Combined Use of Transmyocardial Laser Revascularization and Endothelial Progenitor Cells Enhances Neovascularization and Regional Contractility in a Canine Model of Ischemic Hearts

The purpose of this study was to determine the combined effect of transmyocardial laser re- vascularization （TMLR） and the implantation of endothelial progenitor cells （EPCs） on cardiac function of ischemic hearts in canines. The left anterior descending artery （LAD） was occluded to establish the canine model of acute myocardial infarct （AMI）. Four weeks later, the animals were randomly divided into four groups： TMLR group, in which transmyocardial laser-induced channels were established at the ischemic region; EPCs＋TMLR group, in which EPCs were locally transplanted into laser-induced chan- nels at the ischemic region; EPCs group, in which the EPCs were injected into the ischemic region; con- trol group, in which the AMI animals received neither TMLR nor EPCs. The peripheral blood （50 mL） was sampled in all groups. Mononuclear cells from the peripheral blood were separated and cultured to obtain spindle-shaped attaching （AT） cells in vitro. AT cells were labeled with 1, 1 ＇-dioctadecyl-1 to 3,3, 3＇,3＇-tetramethyl-indocarbocyanine perchlorate （DiI） before injecting into the laser-induced channels or ischemic region. Four weeks after the first operation, TMLR was performed in the TMLR group and EPCs＋TMLR group, and at the same time, the EPCs originating from the AT cells were mixed with cal- cium alginate （CA）. Then the EPCs-CA composites were implanted into myocardial channels induced by laser in the EPCs＋TMLR group, and into the myocardial infarct area in the EPCs group. All dogs underwent echocardiography at second month after LAD occlusion. Finally the samples of myocardium around the LAD were subjected to histochemical and immunohistologic examinations. The results showed there was no significant difference in the diameter of left atrium and ventricle before treatment among all groups （P〉0.05）. Eight weeks after modeling, the regional contractility in the LAD territory in the EPCs＋TMLR group was increased as compared with control group and TMLR group, but there was no significant difference between control group and TMLR group. Neoangiogenesis was observed in the EPCs＋TMLR group, and the fibrosis was seen in the TMLR group. There was no significant dif- ference in neoangiogenesis around the channels induced by laser among EPCs＋TMLR, EPCs and TMLR groups. It was concluded that TMLR combined with EPCs could improve the regional and global cardiac function in AMI, and augment neovascularizaiton in channels of ischemic myocardium induced by laser.

COMPARATIVE EXPERIMENTAL STUDY OF HO-YAG LASER AND TRUE- CUT BIOPSY NEEDLE IN MYOCARDIAL REVASCULARIZATION

Objective.To study the mechanism and effects of blood perfusion on acute ischemic region of myocardium through channel created by Ho- Yag laser and True- cut biopsy needles with myocardial contrast echocardiography. Methods. We partially ligated the left anterior descending coronary artery of canine hearts between the lst and 2nd diagonal branches to produce two groups of acute myocardial ischemia models and then performed tran- smyocardial revascularization (TMR) on this region with Ho- Yag laser and True- cut biopsy needles. Myocardial contrast echocardiography was performed with a new generation of ultrasound contrast agent and second harmonic imaging of this region before, during ischemia and after revascularization. Pictures were taken with“ R” wave trigger skill. Results. Acoustic density (dB) in the ischemic region (anterior wall) with myocardial contrast echocardiography decreased obviously after the left anterior descending artery was ligated (Laser group: 5.40± 1.81, Needle group: 7.11± 2.51) compared with that before (Laser group: 11.69± 1.61, Needle group: 12.96± 2.88, P< 0.01). dB increased remarkably after TMR by either laser or True cut biopsy needle (Laser group: 11.02± 2.01, Needle group: 10.01± 4.45. P< 0.01) compared to that during ischemia and approximated to that before ischemia (P >0.05). We found that the acoustic density of the contrast developed one picture (one cardiac cycle) ahead in the transmyocardial revascularization region than that in the lateral and other region of the left ventricle wall in the scan of both groups. Conclusions. Acute ischemic myocardium can be perfused immediately by oxygenated blood from the left ventricle through channels created with both Ho- Yag laser and True- cut biopsy needles. Evidence of blood perfusion through these channels mainly during systolic phase was detected, and myocardial contrast ultrasound using intravenous perfluorocarbon- exposed sonicated dextrose albumin was regarded as a reliable method in the study of transmyocardial revascularization.

Redo Coronary Artery Bypass Grafting: On-Pump and Off-Pump Coronary Artery Bypass Grafting Revascularization Techniques

Objective To analyze the short-term outcomes of redo coronary artery bypass grafting(CABG) using on-pump and off-pump CABG techniques. Methods From January 2003 to August 2013, non-randomized 80 patients were treated with redo CABG in the Department of Cardiac Surgery, Peking University Third Hospital. Among these patients, 40 underwent on-pump CABG technique(redo-ONCAB group) and 40 underwent off-pump CABG technique(redo-OPCAB group). Furthermore, transmyocardial laser revascularization was performed in high-risk patients who were not suitable to conventional grafting. Clinical data of the two groups were recorded and analyzed including operation time, coronary grafts, incomplete revascularization, postoperative ventilation, perioperative stroke, and low output syndrome, etc. Results There were no significantly differences in age, gender distribution, incidences of hypertension, stroke, and other clinical characteristics between redo-OPCAB group and redo-ONCAB group(all P>0.05), except for incidences of renal dysfunction and pulmonary disease(all P<0.05). The number of grafting vessels in the redo-ONCAB and redo-OPCAB groups was 2.1 ± 0.74 and 1.4 ±0.52 respectively. There was significant difference between the two groups(P=0.0243). Compared with the redo-ONCAB group, there was shorter operation time(P=0.0045), postoperative ventilation(P=0.0211) and intensive care unit stay(P=0.0400), as well as fewer use of platelet(P=0.0338) and blood transfusion(P=0.0034) in the redo-OPCAB group. The incidence of incomplete revascularization(P=0.0253) and the use of transmyocardial laser revascularization(P=0.0052) were higher in the redo-OPCAB group than those in the redo-ONCAB group(all P<0.05). However, no significant differences were showed for the incidence of the use of intra aortic balloon pump and continuous renal replacement therapy, perioperative stroke, low output syndrome, and in-hospital mortality between the two groups(all P>0.05). Conclusion Redo CABG is the safety and efficacy surgical procedure, and redo-OPCAB technique with better outcomes is commended especially in high-risk patients.

Single-center report of 5-year follow-up on 94 patients underwent transmyocardial laser revascularization

Background Transmyocardial laser revascularization （TMLR） has been used in the treatment of patients with end-stage coronary artery disease （CAD） since 1990. The aim of this study was to evaluate the long-term effectiveness of TMLR in patients with diffuse CAD.Methods Ninety-four consecutive patients underwent TMLR in one center from July 1997 to December 2000. The follow-up data of these patients were obtained through face-to-face, mail questionnaires, or telephone interviews in July 2004 and December 2004. Four cases failed to respond. Mean follow-up time was （5.5±1.0） years. Results Mean Canadian Cardiovascular Society （CCS） angina scores of TMLR patients were 3.1±0.8 at baseline, 1.7±0.9 at 1 year （P〈0.05）, 1.7±0.9 at 3 years （P〈0.05）, and 1.9±0.9 at 5 years （P〈0.05）. At an average of 5 years, 69% of the patients had 〉 1 angina class reduction, mean NYHA class level （1.9±0.9） ameliorated compared to the baseline （2.5±0.7, P〈0.001）, the rate of re-hospitalization was 2.7 times/person. Kaplan-Meier survival rate was 87% at 1 year, 69% at 3 years and 64% at 5 years. The causes of death were attributed more to heart failure （58.9%） and myocardial infraction （14.7%） after TMLR. The patients with no angina relief, or who died after TMLR, had a higher percentage of preoperative unstable anginas or prior myocardial infraction compared to the survivors. The assorted shapes of myocardial laser channels were detected in some patients by the color Doppler velocity technique. Conclusions TMLR provided a long-term improvement in the quality of life, including CCS angina class or NYHA heart functional class for about 70% of Chinese patients with severely disabling angina pectoris. The various myocardial laser channels would always be visible after TMLR. 5-years after TMLR as a sole therapy, the survival rate of the patients was 64%.

Histochemical study of transmyocardial laser channels in dogs

Objective Laser-induced myocardial injury was investigated in a canine transmyocardial laser revascularization model.Methods A total of 23 channels were created in the left ventricles of 5 animals with a CO2 laser. Four animals were sacrificed immediately and one at week 2. Lactate dehydrogenase and succinate dehydrogenase in channel regions were examined with a Nitro-BT method staining.Results Immediately after the procedure, laser channels and surrounding injured myocardium could be stratified from the center to the border into 5 concentric zones, i.e., vaporized zone, carbonized zone, enzyme-disappeared zone, enzyme-decreased zone and enzyme-concentrated zone. Two weeks later, the phenomenon disappeared.Conclusions Immediately after transmyocardial revascularization, there is a ring of enzyme-concentrated zone at the outermost region of injured myocardium. Two weeks later, enzyme activities of reversibly injured myocytes appear to have recovered.