Effect of pericardial incision on left ventricular morphology and systolic function in patients during coronary artery bypass grafting.

BACKGROUND: Accurate assessment of left ventricular (LV) systolic function is important after coronary artery bypass grafting (CABG). LV ejection fraction (LVEF) is conventionally used to evaluate LV systolic function; deformation parameters can be used to detect subtle LV systolic dysfunction. It is unclear whether an incised pericardium without sutures during CABG could affect LV morphology and function. We investigated the effect of pericardial incision on LV morphology and systolic function during CABG. METHODS: Intraoperative transesophageal echocardiography was performed in 27 patients during elective off-pump beating heart CABG 5 min before and after pericardial incision. LV longitudinal and mid-cavity transversal diameters, sphericity index, volumes, and LVEF were measured. LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and twist obtained by two-dimensional speckle tracking echocardiography were measured simultaneously. RESULTS: LV mid-cavity transversal diameter increased, while the LV sphericity index decreased (P < 0.001) immediately after pericardial incision. The GLS, GCS, and twist significantly decreased, while the GRS notably increased (P < 0.001). The LV volumes and LVEF remained unchanged. CONCLUSIONS: Pericardial incision immediately transformed LV morphology from an ellipsoid to sphere, with decreased longitudinal and circumferential strain and twist, and increased radial strain, while LVEF remained unchanged. This should be considered when evaluating LV systolic function in patients after CABG.

Overexpression of miR-210 promotes the potential of cardiac stem cells against hypoxia.

OBJECTIVE: To evaluate the effects of miR-210 on cardiac stem cells (CSCs) against hypoxia-induced injury. METHODS: CSCs were isolated from rat ventricular wall and cultured until passage 4. After exposure to hypoxia for 6 h, the expression of miR-210 was determined. Thereafter, transfection of miR-210 mimic and inhibitor was carried out. 1 week later, in vitro experiments were performed to measure the expression of caspase-8-associated protein 2 (Casp8ap2), Caspase 8, protein tyrosine phosphatase, non-receptor type 2 (PTPN2) and CXC chemokine receptor 4 (CXCR4), as well as migration and apoptosis of CSCs under hypoxic condition. RESULTS: Hypoxia induced a significant up-regulation of miR-210 expression in CSCs. Notably, the expression of Casp8ap2, Caspase8, PTPN2 was dramatically inhibited by overexpression of miR-210 in CSCsmiR-210 Group (P < .05), but no changes in CXCR4 (P > .05), compared with the control. Additionally, a decreased apoptosis of CSCs was detected in CSCsmiR-210 Group (26.22 ± 1.15%, P < .001), compared with Control Group (34.97 ± 0.63%). Moreover, the migration of CSCs was significantly promoted in CSCsmiR-210 Group (45.73 ± 2.4, P < .001), compared with Control Group (19.6 ± 1.11). Meanwhile, down-regulation of miR-210 reversed these results (P < .05). CONCLUSIONS: miR-210 was a hypoxia responsive element in CSCs, and its up-regulation inhibited apoptosis of CSCs and promoted their migration under hypoxic condition, through regulating its target genes Casp8ap2/Caspase 8 and PTPN2, which may provide a new strategy for cell therapy of ischemic heart disease.

Transmyocardial drilling revascularization combined with heparinized bFGF-incorporating stent activates resident cardiac stem cells via SDF-1/CXCR4 axis.

OBJECTIVE: To investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction (AMI). METHODS: A model of AMI was generated by ligating the mid-third of left anterior descending artery (LAD) of miniswine. After 6 h, the animals were divided into none-treatment (control) group (n=6) and TMDRSI group (n=6). For TMDRSI group, two channels with 3.5 mm in diameter were established by a self-made drill in the AMI region, into which a stent was implanted. Expression of stromal cell-derived factor-1(α) (SDF-1(α)) and CXC chemokine receptor 4 (CXCR4), cardiac stem cell (CSC)-mediated myocardial regeneration, myocardial apoptosis, myocardial viability, and cardiac function were assessed at various time-points. RESULTS: Six weeks after the operation, CSCs were found to have differentiated into cardiomyocytes to repair the infarcted myocardium, and all above indices showed much improvement in the TMDRSI group compared with the control group (P<0.001). CONCLUSIONS: The new method has shown to be capable of promoting CSCs proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and improving cardiac function. This may provide a new strategy for myocardial regeneration following AMI.

[Effects of mild hypothermia on low cardiac output after cardiac surgery].

OBJECTIVE: To evaluate the effectiveness of mild hypothermia on low cardiac output in patients after cardiac surgery. METHODS: Twelve patients manifesting low cardiac output after cardiac surgery despite of the use of massive doses of catecholamine and intra-aortic balloon pump (IABP) underwent mild hypothermia during May 2009 to February 2011. Changes in hemodynamic parameters of the patients were measured, including cardiac index (CI),mixed venous oxygen saturation [SvO(2)] and urine volume. RESULTS: In the process of mild hypothermia treatment, bladder temperature of patients was lowered to 33-35 centigrade in order to reduce the body oxygen demand. The CI [ml·s(-1)·m(-2)]of patients after mild hypothermia treatment was increased obviously (38.34 ± 5.00 vs. 30.01 ± 5.00), the same as SvO(2) (0.64 ± 0.07 vs. 0.54 ± 0.08) and urine output [ml·kg(-1)·h(-1): 3.0 ± 2.1 vs. 1.5 ± 1.1, all P < 0.05]. However, there was no significant change in heart rate, mean arterial pressure and blood oxygen pressure. CONCLUSION: Mild hypothermia is an effective and simple procedure to improve the cardiac function in patients after cardiac surgery complicated with low cardiac output.

Endothelial factors after selective retrograde coronary venous bypass under different pressures.

BACKGROUND: Selective retrograde coronary venous bypass (SRCVB) may be a promising treatment for patients with advanced coronary artery disease (CAD). The aim of this study is to investigate the effect of SRCVB on plasma endothelial factor levels in dog myocardial ischemic model, and explore the possible mechanisms. METHODS: 24 crossbreed dogs were randomly divided into three groups: (1) control group; (2) SRCVB group with 60 mmHg perfusion pressure; (3) SRCVB group with 90 mmHg perfusion pressure. The posterior descending coronary artery (PDA) was ligated in all groups, and SRCVB was performed in the last two groups. The levels of plasma nitric oxide (NO) and endothelin (ET) at different time points were determined in each group. In SRCVB groups, ink and imaging agent were injected to the heart through SVG graft for assessment of vein perfusion. RESULTS: At the acute period, there were significant increase in the plasma levels of NO and decrease in ET in SRCVB 90 mmHg group compared with the control (P < 0. 01), and a further improvement were found in SRCVB 60 mmHg group (P < 0. 01). The ink or imaging agent was found in the myocardial tissue and flowed back to right atrium through contralateral coronary vein. CONCLUSIONS: SRCVB with low level of perfusion pressure could provide effective perfusion for ischemic myocardium and alleviate the myocardial endothelial cell injury. It may be a new therapeutic strategy for severe CAD.

[Prognosis of different operative procedures of coronary artery bypass grafting in the senile patients].

OBJECTIVE: To investigate myocardial protection and prognosis of the different operative procedures of coronary artery bypass grafting (CABG) for the senile patients with coronary artery disease. METHODS: From July 2008 to June 2009, 125 cases (age ≥ 65 years old) underwent CABG were divided into 3 groups.Group A (70 cases) undertook off-pump CABG, group B (33 cases) undertook on-pump beating heart CABG. group C (22 cases) undertook on-pump CABG with cardiac arrest. Serum level of cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK-MB) activity were examined right before operation and 0, 24, 72 and 168 h after operation. The complications during perioperative period and the mortality were investigated. RESULTS: No significant difference was found in the right before operation and 168 h after operation of the serum level of cTnI and CK-MB in the 3 groups (P > 0.05). The serum level of cTnI and CK-MB activity of group A was the lowest and group B was lower than group C. Group A was the best concerning the complications during perioperative period. The mortality of group A was lower than group B but no significant difference was found in the mortality between group A and C. No significant difference was found in the complications during perioperative period and the mortality between group B and C. CONCLUSION: Off-pump CABG could reduce myocardial injury and the complications during perioperative period in the senile patients.

[Diagnosis and therapy of primary malignant tumors of the heart and pericardium].

OBJECTIVE: To summarize and analyze the experience in diagnosis and treatment of primary malignant tumors of the heart and pericardium. METHODS: The clinical data of 24 patients with malignant tumors of the heart and pericardium treated in our hospital between Jun. 1980 and Mar. 2008 were retrospectively analyzed and the related literature was reviewed. RESULTS: All 24 patients received surgical treatment. Radical resection in 10 cases and partial resection in 6 cases were performed, and the remaining 8 patients received only surgical exploration due to unresectable tumors. One patient died of cardiopulmonary failure in early postoperative stage and all the other patients died within 4 years after operation due to recurrence or metastases. CONCLUSION: Echocardiography, CT, MRI, 3D-CT, CT of coronary artery and cardiac angiography are helpful for the diagnosis and selection of operation mode. Histological examination is necessary for the final diagnosis. Early diagnosis and surgical resection of the tumor as complete as possible, and combination with post-operative radiotherapy and/or chemotherapy may improve the survival of the patients.

Hepatocyte growth factor combined with insulin like growth factor-1 improves expression of GATA-4 in mesenchymal stem cells cocultured with cardiomyocytes.

BACKGROUND: In a suitable microenvironment, bone marrow mesenchymal stem cells (BMSCs) can transdifferentiate into myocardial cells whose special gene can be expressed as structural proteins. Growth factor (GF) plays an important role in the cell migration, survival and differentiation. However, the effect of GF on the cellular differentiation is not well understood. In this study, the hepatocyte growth factor (HGF) and insulin like growth factor-1 (IGF-1) were used in the mixed culture of BMSCs and myocardial cells and the effects of these growth factors on the GATA-4 expression of BMSCs were investigated. METHODS: BMSCs were isolated from the marrow of rabbit femurs and tibias and foetal rabbit ventricular myocytes were isolated with trypsin sequential digestion. These two kinds of cells were cocultured in a ratio of 1:1 for 6 weeks; cocultured cells with added HGF and IGF-1 were the experimental group. The differentiated BMSCs were collected using the laser capture, microdissection system and their RNA isolated. Immunocytochemical staining, transmission electron microscopy and reverse transcription-polymerase chain reaction were used to evaluate the transformation of the stem cells into cardiomyocytes like cells. RESULTS: When cultured separately, BMSCs did not express alpha-actin and the stem cells had many nucleoli. However, when cocultured with cardiomyocytes, BMSCs expressed alpha-actin and the cardiac transcription factor GATA-4 and showed cardiomyocyte like ultrastructure. In comparison with the control group, the experimental group exhibited the enhanced expression level of GATA-4. The GATA-4 expression of BMSCs increased gradually following the addition of HGF and IGF-1, reached the maximal level after two weeks and decreased slightly thereafter. CONCLUSIONS: BMSCs can transdifferentiate into cardiomyocytes like cells and express the cardiac transcription factor GATA-4 after being cocultured with myocardial cells. HGF and IGF-1 can stimulate transdifferentiation of BMSCs into cardiac phenotype and enhance the expression of GATA-4. These results indicate that growth factors have a great potential in clinical cellular therapy.

Comparison of transient changes in renal function between off-pump and on-pump coronary artery bypass grafting.

BACKGROUND: Acute renal failure following coronary artery bypass grafting (CABG) surgery is associated with high morbidity and mortality. Approximately half of all patients who develop acute kidney injury (AKI) subsequently develop acute renal failure (ARF). The purpose of the study was to compare early transient changes in renal function within the first post-operative week following CABG in patients that were either off-pump or on-pump. METHODS: Eight hundred and forty-nine consecutive patients with isolated CABG in a single institution between January 1990 and August 2006 were retrospectively analyzed, including 518 off-pump and 331 on-pump patients. A multivariate Logistic regression model was constructed to identify risk factors for the development of AKI. RESULTS: Sixty-one off-pump patients and 63 on-pump patients developed AKI. Risk factors for the development of post-operative AKI included an ejection fraction > or =50% or < or =30%, a pulse pressure > or =60 mmHg, peripheral vascular disease, diabetes, emergent procedure, triple-vessel disease, body mass index, peri-operative and post-operative. intra-aortic balloon pumping, NYHA class III and IV, and cardiopulmonary bypass. An ejection fraction > or =50% and peri-operative and post-operative intra-aortic balloon pumping were protective (OR <1). Peak serum creatinine for post-operative AKI was noted 12 hours and 24 hours in the off-pump and on-pump patients, respectively. Serum creatinine kinetics revealed rapid recovery in the 24th to 48th hour (off-pump) and the 48th to 72nd hour (on-pump). CONCLUSION: Renal protection strategies are indicated from general anesthesia induction until 48 and 72 hours post-operatively in off-pump and on-pump patients, respectively.

[Two-way concentration-dependent effect of H2O2 on I(Kur) and I(Ca,L) in human atrial myocytes.].

It has been shown that oxidative stress correlates with atrial fibrillation (AF). The purpose of the present study was to investigate the effects of reactive oxygen species (ROS) on the electrophysiological activity of human atrial myocytes. Right atrial appendages were obtained from patients with AF (AF group, n=12) and without AF (non-AF group, n=12). Single human atrial myocytes were isolated through enzymatic dissociation with type XXIV protease and type V collagenase, then divided into three subgroups: control group (n=12), H2O2 group (0.1, 0.2, 0.5, 0.75, 1, 2, 5, 10 mumol/L, n=7 at each concentration) and vitamin C (antioxidant) group (1 mumol/L, n=7). Ultrarapid delayed rectifier K(+) current (I(Kur)), L-type calcium current (I(Ca,L)) and action potential duration (APD) were recorded by whole-cell patch clamp. In AF control group, the maximum current densities of I(Kur) and I(Ca,L) were significantly lower than that in non-AF control group (both P<0.05) and APD(90) was significantly shorter as well (P<0.05). In both non-AF and AF groups, H2O2 showed two-way concentration-dependent effect on I(Kur) and I(Ca,L). The maximum current densities of I(Kur) and I(Ca,L) was significantly increased at lower H2O2 concentration, but was decreased at higher H2O2 concentration. In non-AF group, 0.2 mumol/L H2O2 caused a peak increase in the maximum current identities of I(Kur) [(8.92+/-0.51) pA/pF, P<0.05] and I(Ca,L) [(9.32+/-0.67) pA/pF, P<0.05]. H2O2 at a concentration higher than 0.75 mumol/L decreased I(Kur) and I(Ca,L). When the H2O2 concentrations were 0.2, 1, 2, 5 and 10 mumol/L, APD(90) was significantly shorter compared with that in non-AF control group (P<0.05), meanwhile it had no significant difference from that in AF control group. In AF group, the peak effective concentration of H2O2 was 0.5 mumol/L, and the turning concentration was 1 mumol/L. The H2O2 concentration-current density curve in AF group was similar to that in non-AF group, but the turning point shifted to the right, indicating that the way that H2O2 acted on ion channels in AF was the same as that in non-AF, however, the sensitivity of ion channels to H2O2 was decreased in AF. Vitamin C reversed these changes induced by H2O2, and did not affect the characteristics of ion channels. H2O2-induced electrophysiological changes in human atrial myocytes were similar to atrial electrical remodeling (AER) in AF, suggesting that ROS might induce AF. Meanwhile, H2O2 also could aggravate AER in AF, contributing to the maintenance of AF. The results suggest that antioxidants might play a significant role in the prevention and treatment of AF.

[Bentall operation combined with total arch replacement and stented elephant trunk implantation for serious Debakey I aortic dissecting aneurysm].

OBJECTIVE: To summarize the clinical experience of Bentall operation combined with total arch replacement and stented elephant trunk implantation for serious Debakey I aortic dissecting aneurysm. METHODS: Twelve patients with serious Debakey I aortic dissecting aneurysm underwent surgical treatment from January 2005 to December 2007. There were 10 male and 2 female with the mean age of (40.1 +/- 9.5) years old. There were acute aortic dissection in 9 cases, chronic aortic dissection in 3 cases. The inner diameter of aorta was (5.3 +/- 1.8) cm. There were Marfan syndrome in 4 cases, aortic regurgitation in all cases, severely persistent chest pain in 9 cases, acute left heart failure in 8 cases, and cardiac tamponade in 4 cases. Bentall operations combined with total arch replacement and stented elephant trunk implantation were performed by using deep hypothermic circulatory arrest and antegrade selective cerebral perfusion in all cases. RESULTS: Urgent surgery underwent in 9 cases. The mean interval between the onset of aortic dissection and the accomplishment of surgery was (41.0 +/- 15.9) hours. Cardiopulmonary bypass time was (191 +/- 26) min, average cross clamp time was (134 +/- 31) min, and average deep hypothermic circulatory arrest time was (50.0 +/- 14.5) min. One patient died in hospital. The time stayed in ICU was 3 to 27 d. Mental disorder in 6 cases, hemi-paralysis in 1 case, amputation in 1 case, hemorrhage of anastomosis in 1 case, hemorrhage of alimentary tract in 1 case, and pleural effusion in 4 cases were recorded. Eleven cases were followed-up for 8 weeks to 36 months. There were no bending of the stents and no obstruction in the vascular prosthesis.No re-operation was needed. One case died 6 months postoperatively. CONCLUSION: Bentall operation combined with total arch replacement and stented elephant trunk implantation is safe and effective for serious Debakey I aortic dissecting aneurysm, while good organs protection and consummate cardiopulmonary bypass were taken.

[Incidence and risk factors of acute kidney injury post off-pump and on-pump coronary artery bypass grafting].

OBJECTIVE: To investigate the incidence and risk factors of acute kidney injury (AKI) within the first postoperative week after off-pump or on-pump coronary artery bypass (OPCAB or CCAB) surgery. METHODS: Consecutive patients underwent CABG between January 1990 and August 2006 in our institution and had normal serum creatinine (Scr) and estimated creatinine clearance (Ccr) values before operation were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify risk factors for the development of AKI defined as Scr 130 - 199 micromol/L or Ccr 30 - 60 mlxmin(-1)x1.73 m(-2). RESULTS: Incidence of AKI was significantly higher in patients underwent CCAB compared to those underwent OPCAB (63/331 vs. 61/518, P < 0.01). Peak Scr value was seen at 12th hour post OPCAB and 24th hour post CCAB, respectively. The rapid recovering of Scr occurred between 24th hour to 48th hour in patients underwent OPCAB and 48th hour to 72th hour in patients underwent CCAB surgery. Multivariate forward stepwise logistic regression analysis showed that LVEF < 30%, pulse pressure >/= 60 mm Hg (1 mm Hg = 0.133 kPa), peripheral vascular disease, diabetes, emergent procedure, triple-vessel disease, higher body mass index (kg/m(2)), intraoperative and postoperative IABP, NYHA class III or IV and cardiopulmonary bypass were risk factors for the development of postoperative AKI following CABG, while LVEF > 50% and intraoperative and postoperative IABP were associated with lower incidence of AKI (OR < 1). CONCLUSION: AKI is not a rare complication post OPCAB or CCAB surgery, especially in patients with reduced LVEF, increased pulse pressure, peripheral vascular disease, diabetes, emergent procedure, triple-vessel disease, higher body mass index, intraoperative and postoperative IABP.

[Anatomical basis and short-term effect of in situ coronary venous arterialization].

OBJECTIVE: To study the anatomical basis of in situ coronary venous arterialization (ICVA) and to observe the short-term clinical outcome thereof. METHODS: Five recently isolated pig hearts underwent ligation of the posterior descending artery and the proximal end of middle cardiac vein (MCV), solution of Indian ink was perfused into this vein, and slices of heart were made to observe the distribution of ink through microscope. From January 2002 to December 2005, 64 consecutive patients with diffuse lesion and distal occlusion of right coronary artery received coronary artery bypass grafting (CABG) were randomly divided into 2 equal groups to undergo ICVA during CABG (ICVA group) and conventional CABG only (control group) respectively. The pre- and post-operation clinical data, including ECG, SPECT and ultrasonic cardiograph (UCG) were analyzed. RESULTS: Indian ink was distributed in the intercellular spaces and capillaries of the myocardium and appeared in the micro-arteries in all 5 pig hearts. The mean hospitalization time of the ICVA patients was 16.5 +/- 7.7 days. The mortality rate was 0. After the ICVA the ECG recovery rate in ST segment was 98.88%, and the improvement rate in the grade of the angina was 100%. SPECT and UCG both showed great improvement post-operatively (P < 0.05). CONCLUSION: After the ligation of the proximal end of MCV, the related myocardium can be perfused effectively by distal arterialization in situ. ICVA, fitting to patients with diffused lesion and distal occlusion of coronary artery, can be performed safely with satisfactory clinical outcomes.

Surgical treatment of posttraumatic foreign bodies in the heart or great vessels.

Posttraumatic foreign bodies in the heart or great vessels is rare, which may cause cardiac tamponade, bleeding, shock, infection, embolism, arrhythmia, valve dysfunction, etc. The foreign bodies can be removed by surgery or percutaneous intervention. In this report we reviewed our experience in managing posttraumatic foreign bodies in 13 patients at our institution from 1992 to 2002.

[Effect of implantation of cardiosphere-derived cells combined with rat heart tissue-derived extracellular matrix on acute myocardial infarction in rats].

OBJECTIVE: To investigate whether heart tissue-derived extracellular matrix (ECM) promotes the differentiation of cardiosphere-derived cells (CDCs) implanted in rat infracted myocardium to improve the cardiac structure and function. METHODS: Rat CDCs were cultured by cardiac explant methods, and ECM was prepared by decelluariztion method. In a Wistar rat model of acute myocardial infarction established by ligating the left anterior descending branch, IMDM solution, ECM suspension, 106 CDCs in IMDM solution, or 106 CDCs in ECM suspension were injected into the infracted rat myocardium (6 rats in each group). The cardiac function of the rats was evaluated by cardiac ultrasonography, and the percentage of positive heart fibrosis area after infarction was determined with Masson staining. The differentiation of implanted CDCs in the infarcted myocardium was detected using immunofluorescence assay for the markers of cardiac muscle cells (α-SA), vascular endothelial cells (vWF) and smooth muscle cells (α-SMA). RESULTS: Three weeks after acute myocardial infarction, the rats with injection of CDCs in ECM showed the highest left ventricular ejection fraction (LVEF) and percentage of fraction shortening with the lowest percentage of positive heart fibrosis area; implantation of CDCs with ECM resulted in significantly higher rates of CDC differentiation into cardiac muscle cells, vascular endothelial cells and smooth muscle cell (P<0.05). CONCLUSION: Heart-tissue derived ECM significantly promotes the differentiation of CDCs implanted in the infracted myocardium into cardiac muscle cells, vascular endothelial cells and smooth muscle cells to improve the cardiac structure and cardiac functions in rats.

Edaravone promotes activation of resident cardiac stem cells by transplanted mesenchymal stem cells in a rat myocardial infarction model.

OBJECTIVE: To explore the effect of edaravone on bone marrow mesenchymal stem cells (BMSCs) transplanted to treat acute myocardial infarction (AMI) and the underlying mechanism. METHODS: After pretreatment or treatment with edaravone under conditions of deep hypoxia and serum deprivation, the rat BMSCs were evaluated for reactive oxygen species (ROS), Akt pathway, apoptosis, migration, and paracrine function mediating cardiac stem cell (CSC) activation. Edaravone-pretreated BMSCs, control-released edaravone, and BMSCs were respectively transplanted into a rat AMI model. Apoptosis and paracrine functions of the BMSCs, resident CSC activation, and myocardial regeneration and function were measured at various time points. RESULTS: Compared with the control and edaravone pretreatment, edaravone treatment showed significantly increased apoptosis inhibition, migration, and cytokine secretion of BMSCs under an in vitro deep hypoxia and serum deprivation condition (P < .05), via inhibiting intracellular accumulation of ROS and prolonging the Akt pathway activation. At 24 hours postoperatively, up-regulated expression of cytokines within the transplanted area, and decreased apoptotic BMSCs, were detected in the BMSC + edaravone group, compared with the BMSCs and edaravone pretreatment BMSC groups (n = 10 for each group, P < .05). Four weeks later, the BMSCs + edaravone group showed more CSCs, CSC-derived cardiomyocytes, new vessels, and myocardial density within the ischemic area, and improved ejection fraction, compared with the other groups (n = 10 in each group, P < .05). CONCLUSIONS: Edaravone can protect the BMSCs against hypoxia and activate their potential to activate CSCs via the Akt pathway. The combined treatment can promote angiogenesis, resident CSC-mediated myocardial regeneration, and cardiac function after AMI, providing a new strategy for cell therapy.

Effect of inducible nitric oxide synthase on intestinal microcirculation in endotoxic shock.

To investigate the changes of intestinal microcirculation in endotoxic shock and the effect of inducible nitric oxide synthase (iNOS) on intestinal microcirculation, endotoxic shock was induced by intravenous injection of lipopolysaccharide (LPS) in mice. Mean arterial pressure (MAP) was monitored throughout the experimental procedure. The velocity and flux of red blood cell (RBC) in villus tip arteriole and capillaries were measured by FITC-labeled erythrocytes and intravital microscopy. The effect of iNOS was determined by targeted disruption of mice iNOS-gene and administration of S-methylthiourea sulfate (SMT), a selective inhibitor of iNOS, before LPS injection. No significant differences in MAP, RBC velocity and flux at baseline were found among wild type mice, SMT pretreated mice and iNOS-gene knockout mice. LPS induced a dramatic fall of MAP in wild type mice. The decrease of MAP was significantly restored in iNOS-gene knockout mice and in wild type mice received SMT before LPS injection. The velocity and flux of RBC in villus tip arteriole and capillaries decreased markedly after LPS injection in wild type mice, while significantly higher velocity and flux of RBC were found in iNOS-gene knockout mice and SMT-pretreated mice both 60 and 120 min after LPS injection. The results demonstrate that iNOS plays an essential role in the intestinal microcirculation disturbance which occurs in endotoxic shock.

Delayed enrichment for c-kit and inducing cardiac differentiation attenuated protective effects of BMSCs' transplantation in pig model of acute myocardial ischemia.

OBJECTIVE: To investigate the effects of immature cardiomyocytes differentiated from c-kit(+) bone marrow mesenchymal stem cells (BMSCs) against acute myocardial infarction (AMI). METHODS: Miniswine passage 8 BMSCs were enriched for c-kit and induced by 5 µM 5-azacytidine (AZA) for 14 days, and a second enrichment for the dihydropyridine receptor subunit α2δ1 was performed (enriched BMSCs). Thereafter, enriched BMSCs were analyzed by determining cardiac differentiation, secretion function, and the effects of these secreted factors on cardiac stem cells (CSCs). Miniswine with AMI were divided into control, primary BMSCs' (PB), and enriched BMSCs' (EB) groups. Autologous BMSCs were intramyocardially injected into the ischemic regions in PB and EB groups. The following indices were evaluated at different time points, including paracrine of implanted BMSCs, histological and morphological analysis, myocardial perfusion, and cardiac function. RESULTS: As shown by in vitro study, enrichment + AZA significantly promoted BMSCs to express cardiac-specific markers and format action potential, but down-regulated the expression of VEGF and bFGF, consequently attenuated BMSCs-inducing CSCs proliferation, migration, and differentiation. The in vivo experiments revealed similar results like the in vitro 6 weeks postoperatively. And in EB group, there were decreased angiogenesis and myocardial perfusion, attenuated resident CSCs-mediated myocardial regeneration, and consequently impaired cardiac function compared with PB group. CONCLUSIONS: This pretreatment promoted BMSCs to differentiate into myocardiocytes both in vitro and in vivo, but impaired their paracrine function and effects on resident CSCs, suggesting that inducing cardiac differentiation alone may not improve protective effects of BMSCs transplantation on AMI.

HGF and IGF-1 promote protective effects of allogeneic BMSC transplantation in rabbit model of acute myocardial infarction.

OBJECTIVES: To explore effects of hepatocyte growth factor (HGF) combined with insulin-like growth factor 1 (IGF-1) on transplanted bone marrow mesenchymal stem cells (BMSCs), for treatment of acute myocardial ischaemia. MATERIALS AND METHODS: After ligation of the left anterior descending artery, rabbits were divided into a Control group, a Factors group (HGF+IGF-1), a BMSC group and a Factors+BMSCs group. Allogenous BMSCs (1 × 10(7)) and/or control-released microspheres of 2 µg HGF+2 µg IGF-1 were intramyocardially injected into infarcted regions. Apoptosis and differentiation of implanted BMSCs, histological and morphological results, and cardiac remodelling and function were evaluated at different time points. In vitro, BMSCs were exposed to HGF, IGF-1 and both (50 ng/ml) and subsequently proliferation, migration, myocardial differentiation and apoptosis induced by hypoxia, were analysed. RESULTS: Four weeks post-operatively, the above indices were significantly improved in Factors+BMSCs group compared to the others (P < 0.01), although Factors and BMSCs group also showed better results than Control group (P < 0.05). In vitro, HGF promoted BMSC migration and differentiation into cardiomyocytes, but inhibited proliferation (P < 0.05), while IGF-1 increased proliferation and migration, and inhibited apoptosis induced by hypoxia (P < 0.05), but did not induce myocardial differentiation. Combination of HGF and IGF-1 significantly promoted BMSCs capacity for migration, differentiation and lack of apoptosis (P < 0.05). CONCLUSIONS: Combination of HGF and IGF-1 activated BMSCs complementarily, and controlled release of the two factors promoted protective potential of transplanted BMSCs to repair infarcted myocardium. This suggests a new strategy for cell therapies to overcome acute ischemic myocardial injury.