Effects of sleep deprivation on action potential and transient outward potassium current in ventricular myocytes in rats.

BACKGROUND: Sleep deprivation contributes to the development and recurrence of ventricular arrhythmias. However, the electrophysiological changes in ventricular myocytes in sleep deprivation are still unknown. MATERIAL AND METHODS: Sleep deprivation was induced by modified multiple platform technique. Fifty rats were assigned to control and sleep deprivation 1, 3, 5, and 7 days groups, and single ventricular myocytes were enzymatically dissociated from rat hearts. Action potential duration (APD) and transient outward current (Ito) were recorded using whole-cell patch clamp technique. RESULTS: Compared with the control group, the phases of APD of ventricular myocytes in 3, 5, and 7 days groups were prolonged and APD at 20% and 50% level of repolarization (APD20 and APD50) was significantly elongated (The APD20 values of control, 1, 3, 5, and 7 days groups: 5.66±0.16 ms, 5.77±0.20 ms, 8.28±0.30 ms, 11.56±0.32 ms, 13.24±0.56 ms. The APD50 values: 50.66±2.16 ms, 52.77±3.20 ms, 65.28±5.30 ms, 83.56±7.32 ms, 89.24±5.56 ms. P<0.01, n=18). The current densities of Ito significantly decreased. The current density-voltage (I-V) curve of Ito was vitally suppressed downward. The steady-state inactivation curve and steady-state activation curve of Ito were shifted to left and right, respectively, in sleep deprivation rats. The inactivation recovery time of Ito was markedly retarded and the time of closed-state inactivation was markedly accelerated in 3, 5, and 7 days groups. CONCLUSIONS: APD of ventricular myocytes in sleep deprivation rats was significantly prolonged, which could be attributed to decreased activation and accelerated inactivation of Ito.

Systematic study of the effects of lowering low-density lipoprotein-cholesterol on regression of coronary atherosclerotic plaques using intravascular ultrasound.

BACKGROUND: Conflicting results currently exist on the effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque, and the target level of LDL-C resulting in the regression of the coronary atherosclerotic plaques has not been settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Jan. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. Data concerning the study design, patient characteristics, and outcomes were extracted. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. SMD were calculated using fixed or random effects models. RESULTS: Twenty trials including 5910 patients with coronary heart disease were identified. Mean lowering LDL-C by 45.4% and to level 66.8 mg/dL in the group of patients with baseline mean LDL-C 123.7 mg/dL, mean lowering LDL-C by 48.8% and to level 60.6 mg/dL in the group of patients with baseline mean LDL-C 120 mg/dL, and mean lowering LDL-C by 40.4% and to level 77.8 mg/dL in the group of patients with baseline mean LDL-C 132.4 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.108 mm3, 95% CI -0.176 ~ -0.040, p = 0.002; SMD -0.156 mm3, 95% CI -0.235 ~ -0.078, p = 0.000; SMD -0.123 mm3, 95% CI -0.199 ~ -0.048, p = 0.001; respectively). LDL-C lowering by rosuvastatin (mean 33 mg daily) and atorvastatin (mean 60 mg daily) could significantly decrease the volumes of CAP at follow up (SMD -0.162 mm3, 95% CI: -0.234 ~ -0.081, p = 0.000; SMD -0.101, 95% CI: -0.184 ~ -0.019, p = 0.016; respectively). The mean duration of follow up was from 17 ~ 21 months. CONCLUSIONS: Intensive lowering LDL-C (rosuvastatin mean 33 mg daily and atorvastatin mean 60 mg daily) with >17 months of duration could lead to the regression of CAP, LDL-C level should be reduced by >40% or to a target level <78 mg/dL for regressing CAP.

[Tirofiban improved the prognosis of senior acute coronary syndrome patients received percutaneous coronary intervention].

OBJECTIVE: To examine if tirofiban may improve the prognosis in aged acute coronary syndrome (ACS) patients received percutaneous coronary intervention (PCI). METHODS: Three hundred and twenty-five ACS patients (age ≥ 60 years), all received drug-eluting stents implantation, were assigned into tirofiban group (n = 210) to receive tirofiban+aspirin and clopidogrel and control group (n = 115) to received aspirin and clopidogrel only. The incidence of thrombolysis in myocardial infarction (TIMI) grade 3 after PCI, in-stent thrombosis, slight/severe bleeding, platelet decrease, myocardial infarction (MI) and target vessel revascularization (TVR) within 30 days and 12 months after PCI and 30 days and 12 months mortality post PCI. RESULTS: In comparison with the control group, the tirofiban group had significantly higher TIMI grade 3 flow after PCI (99.05% vs. 94.78%, P < 0.05), lower in-stent thrombosis (0.47% vs. 2.61%, P < 0.05), as well as lower mortality, MI, and TVR in 30 days and 12 months after PCI (30 days: 0, 0.47% and 0.47% vs. 2.61%, 3.48% and 2.61%; 12 months: 0, 0.47% and 0.47% vs. 2.61%, 5.22% and 5.22%, P < 0.05 or P < 0.01). No significant difference was found (both P > 0.05) in slight bleeding (7.14% vs. 4.35%) and severe bleeding (0 vs. 0) between tirofiban group and control group. A slight difference in thrombocytopenia was found between tirofiban group and control group (0.95% vs. 0), but it failed to reach the level of statistical significance (P > 0.05). CONCLUSIONS: Tirofiban may improve the TIMI grade flow in senior ACS patients after PCI. It also decreases the incidence of in-stent thrombosis, mortality, MI, and TVR in 30 days and 12 months after PCI, without causing increase in severe bleeding and platelet penia. Therefore, it may improve the short/long-term prognosis for these patients.

The efficacy of the figure-of-eight suture technique in the treatment of tunnel bleeding of the femoral artery route after percutaneous coronary intervention or angiography.

OBJECTIVE: To evaluate the efficacy of the figure-of-eight (FOE) suture technique in the treatment of tunnel bleeding after femoral artery puncture compared with manual compression (MC). METHODS: This prospective, randomized, controlled study enrolled patients that had received transfemoral coronary artery angiography or percutaneous coronary intervention and then developed tunnel bleeding. They were randomly assigned into two groups: FOE suture group (ES group) and manual compression group (MC group). Total treatment time, performance frequency, performance time, rate of deep vein thrombosis (DVT) and in-hospital time after the procedure were compared. RESULTS: A total of 152 patients were enrolled in the study (ES group, n = 63; MC group, n = 89). Compared with the MC group, the total treatment time (mean ± SD: ES 22.3 ± 5.4 h versus MC 26.8 ± 6.8 h), performance frequency (mean ± SD: ES 2.1 ± 0.7 versus MC 2.6 ± 1.1), performance time (mean ± SD: ES 8.9 ± 2.5 min versus MC 12.3 ± 4.1 min), in-hospital time after the procedure (mean ± SD: ES 3.5 ± 1.2 days versus MC 4.8 ± 2.1 days) and DVT rate (ES 0.0% versus MC 6.7%) were significantly lower in the ES group. CONCLUSION: The FOE suture technique effectively treated tunnel bleeding after femoral artery puncture.

[Influence of cyclosporine A on atrial L-type calcium channel alpha1c subunit in a canine model of atrial fibrillation].

OBJECTIVE: To investigate the impact of cyclosporine A (CsA) on atrial expression change of L-type calcium channel alpha1c subunit in a canine model of atrial fibrillation (AF). METHODS: AF was induced by rapid atrial pacing (400 beats/min) for 8 weeks in adult male dogs and placebo (n = 6) or CsA (5 mg x kg(-1) x d(-1), n = 6) were orally administered to these animals. Sham operated animals served as normal controls (n = 6). The atrial electrophysiological parameters including P wave duration, atrial effective refractory period (AERP) were recorded and analyzed at baseline and 8 weeks later. Animals were scarified at 8 weeks post final electrophysiological examinations and atrial expressions of L-type calcium channel alpha1c subunit were determined by Western blot. RESULTS: Compared to sham group, the P wave duration was significantly prolonged while AERP was significantly decreased in AF and CsA groups (all P < 0.05). AERP was significantly longer in CsA group than that in AF group (P < 0.05). L-type calcium channel alpha1c subunit expression was significantly downregulated in AF group compared to sham group (P < 0.05) and CsA significantly attenuated this downregulation (P < 0.01 vs. AF group). CONCLUSION: CsA could attenuate the downregulation of the L-type calcium channel alpha1c subunit expression and improve the atrial electrophysiological remodeling in this canine model of AF.

[Safety and efficacy comparison between rapamycin-eluting stent with biodegradable polymer or permanent polymer in patients with coronary artery disease].

OBJECTIVE: To evaluate the safety and efficacy of rapamycin-eluting stent with biodegradable polymer (EXCEL) or permanent polymer (Cypher) in patients with coronary artery disease (CAD). METHODS: In this prospective, non-random and comparative study, 60 patients with CAD were divided into EXCEL group (n = 32) and Cypher group (n = 28). The coronary angiography (CAG) and stenting procedure were identical. The safety and efficacy of EXCEL stent was evaluated by major adverse cardiac events (MACE), restenosis rate and percent diameter stenosis rate as well as late luminal loss (LLL) at six months post stenting. RESULTS: During follow-up (mean: 6.04 +/- 2.12 months), there was no MACE in the two groups. Quantitative coronary angiography (QCA) data at 6.0 +/- 2.1 months post stenting were available in 27 patients (84.38%) in EXCEL group and 10 patients (35.71%) in Cypher group. Restenosis rate was zero in both groups. Percent diameter stenosis rate (5.98% +/- 5.52% vs. 5.21% +/- 6.3%) and LLL (-0.02 +/- 0.09 mm vs. -0.01 +/- 0.07 mm) were similar between the 2 groups. CONCLUSIONS: EXCEL stent was safe for the treatment of CAD and comparable as Cypher stent in preventing MACE and restenosis at 6 months post stenting.

Additional manual thrombus aspiration for ST-segment elevation myocardial infarction during percutaneous coronary intervention: an updated meta-analysis.

BACKGROUND: The clinical efficacy and safety of adjunctive thrombus aspiration (TA) in patients with ST-segment elevation myocardial infarction (STEMI) during percutaneous coronary intervention (PCI) remain controversial. METHODS: Twenty five eligible randomized controlled trials were included to compare the use of thrombus aspiration (TA) with PCI and PCI-only for STEMI. The primary endpoint was all-cause mortality and death. The secondary endpoints were major adverse cardiac events (MACE), recurrent infarction (RI), target vessel revascularization (TVR), stent thrombosis (ST), perfusion surrogate markers and stroke. RESULTS: TIMI flow grade 3 and MBG 2-3 were significantly increased in the TA plus PCI arm compared with the PCI-only arm [relative risk (RR): 1.05, 95% confidence intervals (CI): 1.02-1.09, P = 0.004] and (RR: 1.68, 95% CI: 1.40-2.00, P < 0.001), respectively. There were no significant differences in all-cause mortality, MACEs, TVR and ST rates between the two groups. The RI rate was lower in the TA plus PCI arm than that in the PCI-only arm with short-term follow-up duration (RR: 0.60, 95% CI: 0.38-0.96, P = 0.03), but there was no significant difference in RI incidence over the medium- or long-term follow-up periods (RR: 1.00, 95% CI: 0.77-1.29, P = 0.98), and (RR: 0.96, 95% CI: 0.81-1.15, P = 0.69), respectively. There were statistically significant differences in the rates of crude stroke and stroke over the medium- or long-term follow-up periods and the crude stroke rate in the TA plus PCI (RR: 1.60, 95% CI: 1.08-2.38, P = 0.02) and (RR: 1.43, 95% CI: 1.03-1.98, P = 0.03), respectively; this was not observed between the two arms during the short-term follow-up period (RR: 1.47, 95% CI: 0.97-2.21, P = 0.07). CONCLUSIONS: Routine TA-assisted PCI in STEMI patients can improve myocardial reperfusion and get limited benefits related to the clinical endpoints, which may be associated with stroke risk.

[Mechanism of percutaneous myocardial laser revascularization in the treatment of experimental cardiac ischemia].

OBJECTIVE: To evaluate the cardiac angiogenesis after percutaneous myocardial laser revascularization (PMR). METHODS: The left anterior descending coronary arteries of 10 healthy mongrel dogs weighing 14 - 18 kg were ligated partially so as to construct a model of chronic cardiac ischemia. Then the dogs were randomly divided into 2 groups of 5 dogs: PMR and control groups. Cardiogenesis Holmium: YAG laser system was used to make endomyocardial channels (15 +/- 3 channels/dog) in the ischemic ventricular walls in PMR group 2 weeks after the ligation. Sham procedure was conducted on the control group. Myocardial perfusion was examined by single photon emission computed tomography (SPECT) and left ventricle ejection fraction (LVEF) was examined by cardiac ultrasound before the ligation and 1, 4, and 12 weeks after PRM in the PMR group and before and 3, 6, and 14 weeks after the ligation in the control group. In the PRM group one dog was killed after the SPECT and LVEF examination 1 and 4 weeks after the PRM respectively and the remaining 3 dogs were killed after the SPECT and LVEF examination 12 weeks after the PRM. The dogs in the control group were killed after the SPECT and LVEF examination 14 weeks after the ligation. Myocardial pathology and cardiac angiogenesis analysis were conducted in both groups. RESULTS: Three months after PMR or coronary artery ligation, the SPECT scores of the PMR and control groups decreased from 3.2 +/- 0.6 and 3.1 +/- 0.5 to 0.3 +/- 0.2 and 1.2 +/- 0.3 respectively (both P < 0.05), the LVEF of the 2 groups increased from 42.6 +/- 6.5 and 43.2 +/- 8.7 to 55.8 +/- 7.6 and 42.6 +/- 6.5 respectively (both P < 0.05). Microscopy showed that the amount of micrangii was 45.6 +/- 7.4 vessel/field in the PMR region of the PRM group, significantly much more than that in the non-ischemic region of the PRM group (18.2 +/- 4.7), the ischemic region of the control group (21.4 +/- 5.6), and the non-ischemic region of the control group (17.3 +/- 6.9, all P < 0.05). CONCLUSION: PMR promotes angiogenesis in the ischemic myocardial wall, thus improving the blood perfusion of ischemic myocardium and global cardiac systolic function.

[Clinical features and treatment of cardiogenic shock complicated with acute myocardial infarction].

OBJECTIVE: To identify the clinical features and the outcome of patients with cardiogenic shock complicating acute myocardial infarction (AMI). METHODS: One hundred and eight consecutive patients with AMI were included in this retrospective analysis. The characteristics, management, and outcome of patients with AMI were compared between patients with cardiogenic shock (group A, n=11) and without cardiogenic shock (group B, n=9). RESULTS: There was no difference in the age and other characteristics including proportion of women, diabetics, prior myocardial infarction and the position of myocardial infarction. The levels of peak creatine kinase and troponin I were (31979.7+/-22271.1)nmol x s(-1) x L(-1) and (90.7+/-61.1) microg/L respectively in group A, they were higher than those in group B (17795.2+/-14979.7)nmol.s-1.L-1 and (39.9+/-52.1) microg/L, respectively (both P<0.05). The left ventricular ejection fraction was significantly lower in group A than that in group B (0.46+/-0.12 vs. 0.55+/-0.12, P<0.05). Patients in group A had a higher proportion of pump failure, arrhythmia and pneumonia (64% vs. 14%, P<0.001; 55% vs. 21 %, P<0.05; and 46% vs. 12%, P<0.01, respectively) than those in group B. In addition, in group A patients often underwent thrombolysis of urokinase, coronary angiography and intra-aortic balloon counterpulsation (46% vs. 18%, 73% vs. 26% and 36% vs. 4%, all P<0.05, respectively). There was no difference in in-hospital mortality between group A and group B (0 vs. 4%, P>0.05). CONCLUSION: Shock patients more likely have pump failure, arrhythmia, and pneumonia and more often underwent intra-aortic balloon counterpulsation. If cardiogenic shock complicating AMI is managed with rapid evaluation and prompt initiation of supportive measures and definitive therapy, outcomes can be improved.

Radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia guided by magnetic navigation system: a prospective randomized comparison with conventional procedure.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is one of the most common paroxysmal supraventricular tachyarrhythmias. The aim of the study was to prospectively compare the characteristics of radiofrequency catheter ablation of AVNRT guided by a magnetic navigation system with the conventional procedure. METHODS: Patients with AVNRT diagnosed by electrophysiological tests were randomized into two groups. In the conventional technique group (CMT), a common 4-mm-tip quadrapolar temperature-controlled ablation catheter was used. In the magnetic navigation system guidance group (MNS), a magnetic 4-mm-tip quadrapolar temperature-controlled ablation catheter was used. The following parameters were collected and compared between the two groups: ablation procedure time, patient fluoroscopy time, operator fluoroscopy time, energy delivery numbers, maximal energy per deployment, success rate, complication rate and operative cost. RESULTS: Forty patients were enrolled and randomized into CMT and MNS groups. The age, gender, tachycardia history and basic cardiovascular diseases of the two groups were comparable (P > 0.05). All procedures were conducted successfully without complications. No tachycardia recurred during the follow-up period of (9.3 ± 2.6) months. In the MNS group, the patient and operator fluoroscopy times ((11.5 ± 4.3) min, (4.2 ± 1.5) min), energy delivery numbers (3.2 ± 0.9), and maximal energy per deployment ((16.9 ± 3.4) W) were shorter or lower than those of the CMT group ((14.3 ± 6.2) min, (13.6 ± 3.5) min, 6.3 ± 2.1, (23.7 ± 1.3) W, respectively) (P < 0.05). But the operative cost for the MNS group was higher than that of the CMT group (P < 0.01). CONCLUSION: Magnetic navigation system guided radiofrequency catheter ablation of AVNRT has the advantages of shorter fluoroscopy time and lower energy delivery numbers and maximal energy per deployment compared to the present conventional ablation technique.

Chronic kidney disease: an independent risk factor of all-cause mortality for elderly Chinese patients with chronic heart failure.

OBJECTIVE: To evaluate the prognostic value of chronic kidney disease (CKD) in elderly Chinese patients with chronic heart failure (CHF). METHODS: The study consisted of 327 elderly patients with CHF. All-cause mortality was chosen as an endpoint over the median follow-up period of 345 days. Cox regression analysis was used to identify the risk factors of mortality. RESULTS: The median age of the entire cohort was 85 years (60-100 years). The mortality for 168 elderly patients with CHF and CKD (51.4% of entire cohort) was 39.9% (67 deaths), which was higher than the mortality for CHF patients without CKD [25.2% (40/159 deaths)] and the mortality for entire cohort with CHF [32.7% (107/327 deaths)]. The Cox regression analysis showed that old age [hazard ratio (HR): 1.033; 95% confidence interval (95% CI): 1.004-1.064], CKD (HR: 1.705; 95% CI: 1.132-2.567), CHF New York Heart Association (NYHA) class IV (HR: 1.913; 95% CI: 1.284-2.851), acute myocardial infarction (AMI) (HR: 1.696; 95% CI: 1.036-2.777), elevated resting heart rate (HR: 1.021; 95% CI: 1.009-1.033), and decreased plasma albumin (HR: 0.883; 95% CI: 0.843-0.925) were independent risk factors of mortality for elderly patients with CHF. CONCLUSIONS: CKD was an independent risk factor of mortality for elderly Chinese patients with CHF.

Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A.

BACKGROUND: Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported. METHODS: Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium. RESULTS: Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles -CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses. CONCLUSIONS: Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.

[Effect of phosphatase PHLPP1 gene transfer on the proliferation of human umbilical vein endothelial cells].

OBJECTIVE: To investigate the constituent expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) in human umbilical vein endothelial cells (HUVECs) and the effect of PHLPP1 gene transfer on the proliferation of the cells in vitro. METHODS: Cultured HUVECs were transfected with pcDNA3-GFP or pcDNA3HA-PHLPP1 via lipofectamine 2000. The cell proliferation ability was determined by cell counting and MTT colorimetric assay, and Western blotting was used to detect the protein expression of PHLPP1 in the cells. RESULTS: No PHLPP1 protein was detected in the non-transfected cells or pcDNA3-GFP-transfected cells. pcDNA3HA-PHLPP1 gene transfection significantly increased PHLPP1 expression in the HUVECs (P<0.01), but the cell proliferation status remained unchanged (P>0.05). The absorbance of the cells measured by MTT assay was 0.134-/+0.0152, 0133-/+0.014 and 0.137-/+0.016, with cell counts of (8.293-/+0.962)x10(5), (7.937-/+0.101)x10(5) and (8.127-/+0.112)x10(5), respectively, showing no significant differences between the 3 groups (P>0.05). CONCLUSIONS: Phosphatase PHLPP1 may not be the most important signal protein in the regulation of HUVEC proliferation.