Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome: a prospective multicenter single-arm interventional study.

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS: In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study).

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

Percutaneous Coronary Intervention in Elderly Patients with Coronary Chronic Total Occlusions: Current Evidence and Future Perspectives.

The proportion of the elderly in the total population of the world is growing, and the number of elderly patients with coronary chronic total occlusions (CTO) is huge. The elderly patients often have more extensive coronary artery disease, more severe ischemic burden and higher risk of cardiovascular events, as compared to younger patients, and thereby they might greatly benefit from coronary revascularization, even though they may have higher risk of operative complications. Most interventional cardiologists are more likely to be reluctant to operate complex percutaneous coronary intervention (PCI) in elderly patients. The latest refinements in dedicated CTO-PCI equipment and techniques have led to high rates of success and low complications rates and have made the CTO-PCI procedures safe and effective among the elderly patients. However, up to now, there is no widely recognized consensus or guideline on treatment strategy of elderly CTO patients, and the prognosis in this population is unknown. In this review, we aim to provide an overview of the current evidence and future perspectives on PCI in elderly patients with CTOs.

Preferences and attitudes of young Chinese clinicians about using a shared decision making tools for communicating cardiovascular risk.

OBJECTIVE: This study assesses the attitudes and preferences of Chinese clinicians toward their involvement in shared decision making (SDM). METHODS: From May 2014 to May 2015, 200 Chinese clinicians from two hospitals were enrolled to complete a survey on their attitude towards SDM. We conducted the survey via face-to-face interviews before and after an educational intervention on SDM among young Chinese clinicians. The clinicians were asked to give the extent of agreement to SDM. They also gave the extent of difficulty in using decision aids (DAs) during the SDM process. The variation in the range of responses to each question before and after the SDM intervention was recorded. The frequency of changed responses was analyzed by using JMP 6.0 software. Data were statistically analyzed using Chi-square and Mann-Whitney U tests, as appropriate to the data type. Multiple logistic regressions were used to test for those factors significantly and independently associated with preference for an approach for each scenario. RESULTS: Of the 200 young Chinese clinicians sampled, 59.0% indicated a preference for SDM and a desire to participate in SDM before receiving education or seeing the DA, and this number increased to 69.0% after seeing the DA with the sample video of the SDM process on Statin Choice. However, 28.5% of the respondents still reported that, in their current practice, they make clinical decisions on behalf of their patients. The clinicians who denied a desire to use the DA stated that the main barriers to implement SDM or DA use in China are lack of time and knowledge of SDM. CONCLUSIONS: Most young Chinese clinicians want to participate in SDM. However, they state the main barriers to perform SDM are lack of experience and time. The educational intervention about SDM that exposes clinicians to DAs was found to increase their receptivity.

Differences in the cargos and functions of exosomes derived from six cardiac cell types: a systematic review.

Exosomes are bilayer membrane vesicles with cargos that contain a variety of surface proteins, markers, lipids, nucleic acids, and noncoding RNAs. Exosomes from different cardiac cells participate in the processes of cell migration, proliferation, apoptosis, hypertrophy, and regeneration, as well as angiogenesis and enhanced cardiac function, which accelerate cardiac repair. In this article, we mainly focused on the exosomes from six main types of cardiac cells, i.e., fibroblasts, cardiomyocytes, endothelial cells, cardiac progenitor cells, adipocytes, and cardiac telocytes. This may be the first article to describe the commonalities and differences in regard to the function and underlying mechanisms of exosomes among six cardiac cell types in cardiovascular disease.

Long-term clinical outcomes of optimal medical therapy vs. successful percutaneous coronary intervention for patients with coronary chronic total occlusions.

OBJECTIVES: There are little data on the long-term clinical outcomes of optimal medical therapy (OMT) compared with successful percutaneous coronary intervention (PCI) in patients with chronic total occlusions (CTOs). METHODS: A total of 388 patients with ≥1 CTO were enrolled from January 2008 to December 2010. 62 patients were excluded, and 326 patients were divided into an OMT group (n = 125) and PCI group (n = 201) according to the initial treatment strategy. Propensity-score matching was also done to adjust for baseline characteristics. The primary outcome was major adverse cardiac event (MACE), included cardiac death, recurrent myocardial infarction, and repeated revascularization. RESULTS: After a mean follow-up of 47.2 ± 20.0 months, there was no significant difference between the two groups with respect to the prevalence of MACE (successful PCI vs. OMT: 29.6% vs. 21.9%, unadjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 0.95-2.28, p=0.085). After multivariate analyses, there were significant differences in the prevalence of MACE (adjusted HR 1.76, 95% CI 1.09-2.28, p=0.02) and repeated revascularization (2.14; 1.18-3.90, 0.01). In the propensity score-matched population (80 pairs), there were no significant differences in the prevalence of MACE (adjusted HR 1.89, 95% CI 0.96-3.71, p=0.06) and cardiac death (1.30, 0.44-3.80, 0.63) between groups. CONCLUSION: In the treatment of patients with CTOs, successful PCI did not reduce the long-term risk of MACE compared with OMT.

Selectins modify dendritic cells during atherosclerosis.

Dendritic cells (DCs) are professional antigen-presenting cells (APC) that facilitate the development and progression of atherosclerosis. However, DCs also function as novel "switches" between immune activation and immune tolerance and represent a heterogeneous hematopoietic lineage, with cell subsets in different tissues that show a differential morphology, phenotype, and function. Regulatory DCs, depending on their immature state, can be induced by immunosuppressive modulation, which plays an important part in the maintenance of immunologic tolerance via suppression of the immune response. In this review, we describe the current understanding of the generation of regulatory DCs. The novel role of selectins in the modification of DCs in atherosclerosis is also discussed.

Effects of timing on intracoronary autologous bone marrow-derived cell transplantation in acute myocardial infarction: a meta-analysis of randomized controlled trials.

BACKGROUND: Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI). METHODS: A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy. RESULTS: Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001) resulted in a significant increase of left ventricular ejection fraction (LVEF). As for the inhibitory effect on ventricular remodeling, BMC transplantation 3-7 days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to -2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic index after BMC transplantation in the group with LVEF ≤ 50% (WMD = -5.25, 95% CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7-10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P < 0.0001). In the group with a follow-up of more than 12 months, this beneficial effect was significant and increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P = 0.0006) when compared with control. CONCLUSIONS: In this meta-analysis, BMC transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions or LV end-diastolic dimensions. It is more effective in patients with lower baseline LVEF (≤50%) and the effect can last more than 12 months.

Stem cell transplantation dose in patients with acute myocardial infarction: A meta-analysis.

OBJECTIVE: To evaluate whether stem cell transplantation improves global left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction (AMI), and to determine the appropriate stem cell therapy dose as well as the effective period after stem cell transplantation for therapy. METHODS: A systematic literature search included Pubmed, MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Cochrane Evidence-Based Medicine databases. The retrieval time limit ranged from January 1990 to June 2016. We also obtained full texts through manual retrieval, interlibrary loan and document delivery service, or by contacting the authors directly. According to our inclusion and exclusion criteria, data were extracted independently by two evaluators. In case of disagreement, a joint discussion occurred and a third researcher was utilized. Data were analyzed quantitatively using Revman 5.2. Summary results are presented as the weighted mean difference (WMD) with 95% confidence intervals (CIs). We collected individual trial data and conducted a meta-analysis to compare changes in global left ventricular ejection fraction (ΔLVEF) after stem cell therapy. In this study, four subgroups were based on stem cell dose (≤1 × 107 cells, ≤1 × 108 cells, ≤1 × 109 cells, and ≤1 × 1010 cells) and three subgroups were based on follow-up time (<6 months, 6-12 months, and ≥12 months). RESULTS: Thirty-four studies, which included 40 randomized controlled trials, were included in this meta-analysis, and 1927 patients were evaluated. Changes in global LVEF were significantly higher in the stem cell transplantation group than in the control group (95% CI: 2.35-4.26%, P < 0.01). We found no significant differences in ΔLVEF between the bone marrow stem cells (BMCs) group and control group when the dose of BMCs was ≤1 × 107 [ΔLVEF 95% CI: 0.12-3.96%, P = 0.04]. The ΔLVEF in the BMCs groups was significantly higher than in the control groups when the dose of BMCs was ≤1 × 108 [ΔLVEF 95% CI: 0.95-4.25%, P = 0.002] and ≤1 × 109 [ΔLVEF 95% CI: 2.31-4.20%, P < 0.01]. In addition, when the dose of BMCs was between 109 and 1010 cells, we did not observe any significant differences [ΔLVEF 95% CI: -0.99-11.82%, P = 0.10]. Our data suggest stem cell therapy improves cardiac function in AMI patients when treated with an appropriate dose of BMCs. CONCLUSION: Stem cell transplantation after AMI could improve global LVEF. Stem cells may be effectively administered to patients with AMI doses between 108 and 109 cells.

Long-term prognosis of patients with acute non-ST-segment elevation myocardial infarction undergoing different treatment strategies.

BACKGROUND: In cardiology, it is controversial whether different therapy strategies influence prognosis after acute coronary syndrome. We examined and compared the long-term outcomes of invasive and conservative strategies in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and characterized the patients selected for an invasive approach. METHODS: A total of 976 patients with acute NSTEMI were collected from December 2006 to October 2012 in the First Affiliated Hospital of Dalian Medical University Hospital. They are divided into conservative strategy (586 patients) and invasive strategy (390 patients) group. Unified follow-up questionnaire was performed by telephone contact (cut-off date was November, 2013). The long-term clinical events were analyzed and related to the different treatment strategies. RESULTS: The median follow-up time was 29 months. Mortality was 28.7% (n = 168) in the conservative group and 2.1% (n = 8) in the invasive management at long-term clinical follow-up. The secondary endpoint (the composite endpoint) was 59.0% (n = 346) in the conservative group and 30.3% (n = 118) in the invasive management. Multivariate analysis showed that patients in the conservative group had higher all-cause mortality rates than those who had the invasive management (adjusted risk ratio [RR] = 7.795; 95% confidence interval [CI]: 3.796-16.006, P < 0.001), and the similar result was also seen in the secondary endpoint (adjusted RR = 2.102; 95% CI: 1.694-2.610, P < 0.001). In the subgroup analysis according to each Thrombolysis in Myocardial Infarction risk score (TRS), log-rank analysis showed lower mortality and secondary endpoint rates in the invasive group with the intermediate and high-risk patients (TRS 3-7). CONCLUSIONS: An invasive strategy could improve long-term outcomes for NSTEMI patients, especially for intermediate and high-risk ones (TRS 3-7).

Tumor necrosis factor-α and its role as a mediator in myocardial infarction: A brief review.

Tumor necrosis factor-α (TNF-α) contributes to myocardial infarction (MI) injury. Polymorphism of TNF-α gene promoter region and secretion and release of TNF-α and its transformation by a series of signaling pathways are all changed at different points of pathophysiological process in MI. Researches also investigated TNF-α antagonists and their potential therapeutic role in the setting of MI and heart failure at both molecular and clinical level. This article briefly reviews TNF-α and its mechanism as a mediator in MI.

Effects of selenoprotein S on oxidative injury in human endothelial cells.

BACKGROUND: Selenoprotein S (SelS) is an important endoplasmic reticulum and plasma membrane-located selenoprotein implicated in inflammatory responses and insulin resistance. However, the effects of SelS on endothelial cells (ECs) have not been reported. In the present study, the role of SelS in oxidative stress and the underlying mechanism were investigated in human ECs. METHODS: A SelS over-expression plasmid (pc-SelS) and a SelS-siRNA plasmid were transfected into human umbilical vein endothelial cells (American Type Culture Collection, USA). The cells were divided into four groups: control, SelS over-expression (transfected with pc-SelS), vector control, and SelS knockdown (transfected with siRNA-SelS). After treating the cells with H2O2, the effects of oxidative stress and the expression of caveolin-1 (Cav-1) and protein kinase Cα (PKCα) were investigated. RESULTS: Following treatment with H2O2, over-expression of SelS significantly increased cell viability and superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) production and Cav-1 gene and protein expression. However, no effects on PKCα were observed. In contrast, knockdown of SelS significantly decreased cell viability, SOD activity, and PKCα gene and protein expression, and increased MDA production and Cav-1 gene and protein expression. CONCLUSIONS: SelS protects ECs from oxidative stress by inhibiting the expression of Cav-1 and PKCα.

Safety and efficacy of a non-polymeric paclitaxel-eluting microporous stent in real-world percutaneous coronary intervention.

At present, there is an increasing focus on stents that have a biodegradable polymer coating, rather than a permanent polymer coating. This is due to the fact that following the implantation of a drug-eluting stent (DES) with a permanent polymer coating, the continued existence of the coating may result in a foreign body reaction and delayed re-endothelialization. The aim of the present study was to evaluate the safety and efficacy of a non-polymeric paclitaxel-eluting microporous (YINYI™) stent in real-life percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD). A total of 686 YINYI™ stents were implanted in 404 patients with CAD in a PCI procedure and outpatient follow-ups were performed 1, 6, 12 and 15 months subsequent to the PCI, respectively. The observation endpoints were major adverse cardiac events (MACEs), including cardiac death, non-fatal myocardial infarction (MI), restenosis, target lesion revascularization, stent thrombosis and recurrence of angina pectoris. The average follow-up time was 15 months. The results revealed that the cumulative incidences of MACEs were as follows: mortality, 0.99%; non-fatal MI, 0.74%; restenosis, 4.0%; and target lesion revascularization, 2.7%. The results at the short- and long-term clinical follow-ups indicated that YINYI™ stents are effective and safe for use in PCI for patients with CAD.

Gender disparity in early death after ST-elevation myocardial infarction.

BACKGROUND: Females with acute myocardial infarction (AMI) have a higher risk of adverse outcomes because of receiving less evidence-based medical care. Our aim was to investigate the gender disparity in early death after ST-elevation myocardial infarction (STEMI) in the current era. METHODS: A total of 1429 consecutive patients with STEMI in the Liaoning district were analyzed. We compared hospital care and cardiac event data by sex for in-patients with acute STEMI within 24 hours of symptom onset. RESULTS: In the emergency reperfusion group (n = 754), in-hospital mortality occurred in 4.2% of the males and 11.2% of the females (P = 0.001). In the non-emergency reperfusion group (n = 675), in-hospital mortality occurred in 13.0% of the males and 22.9% of the females (P = 0.001). Multivariate Logistic regression analysis revealed female sex as an independent risk factor of death for STEMI patients during hospitalization (OR = 1.691, P = 0.007). After controlling for patients who died within 24 hr after admission, female sex was no longer an independent risk factor (OR = 1.409, P = 0.259). CONCLUSION: Female sex was an independent risk factor for in-hospital mortality of STEMI patients, which is explained by an excess of very early deaths.

Inflammation inhibitory effects of sirolimus and paclitaxel-eluting stents on interleukin-1ß-induced coronary artery in-stent restenosis in pigs.

BACKGROUND: Coronary artery in-stent restenosis (ISR) and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin (IL)-1ß. METHODS: Mini pigs (n = 12; 2-3 months old and weighing 25-30 kg) were subjected to thoracotomy. Segments (10 mm) of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1ß (5 µg). After 2 weeks, the animals were anesthetized and quantitative coronary arteriography (QCA) was performed. The stenosis sites were randomized into three groups for stent insertion: a sirolimus-eluting stent (SES) group (Firebird(TM), n = 7), a paclitaxel-eluting stent (PES) group (TAXUS(TM), n = 9), and a bare-metal stent (BMS) group (YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n = 8). The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), P-selectin and vascular cell adhesion molecule-1 (VCAM-1) was determined by reverse transcription-coupled polymerase chain reaction (RT-PCR). RESULTS: QCA showed severe stenosis in IL-1ß treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss (LLL) within the stent and the lesion compared with BMS (P < 0.05) by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA ((0.15 ± 0.06) mm vs. (0.33 ± 0.01) mm, P < 0.0001). The neointimal hyperplasia areas in SES and PES showed lower than those of BMS (SES (11.6 ± 1.7) mm(2), PES (27.2 ± 1.6) mm(2) vs. BMS (76.2 ± 1.3) mm(2), P < 0.0001). The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting (SES 0.20 ± 0.03, PES 0.48 ± 0.49 vs. BMS 0.58 ± 0.07, P < 0.05). Levels of VCAM-1 in SES were significantly lower than those of PES and BMS (SES 0.35 ± 0.08 vs. PES 0.65 ± 0.13, BMS 0.70 ± 0.06, P < 0.05). Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS. CONCLUSION: SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.

[Intracoronary and hypodermic injection of granulocyte colony-stimulating factor improved cardiac function in Swine with chronic myocardial ischemia].

OBJECTIVES: To compare the efficacy and feasibility between intracoronary and hypodermic injection of granulocyte colony-stimulating factor (G-CSF) on improving cardiac function in a Swine model of chronic myocardial ischemia. METHODS: Eighteen Swine underwent placement of ameroid constrictor on left circumflex coronary artery. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were then randomly assigned into three groups (n = 6 each): (1) administration of vehicle (control), (2) hypodermic injection of G-CSF (5 microgxkg(-1)x;d(-1)) for five days (IH), and (3) intracoronary injection of a bonus G-CSF (60 microg/kg) (IC). Coronary angiogram, cardiac MRI, and (18)F-FDG-SPECT/(99m)Tc-SPECT (DISA-SPECT) measurements were performed at pre-administration and at 4 weeks post administration. Global heart function such as left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVSDV) and left ventricular ejection fraction (LVEF), myocardial perfusion, myocardial viability and myocardial infarct area were evaluated. Myocardial vWF, Bcl-2 and Bax expressions were detected by Western blot and RT-PCR. RESULTS: MRI data showed that left ventricular dilation and dysfunction were similarly prevented in IH and IC G-CSF treated animals at eight weeks after the operation. SPECT revealed that both IH and IC G-CSF equally improved the regional contractility of chronic myocardial ischemia and increased myocardial viability. Myocardial infarct size was also reduced after both G-CSF treatments as detected by MRI. Intracoronary injection of G-CSF did not lead to angiogenesis in other organs. G-CSF treatments were also associated with a significant reduction in myocardial apoptosis and significant increase in angiogenesis. CONCLUSIONS: Both intracoronary and hypodermic injection of G-CSF were safe and feasible and could equally improve cardiac function and increase angiogenesis in this Swine model of chronic myocardial ischemia.