Basic Science ResearchShock Wave-Pretreated Bone Marrow Cells Further Improve Left Ventricular Function After Myocardial Infarction in Rabbits
Introduction
Acute myocardial infarction (AMI) remains the leading cause of death in patients hospitalized for cardiovascular disease.1, 2 Numerous clinical studies have demonstrated that the achievement of brisk thrombolysis in myocardial infarction grade 3 flow immediately after thrombolytic therapy or primary percutaneous coronary intervention in AMI is effective in minimizing the effect of ischemic insult to myocardium, preserving left ventricular (LV) function, and improving overall survival.3, 4, 5, 6 However, there is limited benefit of reperfusion therapy if medical attention is delayed.7, 8 Additionally, despite application of reperfusion therapy,3, 4, 5, 6 nonviable cardiomyocytes after MI cannot be regenerated. Therefore, LV dilatation and remodeling from poor regional and global contractile function mainly account for poor clinical outcomes.9, 10, 11, 12, 13 Therefore, restoring lost myocardium is desirable in treating AMI.
Increasing evidence shows that bone marrow stem cell (SC) therapy seems highly advantageous in improving ischemia-induced or infarct-related cardiac dysfunction.14, 15, 16 Clinical observational studies have further established that the improvement in LV function is mainly because of angiogenesis after SC transplantation.17, 18 Moreover, in vitro studies indicate that extracorporeal shock wave therapy not only can upregulate the expression of vascular endothelial growth factor in cultured human umbilical vein endothelial cells19, 20 and in rat bone marrow cells,21but it can also promote bone marrow cells to develop endothelial phenotype.21 Accordingly, this study tested the hypothesis that autologous transplantation of shock wave (SW)-treated culturing bone marrow-derived mononuclear cells (BMDMNCs) into infarct LV myocardium is superior to BMDMNC therapy alone in improving LV function in a rabbit model of AMI.
Section snippets
Ethics
All experimental procedures had been approved by the Institute of Animal Care and Use Committee at our hospital and performed according to the Guide for the Care and Use of Laboratory Animals (NIH publication No. 85-23, National Academy Press, Washington, DC, revised 1996).
Animals, Protocol, and Procedure
Pathogen-free, male New Zealand rabbits, weighing 2.5-2.8 kg were used in this study. Rabbits were anesthetized by mixture of intraperitoneal ketamin (25 mg/kg) and rompon (12 mg/kg). After being shaved on the chest, each
Body Weight, Echocardiographic, and Angiographic Findings and Mortality (Table I)
The initial and final body weight did not differ among the four groups. Additionally, echocardiographic study demonstrated no differences in terms of initial LVEF, left ventricular end-systolic dimension (LVESD), and LVEDD. By day 30 after AMI induction, the echocardiographic examination revealed that LVEDD was similar among the four groups. However, the echocardiographic findings showed that LVESD was significantly higher, whereas LVEF was significantly lower in groups 2-4 as compared with
An Additional Benefit of Preimplantation SW Application to Culturing BMDMNCs for Improving LV Function and Attenuating LV Remodeling
Both experimental and clinical observational studies have established that bone marrow stem cell therapy improves ischemia- or infarct-related LV dysfunction.14, 15, 16, 17, 18, 19, 24 The present study, using a rabbit AMI model, also revealed that BMDMNC implantation into IA improved 120-day LV function. Therefore, the results of the current study strengthen the findings of those previous studies.
In fact, although growing evidence indicates that various types of cellular therapy improve LV
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2017, Cardiovascular Revascularization MedicineCitation Excerpt :In our cohort most of the benefits of the treatment can be evidenced from the first month, probably suggesting an early local vasodilatatory effect produced by acoustic waves; those beneficial effects persisted during the follow up period demonstrating that there is also a long term effect, probably related to many different angiogenic pathways in a way that could be similar to the natural spreading of collateral vessels in chronic CAD: indeed, through tissue cavitation, shock waves could lead to a variety of biochemical effects including such as shear stress on cell membranes, Ras activation, an increase in nitric oxide synthesis, upregulation of VEGF and of stromal-derived factor-1 [18–26]. Another potential cellular mechanism may involve the recruitment of progenitor cells to the site of the ischemia undergoing ESMR [27–29]. Thus, we can conclude that there are probably involved in the beneficial effects of ESMR.
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Cheuk-Kwan Sun contributed equally to this study compared with the first author.
Steve Leu contributed equally to this study compared with the corresponding author.