Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function
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.
[Show abstract] [Hide abstract] ABSTRACT: To evaluate the midterm results of patients with angina and diffuse coronary artery disease treated with transmyocardial revascularization in combination with autologous stem cell therapy. Nineteen patients with diffuse coronary artery disease and medically refractory class III/IV angina were evaluated between June 2007 and December 2009 for sole therapy TMR combined with intramyocardial injection of concentrated stem cells. At the time of surgery, autologous bone marrow (120cc) was aspirated from the iliac crest. A cardiac MRI and an isotopic test were performed before and after the procedure. Follow-up was performed by personal interview. There were no perioperative adverse events including no arrhythmias. Mean number of laser channels was 20 and the mean total number of intramyocardially injected cells per milliliter were: total mononuclear cells(83.6 × 10(6)), CD34+ cells(0.6 × 10(6)), and CD133+ cells(0.34 × 10(6)). At 12 months mean follow-up average angina class was significantly improved (3.4 ± 0.5 vs 1.4 ± 0.6; p = 0.004). In addition, monthly cardiovascular medication usage was significantly decreased (348 ± 118 vs. 201 ± 92; p = 0.001). At six months follow up there was a reduction in the number of cardiac hospital readmissions (2.9 ± 2.3 vs. 0.5 ± 0.8; p < 0.001). MRI showed no alterations regarding LV volumes and a 3% improvement regarding ejection fraction. The stem cell isolator efficiently concentrated autologous bone marrow derived stem cells while the TMR/stem cell combination delivery device worked uneventfully. An improvement in clinical status was noticed in the midterm follow-up. Images test showed no morphological alterations in the left ventricle after the procedure.
- "These data support the safety of and feasibility of the BMLR technique. Although special methods as three dimensional microvascular lectin angiogram  or the modified Clark electrode has been used in animals models it is believed that conventional methods may not be sensitive enough to identify subtle changes after stem cell injec- tion. The objective of this study was to evaluate the safety and feasibility of the BMLR treatment while initially collecting effeicacy outcomes data. "
- [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: The action of solar light transformed by special screens has been studied on CD-1 male mice. In the active control group, mice were irradiated through screens absorbing the UV-component. In the experimental group, screens transforming the UV-component into the orange-red light were used. In the active control, changes in the swimming activity, as compared to the same parameter before irradiation, were manifested much less than in animals of the experimental group. A morphological analysis showed changes in the structure of all cardiomyocyte organelles studied: the relative area of mitochondria in the experimental mice increased by more than 20% compared to intact animals (p < 0.05). A significant increase in the area of the sarcoplasmic reticulum, by 23.4% (p < 0.05), and in the volume of the myofibrillar apparatus, by 19.4% (p < 0.05), was detected. The results of our experiment show that the irradiation with using an additional orangered component improves the physical endurance 1.5 times and initiates morphogenetic processes in cardiac muscle cells. Key wordsred-orange light-physical endurance-morphology of myocardial cells-solar light