Chest pain after percutaneous coronary intervention in patients with stable angina.

BACKGROUND: Percutaneous coronary intervention (PCI) has been widely used to treat acute coronary syndrome but is only recommended as an additional treatment to medical therapy and risk modification in patients with refractory or progressing angina. The number of PCI in this patient population is still increasing. Post-PCI chest pain (PPCP) is one of the common problems of PCI. Its presentation and causes in patients with stable angina are poorly understood. PATIENTS AND METHODS: This study retrospectively collected clinical information of 167 patients who had stable angina and underwent elective PCI, including 70 patients with PPCP 24 hours after procedure and 97 patients without PPCP. The incidence and predictors of PPCP were analyzed. RESULTS: The incidence of PPCP was 41.9% (70/167). Compared with non-PPCP patients, PPCP patients had more abnormal post-PCI electrocardiogram (ECG) changes (new Q-waves, ST-segment shifts, or T-waves inversion) and serum cardiac troponin I (cTnI) elevation, more PCI vessels, and stent placement (all P<0.05). More PPCP patients required repeat revascularization than non-PPCP patients after PCI (P=0.043). PPCP was correlated with abnormal post-PCI ECG changes (P<0.0001), cTnI elevation (P<0.0001), post-PCI serum level of cTnI (P<0.0001), number of stents placed (P=0.009), and pre-PCI cTnI level (P=0.049). The strongest predictors of PPCP were abnormal post-PCI ECG changes (P<0.0001), post-PCI cTnI level (P<0.0001), and cTnI elevation (P<0.0001), followed by the number of stents placed (P=0.048). CONCLUSION: PPCP is common in patients with stable angina in our cohort. It is associated with abnormal ECG changes, cTnI elevation, and number of stents placed.

Potential advantages of Chinese medicine Taohong Siwu Decoction () combined with tissue-plasminogen activator for alleviating middle cerebral artery occlusion-induced embolic stroke in rats.

OBJECTIVE: To investigate whether combination treatment with Taohong Siwu Decoction (, TSD) and recombinant tissue-type plasminogen activator (rt-PA) potentiate in reducing infarct volume and alleviate thromboembolic stroke in an in vivo rat model. METHOD: Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAO) and treated with rt-PA (4 and 8 mg/kg) alone (n=5), TSD [0.7 g/(kg·day)] alone (n=5), combination of rt-PA and TSD, 24 h after stroke. Rats were sacrificed at 14 days after treatment and lesion volumes were measured. To investigate the underlying mechanism of neuroprotective effect of the combination treatment, cleaved caspase-3, tumor necrosis factor alpha (TNF-α), hypoxia-inducible factor (HIF)-1α, and inducible nitric oxide synthase (iNOS) immunostaining were performed. RESULTS: Combination treatment significantly reduced infarct volume of cerebral ischemic regions compared with treatment of rt-PA and TSD alone and that of the saline control group (P<0.01). A combined treatment of rt-PA (4 mg/kg) with TSD [0.7 g/(kg·day)] significantly increased cerebral blood flow in a time (100 and 120 min) dependent manner (P<0.05). Interestingly, despite treatment of rt-PA (4 mg/kg) alone significantly reduced the expressions of HIF-1α, TNF-α, and iNOS in ischemic regions, reduction of these expressions were more potentiated when combined with TSD (P<0.05). Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared with the MCAO group (P<0.01). CONCLUSIONS: A combination of low-dose rt-PA and TSD after embolic stroke reduced infarct volume, improved cerebral blood flow and provided neuroprotection and these effects were associated with reduction of apoptosis and attenuation of HIF-1α, TNF-α and iNOS expression. These results provide a positive contribution to better understand the therapeutic value of the combination of TSD with rt-PA in ischemic stroke and may support further clinical evaluation.

Andrographolide, a Novel NF-κB Inhibitor, Inhibits Vascular Smooth Muscle Cell Proliferation and Cerebral Endothelial Cell Inflammation.

BACKGROUND: Aberrant vascular smooth muscle cell (VSMC) proliferation and cerebral endothelial cell (CEC) dysfunction contribute significantly in the pathogenesis of cardiovascular diseases. Therefore, inhibition of these cellular events would be by candidate agents for treating these diseases. In the present study, the mechanism of anti-proliferative and anti-inflammatory effects of andrographolides, a novel nuclear factor-κB inhibitor, was investigated in VSMC and CEC cells. METHODS: VSMCs and CECs were isolated from rat artery and mouse brain, respectively, and cultured before experimentation. The effect of andro on platelet-derived growth factor-BB (PDGF-BB) induced VSMC cell proliferation was evaluated by cell number, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of extracellular signal regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA), and the effects on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and, cyclooxygenase-2 (COX2) were detected by Western blotting. RESULTS: Andro significantly inhibited PDGF-BB (10 ng/ml) induced cell proliferation in a concentration (20-100 µM) dependent manner, which may be due to reducing the expression of ERK1/2, and by inhibiting the expression of PCNA. Andro also remarkably diminished LPS-induced iNOS and COX2 expression. CONCLUSIONS: The results of this study suggested that the effects of andro against VSMCs proliferation and CECs dysfunction may represent a promising approach for treatment of vascular diseases. KEY WORDS: Andrographolide; CECs; COX2/iNOS; ERK/PCNA; LPS; PDGF-BB; VSMCs.

Carotid intima-media thickness and plaque occurrence in predicting stable angiographic coronary artery disease.

BACKGROUND: Carotid intima-media thickness (CIMT) and plaque formation have been used as surrogate end-points for evaluating the regression and/or progression of atherosclerotic cardiovascular disease, but their predictive value for stable coronary artery disease (CAD) is inconclusive. METHODS: Carotid ultrasonography was performed in patients who underwent noninvasive multislice computed tomography (MSCT) angiography for CAD suspected, due to chest pain. CIMT and plaque formation on the left and right common carotid arteries (CCAs), carotid bulb (CB), and proximal internal carotid arteries (ICAs) were evaluated, and the relationship between angiographic CAD, CIMT, and plaque formation was determined. RESULTS: 120 patients (95 male; 25 female), with a mean age ± standard deviation of 61 ± 11 years (range: 35-89 years) were recruited. Because age had a significant impact on CAD (r = 0.191; P = 0.036), CCA plaques (r = 0.368; P = 0.001), ICA plaques (r = 0.334; P = 0.004), and mean CIMT (r = 0.436; P = 0.001), patients were divided into two groups aged <60 years and ≥60 years. In the <60 years group, CIMT-CB was significantly higher in patients with CAD (P = 0.041), while in the ≥60 years group, mean CIMT, CIMT-CCA, and CIMT-CB were significantly higher in patients with CAD (P < 0.05, for each). In both groups, the occurrence of carotid plaques was significantly higher in patients with CAD than in those without CAD (P < 0.007, for each). After controlling for other risk factors, carotid plaques were an independent predictor of CAD in both groups (P < 0.05, for each), while CIMT-CB could independently predict CAD only in patients ≥60 years old (P = 0.031). CONCLUSION: Our findings suggest that carotid plaques are a strong predictor of stable CAD. However, CIMT-CB could predict stable CAD only in patients over 60 years of age.

A novel role of sesamol in inhibiting NF-κB-mediated signaling in platelet activation.

BACKGROUND: Platelet activation is relevant to a variety of coronary heart diseases. Our previous studies revealed that sesamol possesses potent antiplatelet activity through increasing cyclic AMP formation. Although platelets are anucleated cells, they also express the transcription factor, NF-κB, that may exert non-genomic functions in platelet activation. Therefore, we further investigated the inhibitory roles of sesamol in NF-κB-mediated platelet function. METHODS: Platelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study. RESULTS: NF-κB signaling events, including IKKß phosphorylation, IκBα degradation, and p65 phosphorylation, were markedly activated by collagen (1 µg/ml) in washed human platelets, and these signaling events were attenuated by sesamol (2.5~25 µM). Furthermore, SQ22536 and ODQ, inhibitors of adenylate cyclase and guanylate cyclase, respectively, strongly reversed the sesamol (25 µM)-mediated inhibitory effects of IKKß phosphorylation, IκBα degradation, and p65 phosphorylation stimulated by collagen. The protein kinase A (PKA) inhibitor, H89, also reversed sesamol-mediated inhibition of IκBα degradation. Moreover, BAY11-7082, an NF-κB inhibitor, abolished IκBα degradation, phospholipase C (PLC)γ2 phosphorylation, protein kinase C (PKC) activation, [Ca(2+)]i mobilization, and platelet aggregation stimulated by collagen. Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca(2+)]i mobilization. CONCLUSIONS: Sesamol activates cAMP-PKA signaling, followed by inhibition of the NF-κB-PLC-PKC cascade, thereby leading to inhibition of [Ca(2+)]i mobilization and platelet aggregation. Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data demonstrating that inhibition of NF-κB interferes with platelet function may have a great impact when these types of drugs are considered for the treatment of cancer and various inflammatory diseases.

Elevated expression of connective tissue growth factor in human atrial fibrillation and angiotensin II-treated cardiomyocytes.

BACKGROUND: Atrial fibrosis is a feature of structural remodeling in atrial fibrillation (AF). Connective tissue growth factor (CTGF) is a potent profibrotic factor, but its role of CTGF in AF is not yet fully understood. METHODS AND RESULTS: Right atrial appendages were obtained from 20 patients who underwent cardiac surgery (10 with sinus rhythm, 10 with AF). The mRNA level, protein level and immunohistochemical staining of CTGF were significantly increased in AF patients. In a porcine AF model, tissue angiotensin II (Ang II) and CTGF levels were significantly upregulated in both atria. In perfused rat hearts, Ang II stimulation increased CTGF expression, which could be inhibited by Ang II type I receptor antagonist. In a cell culture system, both atrial fibroblasts and myocytes were responsible for the increased CTGF expression under Ang II treatment. Ang II type I receptor antagonist could inhibit the Ang II-induced CTGF expression. Treating with recombinant CTGF, atrial fibroblasts expressed an increased level of collagen I. Furthermore, the CTGF level was highly correlated with tissue Ang II content in AF pigs. CONCLUSIONS: AF patients and animals exhibited a significantly increased expression of CTGF. Ang II stimulation upregulated CTGF expression in both atrial fibroblasts and myocytes. Ang II-induced CTGF expression might be involved in atrial substrate remodeling.

The biatrial substrate properties in different types of paroxysmal atrial fibrillation.

BACKGROUND: The biatrial substrate properties in patients with paroxysmal atrial fibrillation (AF) originating from the pulmonary veins (PVs) and superior vena cava (SVC) are not available. OBJECTIVE: The purpose of this study is to characterize the differences of biatrial substrate properties in patients with different types of AF. METHODS: A total of 36 patients with paroxysmal AF originating from the PV (PV-AF) and 9 patients with paroxysmal AF initiating from the SVC (SVC-AF) were included. Regional electrogram voltage, conduction velocity (CV), and spectral analysis to identify the AF nest were performed to characterize the biatrial, PVs, and SVC substrate. RESULTS: In the left atrial (LA) body, the bipolar voltage, total activation time, CV, and dominant frequency (DF) were similar between the PV-AF and SVC-AF. However, in the PV regions, the electrogram voltage, CV, and DF were decreased in the PV-AF. The proportions of AF nest in the LA body (72.2% vs. 22.2%, P = .008) and PV regions (100% vs. 22.2%, P <.001) were higher in PV-AF compared with SVC-AF, respectively. On the other hand, lower bipolar voltage, longer total activation time, and slower CV of RA body were recognized in the SVC-AF as compared with the PV-AF. In the SVC, lower bipolar voltage, slower CV, higher DF, and higher proportions of AF nest in SVC (16.7% vs. 66.7%, P = .002) were identified in SVC-AF. CONCLUSION: These most-remodeled substrates in different types of paroxysmal AF indicated the importance of the atrial substrate in the vicinity of the arrhythmogenic thoracic veins.