 03/2008; 135(2):283-91, 291.e1; discussion 291. DOI: 10.1016/j.jtcvs.2007.09.043
Source: PubMed

ABSTRACT A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization.
Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis.
Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor kappaB (42 +/- 27 intensity units vs 591 +/- 383 intensity units, P = .03) and angiopoietin 1 (0 +/- 0 intensity units vs 241 +/- 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 +/- 8.7 vessels/high-power field vs 31.4 +/- 10.2 vessels/high-power field, P = .02), and perfusion (0.028 +/- 0.009 microm3 blood/microm3 tissue vs 0.044 +/- 0.004 microm3 blood/microm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 +/- 8.5 cardiomyocytes/high-power field vs 50.8 +/- 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 +/- 0.2 L/min vs 2.7 +/- 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% +/- 3.6% vs 76.1% +/- 3.4%, P = .008).
Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.

0 Bookmarks
 · 
76 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with syndrome X coronary disease represent a heterogeneous group of patients. Medical treatment with dilators and calcium channel blockers are not very effective. We evaluated the use of transmyocardial laser revascularization (TMLR) in treating 5 patients with this syndrome. Between May 2002 to December 2005, 5 patients with cardiac syndrome X (mean age of 49.7 years) underwent TMLR. All our cases were postmenopausal women. Mean class of Canadian class of angina was 3.4. Patients were none responding to maximum medical treatment. Angiograms showed small coronary arties with a large gap between branches which corresponded with severe ischemic on Thallium scan. We used Co2 laser between 35 to 45 joules of energy and we made 20 to 30 channels on the beating heart controlled by trans-esophagus echocardiography. Our patients were followed for 2.8 years. During follow up our patients remained asymptomatic and without any need medical treatment. Mean of Canadian class of angina after intervention was 1.8. Our patients returned to full activities. TMLR is an effective treatment in patients with syndrome X and coronary insufficiency.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Recently, several kinds of lasers have been widely employed in the field of medicine and surgery. However, laser applications are very rare in the field of cardiovascular surgery throughout the world. So, we have experimentally tried to use lasers in the field of cardiovascular surgery. There were three categories: 1) Transmyocardial laser revascularization (TMLR), 2) Laser vascular anastomosis, and 3) Laser angioplasty in the peripheral arterial diseases. By the way, surgery for ischemic heart disease has been widely performed in Japan. Especially coronary artery bypass grafting (CABG) for these patients has been done as a popular surgical method. Among these patients there are a few cases for whom CABG and percutaneous coronary intervention (PCI) could not be carried out, because of diffuse stenosis and small caliber of coronary arteries. Materials and methods of TMLR: A new method of tranasmyocardial revascularization by CO2 laser (output 100 W, irradiation time 0.2 sec) was experimentally performed to save severely ill patients. In this study, a feasibility of transmyocardial laser revascularization from left ventricular cavity through artificially created channels by laser was precisely evaluated. In trials on dogs laser holes 0.2mm in diameter have been shown microscopically to be patent even 3 years after their creation, thus this procedure could be used as a new method of transmyocardial laser revascularization. Clinical application of TMLR: Subsequently, transmyocardial laser revascularization was employed in a 55-year-old male patient with severe angina pectoris who had undergone pericardiectomy 7 years before. He was completely recovered from severe chest pain. Conclusions of TMLR: This patient was the first successful case in the world with TMLR alone. This method might be done for the patients who percutaneous coronary intervention and coronary artery bypass grafting could be carried out. Laser vascular anastomosis: At present time, in vascular surgery there are some problems to keep long-term patency after anastomosis of the conventional suture method, especially for small-caliber vessels. Materials and methods of Laser vascular anastomosis: From these standpoints, a low energy CO2 laser was employed experimentally in vascular anastomosis for small-caliber vessels. Resullts of Laser vascular anastomosis: From preliminary experiments it could be concluded that the optimal laser output was 20-40 mW and irradiation time was 6-12 sec/mm for vascular anastomosis of small-caliber vessels in the extremities. And then, histologic findings and intensity of the laser anastomotic sites were investigated thereafter. Subseqently, good enough intensity and good healing of laser anastomotic sites as well as the conventional suture method could be observed. There were no statistic differences between laser and suture methods. A feasibility of laser anastomosis could be considered and clinical application could be recognized. Clinical applications of Laser vascular anastomosis: On February 21, 1985, arterio-venous laser anastomosis for the patient with renal failure was smoothly done and she could accept hemodialysis. Conclusions of Laser vascular anastomosis: This patient was the first clinical successful case in the world. Thereafter, Laser vascular anastomosis were in 111 patients with intermittent claudication, refractory crural ulcer, and coronary disorders. Thereafter, they are going well. Laser angioplasty: Laser angioplasty for peripheral arterial diseases. There are many methods to treat peripheral arterial diseases such as balloon method, atherectomy, laser technique and stenting graft in the field of endovascular treatment. Recent years, minimal invasive treatment should be employed even in the surgical treatment. However, there are different images between these methods. Materials and methods of Laser angioplasty: We have chosen to use laser for endovascular treatment for peripheral arterial diseases. We have tried to check between laser energy and vessel wall. Results of Laser angioplasty: Subsequently, it could be concluded that optimal conditions for laser angioplasty were 6 W in output and irradiation time was 5 sec. And with another method of feedback control system, temperature of metal tip probe was 200°C and irradiation time was 5 sec for each shot. And histological study and feasibility of angioscopic guidance could be done and clinical application was started. Until now, 115 patients were successfully treated with their life longevity. Conclusions of Laser angioplasty: Thus, laser applications were useful methods to treat a lot of patients with some ischemic problems.
    Laser therapy. 01/2011; 20(3):217-232.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Smaller engineered analogs of angiogenic cytokines may provide translational advantages, including enhanced stability and function, ease of synthesis, lower cost, and, most important, the potential for modulated delivery via engineered biomaterials. In order to create such a peptide, computational molecular modeling and design was employed to engineer a minimized, highly efficient polypeptide analog of the stromal cell-derived factor-1α (SDF) molecule. After removal of the large, central β-sheet region, a designed diproline linker connected the native N-terminus (responsible for receptor activation and binding) and C-terminus (responsible for extracellular stabilization). This yielded energetic and conformational advantages resulting in a small, low-molecular-weight engineered SDF polypeptide analog (ESA) that was shown to have angiogenic activity comparable to or better than that of recombinant human SDF both in vitro and in a murine model of ischemic heart failure.
    Trends in cardiovascular medicine 08/2012; · 4.37 Impact Factor