Evaluación de los niveles plasmáticos de células progenitoras en pacientes con enfermedad coronaria crónica / Assessment of Plasmatic Levels of Endothelial Progenitor Cells in Patients with Chronic Coronary Disease

Introducción El ejercicio físico es útil para los pacientes con enfermedad coronaria y es un estímulo para el desarrollo de circulación colateral. Ésta podría estar determinada por un aumento en la producción y circulación de células progenitoras. Objetivo Evaluar el efecto del ejercicio físico programado sobre la producción y el número circulante de células progenitoras en pacientes coronarios crónicos estables. Material y métodos Estudio prospectivo, controlado, aleatorizado y abierto con la inclusión de 18 pacientes (8 en grupo ejercicio y 10 en grupo control) con enfermedad coronaria estable, < 75 años, que no hubieran participado en grupos de ejercicio programado en los últimos 3 meses. La determinación de las células progenitoras se realizó por citometría de flujo utilizando marcaciones con anticuerpos monoclonales CD45-FITC, CD34-FITC y CD133/1-PE. Resultados En el grupo control, el nivel de CD45 no tuvo variación significativa (0,724 ± 0,256 versus 0,765 ± 0,216 [media ± EE cada 100.000 eventos]), mientras que en el grupo ejercicio el nivel de CD45(+)/CD133(+) se incrementó de 0,497 ± 0,161 a 2,265 ± 1,003 luego de un mes de actividad física programada sin alcanzar significación estadística. Al analizar los niveles de CD34 se observó que en el grupo control se incrementaron de 0,196 ± 0,086 a 0,235 ± 0,063 (p = NS). En el grupo ejercicio, la variación fue mucho mayor: 0,220 ± 0,078 a 0,844 ± 0,172 (p = 0,0046; p = 0,0092 versus el grupo control). Conclusión El ejercicio físico programado en pacientes coronarios promueve un incremento de las células progenitoras circulantes. Su estímulo persistente podría ser la base para un mayor desarrollo de circulación colateral.

Background Exercise is useful for patients with coronary artery disease, and it works as a stimulus for the development of collateral circulation, which could be the result of an increase in the production and circulation of endothelial progenitor cells. Objective The objective of this study was to assess the effect of programmed exercise on the production and number of circulating endothelial progenitor cells in patients with chronic and stable coronary disease. Material and Methods We conducted a prospective, randomized, controlled and open study that included 18 patients (8 in the exercise group and 10 in the control group) with demonstrated chronic stable angina, < 75 years. Patients eligible should not have participated in programmed exercise groups within the last 3 months. Progenitor cells were determined by flow cytometry using marked monoclonal antibodies CD45-FITC, CD34-FITC y CD133/1-PE. Results After 1 month of programmed physical activity, CD45 level did not show any significant change in the control group (0.724±0.256 vs 0.765±0.216 [mean ± SE each 100,000 events]), whereas it increased from basal levels of 0.497±0.161 to 2.265±1.003 in the exercise group, though this change was not statistically significant. Analyzing CD34 levels, an increase from 0.196±0.086 to 0.235±0.063 was seen in the control group (p = NS). This increase was greater in the exercise group: 0.220±0.078 to 0.844±0.172 (p=0.0046; p=0.0092 vs control group). Conclusions In patients with coronary artery disease, programmed exercise promotes an increase in the level of circulating progenitor cells. Its persistent stimulus could be the basis of a greater development of collateral circulation.

Pérdida del precondicionamiento isquémico: ¿un fenómeno relacionado con el envejecimiento? / Loss of Ischemic Preconditioning: An Aging Related Phenomenon

Introducción La edad es un predictor independiente de riesgo en pacientes con enfermedad coronaria. Esto podría explicarse por la falta de adaptación a la isquemia miocárdica aguda. El precondicionamiento es un mecanismo por el cual episodios repetitivos de isquemia inducen en el miocardio una tolerancia mayor a episodios subsiguientes. Objetivo Evaluar el desarrollo de precondicionamiento isquémico en pacientes añosos. Material y métodos Se incluyeron 65 pacientes sometidos a angioplastia coronaria electiva (< 70 años [n = 47] y ≥ 70 años [n = 18]). Se evaluó el desarrollo de precondicionamiento durante tres períodos de oclusión coronaria. Por ECG intracoronario se midió la elevación del ST al final de cada dilatación y se registró el porcentaje de resolución del ST a la tercera dilatación respecto del máximo valor registrado. Los datos se presentan como mediana e intervalo intercuartil 25/75%. Resultados No hubo diferencias significativas en las características clínicas basales. El máximo ST registrado, el ST a la tercera dilatación y el porcentaje de resolución del ST fueron 14 (9/24) mm, 8 (4/14) mm y 23,8% (0/55,5) para los pacientes jóvenes y 9,5 (5/18) mm (p = ns), 6,5 (4/ 16) mm (p = ns) y 5,5% (0/20) (p = 0,04) para los añosos. Al estratificar por grupos etarios, la proporción de pacientes que alcanzaron una resolución del ST ≥ 50% mostró una distribución lineal por chi cuadrado de tendencia (p = 0,025). Conclusiones Nuestro estudio sugiere que el precondicionamiento isquémico se encontraría disminuido en pacientes añosos. La funcionalidad de este mecanismo menguaría en forma progresiva con el envejecimiento.

Introduction Age is an independent risk predictor in patients with coronary disease. This could be explained by the lack of adaptation to acute myocardial ischemia. Preconditioning is a mechanism whereby repeated ischemia episodes induce in the myocardium an increased tolerance to further episodes. Objective To assess the development of ischemic preconditioning in elderly patients. Material and methods Sixty five patients who underwent elective coronary angioplasty were enrolled (<70 years [n=47] and ³70 years [n=18]). Preconditioning development was assessed during three periods of coronary occlusion. ST elevation at the end of each dilation was measured by intra coronary EKG, and ST resolution percentage after the third dilation was recorded and compared to the maximum recorded value. Data are presented as mean and inter-quartile interval 25/75%. Results There were no significant differences in the clinical baseline characteristics. The maximum ST recorded, ST after the third dilation and ST resolution percentage were 14 (9/24) mm, 8 (4/14) mm y 23.8% (0/55.5) for the young patients and 9.5 (5/ 18) mm (p = ns), 6.5 (4/16) mm (p=ns) and 5.5% (0/20) (p=0.04) for the elderly. Upon stratification per age group, the ration of patients that reached an ST resolution ≥ 50% showed a linear distribution by chi square for trend (p=0.025). Conclusions Our study suggests that ischemic preconditioning would be decreased in elderly patients. The functionality of this mechanism would progressively decrease with aging.

A new scoring system to stratify risk in unstable angina.

BACKGROUND: We performed this study to develop a new scoring system to stratify different levels of risk in patients admitted to hospital with a diagnosis of unstable angina (UA), which is a complex syndrome that encompasses different outcomes. Many prognostic variables have been described but few efforts have been made to group them in order to enhance their individual predictive power. METHODS: In a first phase, 473 patients were prospectively analyzed to determine which factors were significantly associated with the in-hospital occurrence of refractory ischemia, acute myocardial infarction (AMI) or death. A risk score ranging from 0 to 10 points was developed using a multivariate analysis. In a second phase, such score was validated in a new sample of 242 patients and it was finally applied to the entire population (n = 715). RESULTS: ST-segment deviation on the electrocardiogram, age > or = 70 years, previous bypass surgery and troponin T > or = 0.1 ng/mL were found as independent prognostic variables. A clear distinction was shown among categories of low, intermediate and high risk, defined according to the risk score. The incidence of the triple end-point was 6 %, 19.2 % and 44.7 % respectively, and the figures for AMI or death were 2 %, 11.4 % and 27.6 % respectively (p < 0.001). CONCLUSIONS: This new scoring system is simple and easy to achieve. It allows a very good stratification of risk in patients having a clinical diagnosis of UA. They may be divided in three categories, which could be of help in the decision-making process.

Histopathologic time course of myocardial infarct in rabbit hearts.

INTRODUCTION: The histopathologic evolution of myocardial infarct and of remote zones in rabbit hearts was studied. METHODS: The left coronary artery of 55 rabbits was ligated and rabbits were sacrificed at 2, 4, 6, 8, 12, 14, 16, 18, 26, 35 and 56 days post-ligature (n=5 per group). Two rabbits were used as control and four were sham-operated. The hearts were excised, cut in slices and stained with hematoxylin-eosin, Masson's trichrome and picrosirius red. The histological evaluation was semiquantitative (scale: 0 to ++). RESULTS: At day 2, the presence of neutrophils was ++, decreasing suddenly at day 4 and disappearing completely at day 6. The proliferation of cells with features of fibroblasts increased from days 4 to 14 post-occlusion. Coagulation necrosis in mid-myocardium during the first week was ++. Subendocardial myocytolysis was evident from day 2 up to day 56 post-infarction. During the second week, proliferation of lymphocytes and macrophages (++), granulation tissue formation (++) and incipient traces of fibrosis that peaked at day 35 were observed. Scarring was complete at day 56 (++). In remote zones (right ventricle and septum), the proliferation of cells+ on Vimentin was observed at day 2, and perivascular, interstitial and endocardial fibrosis started to increase at day 6 and peaked at day 16. CONCLUSION: Although myocardial infarction in rabbits maintains the essence of the infarct chronology, some differences as the early presence of cells+ on Vimentin and subendocardial fibrosis in infarcted areas, and also the rapid increase and early disappearance of neutrophils appear when other species are considered. An interesting finding was the early proliferation of cells with features of fibroblasts in remote zones.

Cronodinamia del infarto de miocardio en el conejo / Time course of the myocardial infarction in the rabbit

The histopathologic evolution of myocardial infarct and of areas distant from infarct in rabbit hearts was studied. The left coronary artery of 55 rabbits was ligated, and rabbits were sacrificed at 2, 4, 6, 8, 12, 14, 16, 18, 26, 35 and 56 days post-ligature (n = 5 per group). Two rabbits were used as control and two were sham operated. The hearts were excised, cut in slices and stained with hematoxilin-eosin, Massons trichrome and picrosirius red. Histological evaluation was semi-quantitative (scale: 0 to +++). At day 2, presence of neutrophils was +++, disappearing completely at day 6. Fibroblast proliferation increased from day 4 to day 14 post-occlusion. Coagulation necrosis in medial myocardium during the first week was +++. Subendocardic myocytolysis was evident from day 2 up to day 56 post-infarction. During the second week, proliferation of lymphocytes and macrophages (+++), granulation tissue formation (+++), and incipient traces of fibrosis that peaked at day 35 were observed. Cicatrization was complete at day 56 (+++). In areas far from infarction (right ventricle and septum), proliferation of fibroblasts was observed at day 2, and perivascular, interstitial and endocardic fibrosis at day 16. In conclusion, myocardial infarction in rabbits, unlike myocardial infarction in human beings, is characterized by early presence of fibroblasts and subendocardic fibrosis, and quick increase and precocious disappearance of neutrophils. An interesting finding was the early proliferation of fibroblasts in normal areas far from infarct. (Au)