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Abstract
Therapy with bone marrow-derived cells has been used in ischemic patients with reported success. The aim of this study was to determine the therapeutic efficacy of fresh and frozen human umbilical cord blood cells (hUCB) in Wistar rats submitted to permanent occlusion of the left coronary artery. Three hours after myocardial infarction, 2 x 10(7) hUCB cells or vehicle were administered by intramyocardial injection. The animals were divided into five groups: control (N = 10), sham operated (N = 10), infarcted that received vehicle (N = 9), infarcted treated with cryopreserved hUCB (N = 7), and infarcted treated with fresh hUCB (N = 5). Cardiac function was evaluated by electrocardiogram (ECG) and echocardiogram (ECHO) before cell therapy, and by ECG, ECHO, cardiopulmonary test, and left ventricular pressure measurements 3 weeks later. After 3 weeks, both groups treated with hUCB still had Q wave present in L1, âQRS >90 degrees and reduced shortening fraction (less than 50%). In addition, cardiac indexes of left ventricular contractility and relaxation were 5484 +/- 875 and -4032 +/- 643 mmHg (cryopreserved hUCB) and 4585 +/- 955 and -2862 +/- 590 mmHg (fresh hUCB), respectively. These values were not statistically different from those of saline-treated animals. Cardiopulmonary exercise test profile was typical of infarcted hearts; exercise time was about 14 min and maximal VO2 was 24.77 +/- 5.00 mL.kg-1.min-1. These data show that hUCB therapy did not improve the cardiac function of infarcted animals or prevent cardiac remodeling.
Highlights
Myocardial infarction (MI) leads to myocyte death causing progressive structural and functional changes in the heart
Electrocardiographic analysis Three weeks after cell therapy, electrocardiographic parameters in the groups treated with fresh and cryopreserved human umbilical cord blood cells (hUCB) cells were typical of infarcted animals
Echocardiographic analysis The two-dimension echocardiographic images taken at the level of the papillary muscle 3 h after infarction showed that the percentage of left ventricle (LV) akinesis was 43.4 ± 6.0% (INT); 47.10 ± 9.2%; 43.71 ± 2.8%
Summary
Myocardial infarction (MI) leads to myocyte death causing progressive structural and functional changes in the heart. This cardiac remodeling contributes to abnormal left ventricle (LV) function and to the development of heart failure [1]. The search for compatible donors and immune suppression limit the application of this procedure and alternative therapies are needed For these reasons, cell therapy has become a novel option for patients with ischemic heart disease. Cell transplantation has been investigated intensively in the setting of MI Many cell types such as fetal cardiomyocytes, embryonic stem cells, skeletal myoblasts, and bone marrow stem cells have been evaluated in animal models (for a review, see Ref. 3). Heeschen et al [6] demonstrated that bone marrow mono-
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