Font Size: a A A

Effects Of Bone Marrow Mononuclear Cell Transplantation On Left Ventricular Remodeling Of Swine AMI Models

Posted on:2010-04-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:J P CengFull Text:PDF
GTID:1114360278454012Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Backgrouds:Ideal acute myocardial infarction model should duplicate the pathological process of clinical acute myocardial infarction as far as possible, which is often followed by ventricular remodeling. The swine heart is quite near to human's in heart weight index, anatomic structure and coronary vessels distribution. Especially, there are rare coronary collateral circulations, which resembles the human's. Therefore, swine is the most ideal animal for establishing acute myocardial infarction model.The traditional method to establish acute myocardial infarction model is to unfold the thoracic cavity and ligatured the coronary artery, leading to high mortality. Lately, as the rapid development of coronary artery angiography and percutaneous transluminal coronary angioplasty, more and more used catheters, guide wires, balloons are discarded, which can still be recycled for animal experiments. Compared with coronary artery ligation, occluding coronary with balloon may be a better method to establish acute myocardial infarction model.Objective:To observe the effects of establishing swine acute myocardial infarction and following ventricular remodeling model by occluding Coronary with balloon.Methods:Ten healthy domestic swines were enrolled. Each swine's left anterior descending coronary artery was occluded for three hours by dilated balloon, and then reperfusion was performed by withdrawing the balloon. During the whole course of operation the electrocardiogram was monitored. B-ultrasound and single-photon emission computed tomography examination were performed to detect left ventricular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricular ejection fraction before and one week, three months, six months after acute myocardial infarction. Then all the animals were sacrificed and HE stain was performed to observe the pathomorphological changes in the infarcted myocardium.Results:1. Early five swine died during the period of operation for lack of experiences, the remains survived, and electrocardiogram examination witnessed significant ST-elevation and Q-wave, and one week after operation, B-ultrasound revealed enlarged left ventricular end diastolic dimension and diminished left ventricular tip wall thickness, and single-photon emission computed tomography revealed enlarged left ventricular end diastolic volume and degraded left ventricular ejection fraction.2. Three and six months after operation, B-ultrasound and single-photon emission computed tomography examination were performed again, revealing deteriorating left ventricular end diastolic dimension expansion, left ventricular tip wall thickness thinning, left ventricular end diastolic volume expansion and left ventricular ejection fraction depression. HE stain revealed that there was pervasive myocardiolysis and scarring in the infarcted region.Conclusions:Coronary artery occlusion by balloon can successfully establish acute myocardial infarction and following left ventricular remodeling models. Backgrounds:Early after acute myocardial infarction, the quantities of myocardial cells remarkably reduced, leading to acute left ventricular disfunction, named acute pump failure, mainly responsible for high morbility in early stage after acute myocardial infarction. Even if the patients survived, the following left ventricular remodeling might causing expansion of the infarcted ventricular wall, finally leading to heart failure. Therefore, reconstructing the ruined myocardial tissues may alleviate left ventricular remodeling and inhibit heart failure, and bone marrow stem cells autologous transplantation is a promising method.Objects:Observe the effects of bone marrow stem cells autologous transplantation early after acute myocardial infarction on left ventricular remodeling.Methods:Acute myocardial infarction models were successfully established in 10 swines, which were randomly separated into two groups: placebo group and transplantation group. One week after model establishment, autologous bone marrow mononuclear cells transplantation in infarction related coronary arteries were performed, and control group was administrated with placebo. Before and one week, three months, six months after acute myocardial infarction, B-ultrasound and single-photon emission computed tomography examinations were performed to assess the left ventricular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricle ejection fraction.Results:1. B-ultrasound and emission computed tomography examination revealed deteriorating left ventricular end diastolic dimension enlargement, left ventricular tip wall thickness diminish, left ventricular end diastolic volume enlargement and left ventricle ejection fraction degrading in transplantation groups, indicating that AMI-induced left ventricular remodeling can not be completely blocked by bone marrow cells transplantation.2. Three and six months after acute myocardial infarction, compared with control group, transplantation group witnessed smaller left ventricular end diastolic dimension, thicker left ventricular tip wall, smaller left ventricular end diastolic volume and higher left ventricle ejection fraction.Conclusion:Autologous bone marrow mononuclear cells transplantation early after acute myocardial infarction can alleviate left ventricular remodeling. Backgrouds:For lack of regeneration ability, the necrotic myocardial cells can only be replaced by fibroblasts, which finally form scar tissues. When the scared tissues thinning, ventricular remodeling progresses, and chronic heart failure gradually deteriorates. Recently, marrow stem cells' potential was found in differentiating into myocardial cells and endothelial cells, which can prevent ventricular remodeling and improve heart function. And further researches revealed that marrow stem cell requires suitable opportunity. Commonly, transplantation after one to two weeks is considered eligible. If too early, most marrow stem cells are involved in inflammation reaction and can not survive, on the contrary, too late transplantion may miss appropriate opportunity, for irreversible ventricular remodeling may have taken place. However, in clinical practice, it's often confronted that patients seek help again when heart failure emerges several months after acute myocardial infarction. In this situation, whether late stem transplantation may block the subsequent deteriorating ventricular or not incites our interest.ObjectivesObserve whether stem cells transplantation three months after acute myocardial infarction can alleviate deteriorating left ventricular remodeling.Methods:Acute myocardial infarction models were successfully established in 15 swines, which were randomly evenly divided into three groups: placebo group, early transplantation group and late transplantation group. One week after model establishment, early transplantation group underwent bone marrow mononuclear cells transplantation, then so did the late transplantation group three month after acute myocardial infarction. B-ultrasound and single-photon emission computed tomography examinations were performed to assess the left ventricular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricle ejection fraction before and one week, three months, six months after acute myocardial infarction. Results:1. In both early and late transplantation groups, B-ultrasound and emission computed tomography examination revealed deteriorating left ventricular end diastolic dimension expansion, left ventricular tip wall thinning, left ventricular end diastolic volume expansion and left ventricle ejection fraction depression, indicating that AMI-induced left ventricular remodeling models can not be overly blocked by bone marrow cells transplantation, regardless of the opportunity of transplantation.2. Six months after administration of transplantation, compared with control group, late transplantation group witnessed smaller left ventricular end diastolic dimension, thicker left ventricular tip wall, smaller left ventricular end diastolic volume and higher left ventricular ejection fraction. Yet, the effects of late transplantation group is not so good as early transplantation group's.Conclusions:Bone marrow mononuclear cells transplantation three month after acute myocardial infarction can alleviate progressing ventricular remodeling, but its therapeutic effects are inferior to early transplantation's. Backgrounds:The discovery that stem cells can regenerate damaged organs has started a new intriguing scientific revolution on regeneration treatment, yet hitherto it's still unclear whether transplanted stem cells can differentiate into matures myocardial cells with normal functions. Thereby, more and more attention was concentrated on stem cells' paracrine effects.Objects:Confirm the homing of transplanted bone marrow stem cells to recipient infarcted myocardium; Observe the effects of transplanted bone marrow stem cells on local mRNA expression of SDF-1, Kit ligand, E-selectin, ICAM-1 and VCAM-1.Methods:Two female domestic swines' left anterior descending coronary artery was occluded for three hours by dilated balloon, and then reperfusion was performed by withdrawing the balloon. One week after model establishment, male swines' bone marrow mononuclear cells were transplanted in infarction related coronary arteries. Six month after sex-matched transplantation, we detected the mRNA of sex-determining region on the Y chromosome in the infarcted myocardium of recipient female domestic swines. Moreover, hearts of placebo group and early transplantation group was harvested for detecting mRNA expression of SDF-1, Kit ligand, E-selectin, ICAM-1 and VCAM-1 in infarcted myocardial region.Results:1. The mRNA of sex-determining region on the Y chromosome can be detected in the infarcted myocardial region in recipient female Domestic swines.2. 6 month after autologous transplantation, the mRNA of SDF-1, Kit ligand, E-selectin, ICAM-1 and VCAM-1 was expressed in the early transplantation group' infarcted myocardial region, but not in the placebo groupConclusion:MSCs can home to infarcted myocardium region and survive for quite long time, and promote local mRNA expression of SDF-1, Kit ligand, E-selectin, ICAM-1 and VCAM-1, responsible of the paracrine effects of stem cells.
Keywords/Search Tags:Balloon, Left anterior descending coronary, Acute myocardial infarction, Ventricular remodeling, Bone marrow mononuclear cells, Autologous transplantation, Late transplantation, Homing, Cytokines, paracrine
PDF Full Text Request
Related items