Mid-term effect of stem cells combined with transmyocardial degradable stent on swine model of acute myocardial infarction.

BACKGROUND: We aimed to confirm the mid-term results of the new method combined with bone marrow-derived mesenchymal stem cells (MSCs) transplantation and transmyocardial drilling revascularization (TMDR) with degradable stent incorporated with basic fibroblast growth factor and heparin. METHODS: The miniswine underwent acute myocardial infarction by ligation of the left anterior descending coronary artery. Transmyocardial channels with 3.5 mm diameter (TMDR) were made by mechanical drilling in the infarction territory and basic fibroblast growth factor stents were implanted into the channels. Animals were randomly divided into the following four groups (n=6 in each): control; II: MSCs implantation; III: TMDR+stent implantation; IV: TMDR+stent implantation+MSCs implantation. Three months postoperatively, ECG-gated single photon emission computed tomography, histopathological examination, and reverse transcription-polymerase chain reaction were carried out. RESULTS: Left ventricular ejection fraction and myocardial perfusion were significantly improved in group IV than that in other groups (P<0.05). Compared with other groups, vessel density was augmented and cell apoptosis was reduced in group IV (P<0.01). Reverse transcription-polymerase chain reaction results showed that the expression levels of von Willebrand factor, transforming growth factor-beta3, vascular endothelial growth factor, and interleukin-1beta were much higher in group IV than that in other groups (P<0.05). CONCLUSION: Three months after operation, MSCs transplantation combined with TMDR and degradable stent significantly improved cardiac function, enhanced neovascular density, reduced infarcted size, improved ventricular remodeling, and reduced cardiac myocyte apoptosis, and therefore provides strong information for clinical trial.

A new transmyocardial degradable stent combined with growth factor, heparin, and stem cells in acute myocardial infarction.

AIMS: We developed a new method-transmyocardial drilling revascularization (TMDR) with absorbable stent incorporated with basic fibroblast growth factor (bFGF) and heparin. The present study tested the effect of this method with transplantation of bone marrow-derived stem cells (BMSCs) in acute myocardial infarction. METHODS AND RESULTS: Infarction was produced in mini-swine by ligating the left anterior descending (LAD) coronary artery. TMDR of 3.0 mm in diameter was made by mechanical drilling in the infarcted area. The animals that had LAD ligation were divided into six groups according to the procedures followed (n = 6 in each): control; T (TMDR); C (cell implantation); TS (TMDR+stent implantation); TC (TMDR+cell implantation); TSC (TMDR+stent implantation+cell implantation). Left ventricular (LV) function, myocardial perfusion, vascular density, and histological and morphological analyses were evaluated pre-operatively and at 30 min and 6 weeks post-operatively. Six weeks after operation, the above indices were significantly better in the TSC group than in other groups (P < 0.001 compared with the control group, and P < 0.05 or 0.01 compared with the TS and TC groups), although TS and TC also showed better results than the control group (P < 0.05). CONCLUSION: We have demonstrated in a pig model that an intramyocardial stent implanted with slow release of bFGF, heparin, and BMSC transplantation may significantly increase LV function, cardiac blood flow, and vascular density. Therefore, the present study may provide a new method for the surgical treatment of myocardial infarction.

Degradable PLGA scaffolds with basic fibroblast growth factor: experimental studies in myocardial revascularization.

Our goal was to investigate the efficacy of degradable poly(D,L-lactic-coglycolic acid) (PLGA) scaffolds loaded with basic fibroblast growth factor (bFGF) in inducing cardiac neovascularization, increasing perfusion, and improving cardiac function.For ease of scaffold implantation into the ventricular wall, we developed a channel-producing device. Mini-swine, established as the animal model, were grouped as follows: channels-alone (control) group, channels and blank scaffolds (CBS) group, and channels and bFGF-incorporating scaffolds (CFS) group. Two scaffolds were implanted in each animal in the CBS and CFS groups. Six weeks postoperatively, endothelial cells were immunohistologically stained for von Willebrand factor, and proliferating cells for Ki-67 antigen. The density of new vessels was counted by image-analysis software. Left ventricular function and myocardial perfusion were documented by echocardiography and nuclear scanning, respectively, before implantation and 6 weeks postoperatively.The combined application of PLGA and bFGF ensured sustained release of growth factor in the target region. In the CFS group, Ki-67-positively stained cells, vascular density, and perfusion-defect percentage all showed significant improvement (P < 0.001), compared with the control and CBS groups, which did not. Moreover, the left ventricular fractional shortening percentage in the CFS group (28.98% +/- 1.24%) showed a significant increase, compared with the control group (26.57% +/- 1.92%, P = 0.009) and the CBS group (27.11% +/- 0.71%, P = 0.033), neither of which showed a difference (P = 0.508).The bFGF-incorporating PLGA scaffold can promote neovascular formation, enhance blood-flow perfusion, and improve myocardial function, although the original scaffold lumina were eventually occluded by inflammatory cells and scar tissue.

[Radionuclide pulmonary perfusion imaging in evaluating pulmonary hypertension in patients with rheumatic heart disease].

OBJECTIVE: To evaluate the degree of pulmonary hypertension in patients with rheumatic heart disease using radionuclide pulmonary perfusion imaging. METHODS: The pulmonary perfusion in 25 patients with rheumatic heart disease was examined using scintigram with macroaggregates of (99m)Tc-labeled human serum albumin (PPS) before and 7 days after operation. PPS was analyzed for (1) pulmonary perfusion steady time (PT), right upper and lower lung count ratio (RULR). The results were compared with those of catheterization examination during the operation. RESULTS: The pulmonary arterial systolic pressure (PAs) and total pulmonary resistance (TPR) were (60 +/- 21) mm Hg and (421 +/- 106) dyn if PT > or = 20 seconds and RULR > or = 2; The PAs and TPR were (28 +/- 5) mm Hg and (188 +/- 28) dyn if PT < 20 seconds and RULR < 2. The PPS changed in most of the patients during early operation. CONCLUSION: The degree of injury in pulmonary vascular in patients with rheumatic heart disease could be quantitatively analysed by PPS.