Image quality, radiation dose, and diagnostic accuracy of prospectively ECG-triggered high-pitch coronary CT angiography at 70 kVp in a clinical setting: comparison with invasive coronary angiography.

PURPOSE: To investigate image quality, radiation dose, and diagnostic performance of prospectively ECG-triggered high-pitch coronary CT angiography (CCTA) at 70 kVp compared to invasive coronary angiography (ICA) as reference standard. MATERIALS AND METHODS: Forty-three patients underwent prospectively ECG-triggered high-pitch CCTA at 70 kVp using 30 cc (11 g iodine) contrast medium and ICA. Subjective and objective image quality was evaluated for each CCTA study. CCTA performance for diagnosing ≥50% stenosis was assessed. Results were stratified according to heart rate (HR), body mass index (BMI), Agatston score, and image quality. RESULTS: At CCTA, 94.3% (500/530) of coronary segments were of diagnostic quality. Using ICA as reference standard, sensitivity and accuracy were 100% and 93.0% on a per-patient basis. Per-vessel and per-segment performances were 92.2% and 89.5%; 79.5% and 88.3%, respectively. No differences were found in diagnostic accuracy between different HR, BMI, and calcification subgroups (all P > 0.05) on a per-patient basis. However, low image quality reduced diagnostic accuracy on a per-patient, per-vessel and per-segment basis (all P < 0.05). The mean effective radiation dose was 0.2 ± 0.0 mSv. CONCLUSION: Our presented protocol results in an effective radiation dose of 0.2 mSv and high diagnostic accuracy for stenosis detection in a selected, non-obese population. KEY POINTS: Prospectively ECG-triggered high-pitch CCTA at 70 kVp is feasible. This protocol has a high diagnostic accuracy for stenosis detection. The mean effective radiation dose was 0.2 ± 0.0 mSv. Only 30 cc of contrast material is used in this protocol. Low image quality reduced diagnostic accuracy of CCTA.

Hydroxytyrosol Protects against Myocardial Ischemia/Reperfusion Injury through a PI3K/Akt-Dependent Mechanism.

OBJECTIVE: To investigate the effects and mechanisms of hydroxytyrosol (HT) during the pathogenesis of myocardial ischemia reperfusion (I/R) in rat hearts. METHODS: The rats were randomized into five groups: sham group, I/R group, HT+I/R group, HT+LY294002+I/R group, and LY+I/R group. Myocardial infarct size, markers of oxidative stress, extent of myocardial apoptosis, echocardiographically assessed cardiac function, and expression of Akt and GSK 3ß were measured in each group. RESULTS: Prereperfusion administration of HT was associated with a significantly smaller area of myocardial infarction and remarkably decreased level of myocardial apoptosis and necrosis, as evidenced by a lower apoptotic index, reduced cleaved caspase-3, and the serum activities of lactate dehydrogenase and creatinine kinase MB. Moreover, HT also attenuated the impairment of cardiac systolic function. However, cotreatment with LY294002 and HT completely abolished the above cardioprotective effects of HT. A subsequent mechanistic study revealed that the cardioprotective effects of HT during the process of I/R of the myocardium were dependent on the activation of the Akt/GSK3ß pathway. CONCLUSION: Pretreatment with HT may have antiapoptotic and cardioprotective effects against myocardial I/R injury, and these effects seem to be related to the activation of the Akt/GSK3ß pathway in the myocardium.

Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells.

PURPOSE: To investigate the toxic effect of oscillating high glucose (OHG) versus persistent high glucose (PHG) in inducing oxidative stress and cellular apoptosis in human coronary artery endothelial cells (HCAECs) in vitro. METHODS: HCAECs were incubated for 72 h continuously in normal glucose (5.5 mmol/L glucose), PHG (25 mmol/L glucose), OHG (5.5 mmol and 25 glucose mmol/L alternating every 6 h) and mannitol, respectively. Cellular viability, concentration of oxidative stress biomarkers (MDA and GSH) in the supernatants of cell culture, and intracellular ROS level were quantitated after exposure to different concentrations of glucose for a total 72 h. Apoptosis of HCAECs cultured with various glucose levels was evaluated by annexin V-FITC and PI staining followed by analysis with flow cytometry. The expressions of HO-1 and Nrf2 were measured by RT-qPCR and Western blotting at the end of the experiment. RESULTS: HCAECs cultured with PHG showed decreased cellular viability compared to those with normal level of glucose (p < 0.05). The decrease was more pronounced under OHG condition (p < 0.05). Cellular oxidative stress was provoked in HCAECs exposed to PHG with marked increased MDA level, reduced GSH concentration and elevated ROS production (p < 0.05). The stress was further amplified in the setting of OHG (p < 0.05). The cellular apoptosis was enhanced by culturing with PHG, and to a greater extent when incubated with OHG. Both expressions of HO-1 and Nrf2 were suppressed in HCAECs in persistent hyperglycemia condition, while the inhibition was more intense in the fluctuating hyperglycemia condition (p < 0.05). CONCLUSIONS: These findings indicate that OHG could be more detrimental to HCAECs than PHG. This is probably due to the enhancement of oxidative stress and cellular apoptosis induced by frequent glucose swings through the inhibition of Nrf2/HO-1 pathway.

MicroRNA expression profile in myocardial bridging patients.

BACKGROUND: Myocardial bridging (MB), a common benign coronary anomaly, may bring about some unwanted complications such as angina-like chest pain. The only way of MB detection is coronary arteriography or coronary computed tomographic angiography, which is costly and invasive. This study intended to profile a panel of circulating microRNAs (miRNAs) as potential biomarkers for the diagnosis of MB. METHODS: Using TaqMan Low-Density Array followed by quantitative reverse transcriptase PCR (qRT-PCR) validation, we analyzed the expression of miRNAs in serum samples from 90 MB patients and 50 non-MB controls. RESULTS: The Low-Density Array data showed that 196 miRNAs were differentially expressed in MB patient sera in comparison with controls. After qRT-PCR validation and receiver operating characteristic (ROC) analysis, a list of five miRNAs (miR-29b, miR-151-3p, miR-126, miR-503-3p and miR-645) showed the ability to distinguish MB patients from controls. The area under curve (AUC) values range from 0.722-0.938. CONCLUSIONS: We have demonstrated that this panel of five serum miRNAs is expected to become potential non-invasive biomarkers for detection of MB.

Anoikis-related signature identifies tumor microenvironment landscape and predicts prognosis and drug sensitivity in colorectal cancer.

Background: Anoikis, a mechanism of programmed apoptosis, plays an important role in growth and metastasis of tumors. However, there are still few available comprehensive reports on the impact of anoikis on colorectal cancer. Method: A clustering analysis was done on 133 anoikis-related genes in GSE39582, and we compared clinical features between clusters, the tumor microenvironment was analyzed with algorithms such as "Cibersort" and "ssGSEA". We investigated risk scores of clinical feature groups and anoikis-associated gene mutations after creating a predictive model. We incorporated clinical traits to build a nomogram. Additionally, the quantitative real-time PCR was employed to investigate the mRNA expression of selected anoikis-associated genes. Result: We identified two anoikis-related clusters with distinct prognoses, clinical characteristics, and biological functions. One of the clusters was associated with anoikis resistance, which activated multiple pathways encouraging tumor metastasis. In our prognostic model, oxaliplatin may be a sensitive drug for low-risk patients. The nomogram showed good ability to predict survival time. And SIRT3, PIK3CA, ITGA3, DAPK1, and CASP3 increased in CRC group through the PCR assay. Conclusion: Our study identified two distinct modes of anoikis in colorectal cancer, with active metastasis-promoting pathways inducing an anti-anoikis subtype, which has a stronger propensity for metastasis and a worse prognosis than an anoikis-activated subtype. Massive immune cell infiltration may be an indicator of anoikis resistance. Anoikis' role in the colorectal cancer remains to be investigated.

Association of pericardial adipose tissue volume with presence and severity of coronary atherosclerosis.

PURPOSE: This study was to investigate whether high pericardial adipose tissue (PAT) volume is related to the presence and severity of coronary artery disease (CAD). METHODS: Consecutive patients (310 patients) who underwent both dual-source 64-slice CT and percutaneous coronary angiography were recruited into this study. Waist circumference (WC), body mass index (BMI), blood biochemical variables, coronary artery calcium (CAC) score and Gensini score were measured. Pericardial adipose tissue (PAT) volume was determined by dual-source CT. RESULTS: PAT volume was positively correlated with BMI, WC, gender (male), hypertension, diabetes, age, total cholesterol and low-density lipoprotein-cholesterol. PAT volume in CAD patients was significantly higher than that in patients without CAD (238.36 ± 81.21 cm3 vs. 200.13±72.34 cm3). PAT volumes in patients with multi-vessel lesions were significantly higher than those with one-vessel lesions (P < 0.001). A significant correlation between PAT volume and CAC score (r=0.305, P < 0.001) was found. PAT volume was an independent factor affecting Gensini score. CONCLUSION: PAT volume was significantly correlated with traditional cardiovascular risk factors, the severity of coronary atherosclerosis and the number of stenotic coronary vessels. Thus, PAT volume may be a reliable marker to evaluate the presence and severity of CAD.

CETP gene polymorphisms and risk of coronary atherosclerosis in a Chinese population.

BACKGROUND: Coronary atherosclerosis, the most common form of coronary artery disease (CAD), is characterized by accumulation of lipid in the walls of coronary arteries. Recent data from clinical trials have showed that high-density lipoprotein cholesterol (HDL-C) has causal role in the pathogenesis and development of coronary atherosclerosis. Cholesteryl ester transfer protein (CETP) is an important regulator of plasma HDL-C. Several genetic mutations in the CETP gene were found to be associated with HDL-C levels. The aim of the present study is to evaluate the association of HDL-C-related CETP polymorphisms and risk of coronary atherosclerosis. METHODS: We investigated the association of seven single nucleotide polymorphisms (SNP) (rs1800775, rs708272, rs5882, rs1532624, rs1864163, rs7499892, and rs9989419) in the CETP gene with the risk of coronary atherosclerosis and levels of HDL-C in a case-control study in China. Included in the study were 420 patients with coronary atherosclerosis and 424 healthy controls. SNP genotyping was performed by TaqMan allelic discrimination assay and serum lipid levels were measured by standard laboratory methods. RESULTS: Carriers of the AA and GA + AA genotypes of rs708272 had significant lower risks of coronary atherosclerosis (OR = 0.55, 95% CI: 0.36-0.85, p = 0.003; OR = 0.67, 95% CI: 0.50-0.90, p = 0.007, respectively) compared to those with GG genotype. These relations remained significant after adjustment for confounding effects of age, smoking, diabetes and hypertension. The rs1800775 polymorphism was significantly associated with serum levels of HDL-C in healthy controls (p = 0.04). Besides, rs708272 was in close linkage disequilibrium (LD) with rs1800775 in this study. CONCLUSIONS: Our findings indicated that CETP rs708272 may be associated with the risk of coronary atherosclerosis and rs1800775 may influence serum HDL-C levels in healthy controls in Chinese.

Protective effect of ligustrazine against myocardial ischaemia reperfusion in rats: the role of endothelial nitric oxide synthase.

1. The aim of the present study was to determine whether ligustrazine (2,3,5,6-tetramethylpyrazine; TMP) exerts a cardioprotective effect during myocardial ischaemia reperfusion (IR), and to investigate the underlying mechanisms and the role of endothelial nitric oxide synthase (eNOS) in cardioprotection. 2. Sprague-Dawley rats were divided into a sham group and five IR groups: IR control, TMP pretreated, TMP + wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor), N(G) -nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) and TMP + L-NAME. IR was produced by 35 min of regional ischaemia followed by 120 min of reperfusion. Myocardial infarct size, oxidative stress, myocardial apoptosis, nitric oxide (NO) production, and expression of phosphorylated protein kinase B (Akt) and eNOS were measured. 3. TMP markedly decreased infarct size and attenuated myocardial apoptosis, as evidenced by a decrease in the apoptotic index and reduced caspase-3 activity. TMP treatment caused a marked increase in NO production. Cotreatment with wortmannin or L-NAME completely blocked the TMP-induced NO increase. TMP induced phosphorylation of Akt at Ser 473 (1.61 ± 0.18 vs 0.79 ± 0.10 in the IR control group) and phosphorylation of eNOS at Ser1177 (1.87 ± 0.33 vs 0.94 ± 0.22 in the IR control group). Wortmannin abrogated the phosphorylation of Akt and eNOS induced by TMP. 4. These data suggest that ligustrazine has anti-apoptotic and cardioprotective effects against myocardial IR injury and that it acts through the PI3K/Akt pathway. In addition, the phosphorylation of eNOS with subsequent NO production was found to be an important downstream effector that contributes significantly to the cardioprotective effect of TMP.

[Membrane testosterone receptors in cultured vascular smooth muscle cells].

OBJECTIVE: To determine the presence of membrane testosterone receptors in cultured vascular smooth muscle cells (VSMC), and investigate their relationship with classical intracellular androgen receptors (iAR). METHODS: VSMCs were cultured from the thoracic aorta of male Sprague-Dawley rats by the explant method. Subconfluent VSMCs were incubated with serum-free medium for 24 h to obtain quiescent non-dividing cells, and then treated with the indicated agents. The aliquots of VSMCs were labeled with testosterone-BSA-FITC (T-BSA-FITC) and analyzed by flow cytometry. Classical iARs in intact- and permeabilized-cells were detected with anti-iAR antibodies and FITC-labeled secondary antibodies by immunofluorescence, followed by flow cytometry analysis. RESULTS: Incubation of VSMCs with T-BSA-FITC obviously increased their relative fluorescence intensity at 10 sec as compared with the untreated controls (P < 0.01), and so did it at 10 min in comparison with the treatment with BSA-FITC alone or together with free testosterone (P < 0.01). Pretreatment with iAR antagonist flutamide exhibited no significant influence on the relative fluorescence intensity of VSMCs (P = 0.318). Traditional iARs were not detectable on the surface of intact VSMCs, although permeabilized cells contained iARs. CONCLUSION: VSMCs contain testosterone receptors in the plasma membrane, and these membrane receptors are not identical to classical iARs.

[Testosterone at physiological level inhibits PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells].

OBJECTIVE: To explore the acute effects of testosterone at the physiological level on PGF2alpha-induced increase in intracellular Ca2+ in cultured vascular smooth muscle cells (VSMCs). METHODS: VSMCs from the thoracic aorta of male Sprague-Dawley rats were cultured using the explant method. The subconfluent VSMCs were incubated with serum-free medium for 24 hours to obtain quiescent non-dividing cells and then treated with the indicated agents. For the measurement of [Ca2+]i, the VSMCs were loaded with fura-2. Changes of [Ca2+]i were determined ratiometrically with a Nikon TE-2000E system. RESULTS: The resting level of [Ca2+]i was around 100 nmol/L in the VSMCs. Exposing cells to perfusate containing 10 micromol/L PGF2alpha triggered an immediate and transient peak in [Ca2+]i, which gradually decreased afterwards. Interference at the peak with the physiological concentration (40 nmol/L) of testosterone significantly decreased the peak-to-baseline time of [Ca2+]i, compared with ethanol vehicle (104.9 +/- 27.0 s vs 153.5 +/- 40.4 s, P < 0.01). Pretreatment with testosterone at 40 nmol/L for 2 minutes also reduced the peak-to-baseline time of [Ca2+]i significantly in comparison with the ethanol control (120.6 +/- 32.0 s vs 151.4 +/- 27.4 s, P < 0.01), but it had no significant effect on the peak level of PGF2alpha-induced intracellular Ca2+ (390.0 +/- 126.0 nmol/L vs 403.4 +/- 160.7 nmol/L, P > 0.05). CONCLUSION: Testosterone at physiological concentration inhibits PGF2alpha-induced Ca2+ fluxes, probably via receptor-operated calcium channels by a non-genomic mechanism in VSMCs, which may be involved in the vasodilatory effect of testosterone.

[Coronary artery lesion comparison between Chinese and Australian patients with coronary artery disease].

OBJECTIVE: To compare coronary lesion characteristics by coronary angiography (CAG) between yellows and whites. METHODS: CAG results of 3021 Chinese patients, defined as yellows, from Nanjing and 3230 Australian patients, defined as whites, from Sydney were analyzed. The coronary artery lesion was evaluated by the number and location of coronary lesion and Gensini scores. RESULTS: (1) Coronary stenosis was diagnosed in 69.4% Chinese patients and 75.5% in Australians. The involved coronary arteries were left anterior descending branch, right coronary artery, left circumflex branch and left main coronary artery in a descending order in both Chinese and Australians. (2) The incidences of three-vessel disease and left main disease of yellows were significantly lower than that of whites in both male (29.8% vs. 34.0% and 9.6% vs. 14.2%) and female patients (15.8% vs. 26.2% and 4.9% vs. 11.6%) respectively, all P < 0.05. (3) There was an age-dependent Gensini scores increase in both yellows and whites patients and Gensini scores at age 40 and more of whites were significantly higher than those of yellows in comparable age groups. CONCLUSION: The incidences of three-vessel disease and left main disease as well as Gensini score were significantly higher in Australian patients than those of Chinese patients.

[Expression of Toll-like receptor 2/4 mRNA in myocardium in mice with hemorrhagic shock].

OBJECTIVE: To investigate the effect of hemorrhagic shock without resuscitation on expression of Toll-like receptor (TLR) in myocardium of rats and its significance. METHODS: Forty-five C57BL/6 mice were randomly divided into 3 groups: hemorrhagic group, sham operation group and lipopolysaccharide (LPS) group, with 15 mice in each group. The hemorrhagic shock mouse model was reproduced by heart puncture. Expression levels of TLR2 mRNA and TLR4 mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR). Left ventricular end-systolic pressure (LVESP) was determined and adopted as an index of left ventricle contractile function. RESULTS: (1)Both hemorrhagic shock and LPS challenge led to a reduction in arterial blood pressure in mice when compared with sham operation group. Both hemorrhagic shock and LPS challenge could result in left ventricle contractile dysfunction when compared with sham operation group. (2)Expression levels for TLR2 and TLR4 genes were upregulated in myocardium to various extents after hemorrhagic shock and LPS challenge, while in contrast the changes were absent in sham operation group. CONCLUSION: (1)The up-regulation of TLR2 and TLR4 genes is closely related with hemorrhagic shock and LPS-induced left ventricle contractile dysfunction, and there may exist a difference in signal transduction pathway between the two pathological conditions. (2)The host ability of innate immune response may be reinforced by the up-regulation of TLR2 and TLR4, whereas overexpression of them may also impair the function of tissues or organs.

[Effects of bisoprolol pretreatment on hypoxia/reoxygenation-induced injury in H9c2 cardiomyocytes].

OBJECTIVE: To investigated the effects of bisoprolol pretreatment on hypoxia/reoxygenation (H/R)-induced injury in H9c2 cardiomyocytes. METHODS: Cultured H9c2 cells were exposed to hypoxia for 6 h followed by reoxygenation for 2 h with or without pretreatments with bisoprolol or bisoprolol + LY294002. The cell survival was measured by MTT assay, and the cell apoptosis and levels of radical oxygen species (ROS) were evaluated with flow cytometry. The protein levels of phosphyorylated AKT and phosphorylated GSK3ß in the cells were determined by Western blotting. RESULTS: Compared with the normal control cells, the cells exposed to H/R injury showed significantly decreased cell survival and increased cell apoptosis and ROS production; pretreatment of the cells with bisoprolol significantly decreased the cell apoptotic rates and ROS production and obviously enhanced the cell survival and protein levels of p-AKT and p-GSK3ß in the exposed cells. The protective effect of bsioprolol against H/R-induced cell injury was significantly attenuated by LY294002. CONCLUSION: Bisoprolol can protect H9c2 cells against H/R-induced injury and oxidative stress by activating PI3K/AKT/Gsk-3ß pathway to increase the phosphorylation of AKT and GSK3ß and reduce ROS production.

Associations of C1q/TNF-Related Protein-9 Levels in Serum and Epicardial Adipose Tissue with Coronary Atherosclerosis in Humans.

OBJECTIVE: To investigate the correlation of CTRP9 with coronary atherosclerosis. METHODS: Coronary angiography confirmed CAD in 241 patients (62 received CABG) and non-CAD in 121 (55 received valve replacement). RESULTS: Serum levels of LDL-C, CRP, TNF-α, IL-6, and leptin in CAD patients were significantly higher than those in non-CAD patients (P < 0.05), but APN and CTRP9 were lower (P < 0.05). Serum levels of CTRP9 and APN were negatively related to BMI, HOMA-IR, TNF-α, IL-6, and leptin but positively to HDL-C (P < 0.05) in CAD patients. After adjustment of APN, CTRP9 was still related to the above parameters. Serum CTRP9 was a protective factor of CAD (P < 0.05). When compared with non-CAD patients, leptin mRNA expression increased dramatically, while CTRP9 mRNA expression reduced markedly in epicardial adipose tissue of CAD patients (P < 0.05). The leptin expression and macrophage count in CAD group were significantly higher than in non-CAD group, but CAD patients had a markedly lower CTRP9 expression (P < 0.05). CONCLUSIONS: Circulating and coronary CTRP9 plays an important role in the inflammation and coronary atherosclerosis of CAD patients. Serum CTRP9 is an independent protective factor of CAD.

Influence of phenotype conversion of epicardial adipocytes on the coronary atherosclerosis and its potential molecular mechanism.

OBJECTIVE: To investigate the phenotype conversion of epicardial adipocytes and its potential molecular mechanism during the occurrence and development of coronary atherosclerosis. METHODS: A total of 30 health male New Zealand white rabbits were used. In experiment group (n=15), rabbits were fed with high fat food to establish atherosclerosis animal model; rabbits in control group (n=15) were fed with normal food. RESULTS: At week 0, UCP-1 and PPARγ mRNA expressions in EAT and sBAT were significantly higher than in eWAT, and leptin mRNA expression lower than (P<0.05). In experiment group, the mRNA expressions of UCP-1 and PPARγ reduced gradually, but leptin mRNA increased progressively in EAT (P<0.05). UCP-1 expression reduced gradually, the newly generated blood vessels reduced significantly, but leptin and RAM11 increased gradually (P<0.05). The adipocyte volume in EAT increased gradually, but the adipocyte number reduced progressively (P<0.05). The number of mitochondria with multiple crests reduced gradually in EAT; IL-6 reduced the mRNA expressions of UCP-1 and PPARγ in adipocytes of BAT in a dose dependent manner, but it increased the mRNA expressions of leptin and STAT3 (P<0.05). In the presence of IL-6, JSI-124 increased the mRNA expressions of UCP-1 and PPAR-γ in adipocytes of BAT in a dose dependent manner, but it reduced the mRNA expressions of leptin and STAT3 (P<0.05). CONCLUSION: During the progression of atherosclerosis, there is a phenotype conversion of EAT from BAT to WAT, which further promotes the focal occurrence and development of atherosclerosis; IL-6 may activate JAK-STAT3 pathway to induce this conversion.

Influence of the ORM1 phenotypes on serum unbound concentration and protein binding of quinidine.

BACKGROUND: Only unbound or free drug in plasma can be transported to its site of action. The fraction of unbound drug in plasma varies widely for highly bound drugs among individuals. The genetic polymorphism of orosomucoid (ORM) could be related to the interindividual variability in plasma binding of basic drugs, as ORM is the transport protein for these drugs in plasma. The ORM is a major binding protein in plasma for various basic drugs and is coded by two loci, ORM1 and ORM2, which are closely linked on chromosome 9q31-->34.1. ORM1 locus is highly polymorphic and the ORM2 locus is monomorphic in most population. METHODS: Twenty-eight healthy volunteers were selected with three ORM1 phenotypes, containing homozygotes ORM1 F1 (n=10) and ORM1 S (n=8), and heterozygote ORM1 F1S (n=10), identified by isoelectric focusing on polyacrylamide gels followed immunoblotting after desialylation of sera. After a single oral dose of quinidine 200 mg, serum total (HPLC) and unbound concentrations in ultrafiltrate (ultrafiltration/HPLC) were determined, and the pharmacokinetic parameters and protein binding rate were calculated. RESULTS: Serum concentrations of ORM (553.8-573.2 mg/l) and albumin proteins (57.5-58.4 mg/l) were similar in the three groups (P>0.05). Unbound quinidine concentration in ORM1 F1 phenotype subjects was higher than that in ORM1 S and ORM1 F1S phenotype; the free drug percentage for the subjects with ORM1 F1 phenotype (19.79%) was twice as high as that with ORM1 S phenotype (10.96%) (P<0.01) at 24 h after administration of oral quinidine when the state of disposition equilibrium occurred. The elimination t(1/2) values and the other pharmacokinetic parameters of quinidine were not affected by the different ORM1 phenotypes. CONCLUSIONS: Different ORM1 phenotypes may affect the disposition of quinidine, a basic drug, rather than its hepatic metabolism and elimination. The functional heterogeneity of ORM1 could be responsible for the differences in plasma binding of quinidine. Therefore, monitoring of the unbound quinidine concentration would be important for the patients with different ORM1 phenotypes who are treated with quinidine.

[Impact of anti-OX-LDL antibodies on CD36 mRNA expression in monocytes].

AIM: To investigate the impact of antibodies to oxidized low-density lipoprotein (OX-LDL) on CD36 mRNA expression in monocytes and explore the mechanism underlying the impact on the formation of foam cells. METHODS: U937 cells and the monocytes of New Zealand rabbit were respectively cultured in vitro and divided into 4 groups: the control group (cultured in nutrient medium of RPMI1640), the OX-LDL group (with additional OX-LDL of 50 µg/L in nutrient medium), the OX-LDL+Ab-OX-LDL group (with additional OX-LDL of 50 µg/L and Ab-OX-LDL of 100 µg/L in nutrient medium) and the Ab-OX-LDL group (with additional Ab-OX-LDL of 100 µg/L in nutrient medium). After 24-hour culture, the expression of CD36 mRNA was detected by semi-quantitative RT-PCR. RESULTS: The expression of CD36 mRNA, either in the OX-LDL group or in the OX-LDL+Ab-OX-LDL group, was higher than that in the control group. After intervened by Ab-OX-LDL, the expression was respectively down-regulated by 64.80% in U937 cells and 35.18% in the monocytes of rabbit, which was statistically significant between the two species. CONCLUSION: Antibodies to OX-LDL could negatively regulate the expression of CD36 mRNA in monocytes, and prevent monocyte in taking OX-LDL through the pathway of antigen CD36.

Reversible cardiogenic shock caused by atrioventricular junctional rhythm after percutaneous coronary intervention.

An 82-year-old female patient undergoing cardiogenic shock caused by atrioventricular junctional rhythm immediately after percutaneous coronary intervention (PCI) is described. Pharmacotherapy was invalid, and subsequent application of atrial pacing reversed the cardiogenic shock. PCI-related injury of sinuatrial nodal artery leading to acute atrial contractility loss, accompanied by atrioventricular junctional arrhythmia, was diagnosed. We recommend that preoperative risk evaluation be required for multi-risk patients. Likewise, emergent measures should to be established in advance. This case reminds us that atrial pacing can be an optimal management technique once cardiogenic shock has occurred.

Lipoprotein(a) complexes with beta2-glycoprotein I in patients with coronary artery disease.

AIM: To investigate the possible mechanisms and association of increased complexes of ß(2)-glycoprotein I with lipoprotein(a) [ß(2)-GPI-Lp(a)] levels with the presence and extent of coronary artery disease (CAD). METHODS: ß(2)-GPI-Lp(a) levels were measured in 116 patients with acute coronary syndromes (ACS), 72 patients with stable CAD and 100 control subjects. RESULTS: Compared to the control, ß(2)-GPI-Lp(a) levels (expressed after logarithmically transformation: ACS, 0.22±0.45 U/mL; stable CAD, 0.05±0.55 U/mL; control, -0.31±0.61 U/mL) significantly increased in both patients with ACS (p <0.001) and stable CAD (p <0.001). Univariate logistic regression analysis of risk factors revealed that the presence of ß(2)-GPI-Lp(a), ox-Lp(a) or Lp(a) was a strong risk factor for stable CAD [ß(2)GPI-Lp(a), OR 3.17, 95% CI 1.65, 6.07; ox-Lp(a), OR 2.54, 95% CI 1.33, 4.85; Lp(a), OR 3.00, 95% CI 1.56, 5.75; respectively], and especially for ACS [ß(2)-GPI-Lp(a), OR 5.38, 95% CI 2.97, 9.74; ox-Lp(a), OR 7.55, 95% CI 4.12, 13.84; Lp(a), OR 4.33, 95% CI 2.40, 7.80; respectively]. In multivariate analysis, adjusting for age, sex and plasma lipid levels, the presence of ß(2)-GPI-Lp(a) or Lp(a) was a risk factor for both stable CAD and ACS. Ox-Lp(a) was a risk factor only for ACS, while not for stable CAD. ß(2)-GPI-Lp(a) levels were found to be positively associated with Lp(a), ox-Lp(a), maximal stenosis and a number of vessel diseases in patients with ACS or stable CAD, respectively. Multiple linear regression analysis found that ox-Lp(a) and maximal stenosis accounted for 46.2% of the variation in ß(2)-GPI-Lp(a) levels. CONCLUSIONS: Elevated levels of ß(2)-GPI-Lp(a) are associated with the presence and severity of CAD, and may be a strong risk factor for atherosclerosis.