Pharmacological Effect of Nuanxinkang Powder on Ventricular Remodeling in Post-infarction Mice Through"Metabolic-Inflammatory"Network Regulating Macrophage Polarization / 中药新药与临床药理

Objective To explore the mechanism of Nuanxinkang Powder(aka.NXK,composed of Ginseng Radix et Rhizoma Rubra and Ilex Pubescens Radix)on improving ventricular remodeling in post-infarction mice based on the"metabolic-inflammatory"network regulating macrophage polarization.Methods ①Thirty C57BL/6J male mice were randomly divided into three groups:sham-operation group,model group,and NXK group(1.65 g·kg-1),with 10 mice in each group;the mouse model of myocardial infarction was replicated using left anterior descending coronary artery ligation;and the drug was administered by gavage once a day for 4 consecutive weeks.Masson staining was used to detect collagen deposition in myocardial tissue;ultrasound was used to detect cardiac function in mice:left ventricular ejection fraction(LVEF),left ventricular anterior wall thickness at end-systole(LVAWS)and left ventricular anterior wall thickness at end-diastole(LVAWD);flow cytometry was used to detect distribution of cardiac macrophages in mice;qPCR was used to detect mRNA expressions of lactate dehydrogenase A(LDHA),carnitine palmitoyltransferase 1(CPT-1),glucose transport protein 4(GLUT4),isocitrate dehydrogenase(IDH),and succinate dehydrogenase(SDHa)in heart tissue.②NXK was given 1.15 g·kg-1 NXK suspension to rats by gavage twice a day for 5 consecutive days to prepare NXK-containing serum.Lipopolysaccharide(LPS)-induced RAW 264.7 cells were used to construct a pro-inflammatory macrophage model.The cells were grouped into the following groups:blank serum control group(medium containing 5%blank serum+5%fetal bovine serum),NXK drug-containing serum group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum),lipopolysaccharide group(medium containing 5%blank serum+5%fetal bovine serum+200 μg·mL-1 lipopolysaccharide),NXK drug-containing serum+ lipopolysaccharide group(medium containing 5%NXK drug-containing serum+5%fetal bovine serum+200 μ g·mL-1 lipopolysaccharide),all the groups were intervened for 16 hours.Glycolysis stress test was used to detect the level of glycolysis in RAW 264.7 cells;qPCR was used to detect the mRNA expression of mitochondrial pyruvate carrier(MPC1)in RAW 264.7 cells;and MitoSox Red fluorescent staining was used to detect the level of oxidative stress damage in mitochondria of RAW 264.7 cells.Results ①Compared with the sham-operation group,the blue-stained area of cardiac collagen fibres in mice of the model group was significantly increased,accompanied by thinning of the ventricular wall and enlargement of the left ventricular cavity;cardiac function indexes,such as LVEF,LVAWS,LVAWD,etc.,were all significantly reduced(P＜0.01,P＜0.001);the mRNA expressions of LDHA and CPT-1 were significantly up-regulated in the cardiac tissues of mice(P＜0.05),and the mRNA expressions of GLUT4,IDH and SDHa were significantly down-regulated(P＜0.05,P＜0.01),and CD86 staining positive cell was significantly increased(P＜0.001).Compared with the model group,mice in the NXK group showed a significant decrease in cardiac collagen fiber deposition and an increase in the thickness of the ventricular wall;cardiac function indexes such as LVEF,LVAWS and LVAWD were significantly increased(P＜0.05,P＜0.01,P＜0.001);and the mRNA expressions of LDHA and CPT-1 in the cardiac tissues of the mice were significantly down-regulated(P＜0.01,P＜0.001),mRNA expressions of GLUT4,SDHa and IDH were significantly up-regulated(P＜0.01),and the number of CD86 positive cells was significantly reduced(P＜0.001).②Compared with the blank serum control group,the cytosolic glycolysis level and ROS level of macrophages in the NXK serum-containing group did not change significantly(P＞0.05),whereas the glycolysis level and ROS level of macrophages in the lipopolysaccharide group were significantly increased(P＜0.01),and the mRNA expression of MPC1 was significantly down-regulated(P＜0.001).Compared with the lipopolysaccharide group,the macrophage glycolysis level and ROS level were significantly reduced in the NXK serum-containing + lipopolysaccharide group(P＜0.05,P＜0.01),and mRNA expression of MPC1 was significantly up-regulated(P＜0.001).Conclusion NXK can reduce myocardial fibrosis and ventricular remodeling after myocardial infarction and improve cardiac function in mice,and its mechanism may be related to the down-regulation of mRNA expression of LDHA in cardiac tissues,the up-regulation of mRNA expression of GLUT4,the improvement of cardiac glucose uptake after myocardial infarction,the inhibition of pro-inflammatory macrophage glycolysis,the increase in the expressions of SDHa and IDH to alleviate the accumulation of succinate and citrate,and the reduction of reactive oxygen species(ROS)generation,thereby reducing pro-inflammatory macrophage hyperpolarisation.

Valor pronóstico de los niveles de propéptido N-terminal del procolágeno tipos I y III asociados al remodelamiento ventricular en pacientes con insuficiencia cardiaca crónica / Prognostic value of procollagen types I and III N-terminal propeptide as regards ventricular remodelling in patients with chronic heart failure

Resumen Introducción: La insuficiencia cardiaca constituye el estadio final de muchas cardiopatias. Aunque los cambios en la composición de la matriz extracelular relacionados con el proceso de remodelamiento ventricular han sido descritos, ni la evolución ni el impacto clínico de la fibrogénesis miocárdica en pacientes con IC están completamente entendidos. Objetivo: Determinar si los precursores de la síntesis y degradación del colágeno son útiles en la predicción de hospitalización, muerte o necesidad de trasplante cardiaco en pacientes con insuficiencia cardiaca crónica. Métodos: Se estudiaron 204 pacientes con insuficiencia cardiaca crónica entre 2015 y 2016; 106 con miocardiopatía isquémica y 98 con miocardiopatía dilatada. Se midieron los niveles séricos de noradrenalina, fracción N-terminal del propéptido natriurético cerebral, propéptido N-terminal del procolágeno tipo I (PINP) y propéptido N-terminal del procolágeno tipo III (PIIINP). Se determinaron volúmenes y fracción de eyección del ventrículo izquierdo, clase funcional y tratamiento médico. Resultados: Durante el seguimiento hubo 55 hospitalizaciones, 7 muertes y 9 trasplantes. La edad (p < 0,001), los niveles de PINP (p = 0,04), PIIINP (p = 0,016) y volúmenes del ventrículo izquierdo (p < 0,05), fueron significativamente mayores en los pacientes que alcanzaron el desenlace primario. En pacientes con dilatación severa del ventrículo izquierdo (IVTDVI > 110ml/m2, IVTSVI > 50ml/m2), niveles de PIIINP > 6,2 (g/L y PINP > 40 (g/L se asociaron con mayor riesgo de hospitalización, muerte o necesidad de trasplante (sobrevida libre de eventos a 12 meses: 45% versus 95%, p < 0,0001). Conclusiones: Los niveles circulantes de PINP y PIIINP, se correlacionan con el remodelamiento del ventrículo izquierdo y predicen desenlaces en pacientes con insuficiencia cardiaca crónica.

Abstract Introduction: Heart failure (HF) is the end-stage of many heart diseases. Although the changes in the composition of the extracellular matrix associated with the ventricular remodelling process have been described, neither the evolution nor the clinical impact of the myocardial fibrogenesis in patients with HF are completely understood. Objective: To determine if the precursors of the synthesis and degradation of collagen are useful in the prediction of hospital admissions, death, or the need for a heart transplant in patients with chronic heart failure (CHF). Methods: A total of 204 patients with chronic heart failure were studied between the years 2015 and 2016, of whom 106 had ischaemic heart disease, and 98 had dilated cardiomyopathy. Measurements were made of the serum levels of noradrenaline, N-terminal pro-B-type natriuretic peptide, procollagen type I N-terminal propeptide, and procollagen type III N-terminal propeptide (PIIINP). The left ventricular volumes and ejection fraction were determined, as well a record made of the functional class and medical treatment. Results: During follow-up, there were 55 hospital admissions, 7 deaths and 9 transplants. Age (p<0,001), PINP levels (p=0,04), PIIINP levels (p=0,016), and left ventricular volumes (p<0,05), were significantly higher in patients who achieved the primary outcome. In patients with severe dilation of the left ventricle (LV diastolic volume index, LVDVI > 110 ml/m2, LV systolic volume index, LVTSVI > 50 ml/m2), PIIINP levels > 6.2 (g/L and a PINP > 40 (g/L, were associated with a higher risk of hospital admission, death, or need of a transplant (event-free survival at 12 months: 45% versus 95%, p<0,0001). Conclusions: The circulating levels of PINP and PIIINP are associated with left ventricular remodelling, and predict the outcomes in patients with chronic heart failure.

Síndrome cardiorrenal / Cardiorenal syndrome

Resumen La insuficiencia cardiaca origina inicialmente una lesión miocárdica que conlleva remodelamiento ventricular, lo cual induce a la activación de mecanismos compensadores, entre los cuales el riñón es pieza fundamental ya que regula la homeostasis hidroelectrolítica y así el volumen circulante. El sistema nervioso simpático y el sistema renina-angiotensina-aldosterona aportan una retención de sodio y agua que afecta negativamente la función cardiaca y conduce a compromiso cardiovascular, miocárdico y renal; de allí nace la definición clínica de síndrome cardiorrenal que se clasifica de acuerdo con su forma de presentación y componentes fisiopatológicos. Esto motivó la definición y conceptualización del síndrome cardiorrenal, que incluye interacciones bidireccionales, en la que alteraciones, tanto agudas como crónicas de cualquier órgano, pueden afectar de manera funcional o estructural la función ventricular, la renal o ambas.

Abstract Heart failure initially causes myocardial damage that leads to ventricular remodelling. This, in turn, leads to activation of compensatory mechanisms where the kidney plays a fundamental role, as it regulates electrolyte homeostasis and thus the circulating volume. The sympathetic nervous system and the renin angiotensin-aldosterone system lead to the retention of sodium and water, which adversely affects cardiac function. This leads to cardiovascular, renal and myocardial compromise, or a cardiorenal syndrome, which is classified according to its presentation and pathophysiological components. The definition and conceptualization of cardiorenal syndrome includes two-way interactions, where acute and chronic changes of any organ can functionally or structurally affect the ventricular and/or renal function

Hallazgos ecocardiográficos en pacientes con preeclampsia en la Unidad de alta dependencia obstétrica en el Hospital Universitario de San José, 2012-2014 / Echographic findings in patients with pre-eclampsia see at the critical obstetrics unit of the San Jose Children's Teaching Hospital, 2012-2014

Objetivo: describir las alteraciones ecocardiográficas encontradas en pacientes con diagnóstico de preeclampsia severa.Materiales y métodos: estudio de corte transversal. Se describen los hallazgos ecocardiográficos en las pacientes con preeclampsia severa (PS), de acuerdo con los criterios del Congreso Americano de Obstetras y Ginecólogos, atendidas en un hospital universitario de referencia ubicado en Bogotá (Colombia), entre enero 1 de 2012 y junio 30 de 2014. Se excluyeron las pacientes con control adecuado de tensión arterial o con patología cardiaca estructural previa conocida. Se describen las variables sociodemográficas, clínicas y los hallazgos ecocardiográficos más frecuentes, globalmente y por momento de aparición. Se presentan los datos mediante estadística descriptiva.Resultados: se diagnosticaron 228 pacientes con PS. A 124 se les realizó ecocardiograma: en 8 de ellas el informe de ecocardiografía fue no concluyente. Se hallaron 78 pacientes (67 %) con alguna alteración. Los principales hallazgos fueron: hipertensión pulmonar leve, n = 34 (29 %); hipertrofia del ventrículo izquierdo, n = 32 (27 %); hipertensión pulmonar moderada, n = 21 (18 %); disfunción diastólica, n = 16 (13 %). Las pacientes con PS pretérmino (69 %) presentaron alteraciones ecocardiográficas más frecuentes que las pacientes a término (20 %) y que las que comenzaron con PS en el puerperio (11 %). La disfunción diastólica se presentó más en pacientes con preeclampsia que comenzó en el puerperio.Conclusiones: la prevalencia de alteraciones ecocardiográficas en PS es del 67 %, con mayor frecuencia de hipertensión pulmonar e hipertrofia ventricular izquierda. Se requieren más estudios que validen estos hallazgos regionalmente.

Objective: To describe echographic abnormalities found in patients diagnosed with severe preeclampsia.Materials and methods: Cross-sectional study describing ultrasound findings in patients with severe preeclampsia (SP) in accordance with the criteria of the American Congress of Obstetricians and Gynecologists. The patients were seen in a referral teaching hospital in Bogota (Colombia), between January 1, 2012 and June 30, 2014. Patients with adequate blood pressure control or with known pre-existing structural heart disease were excluded. Social, demographic and clinical variables are described, as well as the most frequent global echographic findings, also by time of onset. The data are presented using descriptive statistics.Results: Overall, 228 patients were diagnosed with SP. An echographic examination was performed in 124 and in 8 of them the echographic report was non-conclusive. Some form of abnormality was found in 78 patients (67 %). Mild pulmonary hypertension [n=34 (29 %)], left-ventricular hypertrophy [n=32 (27 %)], moderate pulmonary hy per tension [n=21 (18 %)] and diastolic dysfunction [n= 16 (13 %)] were the main findings observed. Echographic abnormalities were found more frequently in patients with pre-term SP (69 %) than in term patients (20 %) or those who developed SP during the post-partum period (11 %). Diastolic dysfunction was found to occur more frequently in patients who developed preeclampsia in the post-partum period.Conclusions: The prevalence of echographic abnormalities in SP is 67 %, the most frequent being pulmonary hypertension and left ventricular hypertrophy. More studies are needed in order to validate these findings regionally.

Hypoxia training attenuates left ventricular remodeling in rabbit with myocardial infarction / 老年心脏病学杂志（英文版）

Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infarction is still unclear. This study therefore aims to investigate the effects of hypoxia training on left ventricular remodeling in rabbits post myocardial infarction. Methods Adult male rabbits were randomly divided into three groups: group SO (sham operated), group MI (myocardial infarc-tion only) and group MI-HT (myocardial infarction plus hypoxia training). Myocardial infarction was induced by left ventricular branch ligation. Hypoxia training was performed in a hypobaric chamber (having equivalent condition at an altitude of 4000 m, FiO214.9%) for 1 h/day, 5 days/week for four weeks. At the endpoints, vascular endothelial growth factor (VEGF) in the plasma was measured. Infarct size and capillary density were detected by histology. Left ventricular remodeling and function were as-sessed by echocardiography.Results After the 4-week experiment, compared with the group SO, plasma VEGF levels in groups MI (130.27 ± 18.58 pg/mL,P< 0.01) and MI-HT (181.93 ± 20.29 pg/mL,P< 0.01) were significantly increased. Infarct size in Group MI-HT (29.67% ± 7.73%) was deceased remarkably, while its capillary density (816.0 ± 122.2/mm2) was significantly increased. For both groups MI and MI-HT, left ventricular end-diastolic and end-systolic dimensions were increased whereas left ventricular ejection fraction was decreased. However, compared with group MI, group MI-HT diminished left ventricular end-diastolic (15.86 ± 1.09 mm,P< 0.05) and end-systolic dimensions (12.10 ± 1.20 mm,P< 0.01) significantly and im-proved left ventricular ejection fraction (54.39 ± 12.74 mm,P< 0.05).ConclusionHypoxia training may improve left ven-tricular function and reduce remodeling via angiogenesis in rabbits with MI.

Morfologia e função cardíacas em pacientes renais crônicos, com ou sem diurese residual, em tratamento hemodialítico / Cardiac morphology and function in patients with and without residual diuresis on hemodialysis

Em pacientes com doença renal crônica (DRC) em hemodiálise (HD), a hipertrofia ventricular esquerda (HVE) está relacionada ao aumento do índice de resistência vascular periférica (IRVP) total e à sobrecarga de volume. A presença da diurese residual (DR) nesses pacientes possibilita maior controle volêmico. Avaliamos as modificações morfofuncionais do ventrículo esquerdo (VE) em pacientes com DRC em HD com e sem diurese residual. Trinta e um pacientes não diabéticos foram divididos em dois grupos: com diurese residual (DR+) (n = 17) e sem diurese residual (DR-) (n = 14). Em ambos os grupos, DR+ vs. DR-, ocorreram diferenças no índice cardíaco (3,9 ± 0,20 vs. 3,0 ± 0,21 L/min/m²; p = 0,0056), no índice sistólico (54 ± 2,9 vs. 45 ± 3,3 mL/b/m²; p = 0,04), no volume diastólico final (141 ± 6,7 vs. 112 ± 7,6 mL; p = 0,008), no diâmetro diastólico final (52 ± 0,79 vs. 48 ± 1,12 mm; p = 0,0072) e no IRVP total (1.121 ± 56 vs. 1.529 ± 111 dina.seg.cm-5; p = 0,001). O grupo DR+ apresentou menor espessamento relativo de parede (ERP) do que o DR- (0,38 ± 0,01 vs. 0,45 ± 0,01; p = 0,0008). A fração de ejeção (66,00 ± 1,24 vs. 66,0 ± 1,46 por cento; p = 0,873) e o índice de massa ventricular esquerda (132 ± 6,0 vs. 130 ± 8,3 g/m; p = 0,798) foram similares em ambos os grupos. O volume de diurese residual correlacionou-se com o espessamento da parede ventricular (r = 0,42; p = 0,0186) e com o índice de resistência vascular periférica (r = -0,48; p = 0,0059). Em conclusão, a presença ou não da diurese residual, em pacientes com doença renal crônica e em hemodiálise, pode ser responsável por modificações na função cardíaca sistólica.

In patients with chronic renal failure on hemodialysis, left ventricular hypertrophy is related to the increase in total peripheral vascular resistance and volume overload. The presence of residual diuresis enables greater control of the volemia of these. We evaluated the morpho-functional changes of the left ventricle in patients with chronic kidney disease on hemodyalisis treatment with and without residual diuresis. A total of 31 non diabetic patients were studied and they were divided into two groups: with residual diuresis (RD+) (n = 17) and without residual diuresis (RD-) (n = 14). In both groups, RD+ vs. RD-, using data from a Doppler echocardiogram differences were found, respectively, in the cardiac index (3.9 ± 0.2 vs. 3.0 ± 0.2 L/min/m²; p = 0.0056), systolic index (54 ± 2.9 vs. 45 ± 3.3 mL/b/m²; p = 0.04), end diastolic volume (141 ± 6.7 vs. 112 ± 7.6 mL; p = 0.008), end diastolic diameter (52 ± 0.7 vs. 48 ± 1.1 mm; p = 0.0072) and total peripheral resistance index (1121 ± 56 vs. 1529 ± 111 dyne.sec.cm-5; p = 0.001). RD+ had lower relative wall thickness than RD- (0.38 ± 0.01 vs. 0.45 ± 0.01; p = 0.0008). The ejection fraction and the left ventricular mass index were similar in both groups. The urinary 24-hour volume correlated with the relative wall thickness (r = -0.42; p = 0.0186) and with peripheral resistance index (r = -0.48; p = 0.0059). In conclusion, there were distinct ventricular geometric patterns and different functional performances between RD+ and RD- groups. The presence of residual diuresis can be responsible by these modifications in systolic function.

Clinical study of anti-neurohormone drugs on heart function and the plasma concentrations of neurohormone of patients with different grade heart function after myocardial infarction / 中国实用内科杂志

ObjectiveTo observe the effects of anti-neurohormone drugs on ventricular remodelling and the plasma concentrations of neurohormone of patients with different grade heart function after myocardial infarction.MethodsAccording to ejection fraction of patients,103 consective patients with myocardial infarction were divided into two groups:normal heart function group:ejection fraction ranged from 50% to 70%.Abnormal heart function group:ejection fraction was less than 50%.All patients were given the same beta-receptor blocking agent and angiotensin-converting enzyme inhibitor and then were followed up 6 months.Heart function and the plasma concentrations of neurohormone were compared before and after anti-neurohormone drugs were given;at the same time,changes of heart function and the plasma concentrations of neurohormone were compared in statistical aspect between two groups.ResultsThe improvement of heart function and change of the plasma concentrations of neurohormone were significantly different in statistics before and after drugs were used.Besides,the patients with different grade heart function had significantly different changes of heart function and plasma concentrations of neurohormone.ConclusionAnti-neurohormone drugs can significantly reduce the level of the plasma neurohormone,improve heart function and inhibit heart remodeling.What’s more,there are better treatment effects in patients with heart failure.

The effect of delayed PTCA and stenting on chronic phase of left ventricular remodelling and cardiac events in patients with acute myocardial infarction / 介入放射学杂志

Objective To investigate the effect of delayed PTCA and stenting for infarct related artery on the chronic phase of left ventricular remodelling and cardiac events in patients with acute myocardial infarction. Methods Fifty two patients with primary acute myocardial infarction were divided into PTCA group ( n =27) and non PTCA group ( n =25). Twenty seven patients underwent PTCA and coronary stenting with an average of 12 days after the acute onset. Left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF) and cardiac events in each group were followed up. Results There were no significant differences in preoperation and postoperation for LVEDV and LVESV in the PTCA group, on the contrary a significant increase for before and after follow up for LVEDV and LVESV in the non PTCA group( P 0.05). Conclusions Delayed PTCA and stenting for infarct related artery would inhibit ventricular enlargement and delay chronic phase of left ventricular remolding. Moreover, cardiac events were significantly reduced in patients with acute myocardial infarction after delayed PTCA and stenting.

Rat model of abdominal aortic banding and its clinical significance / 重庆医科大学学报

Objective:To establish rat model of ventricular hypertrophy and heart failure by partially banding abdominal aorta for different time limits.Methods:60 Wistar rats were randomly divided into three groups:A group which were ligated for 4 weeks;B group being ligated for 8 weeks;and sham-operated group (each containing 20 Wistar rats).Left and right ventricular mass index,hemodynamic parameters,cardiac morphological changes and the time of achieving heart failure model were investigated in different groups.Results:There were 16.67% heart failure rats in A group,while 73.68% in B group.The death of models occurred in the first week after experimental procedure.MBP and LVSP were increased greatly in A group,and HR,MBP,LVSP and ?dp/dt were decreased while LVEDP increased in B group compared with A and sham-operated groups( P