Xanthine-based KMUP-1 improves HDL via PPARγ/SR-B1, LDL via LDLRs, and HSL via PKA/PKG for hepatic fat loss.

The phosphodiesterase inhibitor (PDEI)/eNOS enhancer KMUP-1, targeting G-protein coupled receptors (GPCRs), improves dyslipidemia. We compared its lipid-lowering effects with simvastatin and explored hormone-sensitive lipase (HSL) translocation in hepatic fat loss. KMUP-1 HCl (1, 2.5, and 5 mg/kg/day) and simvastatin (5 mg/kg/day) were administered in C57BL/6J male mice fed a high-fat diet (HFD) by gavage for 8 weeks. KMUP-1 inhibited HFD-induced plasma/liver TG, total cholesterol, and LDL; increased HDL/3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)/Rho kinase II (ROCK II)/PPARγ/ABCA1; and decreased liver and body weight. KMUP-1 HCl in drinking water (2.5 mg/200 ml tap water) for 1-14 or 8-14 weeks decreased HFD-induced liver and body weight and scavenger receptor class B type I expression and increased protein kinase A (PKA)/PKG/LDLRs/HSL expression and immunoreactivity. In HepG2 cells incubated with serum or exogenous mevalonate, KMUP-1 (10(-7)∼10(-5) M) reversed HMGR expression by feedback regulation, colocalized expression of ABCA1/apolipoprotein A-I/LXRα/PPARγ, and reduced exogenous geranylgeranyl pyrophosphate/farnesyl pyrophosphate (FPP)-induced RhoA/ROCK II expression. A guanosine 3',5'-cyclic monophosphate (cGMP) antagonist reversed KMUP-1-induced ROCK II reduction, indicating cGMP/eNOS involvement. KMUP-1 inceased PKG and LDLRs surrounded by LDL and restored oxidized LDL-induced PKA expresion. Unlike simvastatin, KMUP-1 could not inhibit (14)C mevalonate formation. KMUP-1 could, but simvastatin could not, decrease ROCK II expression by exogenous FPP/CGPP. KMUP-1 improves HDL via PPARγ/LXRα/ABCA1/Apo-I expression and increases LDLRs/PKA/PKG/HSL expression and immunoreactivity, leading to TG hydrolysis to lower hepatic fat and body weight.

Impact of chronic kidney disease in early invasive versus early conservative revascularization strategies in non-ST-segment elevation acute coronary syndromes: a population-based study from NHIRD of Taiwan.

BACKGROUND: Patients with chronic kidney disease (CKD) sustaining a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are considered high risk and an early invasive strategy (EIS) is often recommended. However, the impact of CKD on patients receiving an EIS or an early conservative strategy (ECS) is unclear in real-world practice. METHODS: Data were analyzed from the 2005-2008 National Health Insurance Research Database (NHIRD) in Taiwan. The diagnosis of CKD was based on the International Classification of Disease-9 codes recorded by physicians. EIS was defined as coronary angiography with intent to revascularization performed within 72 h of symptom onset. The primary endpoint was time to first major adverse cardiac event (MACE) comprising cardiovascular death, myocardial infarction (MI) and stroke. The secondary endpoints included major bleeding (MB), heart failure (HF) and dialysis during admission (DDA). RESULTS: 834 patients (466 EIS and 368 ECS) were enrolled and age was 64.3 ± 12.6 years. Mean follow-up time was 1,163.96 ± 19.99 days. In the whole population an EIS was associated with a reduction in MACE (HR 0.69; 95% CI 0.50-0.95, p = 0.024) but not in the CKD population (HR 1.08; 95% CI 0.66-1.78, p = 0.76). Kaplan-Meier curves showed CKD subjects receiving an EIS had the highest MACE, HF and DDA rate (all p < 0.019) and CKD subjects receiving an ECS had the highest MB rate (p = 0.018). Cox regression analysis showed CKD predicted higher HF and DDA in those receiving an EIS and higher DDA and MB in those receiving an ECS. CONCLUSION: An EIS reduced MACE in the overall population, and CKD was a poor outcome predictor for both revascularization strategies in NSTE-ACS.

Impact of short-duration administration of N-acetylcysteine, probucol and ascorbic acid on contrast-induced cytotoxicity.

BACKGROUND: The best pharmaceutical prevention of contrast-medium-induced nephropathy for emergency procedures remains unknown. The aim of this study was to examine the impact of short-duration antioxidant pretreatment on contrast-medium-induced cytotoxicity. METHODS: Human embryonic kidney cells were treated with three different contrast media: ionic ioxitalamate, non-ionic low-osmolar iopromide, and iso-osmolar iodixanol. The doses and durations of pretreatment with antioxidants were 2 mM/L N-acetylcysteine for 15 minutes, 40 µM/L probucol for 30 minutes, and 30 µM/L ascorbic acid for 30 minutes. A supplementary dose of 2 mM/L N-acetylcysteine was administered 12 hours after contrast medium treatment. Cell viability was determined by tetrazolium MTT assay. RESULTS: All three contrast media caused significant reduction of cell viability at 24 hours (p<0.001). In the groups receiving iopromide or iodixanol, N-acetylcysteine pretreatment significantly improved cell viability compared with no N-acetylcysteine pretreatment (p<0.001). In the group receiving ioxitalamate, N-acetylcysteine pretreatment followed by a supplementary dose of N-acetylcysteine at 12 hours rather than N-acetylcysteine pretreatment alone significantly improved cell viability compared with no N-acetylcysteine pretreatment (p=0.038). Probucol or ascorbic acid pretreatment was unable to reduce cell death caused by the three contrast media. CONCLUSIONS: Short-duration pretreatment with N-acetylcysteine significantly reduced contrast-medium-induced cytotoxicity. These findings provide new insight into the prevention of contrast-medium-induced nephropathy in clinical emergency scenarios.

Acupuncture-induced popliteal arteriovenous fistula successfully treated with percutaneous endovascular intervention.

A 39-year-old female visited our cardiovascular outpatient department with paresthesia and soreness around the right popliteal fossa, where thrill was palpable. There was no history of trauma, apart from her having undergone acupuncture several years previously. An arteriovenous fistula (AVF) was diagnosed by vascular ultrasonography and magnetic resonance imaging. Angiography confirmed the presence of an AVF fed by the medial geniculate artery. Transarterial embolization was performed to close the AVF using coils and tissue adhesive. To the best of our knowledge, acupuncture-induced AVF has not been previously reported. We present a case demonstrating the merits of percutaneous endovascular intervention for treating this rare complication. The additional administration of a tissue adhesive can achieve complete closure of the AVF in the event of an unsatisfactory result following coil embolization. Doctors should be aware of the potential vascular complications of acupuncture, and of the management options.

Effects of heart rate on brachial-ankle pulse wave velocity and ankle-brachial pressure index in patients without significant organic heart disease.

This study evaluated the effects of heart rate (HR) on brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI). Thirty-two patients without significant organic heart disease underwent elective cardiac catheterization or electrophysiologic study, and were then enrolled in right atrial pacing (RAP; 11 men, 9 women; aged 48 -/+ 15 years) or right ventricular pacing (RVP; 6 men, 6 women, aged 45 -/+ 13 years) studies. Three different HR levels (90, 100, and 110 beats per minute) were paced in random order. By stepwise, multiple linear regression analysis, age, systolic blood pressure (SBP), and pulse pressure (PP) correlated positively with baseline baPWV. In the RAP group, as HR increased, baPWV and left brachial diastolic blood pressure increased significantly (p < or = 0.015), while ABI, left ankle SBP, left brachial PP, and left ankle PP decreased significantly (p < or = 0.013). In the RVP group, as HR increased, baPWV also increased significantly (p = 0.001), while ABI, left ankle SBP, and PP decreased significantly (p < or = 0.034). Values of baPWV and ABI may be influenced by HR in young and middle-aged patients without significant organic heart disease. When these values are used to evaluate and follow up cardiovascular risk in patients, HR changes should be considered.

Effects of right bundle branch block during atrioventricular nodal reentrant tachycardia.

BACKGROUND: The significant role of bundle branch block during atrioventricular nodal reentrant tachycardia (AVNRT) is not clear. The purposes of this study were to study the effects of complete right bundle branch block (RBBB) on electrophysiological parameters during AVNRT and to define the significance of complete RBBB during AVNRT. METHODS AND RESULTS: According to characteristics of electrocardiogram during sinus rhythm and AVNRT, 50 patients who underwent catheter ablation for slow-fast AVNRT were divided into three groups. Group I included 20 patients who had narrow QRS (< or = 110 ms) during sinus rhythm and AVNRT. Group II included 18 patients who had persistent RBBB (< or = 120 ms) during sinus rhythm and AVNRT. Group III included 12 patients who had narrow QRS during sinus rhythm, but they had narrow QRS and transient RBBB during AVNRT. The atrio-His (AH) interval (296+/-60 vs. 288+/-75 ms), His-ventricular (HV) interval (36+/-11 vs. 35+/-11 ms), His-atrial (HA) interval (72+/-24 vs. 71+/-28 ms), VA(HRA) interval (defined as the interval between the onset of ventricular depolarization and the onset of atrial activity of right high atrium; 34+/-24 vs. 37+/-25 ms), VA(CSO) interval (defined as the interval between the onset of ventricular depolarization and the onset of atrial activity of coronary sinus ostium; 13+/-28 vs. 26+/-23 ms) and tachycardia cycle length (TCL; 368+/-67 vs. 359+/-73 ms) during AVNRT were similar between group I and group II (all P > 0.05). In group III, the AH interval (255+/-81 vs. 246+/-83 ms), HV interval (44+/-5 vs. 42+/-11 ms), HA interval (66+/-19 vs. 70+/-15 ms), VA(HRA) interval (27+/-15 vs. 29+/-16 ms), VA(CSO) interval (23+/-25 vs. 21+/-25 ms) and TCL (322+/-76 vs. 316+/-77 ms) were not significantly different between AVNRT with narrow QRS and those with transient RBBB (all P > 0.05). CONCLUSIONS: Persistent RBBB and transient RBBB have no significant effects on the electrophysiological parameters during AVNRT. These findings suggest that RBBB might not influence the conduction of lower common pathway or the circuit of AVNRT.

Choosing calcium channel blockers for pregnant women with paroxysmal supraventriclar tachycardia and preterm labor: a case report.

Preterm labor is a major clinical hazard causing both maternal and neonatal morbidity and mortality. Paroxysmal supraventricular tachycardia (PSVT) complicated by preterm labor is rare. Of the many drugs used to treat PSVT, only calcium channel blockers are tocolytics. Here, we present the case of a 29-year-old female admitted to our ward with previously diagnosed PSVT and preterm labor at 31 weeks' gestation of her fourth pregnancy. Calcium channel blockers were administered and her uterine contractions subsided. Afterwards, no side effects were noted and she suffered no further tachycardic attacks during her pregnancy. She successfully delivered a full-term baby and received subsequent regular follow-up at the outpatient clinic.

Effect of electrophysiologic character of ventricular premature beat on heart rate turbulence.

Heart rate turbulence (HRT) has been described as a predictor of high-risk patients with cardiac diseases. The purpose of this study is to determine how the degree of prematurity of a ventricular premature beat (VPB%) and retrograde ventriculoatrial (VA) conduction of VPBs affect HRT. We studied 30 patients without organic heart disease. We calculated turbulent slope (TS) and turbulent onset (TO) from VPBs induced by programmed stimulation from the right ventricular apex. TS was inversely and TO was positively correlated to VPB%. Without retrograde VA conduction of VPBs, TS was inversely and TO was positively correlated to VPB%. In VPBs with retrograde VA conduction, there were no significant correlations between TO and TS with VPB%. In conclusion, TS and TO calculated from VPBs with different degrees of prematurity varied widely. Both VPB% and characteristics of retrograde VA conduction may affect HRT.