Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Acute hemodynamic impact of atrioventricular delay and left ventricular pacing vector programming in MultiPoint Pacing.

BACKGROUND: The benefits of cardiac resynchronization therapy (CRT) in heart failure patients have been shown to depend on device programming, particularly atrioventricular delay (AVD) and left ventricular (LV) pacing site selection. This study compared the hemodynamic AVD optimization for commonly used biventricular (BiV) and MultiPoint Pacing(MPP, Abbott) LV vector selection strategies. METHODS: After de novo CRT-D (Abbott Quadra Assura MP) and quadripolar LV lead (Abbott Quartet) implant, acute LV pressure was measured across a range of AVDs (60-225 ms) in four pacing modes: BiV with most proximal cathode, BiV with most distal cathode, MPP using two cathodes with earliest and latest right ventricle (RV)-LV activation times, and MPP using two cathodes with maximal anatomical separation. Hemodynamic improvement was evaluated by changes in maximum LV pressure first-derivative versus RV pacing (ΔdP/dt). RESULTS: Twenty patients (64 years old, 68% male) completed the acute pacing protocol at six centers in China. Hemodynamic improvement versus RV pacing for BiV (proximal), BiV (Distal), MPP (electrical), and MPP (anatomical) was 22.1% ± 13.6%, 23.7% ± 13.4%, 24.5% ± 13.4%, and 25.1% ± 13.9%, respectively. The best MPP setting was marginally superior to the best BiV across all patients (25.8% ± 13.4% vs. 24.5% ± 13.1%, p = .040) and in the majority of patients (75.0% vs. 25.0%, p = .004). AVD programmed as little as 20 ms from optimum significantly reduced the ΔdP/dt benefit for all modes. CONCLUSIONS: The maximal hemodynamic improvement across AV delays in this population was greater with MPP than BiV. Furthermore, patient-specific AVD programming was critical in achieving the full hemodynamic response for all BiV and MPP modes.

Left ventricular-only fusion pacing versus cardiac resynchronization therapy in heart failure patients: A randomized controlled trial.

BACKGROUND: It is unclear whether clinical benefits of cardiac resynchronization can be achieved by pacing only the left ventricle. HYPOTHESIS: We aimed to compare the effect of a novel adaptive left ventricular-only fusion pacing (LVP) on ventricular function with conventional biventricular pacing (BVP) in cardiac resynchronization therapy (CRT) indicated patients. METHODS: This prospective, randomized, multicenter study enrolled CRT-indicated patients with PR interval ≤ 200 ms who were randomized in the adaptive LVP group (using the AdaptivCRT™ algorithm with intentional non-capture right ventricular pacing) or the echocardiography-optimized BVP group. Cardiac function and echocardiography were evaluated at baseline and follow-ups. CRT super response was defined as two-fold or more increase of left ventricular ejection fraction (LVEF) or final LVEF >45%, and LV end-systolic volume (LVESV) decrease >15%, and New York Heart Association (NYHA) class improved by at least one level. RESULTS: Sixty-three patients were enrolled in the study (LVP = 34 vs. BVP = 29). At 6-month follow-up, significant improvements in LVEF, LVESV, and NYHA class were observed in both groups. The CRT super response rate was significantly higher in patients with high-percentage adaptive LV-only pacing in LVP group (68.4%) than in BVP group (36.4%, p = .04). CONCLUSIONS: Adaptive LV-only pacing was comparable to BVP in improving cardiac function and clinical condition in CRT-indicated patients. This finding raises the possibility that an adaptive LVP algorithm with appropriate right ventricular sensing to fuse with intrinsic right ventricular activation in a two-lead (right atrium and left ventricle) device may provide clinical benefit in a subset of CRT patients with intact atrioventricular conduction.

Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Prognostic value of von Willebrand factor in patients with atrial fibrillation: A meta-analysis.

BACKGROUND: Studies on the prognostic role of von Willebrand factor (vWF) in patients with atrial fibrillation (AF) are conflicting. This meta-analysis aimed to evaluate the association of elevated circulating vWF level with adverse outcomes in patients with AF. METHODS: PubMed and Embase were used to search literature through August 2017. Prospective observational studies that evaluated the association of elevated vWF level with major adverse cardiac events (MACEs) and all-cause mortality in patients with AF were deemed eligible. The MACEs included death, stroke/transient ischemic attack, heart failure, myocardial infarction, and systemic/peripheral embolism. RESULTS: A total of 6 studies were included this meta-analysis. Patients with AF with the highest vWF level were independently associated with greater risk of MACEs (risk ratio [RR] 2.20; 95% confidence intervals [CI] 1.61-3.01) and all-cause mortality (RR 1.63; 95% CI 1.39-1.91). Subgroup analysis showed that the prognostic role of higher vWF level was consistently observed in each defined subgroups. CONCLUSION: Patients with AF with elevated vWF level are independently associated with a higher risk of MACEs and all-cause mortality. However, more well-designed prospective studies are needed to confirm these findings.

Evaluation of the therapeutic effects of QuickOpt optimization in Chinese patients with chronic heart failure treated by cardiac resynchronization.

In this trial, long-term therapeutic effects and clinical improvements in Chinese chronic heart failure patients optimized by QuickOpt or echocardiography were compared for atrioventricular (AV) and interventricular (VV) delay optimizations after cardiac resynchronization therapy (CRT) with pacing (CRT-P) or with pacing and defibrillator (CRT-D) therapy. One hundred and ninety-six subjects (50%) had dilated cardiomyopathy, 108 (27.6%) had ischemic heart disease and 112 (28.6%) were hypertensive and were randomized into QuickOpt (198) or echocardiographic optimization (control) (194) groups at ≤2-weeks post-implantation. Programmed AV/VV delay was optimized at baseline and at 3 and 6 months. Left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) class, specific activity scale (SAS), and the six-minute walk tests (6MWT) were evaluated by blinded researchers at 12 months. Of the QuickOpt group, LVESV decreased significantly by 24.7% ± 33.9% compared with baseline, while LVESV of Controls decreased by 25.1% ± 36.1% (P = 0.924). NYHA class, SAS and 6MWT also improved similarly in both groups at 12 months. Mortality in both groups was not significantly different (11.0% vs 7.6%, P = 0.289). However, there was a significant difference in the time required for optimization by QuickOpt compared with echocardiography (3.33 ± 3.11 vs 58.79 ± 27.03 minutes, P < 0.000).

[Efficacy comparison between 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension].

OBJECTIVE: To compare the efficacy and safety of 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension. METHODS: The study was designed as multicenter, randomized, double-blind, active controlled trial with two parallel groups enrolling 524 participants with mild to moderate essential hypertension. After 2-week run-in period, 186 patients were enrolled and randomly treated with 5 mg perindopril arginine salt and 183 patients were enrolled and randomly treated with 4 mg perindopril tert-butylamine salt. The random sequence was generated by the I.R.I.S., and a balance was made in each center. After double-blind treatment for 8 weeks, the dose could be doubled for patients with uncontrolled BP ((SBP) ≥ 140 mmHg (1 mmHg = 0.133 kPa) or diastolic blood pressure (DBP) ≥ 90 mmHg) and patients were treated for another 4 weeks. RESULTS: The sitting SBP was similarly decreased by (19.9 ± 17.2) mmHg in perindopril arginine group and (18.5 ± 14.7) mmHg (P = 0.000 5) in perindopril tert-butylamine group post 8 weeks treatment. Dose was doubled in 109 patients (59.9%) in perindopril arginine group and 116 patients (63.7%) in perindopril tert-butylamine group. At 12 weeks post therapy, the sitting SBP decreased by (19.8 ± 16.2) and (19.6 ± 16.3) mmHg respectively in the 2 groups. The decrease of sitting DBP was also similar in both groups (-12.0 ± 10.0) mmHg and (-11.0 ± 8.9) mmHg (P < 0.000 1), respectively. The control rate or response rate was also similar between the two groups (control rate over 8 weeks was 38.5% vs. 31.3%, 95% CI (-2.6-16.9), control rate over 12 weeks was 36.3% vs. 35.7%, 95% CI (-9.3-10.4), response rate over 8 weeks was 64.3% vs. 63.2%, 95% CI (-8.8-11.0), response rate over 12 weeks was 65.9% vs. 64.8%, 95% CI (-8.7-10.9)). Incidence of adverse events was low and similar in both therapy groups. CONCLUSIONS: The results show that perindopril arginine salt 5 mg is as efficient as perindopril tert-butylamine 4 mg on lowering BP for patients with mild to moderate essential hypertension. Both drugs have good safety profile and are well tolerated by patients in this cohort.

Reduction of unnecessary right ventricular pacing by managed ventricular pacing and search AV+ algorithms in pacemaker patients: 12-month follow-up results of a randomized study.

AIMS: The present study was to assess the reduction of right ventricular pacing (RVP) by pacemaker algorithms of Managed Ventricular Pacing (MVP) and Search AV+ (SAV+) interval over a period of 12 months. METHODS AND RESULTS: A total of 385 patients indicated for a dual-chamber pacemaker (DC-PM) were enrolled in the prospective, randomized COMPARE study at 29 centres in China between June 2009 and April 2011. Patients implanted with DC-PMs were randomized in a 1 : 1 ratio to the MVP group or the SAV+ group. The percentage of VP (%VP) was obtained from the device diagnostic data at 1-, 6-, and 12-month follow-ups and was expressed as the median %VP over all beats in patients with sinus node dysfunction (SND) and atrioventricular block (AVB) excluding persistent third-degree AVB. Of 385 enrolled patients, 253 had SND and 72 had AVB. The %VP in the MVP group was significantly lower than that in the SAV+ group at 1-, 6-, and 12-month follow-ups, respectively. At 12-month follow-up, the median %VP in SND patients was 0.20% in the MVP group and 1.4% in the SAV+ group (P < 0.0001) and the median %VP in AVB patients was 11.8% in the MVP group and 98.1% in the SAV+ group (P < 0.001). There was no statistical difference in %VP from 1- to 12-month follow-up. A trend in the correlation between %VP and AT/AF burden was observed. CONCLUSION: Over 12-month follow-up, the %VP was lower for MVP than SAV+ in patients with either SND or AVB. The sustainable %VP reduction has potential implications in reducing the development of heart failure and/or atrial arrhythmia morbidity.

Reduction of atrial fibrillation in remotely monitored pacemaker patients: results from a Chinese multicentre registry.

BACKGROUND: Many recipients of implantable cardiac electronic devices have atrial fibrillation (AF) occurrences after device implantation, even if there is no previous history of AF, and some of the episodes are asymptomatic. The purpose of this study was to evaluate trends in AF burden following early AF detection in patients treated with pacemakers equipped with automatic, daily Home Monitoring function. METHODS: Between February 2009 and December 2010, the registry recruited 701 pacemaker patients (628 dual-chamber, 73 biventricular devices) at 97 clinical centers in China. Daily Home Monitoring data transmissions were analyzed to screen for the AF burden. In-office follow-ups were scheduled for 3 and 6 months after implantation. Upon first AF (i.e., mode-switch) detection in a patient, screening of AF burden by Home Monitoring was extended for the next 180 days. RESULTS: At least one episode of AF was observed in 22.9% of patients with dual-chamber pacemakers and in 28.8% of patients with biventricular pacemakers. The first AF detection in a patient occurred, on average, about 2 months before scheduled follow-up visits. In both pacemaker groups, mean AF burden decreased significantly (P < 0.05) over 180 days following first AF detection: from 12.0% to 2.5% in dual-chamber and from 12.2% to 0.5% in biventricular pacemaker recipients. The number of patients with an AF burden >10% per month was significantly reduced over 6 months of implantation in both dual chamber (38 patients in the first month vs. 21 patients in month 6, P < 0.05) and biventricular (7 patients in the first month vs. 0 patient in months 4-6, P < 0.05) pacemaker recipients. CONCLUSIONS: Automatic, daily Home Monitoring of patients treated with cardiac pacemakers allows early detection of AF, and there is a gradual and significant decrease in AF burden.

[Efficacy of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm post cardioverter-defibrillators implantation].

OBJECTIVE: To evaluate the acute and long-term effects of catheter radiofrequency ablation for the treatment of ventricular arrhythmia storm (VAS) post implantable cardioverter-defibrillators (ICD) implantation. METHODS: Acute and long-term effects of catheter radiofrequency ablation for the treatment of VAS post ICD implantation were retrospectively assessed in 11 patients from September 2008 to August 2011. RESULTS: A total of 15 ablation procedures were performed in 11 patients. Six ablation procedures were performed through epicardial approach. In 9 patients, 20 types of ventricular tachycardia (VT) (including 20% hemodynamically unstable VT) were induced during the procedures [mean cycle length (384 ± 141) ms] and polymorphic ventricular tachycardia were induced in 7 patients. The average X-ray fluoroscopy time and procedural time were (26 ± 17) min and (189 ± 60) min, respectively. Complete success, partial success, and failure rates immediately post catheter radiofrequency ablation were 46.7% (7/15), 26.7% (4/15) and 26.7% (4/15), respectively. All patients are alive at follow-up[(2.45 ± 9.6) months after the last catheter ablation] and the complete success, partial success, and failure rates during follow-up were 72.7% (8/11), 9.1% (1/11) and 18.2% (2/11), respectively. CONCLUSION: VAS can be effectively treated by catheter radiofrequency ablation in patients post ICD implantation.

Gorham-Stout syndrome in mainland China: a case series of 67 patients and review of the literature.

OBJECTIVE: Gorham-Stout syndrome (GSS) is a rare disorder of uncertain etiology and unpredictable prognosis. This study aims to present a comprehensive understanding of this rare entity. METHODS: A literature search in PubMed and three Chinese databases was performed to screen histologically proven GSS cases among Chinese residents in the mainland. We analyzed the patients' clinical characteristics, the value of different treatment modalities and their influence on the clinical outcome. RESULTS: Sixty-seven cases were finally enrolled. There were 43 men (64.2%) and 24 women (35.8%). The mean age at diagnosis was 28 years (1.5-71 years). The most common clinical symptoms included pain (n=40, 59.7%), functional impairment (n=13, 19.4%), and swelling (n=12, 17.9%). The radiographic presentation of 37 cases (55.2%) was disappearance of a portion of the bone. The others presented as radiolucent foci in the intramedullary or subcortical regions. A total of 42 cases provided data on therapy, these included surgery (n=27, 40.3%), radiation therapy (n=6, 9.0%), surgery combined with radiation therapy (n=2, 3.0%), and medicine therapy (n=7, 10.4%). For 30 of these 42 cases, follow-up data were available: 21 cases had the disorder locally controlled and 9 had a symptom progression. Fortunately, the disease is not fatal in the majority of cases. CONCLUSIONS: GSS has no specific symptoms and it should be taken into consideration when an unclear massive osteolysis occurs. The efficacies of different treatment modalities are still unpredictable and further research is required to assess the values of different treatments.

Control of turbulence in heterogeneous excitable media.

Control of turbulence in two kinds of typical heterogeneous excitable media by applying a combined method is investigated. It is found that local-low-amplitude and high-frequency pacing (LHP) is effective to suppress turbulence if the deviation of the heterogeneity is minor. However, LHP is invalid when the deviation is large. Studies show that an additional radial electric field can greatly increase the efficiency of LHP. The underlying mechanisms of successful control in the two kinds of cases are different and are discussed separately. Since the developed strategy of combining LHP with a radial electric field can terminate turbulence in excitable media with a high degree of inhomogeneity, it has the potential contribution to promote the practical low-amplitude defibrillation approach.

A prospective study to evaluate the efficacy of an intracardiac electrogram-based atrioventricular and interventricular intervals optimization method in cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) with biventricular pacing improves cardiac function, functional capacity and quality of life in selected patients with heart failure. The current study aimed to evaluate the efficacy of the intracardiac electrogram (IEGM)-based optimization method, QuickOpt(TM), in Chinese patients treated with CRT. METHODS: Aortic time velocity integrals (AVTI) achieved at the sensed atrioventricular (AV), paced AV and interventricular (VV) interval settings recommended by both QuickOpt(TM) and standard echocardiographic optimization were measured in 101 patients. Consistency and the strength of the relationship between the two timing cycle optimization methods were assessed by intra-class correlation coefficient (ICC). RESULTS: The ICC showed good agreement and correlation with what the AVTI achieved at the optimal sensed AV (ICC = 0.9683 (0.9535 - 0.9785)), paced AV (ICC = 0.9642 (0.9475 - 0.9757)) and VV (ICC = 0.9730 (0.9602 - 0.9817)) interval settings determined by the two optimization methods. The average time required by echocardiographic optimization and by QuickOpt(TM) were (78.32 ± 32.40) minutes and (1.98 ± 1.64) minutes respectively (P < 0.0001). CONCLUSION: The QuickOpt(TM) algorithm provides a quicker, simpler and reliable alternative to the standard method for timing cycle optimization.

[Effects of metoprolol on electrophysiology of ischemic and anoxic myocardium in diabetic rats].

OBJECTIVE: To investigate the effects of metoprolol on electrophysiology of ischemic and anoxic myocardium in diabetic rats. METHODS: Forty Sprague-Dawley (SD) rats were divided into 4 groups: diabetes group; diabetes and ablation of left sympathetic nerve group; diabetes and metoprolol group and sham group. The diabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). The ventricular diastolic effective threshold (DET), effective refractive period (ERP), and Ventricular fibrillation threshold (VFT) were measured. The serum concentration of nerve growth factor (NGF) was measured. RESULTS: Metoprolol increased DET of ischemic and anoxic myocardium in diabetic rats. The ablation of the left sympathetic nerve increased VFT of diabetic rats. VFT in metoprolo group was significantly increased compared to diabetes group after ischemia. The concentrations of NGF in diabetic group and metoprolol group were higher than those in sham group. There were no difference in NGF levels between ablation of left sympathetic nerve group and sham group. CONCLUSION: The remodeling of sympathetic nerve affects the electrophysiology of ischemic myocardium of diabetic rats. Metoprolol can increase the VFT and decrease the excitation threshold of the ischemic myocardium in diabetic rats.

[Application of double source multidetector computed tomography in visualization of cardiac veins].

OBJECTIVE: To evaluate the value of double source multidetector computed tomography (MDCT) in visualization of cardiac veins in patients with chronic heart failure. METHODS: Thirty-five patients with chronic heart failure (aged 65.4 ± 8.8, 21 males and 14 females) were enrolled in the study. In Group A, MDCT and retrograde coronary venography (RCV) were performed consecutively; in Group B anterograde visualization of the coronary venous and RCV were performed. RESULTS: Coronary sinus, GCV and MCV of all individuals were identified in MDCT. LVPV was observed in 65% patients of Group A, and 66.7% patients of Group B. The correlation coefficient between MDCT and RCV was 0.944, and that between CVG and RCV was 0.42. CONCLUSION: Non-invasive evaluation of cardiac veins with double source CT is feasible and may be used in cardiac resynchronization therapy.

[COX-2 and HO-1 are involved in the delayed preconditioning elicited by bradykinin in rat hearts].

OBJECTIVE: To investigate whether cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) are involved in the bradykinin-induced delayed protection. METHODS: Cardiac contractility, lactate dehydrogenase (LDH) and infarct area were analyzed in isolated rat hearts undergoing ischemia-reperfusion injury induced by Langendorff method. RESULT: Conscious rats received bradykinin (40 microg/kg), and the isolated hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion 24 h later. Bradykinin pretreatment would improve post-ischemic performance, and reduced the release of LDH and infarct size. COX-2 inhibitor celecoxib (3 mg/kg) abolished bradykinin-induced protection, leading to poorer myocardial performance, release of more LDH and larger infarct sizes. Administration of HO-1 inhibitor ZnPP IX(20 microg/kg) before bradykinin partially abrogated the delayed protection. Pretreatment with the mitochondrial ATP sensitive potassium channel(mitoK(ATP) antagonist 5-HD before or 24 h after bradykinin administration also abolished the effect of protection. CONCLUSION: The results indicate that activation of HO-1 and COX-2 might be involved in the delayed cardioprotection evoked by bradykinin, and mitoK(ATP) channel may serve as both a trigger and a mediator in the cardioprotection.

[Involvement of potassium channel in hemin-induced cardioprotection in rat hearts].

OBJECTIVE: To investigate the effects of heme oxygenase 1 inducer hemin on protection of ischemia-reperfusion injury in rats and its mechanisms. METHODS: The Langendorff model of isolated rat heart was used; the left anterior descending coronary artery was occluded for 30 min and subsequently reperfused for 2 h. Then the ventricular function and infarct size were measured. RESULT: Hemin preconditioning prevented the increase in LVEDP, decrease in LVDP and +/- dp/dt(max) in the isolated ischemia-reperfusion rat hearts. The leakage of LDH and CK in the coronary effluent was significantly declined in hemin-treated rat hearts. And the infarct size was also reduced. Administration of a blocker of mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) 5-HD (5 mg/kg) before hemin preconditioning increased the LVEDP, and reduced the LVDP and +/- dp/dt(max). The leakage of LDH and CK in the coronary effluent and the infarct size were also increased compared with only hemin-treated rat hearts. Pretreatment of the rats with a blocker of sarcolemmal ATP-sensitive potassium channel (sarcK(ATP)) HMR-1098 (6 mg/kg) before hemin preconditioning also abolished the protective effect. Infusion of paxilline (1 micromol/L), a blocker of calcium activated potassium channel (K(Ca)) for 10 min before ischemia/reperfusion led to larger infarct size and poorer myocardial performance as compared with the hemin group. The leakage of LDH and CK in the coronary effluent was also increased. CONCLUSION: Both mitoK(ATP)and sarcK(ATP)channels activation are required for the delayed cardioprotection induced by hemin. The opening of K(Ca) channels-dependent mechanism may be involved in the protection.

[Comparison of the antithrombotlic effect and safety between intravenous nadroparin and unfractionated heparin in patients undergoing percutaneous coronary intervention].

OBJECTIVE: The study was designed to compare the antithrombotic property and safety between nadroparin and unfractionated heparin during percutaneous coronary intervention (PCI). METHODS: A prospective, single blind, randomized study was performed. A total of 98 patients (aged 65.1 +/- 8.6 years, female, 28.6%, diabetes, 7.1%) undergoing selective PCI were randomized to be administered intravenously either nadroparin (0.075 ml/10 kg) or unfractionated heparin (100U/kg) for procedural anticoagulation, in whom stable angina was 42.9%, unstable angina, 27.6%, myocardial infarction, 29.6%, two or three-vessel disease, 23.5%, stent, 100%. Blood samples for anti-Xa level were assayed in the first 22 patients of the nadroparin group before and after administration at the following intervals: 8 min, 1 h, 2 h and 4 h. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. The bleeding index (change in hemoglobin) was calculated. All patients were monitored for adverse clinical events (i.e. death, myocardial infarction, need for revascularization) during the period of 30 days after PCI. RESULTS: (1) There were no significant differences in baseline characteristics between the two randomized groups. (2) Plasma anti-Xa activities were 0.10 +/- 0.00 IU/ml at the time just before the administration of nadroparin, 1.89 +/- 0.24 IU/ml, 0.96 +/- 0.24 IU/ml, 0.47 +/- 0.13 IU/ml, and 0.30 +/- 0.12 IU/ml at the time of 8 min, 1 h, 2 h and 4 h after the use of nadroparin (and the rate of > 0.5 IU/ml were 100%, 100%, 45% and 9% patients), respectively. (3) There were no significant differences in the mean bleeding index, post-PCI hemoglobin and hematocrit between nadroparin and unfractionated heparin group [(1.16 +/- 5.80) g/L vs (0.90 +/- 6.50) g/L, P = 0.858; (129.5 +/- 13.6) g/L vs (125.5 +/- 14.9) g/L, P = 0.175; (39.0 +/- 3.9)% vs (37.9 +/- 4.6)%, P = 0.205]. (4) None of the patients in two randomized groups were observed hemorrhagic events, which including TIMI major or minor bleeding complications, gross or microscopic hematuria, melena, positive stool occult blood. There were no blood transfusions and no hematoma at the vascular access site in either of the group. (5) No death, no recurrent angina pectoris, and no urgent revascularization occurred within 30 days in both groups. One patient in nadroparin group was observed "no reflow" phenomenon that was accompanied with an elevated ST segment and a risen serum level of cTnI. This patient was diagnosed as non-Q-wave myocardial infarction. Though no myocardial infarction was found in unfractionated heparin group, there was no significant difference in the rate of myocardial infarction between the two groups of the study (P = 0.970). CONCLUSIONS: The administration of nadroparin before PCI seems effective and safe. Compared with unfractionated heparin, nadroparin was associated with neither an excess of bleeding nor an increase of clinical complications in this study.