Successful bailout stenting strategy against rare spontaneous retrograde dissection of partially absorbed magnesium-based resorbable scaffold: A case report.

BACKGROUND: In the development of coronary stent technology, bioresorbable scaffolds are promising milestones in improving the clinical treatment of coronary artery disease. The "leave nothing behind" motto is the premise of the fourth revolution in percutaneous coronary intervention (PCI). Studies proving the safety and efficacy of the magnesium-based resorbable scaffolds (MgBRSs) include the BIOSOLVE-I and BIOSOLVE-II trials and the latest BIOSOLVE-IV registry. However, spontaneous retrograde dissection of a partially absorbed MgBRS may still occur, albeit rarely. CASE SUMMARY: We describe an unusual case of coronary artery disease in a patient who had undergone a successful PCI 8 mo earlier, where an MgBRS was implanted into the left anterior descending artery (LAD) and left circumflex artery with drug-coated balloons for a ramus intermedius branch stenosis to achieve the "leave nothing behind" therapeutic intention and was currently presenting with a gradual worsening of chest tightness. The distal edge vascular response, during subsequent attempts with balloon angioplasty was performed smoothly. However, spontaneous retrograde dissection of a partially absorbed MgBRS in the LAD ensued. Successful bailout stenting was performed with revascularization of the entry and exit sites created by spontaneous dissection and complete sealing of the intramural hematoma. The patient recovered well and was discharged after 2 d of intervention. When followed up in August 2020 (7 mo later), the patient showed uneventful recovery. CONCLUSION: Spontaneous retrograde dissection of a partially absorbed MgBRS was successfully treated using bailout sirolimus-eluting coronary stent strategy.

Complete AV Block and Torsades de Pointes in a Case of Primary Cardiac T-Cell Lymphoma.

UNLABELLED: Primary cardiac lymphoma is very rare, and the most common electrocardiographic finding in this condition is complete atrioventricular block. After electrolytic, metabolic, ischemic, infectious, and traumatic etiologies have been excluded, primary cardiac lymphoma should be consided as a possible cause of reversible atrioventricular block. Most patients with primary cardiac lymphoma are immunocompromised and have disease with a B-cell etiology. This is the first case report of a primary cardiac T-cell lymphoma with complete atrioventricular block and torsades de pointes in an immunocompetent patient who was successfully treated using chemotherapy. KEY WORDS: Atrioventricular block; T-cell lymphoma; Torsades de pointes.

Gender and Age Differences in Short- and Long-Term Outcomes Following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Studies have reported that women with ST elevation myocardial infarction (STEMI) have worse short- and long-term outcomes than men. It has not yet been confirmed whether these differences reflect differences in age between men and women. METHODS: We retrospectively enrolled 1035 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Baseline clinical characteristics, coronary anatomy, and outcome were compared between young (< 65 years old) and older patients (≥ 65 years old) of both sexes. RESULTS: Younger women presented with a lower incidence of typical angina (83% vs. 93%, p = 0.03), single-vessel disease (21% vs. 35%, p = 0.03), and total occlusion of infarct-related artery (65% vs. 83%, p = 0.001) than younger men, with no gender difference noted in the older group. Younger women in the study had a higher incidence of reinfarction, heart failure requiring admission, or mortality (23% vs. 6%, p < 0.001) during follow-up, compared with younger men, with no gender difference in the older group. Using the Kaplan-Meier analysis, younger women had lower rates of event-free survival (p < 0.001 by log-rank test) than younger men, with no gender difference in the older group. In multivariate analysis, age could predict long-term outcome in men (Hazard ratio 4.43, 95% confidence interval: 2.89-6.78, p < 0.001) but not in women. CONCLUSIONS: In STEMI patients receiving primary PCI, sex-related long-term outcome differences were age-dependent, with younger women likely to have a worse long-term outcome when compared with younger men. KEY WORDS: Coronary heart disease; Gender; Myocardial infarction.

Diagnostic Performance of 64- versus 256-Slice Computed Tomography Coronary Angiography Compared with Conventional Coronary Angiography in Patients with Suspected Coronary Artery Disease.

PUPOSE: The newer 256-slice computed tomography coronary angiography (CTCA) has the capability of improving diagnostic performance in the detection of obstructive coronary artery disease (CAD) compared to 64-slice CTCA. The aim of this study was to compare the diagnostic performance of 64- versus 256-slice CTCA in two similar populations. METHODS: Our study included 120 consecutive patients who were referred for CTCA and subsequently underwent conventional coronary angiography (CCA). Sixty patients were studied by 64-slice CTCA, with the other 60 by 256-slice CTCA. We compared the technical characteristics and diagnostic performance of 64- and 256-slice CTCA for the detection of ≥ 50% stenosis of the coronary arteries on CCA. RESULTS: The 256-slice CTCA had a shorter scanning time (4.4 ± 0.6 sec vs. 5.0 ± 0.7 sec, p < 0.001) compared to 64-slice CTCA. The diagnostic accuracy rates of 256-slice CTCA based on patient analysis (97% vs. 83%, p < 0.05), vessel analysis (95% vs. 85%, p < 0.05), and segment analysis (94% vs. 88%, p < 0.05) were significantly superior to those of 64-slice CTCA. The diagnostic accuracy rates of 64- and 256-slice CTCA were affected by the presence of stent (65% vs. 75%, respectively, p > 0.05) and severe calcifications (75% vs. 82%, respectively, p > 0.05). CONCLUSIONS: In two similar populations, 256-slice CTCA displayed superior diagnostic performance than 64-slice CTCA. However, the performance of 256-slide CTCA is affected in those segments that are severely calcified and/or stented. KEY WORDS: Computed tomography coronary angiography (CTCA); Conventional coronary angiography; Diagnostic performance; 64-slice helical CTCA; 256-slice helical CTCA.

Infective endocarditis detected by ¹8F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in a patient with occult infection.

Integrated (18)F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG PET/CT) has been clinically used to detect infectious lesions. We present a case with pyrexia and bacteremia of unknown origin. Whole body FDG PET/CT was arranged to look for an occult source of infection and it revealed a focal lesion with increased FDG uptake in the mitral valve area. Under suspicion of infective endocarditis, transthoracic echocardiography was repeated and then the presence of linear vegetation over the calcified mitral annulus was confirmed. Ultimately, definite infective endocarditis was diagnosed according to the Duke criteria. The patient recovered after the antibiotic therapy. In our case, FDG PET/CT can help to localize the exact site of occult infection, thereby guiding additional testing and facilitating timely definitive diagnosis and therapy.

Gastrointestinal bleeding and outcomes after percutaneous coronary intervention for ST-segment elevation myocardial infarction.

BACKGROUND: Gastrointestinal bleeding is a hemorrhagic complication after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: To determine predictors of gastrointestinal bleeding and the impact of gastrointestinal bleeding on outcomes in STEMI patients undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: Gastrointestinal bleeding occurred in 18 (3.5%) of 519 consecutive patients with STEMI undergoing primary percutaneous coronary intervention. Univariate predictors of gastrointestinal bleeding were previous gastrointestinal bleeding (33% vs 4%, P < .001), impaired renal function (89% vs 37%, P<.001), Killip class IV at presentation (61% vs 18%, P<.001), higher peak creatinine kinase level (mean [SD], 3801.6 [3280.2] vs 2721.3 [2286.6] IU/L, P=.05), and mechanical ventilator support (44% vs 12%, P<.001). Coprescription of proton-pump inhibitors did not reduce the risk of gastrointestinal bleeding (22.2% vs 13.4%, P=.22). Multivariate analysis showed an odds ratio (95% confidence interval) for gastrointestinal bleeding of 22.1 (5.6-86.89, P<.001) for previous gastrointestinal bleeding, 6.74 (1.30-34.89, P=.02) for impaired renal function, and 4.68 (1.35-16.2, P=.01) for Killip class IV at presentation. Gastrointestinal bleeding was associated with longer intensive care unit stay (mean [SD], 5.4 [6.7] vs 3.6 [3.6] days, P=.04), and higher in-hospital (44% vs 9%, P<.001) and overall (44% vs 13%, P<.001) mortality rate. CONCLUSIONS: Although rare, gastrointestinal bleeding in patients with STEMI significantly prolongs intensive care unit stay and increases mortality. Previous gastrointestinal bleeding, impaired renal function, and Killip class IV at presentation are associated with higher incidence of gastrointestinal bleeding.

Long-term clinical outcomes following elective stent implantation for unprotected left main coronary artery disease.

BACKGROUND/PURPOSE: Percutaneous coronary intervention (PCI) has been increasingly adopted for unprotected left main coronary artery (LMCA) disease. The aim of this study was to evaluate the predictors of long-term clinical outcomes in patients after elective stent implantation for unprotected LMCA disease. METHODS: A total of 122 patients with medically refractory angina who received coronary stenting for unprotected LMCA disease between August 1997 and December 2008 were included. RESULTS: During the follow-up period of 45 ± 35 months (range: 1-137 months), the incidence of repeated PCI and/or coronary artery bypass grafting (CABG), and cardiovascular and total mortality were 28% (34 patients), 20% (24 patients), and 25% (31 patients), respectively. Multivariate analysis revealed that young age [p = 0.02; hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.11-4.30] and bare-metal stent (BMS) use (p = 0.02; HR: 5.35, 95% CI: 1.27-22.57) were the independent predictors of repeated PCI and/or CABG. Only lower left ventricular ejection fraction (LVEF) could predict both cardiovascular mortality (p = 0.003; HR: 4.25, 95% CI: 1.63-11.08) and total mortality (p = 0.002; HR: 3.95, 95% CI: 1.65-9.45). Lower LVEF (p = 0.001; HR: 0.31, 95% CI: 0.16-0.61) and small stent size (p = 0.01; HR: 5.95, 95% CI: 1.43-24.80) could predict the composite endpoint, including target vessel revascularization and total mortality. CONCLUSION: We showed that young age and BMS implantation could predict repeated PCI and/or CABG after stent implantation for unprotected LMCA disease. Only lower LVEF could predict both cardiovascular and total mortality. Lower LVEF and small stent size but not BMS implantation could predict composite target vessel revascularization/total mortality.

Nicorandil inhibits angiotensin-II-induced proliferation of cultured rat cardiac fibroblasts.

BACKGROUND/AIMS: Nicorandil, an ATP-sensitive potassium (K(ATP)) channel opener, nitric oxide (NO) donor and antioxidant, was shown to exert a variety of pharmacological effects including cardioprotective properties. However, its mechanisms of action are not completely understood. The aims of this study were to examine whether nicorandil may alter angiotensin-II (Ang II)-induced cell proliferation and to identify the putative underlying signaling pathways in rat cardiac fibroblasts. METHODS: Cultured rat cardiac fibroblasts were pretreated with nicorandil, then stimulated with Ang II, and cell proliferation and endothelin-1 (ET-1) expression were examined. The effects of nicorandil on Ang-II-induced reactive oxygen species (ROS) formation and extracellular signal-regulated kinase (ERK) phosphorylation were also examined. In addition, the effects of nicorandil on NO production and endothelial nitric oxide synthase (eNOS) phosphorylation were tested to elucidate the intracellular mechanism. RESULTS: Nicorandil (0.1-10 µmol/l) caused a concentration-dependent inhibition of Ang-II-increased cell proliferation and ET-1 expression which were prevented by the K(ATP) channel blocker glibenclamide (1 µmol/l). Nicorandil also inhibited Ang-II-increased ROS and ERK phosphorylation. In addition, nicorandil was found to increase the NO and eNOS phosphorylation. N-nitro-L-arginine methyl ester, an inhibitor of NOS, and the short interfering RNA transfection for eNOS markedly attenuated the inhibitory effect of nicorandil on Ang-II-induced cell proliferation. CONCLUSION: Our results suggest that nicorandil prevents cardiac fibroblast proliferation, and the inhibitory effect might be associated with the opening K(ATP) channels, by interfering with the generation of ROS, and the activation of the eNOS-NO pathway.

Incidence, predictors and outcomes of subacute stent thrombosis following primary stenting for ST-elevation myocardial infarction.

BACKGROUND/PURPOSE: Knowledge concerning subacute stent thrombosis (SST) following primary stenting for ST-elevation myocardial infarction (STEMI) is not widely available. We studied the incidence, predictors, and clinical outcomes of SST following STEMI. METHODS: We analyzed data from 455 consecutive patients who underwent primary stenting for STEMI. Baseline clinical characteristics, coronary angiographic features, medication and outcome were compared in patients with and without SST. RESULTS: SST occurred in 17 patients, and the incidence was 3.7%. Univariate predictors of SST were being a current smoker (53.0%vs. 82.4%, p = 0.01), Killip class >or= II (38.4%vs. 58.8%, p = 0.05), no coronary re-flow after stenting (6.2%vs. 17.6%, p = 0.05) and lack of coprescription with a statin (39.5%vs. 5.9%, p<0.01). After multivariate analysis, being a current smoker (odds ratio = 4.76; 95% confidence interval 1.20-18.95) and using statin therapy (odds ratio = 0.09; 95% confidence interval = 0.01-0.75) were independent correlates of SST. Patients with SST were associated with higher 30-day mortality (37.5%vs. 3.1%, p<0.01) and all-cause mortality (23.5%vs. 5.3%, p = 0.01) at long-term follow-up. CONCLUSION: Although SST is rare in patients with STEMI treated by primary stenting, it imparts a significantly higher mortality at short-term and long-term follow-up. Being a current smoker and the lack of co-prescription with a statin were associated with higher incidence of SST. Our results suggest initiation of statin therapy in patients with STEMI should be considered before discharge.

Acute ST-elevation myocardial infarction in young patients: 15 years of experience in a single center.

BACKGROUND: There have been few studies done regarding young patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate the clinical characteristics and coronary angiographic features in young patients with STEMI. METHODS: We collected data on 849 consecutive patients with STEMI from 1992 to 2006. Baseline clinical characteristics, coronary anatomy, and outcome were compared in young (< or =45 yrs) and older patients (>45 yrs). RESULTS: Young patients presented 11.6% of all patients with STEMI. These patients were predominantly male (92.9% vs 80.3%, P < 0.001), more likely to smoke (75.8% vs 47.2%, P < 0.001), obese (48.2% vs 27.9%, P = 0.002), have higher triglyceride levels (176.9 +/- 153.8 mg/dL vs 140.7 +/- 112.7 mg/dL, P = 0.005), and lower high-density lipoprotein cholesterol (37.1 +/- 7.9 mg/dL vs 42.8 +/- 14.3 mg/dL, P = 0.005) than older patients. Also, younger patients had a shorter hospital stay (7.1 +/- 4.9 d vs 8.5 +/- 6.7 d, P = 0.04), less in-hospital morbidity (29.3% vs 39.7%, P = 0.02), and mortality (3.0% vs 12.3%, P = 0.002). Killip class III or IV could predict in-hospital morbidity and mortality in young patients. Both groups had similar rates of repeated percutaneous coronary intervention (PCI; 45.5% vs 41.5%, P = 0.23) and reinfarction (6.1% vs 3.2%, P = 0.32). Mortality rate during follow-up was significantly lower in younger patients (3.0% vs 19.6%, P < 0.001). CONCLUSION: Cigarette smoking, obesity, and dyslipidemia were the most important modifiable risk factors in young patients with STEMI. These patients had a better outcome than older patients without differences in repeated PCI and reinfarction between them. Only Killip class III or IV could predict in-hospital morbidity and mortality in young patients with STEMI.

Significance of left circumflex artery-related acute myocardial infarction without ST-T changes.

INTRODUCTION: Left circumflex (LC)-related acute myocardial infarction (AMI) presenting without ST-T changes has been underdiagnosed in the emergency department. There is little information on its clinical features and significance. AIMS: The aims of the study were to investigate the clinical characteristics and outcomes of LC-related AMI without ST-T changes. POPULATION AND METHODS: Ninety-six patients were admitted for LC-related AMI. Comparisons between those with and without ST-T changes were analyzed. RESULTS: Twenty-two patients (23%) did not have ST-T changes, whereas 74 patients (77%) had them. Patients without ST-T changes had younger age (55.6 + or - 16.8 vs 62.6 + or - 12.0 years, P = .03), fewer presented as Killip III/IV (4.5% vs 27.4%, P = .02) and with lower creatine kinase (1647.3 + or - 1602.2 vs 2778.2 + or - 2343.3 IU/L, P = .037) and creatine kinase-MB (136.8 + or - 130.3 vs 247.7 + or - 200.0 IU/L, P = .017), and more were with concurrent culprit lesion in the middle or distal LC and right- or balanced-dominant coronary circulation (86.4% vs 44.6%, P < .001). During follow-up, the need for repeat percutaneous coronary intervention (48.6% vs 45.5%, P = .40) and recurrent infarction (13.5% vs 13.6%, P = .62) were similar between the 2 groups. The 30-day mortality (0% vs 5.4%, P = .35) and overall mortality rate (4.5% vs 12.2%, P = .28) between them were not different statistically. CONCLUSION: The relatively lower prevalence of LC-related AMI without ST-T changes in the study might be underestimated. These patients have smaller infarct size than patients with ST-T changes without differences in the short- and long-term outcomes between them.

Magnolol depresses urotensin-II-induced cell proliferation in rat cardiac fibroblasts.

1. Accumulating evidence suggests that oxidative stress plays a key role in the development of cardiac fibrosis. Urotensin-II (U-II) has been reported to play an important role in cardiac remodelling and fibrosis. Recently, we demonstrated the involvement of reactive oxygen species (ROS) production in U-II-induced cardiac fibroblast proliferation. Magnolol is an anti-oxidant compound extracted from the cortices of Magnolia officinalis. Thus, it is feasible that magnolol may attenuate cardiac fibroblast proliferation by inhibiting ROS production. Therefore, the aims of the present study were to determine whether magnolol alters U-II-induced cell proliferation and to identify the putative underlying signalling pathways in rat cardiac fibroblasts. 2. Cultured rat cardiac fibroblasts were pretreated with magnolol (1, 3 and 10 micromol/L) for 30 min, followed by exposure to U-II (30 nmol/L) for 24 h, after which cell proliferation and endothelin-1 (ET-1) protein secretion was examined. The effects of magnolol on U-II-induced ROS formation and extracellular signal-regulated kinase (ERK) phosphorylation were examined to elucidate the intracellular mechanisms by which magnolol affects cell proliferation and ET-1 expression. 3. Urotensin-II (30 nmol/L) stimulated cell proliferation, ET-1 protein secretion and ERK phosphorylation, all of which were inhibited by magnolol (10 micromol/L). Pretreatment of cardiac fibroblasts with N-acetylcysteine (5 mmol/L) for 30 min prior to exposure to U-II resulted in inhibition of U-II increased ROS formation. Similar effects were observed with 10 micromol/L magnolol. 4. In conclusion, the results suggest that magnolol inhibits cardiac fibroblast proliferation by interfering with ROS generation. Thus, the present study provides important new insights into the molecular pathways involved, which may contribute to our understanding of the effects of magnolol on the cardiovascular system.

Angiographic and clinical manifestations of coronary fistulas in Chinese people: 15-year experience.

BACKGROUND: Coronary artery fistula (CAF) is an anomaly resulting in the steal phenomenon of coronary blood flow, which may cause morbidity or mortality. CAFs in Chinese patients after long-term follow-up of 15 years were retrospectively analyzed. METHODS AND RESULTS: From September, 1992 to August, 2007, 152 CAFs were detected in 28,210 coronary angiograms from 125 patients. Clinical and angiographic data of all patients were analyzed retrospectively. Two types of CAFs were characterized: type I in 99 patients with 124 solitary coronary to cardiac chamber or great vessel fistula; type II: 26 patients with 28 coronary artery--left ventricular multiple microfistulas. Single-, double-, and triple-CAFs were detected in 79%, 20%, and 1% of patients, respectively. Coexistent coronary lesions were noted in 41% of patients. Fistula-related symptoms included stable angina in 55, myocardial infarction in 2, heart failure in 2, sudden death with ventricular fibrillation in 1, and syncope in 1. Twenty-four patients had coexistent congenital anomalies. Only 9 patients underwent coronary intervention or/and surgery for CAFs. CONCLUSIONS: CAFs may cause trivial or lethal cardiac events, and may coexist with coronary lesion or congenital anomaly. Coronary to cardiac chamber or great vessel fistula and coronary-left ventricular multiple microfistulas have different morphologic and pathological phenomena.

Correlation of intraoperative blood flow measurement with autogenous arteriovenous fistula outcome.

BACKGROUND: Autogenous arteriovenous fistula (AVF) has proven to be the optimal vascular access for the majority of hemodialysis patients due to its durability and low complication rates. The purpose of this study is to determine the value of intraoperative blood flow measurement with respect to AVF short-term outcome. METHODS: A prospective cohort study enrolled patients undergoing first time AVF creation surgery for hemodialysis from November 2001 to April 2007. Intraoperative blood flow measurements were collected using transit time flowmeter, and primary and secondary patency rates of AVF were examined. Other variables including age, sex, the presence of diabetes, hypertension, or cerebrovascular disease, current smoking, systolic and diastolic blood pressure, heart rate, serum calcium-phosphate product, and triglyceride and cholesterol level were analyzed. RESULTS: Autogenous radiocephalic AVFs (n = 109) in 109 patients were constructed and followed up for an average of 21 months. Among these, 54% of patients were 60 years or older, 51% were male, and 56% were diabetics. One-year primary and secondary patency rates for the high-flow group (> or =200 mL/min) were 69% and 94%, respectively. One-year primary and secondary patency rates for the low-flow group (<200 mL/min) was 52% and 80%, respectively. Using hazard analysis, intraoperative blood flow was the most important determinant of primary and secondary patency, in addition to the presence of diabetes. CONCLUSION: Intraoperative blood flow measurement is a predictor of the primary and secondary patency of autogenous radiocephalic AVFs. Awareness of the significant correlation between intraoperative AVF blood flow and the short-term outcome would enhance the surgical efficiency and maximize the usefulness of autogenous AVF.

Predictors of long-term outcomes in patients after elective stent implantation for unprotected left main coronary artery disease.

The purpose of this study was to investigate the predictor of long-term outcomes in patients after stent implantation for unprotected left main coronary artery (LMCA) disease. Coronary stenting has recently been advocated as an alternative procedure for LMCA disease. Information on the predictors of long-term outcomes in patients after stent implantation for unprotected LMCA disease is not clear. Seventy six patients (51 men and 25 women, age 68 +/- 10 years) with medically refractory angina received coronary stenting for unprotected LMCA disease. During a follow-up period of 40 +/- 26 months, 7 patients (9%) died because of cardiovascular disease in 5 (7%) and noncardiovascular disease in 2 (3%). In the other 69 patients, 19 patients (25%) needed repeated percutaneous coronary intervention (PCI) and/or coronary artery bypass grafting (CABG). In a univariate analysis, only female sex was related to the repeated PCI and/or CABG (P = 0.04). A history of cerebral vascular attack (CVA) (P = 0.005), anemia (P = 0.03) and lower left ventricular ejection fraction (LVEF) (P = 0.008) were related to the cardiovascular mortality. A history of myocardial infarction (P = 0.03), a history of CVA (P = 0.02), anemia (P = 0.02), and lower LVEF (P = 0.002) were related to the total mortality. In a multivariate analysis, female sex (P = 0.007; odds ratio 5.29, 95% confidence interval [CI] 1.57-17.80) and young age (P = 0.025; odds ratio 3.92, 95% CI 1.19-12.98) could predict the repeated PCI and/or CABG. Only a history of CVA could predict the cardiovascular mortality (P = 0.027; odds ratio 34.18, 95% CI 1.49-783) and only lower LVEF could predict the total mortality (P = 0.027; odds ratio 13.26, 95% CI 1.34-131). Female sex and young age could predict the repeated PCI and/or CABG in patients after stent implantation for unprotected LMCA disease. Furthermore, a history of CVA could predict the cardiovascular mortality and lower LVEF could predict the total mortality.

Hypertension due to co-existing paraganglioma and unilateral adrenal cortical hyperplasia.

A rare case of combined unilateral adrenal hyperplasia and paraganglioma is reported. A 27-year-old woman presented with hypertension, palpitation, dizziness, and headache for about 3 months. Elevated plasma aldosterone with low renin and a high level of urine vanillylmandelic acid (VMA) were found. Computed tomography showed a microadenoma of the left adrenal gland and a well demarcated left retroperitoneal para-aortic mass. Adrenal vein sampling for aldosterone and renin levels suggested left adrenal lesion. Surgical removal of the left adrenal gland and para-aortic mass was performed. Pathologic examination of the resected left adrenal gland showed adrenal cortical hyperplasia and the left retroperitoneal para-aortic mass showed a paraganglioma. Postoperatively, blood pressure, plasma renin, aldosterone and urine VMA all returned to within normal ranges. The possible relationship of these two diseases is discussed.

Pericardial fluid and serum levels of vascular endothelial growth factor and endostatin in patients with or without coronary artery disease.

BACKGROUND/PURPOSE: Vascular endothelial growth factor (VEGF) and endostatin are related to ischemic heart disease. This study investigated pericardial fluid and serum levels of VEGF and endostatin in patients with or without ischemic heart disease. METHODS: A total of 39 patients (24 patients in the CAD group with significant coronary artery disease; 15 patients in the non-CAD group without coronary artery disease) undergoing open heart surgery were enrolled. In the CAD group, patients were classified according to good coronary collateralization (Group A; n = 11) or poor coronary collateralization (Group B; n = 13). Pericardial fluid and serum samples were obtained at the time of surgery. VEGF and endostatin were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of endostatin in both serum and pericardial fluid were significantly lower in the CAD group than in the non-CAD group (130.5 +/- 37.3 ng/mL vs. 172.4 +/- 37.8 ng/mL and 119.0 +/- 25.0 ng/mL vs. 143.0 +/- 23.5 ng/mL). The concentration of serum VEGF in the CAD group (92.6 +/- 18.2 pg/mL) was significantly higher than that in the non-CAD group (75.2 +/- 22.3 pg/mL). The concentration of serum VEGF in Group A (100.1 +/- 20.7 pg/mL) was significantly higher than that in Group B (84.3 +/- 12.4 pg/mL). The levels of pericardial fluid VEGF, serum and pericardial fluid endostatin were not significantly different between Groups A and B. CONCLUSION: Patients with coronary artery disease have lower serum and pericardial fluid levels of endostatin and higher serum levels of VEGF. Serum level VEGF, but not endostatin, is associated with good or poor collateralization in patients with coronary artery disease.

Carvedilol prevents cardiac hypertrophy and overexpression of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in pressure-overloaded rat heart.

The use of beta-blockers has emerged as a beneficial treatment for cardiac hypertrophy. Hypoxia-inducible factor-1alpha (HIF-1alpha) is tightly regulated in the ventricular myocardium. However, the expression of HIF-1alpha in cardiac hypertrophy due to pressure overload and after treatment with beta-blocker is little known. To evaluate the effect of carvedilol on both myocardial HIF-1alpha expression and cardiac hypertrophy, infra-renal aortic banding was performed for 4 weeks in adult Sprague-Dawley rats to induce cardiac hypertrophy. Carvedilol at 50 mg/kg body weight per day after surgery was given. Heart weight and the ratio of heart weight and body weight increased significantly after aortic banding for 4 weeks in the absence of drug treatment. Mean arterial pressure increased from 80 +/- 9 mmHg in the sham group to 94 +/-5 mmHg (p < 0.001) in the banding group. Echocardiography showed concentric hypertrophy after aortic banding. Mean arterial pressure decreased after treatment with carvedilol. The increased wall thickness and heart weight was reversed to normal by carvedilol. Western blot showed that HIF-1alpha, vascular endothelial growth factor (VEGF) and brain natriuretic peptide (BNP) proteins were up-regulated and nerve growth factor-beta (NGF-beta) down-regulated in the banding group. Treatment with valsartan, doxazosin, or N-acetylcysteine did not significantly affect HIF-1alpha and VEGF proteins expression in the banding groups. Real-time polymerase chain reaction showed that mRNA of HIF-1alpha, VEGF and BNP increased and mRNA of NGF-beta decreased in the banding group. Treatment with carvedilol reversed both protein and mRNA of HIF-1alpha, VEGF, BNP, and NGF-beta to the baseline values. Increased immunohistochemical labeling of HIF-1alpha, VEGF, and BNP in the ventricular myocardium was observed in the banding group and carvedilol again normalized the labeling. In conclusion, HIF-1alpha, VEGF, and BNP mRNA and protein expression were up-regulated, while NGF-beta mRNA and protein was downregulated in the rat model of pressure-overloaded cardiac hypertrophy. Treatment with carvedilol is associated with a reversal of abnormal regulation of HIF-1alpha, VEGF, BNP, and NGF-beta in the hypertrophic myocardium.

Role of mitogen-activated protein kinase pathway in reactive oxygen species-mediated endothelin-1-induced beta-myosin heavy chain gene expression and cardiomyocyte hypertrophy.

Endothelin-1 (ET-1) has been found to increase cardiac beta-myosin heavy chain (beta-MyHC) gene expression and induce hypertrophy in cardiomyocytes. ET-1 has been demonstrated to increase intracellular reactive oxygen species (ROS) in cardiomyocytes. The exact molecular mechanism by which ROS regulate ET-1-induced beta-MyHC gene expression and hypertrophy in cardiomyocytes, however, has not yet been fully described. We aim to elucidate the molecular regulatory mechanism of ROS on ET-1-induced beta-MyHC gene expression and hypertrophic signaling in neonatal rat cardiomyocytes. Following stimulation with ET-1, cultured neonatal rat cardiomyocytes were examined for 3H-leucine incorporation and beta-MyHC promoter activities. The effects of antioxidant pretreatment on ET-1-induced cardiac hypertrophy and mitogen-activated protein kinase (MAPKs) phosphorylation were studied to elucidate the redox-sensitive pathway in cardiomyocyte hypertrophy and beta-MyHC gene expression. ET-1 increased 3H-leucine incorporation and beta-MyHC promoter activities, which were blocked by the specific ET(A) receptor antagonist BQ-485. Antioxidants significantly reduced ET-1-induced 3H-leucine incorporation, beta-MyHC gene promoter activities and MAPK (extracellular signal-regulated kinase, p38, and c-Jun NH2 -terminal kinase) phosphorylation. Both PD98059 and SB203580 inhibited ET-1-increased 3H-leucine incorporation and beta-MyHC promoter activities. Co-transfection of the dominant negative mutant of Ras, Raf, and MEK1 decreased the ET-1-induced beta-MyHC promoter activities, suggesting that the Ras-Raf-MAPK pathway is required for ET-1 action. Truncation analysis of the beta-MyHC gene promoter showed that the activator protein-2 (AP-2)/specificity protein-1 (SP-1) binding site(s) were(was) important cis-element(s) in ET-1-induced beta-MyHC gene expression. Moreover, ET-1-induced AP-2 and SP-1 binding activities were also inhibited by antioxidant. These data demonstrate the involvement of ROS in ET-1-induced hypertrophic responses and beta-MyHC expression. ROS mediate ET-1-induced activation of MAPK pathways, which culminates in hypertrophic responses and beta-MyHC expression.

Berberine inhibits HIF-1alpha expression via enhanced proteolysis.

We have studied the antiangiogenic property of berberine. We showed that berberine could directly inhibit in vitro human umbilical vein endothelial cell (HUVEC) tube formation and migration. In addition, to determine whether berberine could influence the cross-talk between the gastric adenocarcinoma cell line SC-M1 and vascular endothelial cells, we performed modified confrontation culture experiments and showed that berberine (7.5 microM, 16 h) could inhibit the capacity of hypoxic SC-M1 cells to stimulate HUVEC migration. These results demonstrated berberine's antiangiogenic property and its clinical potential as an inhibitor of tumor angiogenesis. Parallel Western blot analyses revealed that berberine prevented hypoxic SC-M1 cultures from expressing vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha, two key factors in mediating tumor angiogenesis. However, overexpression of HIF-1alpha in SC-M1 cells dramatically reversed the inhibitory effect of berberine on SC-M1-induced in vitro HUVEC migration. These data indicated that HIF-1alpha repression is a critical step in the inhibitory effect of berberine on tumor-induced angiogenesis. Northern blot analyses plus pulse-chase assays revealed that berberine did not down-regulate HIF-1alpha mRNA but destabilized HIF-1alpha protein. We found that berberine-induced HIF-1alpha degradation was blocked by a 26S proteasome inhibitor. Moreover, immunoprecipitation and Western blot analyses showed that berberine increased the lysine-acetylated HIF-1alpha in hypoxic SC-M1 cultures. These data indicated that a proteasomal proteolytic pathway and lysine acetylation were involved in berberine-triggered HIF-1alpha degradation. In conclusion, our data provided molecular evidence to support berberine as a potent antiangiogenic agent in cancer therapy.