Abstract P021: Adipose-Derived Stromal Cell Therapy Stabilizes Cardiac Function and Improves Border Zone Remodeling After Coronary Occlusion in Rats

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Antonio C Campos de Carvalho ◽  
Luiza Bagno ◽  
João Pedro Werneck de Castro ◽  
Patricia Oliveira ◽  
Marcia Abreu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Coronary Artery ◽  
Cardiac Function ◽  
Left Coronary Artery ◽  
Enzymatic Digestion ◽  
Left Ventricular ◽  
Female Rats ◽  
Border Zone ◽  
Functional Improvement ◽  
Vehicle Group

Recent studies have identified adipose tissue as a new source of mesenchymal stem cells for therapy. The purpose of this study was to investigate the therapy with rat adipose derived stromal cells (ASC) in a rat model of healed myocardial infarction (MI). ASC from inguinal subcutaneous adipose tissue of male Wistar rats were isolated by enzymatic digestion and filtration. Cells were then cultured until passage 3. Four weeks after ligation of the left coronary artery of female rats, a suspension of either 100µl with PBS + Matrigel + 2 x 106 ASC labeled with Hoechst (n=11) or 100µ;l of PBS + Matrigel (n=10) was injected along the borders of the ventricular wall scar tissue. A sham operated group (n=5) was submitted to the same surgical procedure except permanent ligation of left coronary artery. Cardiac performance was assessed by electro and echocardiogram. Echo was performed prior to injections (baseline-BL) and six weeks after injections (follow-up - FU), and values after treatment were normalized by values obtained before treatment. Hemodynamic measurements were performed 6 weeks after injections. All data are expressed as mean ± SEM. Student's paired or unpaired T test was used to compare the same group in two different times or two distinct groups, while two way ANOVA was used to compare more than two groups along different times and p was set at <0.05. All infarcted animals exhibited cardiac function impairment. Ejection fraction (EF), shortening fractional area (SFA) and left ventricular akynesia (LVA) were similar between infarcted groups before treatment. Six weeks after therapy, ASC group showed significant improvement in all three Echo indexes in comparison to vehicle group. In non-anesthetized animals dp/dt+ was also significantly higher in ASC when compared to vehicle. In agreement with functional improvement scar area was diminished in the ASC group. We conclude that ASC stabilize cardiac function in infarcted rats when administered directly to the myocardium.

Repair of Anomalous Left Coronary Artery from Pulmonary Artery (ALCAPA) beyond Infancy

2013 ◽  
Vol 16 (4) ◽  
pp. 210 ◽  
Author(s):  
Sachin Talwar ◽  
Aandrei Jivendra Jha ◽  
Shiv Kumar Choudhary ◽  
Saurabh Kumar Gupta ◽  
Balram Airan
Keyword(s):  
Coronary Artery ◽  
Pulmonary Artery ◽  
Respiratory Tract ◽  
Left Coronary Artery ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Anomalous Left Coronary Artery ◽  
Tract Infections ◽  
Anomalous Left Coronary

Between January 2002 and December 2012, five patients (4 female) underwent corrective surgery for anomalous left coronary artery from pulmonary artery (ALCAPA). They were older than 1 year (range, 3-56 years). One of the 2 patients younger than 10 years had presented with congestive heart failure, and the other had experienced repeated episodes of lower respiratory tract infection since childhood. Of the remaining 3 adult patients, 2 had experienced angina with effort, and 1 patient had had repeated respiratory tract infections since childhood, with mild dyspnea on effort of New York Heart Association (NYHA) class II. Three patients had the anomalous left coronary artery implanted directly into the ascending aorta via coronary-button transfer, and 2 patients underwent coronary artery bypass with obliteration of the left main ostium. Two patients underwent concomitant mitral valve repair procedures, and 1 patient underwent direct closure of a perimembranous ventricular septal defect. Four patients survived the surgery, and 1 patient died because of a persistently low cardiac output. Follow-up times ranged from 3 months to 4 years. All survivors are in NYHA class I and have left ventricular ejection fractions of 45% to 60%, with moderate (n = 1), mild (n = 1), or no (n = 2) mitral insufficiency. We conclude that a few naturally selected patients with ALCAPA do survive beyond infancy and can undergo establishment of 2 coronary systems with satisfactory results.

Outcomes of surgical repair of anomalous origin of the left coronary artery from the pulmonary artery in infants and children

2021 ◽  
pp. 1-6
Author(s):  
Tong Feng ◽  
Guo Zhangke ◽  
Bai Song ◽  
Fan Fan ◽  
Zhen Jia ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Pulmonary Artery ◽  
Left Coronary Artery ◽  
Surgical Repair ◽  
Left Ventricular ◽  
Anomalous Origin ◽  
Dimension Index

Abstract Objectives: Anomalous origin of the left coronary artery from the pulmonary artery is associated with high mortality if not timely surgery. We reviewed our experience with anomalous origin of the left coronary artery from the pulmonary artery to assess the preoperative variables predictive of outcome and post-operative recovery of left ventricular function. Methods: A retrospective review was conducted and collected data from patients who underwent anomalous origin of the left coronary artery from the pulmonary artery repair at our institute from April 2005 to December 2019. Left ventricular function was assessed by ejection fraction and the left ventricular end-diastolic dimension index. The outcomes of reimplantation repair were analysed. Results: A total of 30 consecutive patients underwent anomalous origin of the left coronary artery from the pulmonary artery repair, with a median age of 14.7 months (range, 1.5–59.6 months), including 14 females (46.67%). Surgery was performed with direct coronary reimplantation in 12 patients (40%) and the coronary lengthening technique in 18 (60%). Twelve patients had concomitant mitral annuloplasty. There were two in-hospital deaths (6.67%), no patients required mechanical support, and no late deaths occurred. Follow-up echocardiograms demonstrated significant improvement between the post-operative time point and the last follow-up in ejection fraction (49.43%±19.92% vs 60.21%±8.27%, p < 0.01) and in moderate or more severe mitral regurgitation (19/30 vs 5/28, p < 0.01). The left ventricular end-diastolic dimension index decreased from 101.91 ± 23.07 to 65.06 ± 12.82 (p < 0.01). Conclusions: Surgical repair of anomalous origin of the left coronary artery from the pulmonary artery has good mid-term results with low mortality and reintervention rates. The coronary lengthening technique has good operability and leads to excellent cardiac recovery. The decision to concomitantly correct mitral regurgitation should be flexible and be based on the pathological changes of the mitral valve and the degree of mitral regurgitation.

scholarly journals Induction of myocardial infarcts of a predictable size and location by branch pattern probability-assisted coronary ligation in C57BL/6 mice

2004 ◽  
Vol 286 (3) ◽  
pp. H1201-H1207 ◽  
Author(s):  
Dongchoon Ahn ◽  
Linda Cheng ◽  
Chanil Moon ◽  
Harold Spurgeon ◽  
Edward G. Lakatta ◽  
...  
Keyword(s):  
Heart Disease ◽  
Coronary Artery ◽  
Left Coronary Artery ◽  
Left Ventricular ◽  
Myocardial Infarctions ◽  
Branch Points ◽  
Left Main ◽  
Uniform Size ◽  
Disease Research ◽  
Coronary Ligation

The ability to create experimental myocardial infarctions of reproducible size and location is tantamount to progress in multiple facets of ischemic heart disease research. Branches of the mouse left main descending coronary artery penetrate the myocardium close to their origin and require “blind” ligation. Our objective was to develop a technique for ligation of nonvisible coronary artery branches to permit the reliable creation of infarcts of uniformly small size and location. From latex castings of the left coronary artery of C57BL/6J mice ( n = 53), we calculated the highest probability for the location of branch points of two of three left ventricular (LV) branches distal to the origin of the left main descending artery. On the basis of these anatomic probabilities, we blindly ligated two areas that were likely to be locations of these nonvisible LV branches. We were successful in producing two types of small transmural myocardial infarctions (16.04 ± 3.64 and 4.68 ± 1.47% of the LV) in 57% of attempts. Thus our branch pattern probability-assisted method permits routine creation of small infarcts of uniform size in the mouse.

Abstract 132: Cardiomyocyte Specific Conditional Overexpression Of Stromal Cell Derived Factor 1 Facilitates Cardiac Regeneration After Permanent Coronary Artery Ligation In Mice.

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Detlef Obal ◽  
Kenneth Brittian ◽  
Michael Book ◽  
Aruni Bhatnagar ◽  
Yiru Guo ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Stromal Cell ◽  
Cardiac Regeneration ◽  
Left Ventricular ◽  
Border Zone ◽  
Coronary Artery Ligation ◽  
Artery Ligation ◽  
Casein Kinase 1 ◽  
Coronary Ligation ◽  
Stromal Cell Derived Factor

Background: Interruption of cardiac stromal cell derived factor 1 (SDF1)-CXCR4 axis by chronic AMD3100 administration increased myocardial injury after permanent coronary artery ligation demonstrating the important role of this chemokine in cardiac regeneration. Hypothesis: Cardiomyocyte specific conditional overexpression of SDF1 prevents heart failure after permanent coronary ligation and facilitates cardiac regeneration. Methods and Results: Tetracycline-controlled, αMyHC promoter directed overexpression of cardiac SDF1, resulted in a significant increase of SDF1 expression (SDF1: 8.1 ng/mg protein) compared to littermate WT mice (0.02 ng/mg protein) four weeks after doxycycline withdraw. SDF1 overexpression increased AKT and casein kinase 1 levels in the heart. Although there was no difference in cardiac function and scar size 1 week after infarction, SDF1 overexpression improved left ventricular (LV) ejection fraction (SDF1 [n=13]: 47±5% [mean±SEM] vs. WT [n=15]: 29±4%, p<0.05) decreased end-diastolic volume (78±10 vs. 158±30, p<0.05) and reduced infarct size measured by trichrome staining (13±3% vs. 23±3% of LV wall, p<0.05) 4 weeks after permanent ligation. Bromodeoxyuridine (BrdU) staining revealed increased regeneration indicated by a 5-fold increase in BrdU + cardiomyocyte (CM) nuclei in the borderzone of the infarct (22±3% vs. 5±1% CM nuclei, p<0.01). Increased proliferation in SDF1 mice was confirmed by a higher number of KI67 + cells compared to WT mice. Cardiomyocyte cross sectional area in the border zone was significantly reduced in SDF1 mice (365±13 μm 2 vs. 434±10 μm 2 , p<0.001) while capillary density was unchanged (2348±151/ mm 2 vs. 2498±153/ mm 2 ) compared to WT mice. Conclusion: This study demonstrates for the first time that cardiac specific overexpression of SDF1 increases myocardial regeneration and improves LV function 4 weeks after permanent coronary ligation.

scholarly journals Ultrasound assessment of heart remodelling affected by therapeutic hypothermia and MSC on myocardial infarction model

2020 ◽  
Vol 28 (3) ◽  
pp. 222-240
Author(s):  
M. O. Chyzh ◽  
A. O. Manchenko ◽  
A. V. Trofimova ◽  
I. V. Belochkina
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Ejection Fraction ◽  
Stroke Volume ◽  
Therapeutic Hypothermia ◽  
Left Coronary Artery ◽  
Left Ventricular ◽  
Control Group ◽  
Normal Range ◽  
Allogeneic Mscs

Background. Late seeking medical advice, limited number of cardiac surgery hospitals and conservative treatment, which does not seem to be always efficacious, trigger the search for new, more effective mode therapy of acute myocardial infarction (MI). Recently, mesenchymal stromal cells (MSCs) have come into sharp focus of scientists due to the prospects for clinical use. On the other hand, multicenter studies have proved that therapeutic hypothermia (TH) has neuro- and cardioprotective effects, and it is administered as one of the urgent methods in providing primary health care. Purpose. Providing and analyzing ultrasonography (US) of rat hearts with experimental MI in order to determine the nature of heart remodelling under combined use of TH and introducing allogeneic MSCs. Materials and methods. The study involved 90 outbred white rats weighing 240–270 g. Myocardial infarction was reproduced by ligating the descending branch of the left coronary artery on the border of the upper and middle third of the vessel. Therapeutic hypothermia was performed in a cold chamber, 60 minutes long. The local skin temperature of the neck area was maintained at +4 оC, while the rectal and tympanic temperature decreased to + 25 оC. A suspension of allogeneic cryopreserved MSCs of the placenta with a concentration of 1.2 × × 106 cells/ml was administered once intravenously through v. saphena magna. Heart sonography was carried out by means of «Сономед 500» («СПЕКТРОМЕД», Russia) ultrasound scanner in B- and M-mode using a linear sensor 7.5L38 with frequency of 7.5 MHz. Results and discussion. The control group with experimental MI showed significantly suppressed function of the left ventricle (LV). It resulted in decreasing stroke volume (SV) and cardiac output (CO) and on the whole indicated reduced ejection fraction (EF) to 46.04 %, that was 35 % less than the corresponding normal range. According to the values of relative wall thickness (RWT) and left ventricular mass (LVM) on day 7 and day 30 after ligating the left coronary artery, LV remodelling was proceeding via eccentric mode of LV alteration. Therapeutic hypothermia was not able to completely stop the pathophysiological processes associated with coronary ligation. EF was not significantly different from the control group, and was 51.08 ± ± 2.68 %. On day 7 of the experiment, heart remodelling in this group was proceeding according to the normal geometry model, and on day 30 – according to the eccentric model. In spite of the volume overload causing post-infarction extension of the left ventricular cavity, in the group with applying MSCs, on day 7 there was a compensatory increase of the stroke volume, 1.8 times over compared to the group with normal range values and 2.3 over compared to the control group. The ejection fraction was 17 % less than the normal range, but statistically significantly higher than the corresponding indicator of the control group of this observation period. Heart remodelling after applying allogeneic MSCs associated with MI at all stages of observation was proceeding by eccentric LV hypertrophy. Аfter therapeutic hypothermia and applying MSCs associated with experimental myocardial infarction on day 7 and day 30, the group recorded the best values of echo params of LV anatomical structures, indicating no dilatation along with occuring moderate myocardial hypertrophy. The ejection fraction showed the best outcome, i. e. 58.78 %, while LV remodelling was minimal, occurring according to normal heart geometry. Conclusions. Applying echocardiography in rats is a very informative diagnosis method which makes it possible to describe the type of structural and functional remodelling of the myocardium associated infarction at early and late observation stages. The ultrasound study showed that the closest to the normal range was the group of animals exposed to therapeutic hypothermia and MSC transplantation. According to LVM and RWT values, in the rats of that group on day 7 and day 30 of the experiment, LV remodelling was characterized by normal geometry.

Abstract 15555: Administration of c-Kit+ Cardiac Stem Cells (CSCs) Results in Increased Proliferation and Cardiac Content of CSCs 1 Year Later

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Qianhong Li ◽  
Ning Chen ◽  
Li Luo ◽  
Qinghui Ou ◽  
Wei Xie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Border Zone ◽  
Functional Improvement ◽  
Vehicle Group ◽  
Lv Function ◽  
Female Rat ◽  
Infarct Zone ◽  
Hematopoietic Stem ◽  
Beneficial Effects ◽  
Rat Hearts

Background: We have previously shown in rats that the beneficial effects of c-kit + CSCs on LV function and remodeling post-myocardial infarction persist for at least 1 year after CSC administration. However, in that study the retention of transplanted Y-chromosome + cells in the risk region (RR) of female rat hearts at 1 year was low (<10% of total nuclei) and not sufficient to account for the functional improvement, suggesting that other mechanisms must be at work. Methods and Results: To address this issue, rats received intracoronary vehicle or 1x10 6 syngeneic CSCs 4 h after a 90-min coronary occlusion; 11 months later, BrdU treatment was given for 1 month. CSCs, which are c-kit + /CD45 − , were distinguished from c-kit + hematopoietic stem cells/mast cells, which are CD45 + . At 1 year after CSC administration, the total number of c-kit + or c-kit + /BrdU + cells in the heart (the sum of c-kit + /CD45 − and c-kit + /CD45 + cells) did not differ between CSC and control groups (Figs. H and I). However, CSC transplantation resulted in increased numbers of CSCs (c-kit + /CD45 − cells) in the RR (i.e., the infarct zone plus border zone)(47.6±7.0% of total c-kit + cells vs. 27.9±4.1% in vehicle group; n=5, P <0.05; Fig. J). Among CSCs (c-kit + /CD45 − cells), the fraction that was newly formed (c-kit + /CD45 − /BrdU + ) was dramatically increased in the RR of the CSC group (+ 2.6-fold vs. vehicle group; n=4, P <0.05; Fig. M), indicating increased CSC proliferation and turnover. Conclusions: These data reveal, for the first time, that a single intracoronary infusion of CSCs is followed by an increase in both the proliferation and the total number of c-kit + CSCs in the myocardium that persists, surprisingly, for at least 1 year after cell delivery. Since transplanted cells do not differentiate into adult myocytes, these data suggest that the long-term salubrious effects of CSCs on cardiac function are mediated by sustained activation of the CSC pool in the heart.

Algorithm for diagnosis and typing of ALCAPA syndrome

2021 ◽  
Vol 3 (2) ◽  
pp. 01-07
Author(s):  
Mariela Céspedes Almira ◽  
Adel Eladio González Morejón ◽  
Giselle Serrano Ricardo ◽  
Tania Rosa González Rodríguez ◽  
Judith Escobar Bermúdez
Keyword(s):  
Coronary Artery ◽  
Left Ventricle ◽  
Left Coronary Artery ◽  
Cross Sectional Study ◽  
Left Ventricular ◽  
Volume Index ◽  
Cross Sectional ◽  
End Diastolic Volume ◽  
Congenital Origin ◽  
Diagnostic Modalities

ALCAPA syndrome was characterized by anomalous origin of left coronary artery from pulmonary artery. Its clinical presentation is varied and although it is an anomaly of congenital origin, it is not exclusive to pediatric ages. Its epidemiological documentation is difficult. We aimed to make the non-invasive diagnosis of the ALCAPA syndrome and its variants. An observational, prospective and cross-sectional study was conducted with 31 patients with a positive echocardiographic diagnosis of ALCAPA syndrome at Pediatric Cardio Center “William Soler” from 2005 to 2018. The variables with significance for diagnosis were the echocardiographic visualization of the anomalous connection and the reversed flow in the left coronary artery. The variables with significance for typing were age at diagnosis, ischemia in the electrocardiogram, echocardiographic visualization of left ventricle papillary muscles fibrosis, presence of severe mitral regurgitation, left ventricle spheroidal remodeling, left ventricle ejection fraction, left ventricular end-diastolic volume index, and left ventricular end-diastolic diameter index. An algorithm integrated by various diagnostic modalities associated with echocardiography as a tool for the detection of ALCAPA was developed. The documentation of the diagnostic and classificatory aspects of the syndrome is possible by detecting echocardiographic elements in conjunction with electrocardiographic and radiological aspects.

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