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Chu-Pak Lau

Publications and source records attributed to Chu-Pak Lau.

At least 73 records · Page 4Linked to original sources
PubMed2004

Inhibition of ultra-rapid delayed rectifier K+ current by verapamil in human atrial myocytes.

Verapamil is a widely used Ca(2+) channel antagonist in the treatment of cardiovascular disorders including atrial arrhythmias. However, it is unknown whether the drug would inhibit the repolarization currents transient outward K(+) current (I(to1)) and ultra-rapid delayed rectifier K(+) current (I(Kur)) in human atrium. With whole-cell patch configuration, we evaluated effects of verapamil on I(to1) and I(Kur) in isolated human atrial myocytes. It was found that verapamil did not decrease I(to1) at 1-50 microM. However, verapamil reversibly inhibited I(Kur) in a concentration-dependent manner (IC(50) = 3.2 microM). At test potential of +50 mV, 5 microM verapamil decreased I(Kur) by 61.3 +/- 7.5%. Verapamil significantly accelerated inactivation of I(Kur), suggesting an open channel block mechanism. The results indicate that verapamil significantly blocks the repolarization K(+) current I(Kur), but not I(to1), in human atrial atrium, which may account at least in part for the atrial effect of the drug.

4-Aminopyridine↗
PubMed2004

Demonstration of calcium-activated transient outward chloride current and delayed rectifier potassium currents in Swine atrial myocytes.

Cellular electrophysiology is not fully understood in the atrium of pig heart. The objective of the present study was to determine whether transient outward current (I(to)), ultra-rapid delayed rectifier potassium current (I(Kur)), and rapid and slow delayed rectifier K(+) currents (I(Kr) and I(Ks)) were present in pig atrium. The whole-cell patch technique was applied to record membrane currents and action potentials in myocytes isolated from pig atrium. It was found that an I(to) was activated upon depolarization voltage steps to between -10 and +60 mV from -50 mV in pig atrial cells, and the I(to) was sensitive to the inhibition by the blockade of L-type calcium (Ca(2+)) current, showed a "bell-shaped" I-V relationship, typical of I(to2) (i.e. I(Cl.Ca)). The I(to2) was inhibited by the chloride (Cl(-)) channel blocker anthracene-9-carboxylic acid (9-AC, 200 micromol/l) or 4,4'-diisothiocyanostilben-2,2'disulfonic acid (200 micromol/l), and by Cl(-) substitution in the superfusate. I(Kur) was found in pig atrial myocytes, and the current showed properties of weak inward rectification and use- and frequency-dependent reduction. I(Kur) was resistant to tetraethylammonium, but sensitive to inhibition by 4-aminopyridine (4-AP) (IC(50) = 71.7 +/- 3.5 micromol/l). In addition, E-4031-sensitive I(Kr) and chromanol 293B-sensitive I(Ks) were observed in pig atrial myocytes. Blockade of I(to2), I(Kur), I(Kr) or I(Ks) with corresponding blockers significantly prolonged atrial action potentials. These results indicate that Ca(2+)-activated I(to2), 4-AP-sensitive I(Kur), E-4031-sensitive I(Kr), and 293B-sensitive I(Ks) are present in pig atrial myocytes, and these currents play important roles in action potential repolarization of pig atria.

4-Aminopyridine↗
PubMed2004

Future prospects for implantable devices for atrial defibrillation.

The success of the implantable cardioverter defibrillator (ICD) led to the concept of a device that would terminate atrial fibrillation (AF) using an implantable device. Implantable devices for AF are undergoing rapid evolution. Currently used devices combine pacing and cardioversion therapies to prevent and to treat AE Recent studies have shown that these devices are safe and can decrease the incidence of AF and improve quality of life significantly. Implantable devices for atrial defibrillation are likely to have an increasing role in the near future, particularly when they are used in combination with ICD and cardiac resynchronization therapy in which AF is both common and its termination is clinically beneficial.

Atrial Fibrillation↗
PubMed2004

Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes.

AIMS: Since 2002, there have been five major outcome trials of statins reporting findings from more than 47,000 subjects. As individual trial results differed, we performed a meta-analysis to ascertain the effectiveness and safety of statins overall and in subgroups. The aim of the study was to estimate the effect of statins on major coronary events and strokes, all-cause mortality and noncardiovascular mortality, and in different subgroups. METHODS: PubMed was searched for trials published in English. Randomized placebo-controlled statin trials with an average follow up of at least 3 years and at least 100 major coronary events were included. For each trial, the statin used, number and type of subjects, proportion of women, mean age and follow up, baseline and change in lipid profile, cardiovascular and non-cardiovascular outcomes were recorded. RESULTS: Ten trials involving 79,494 subjects were included in the meta-analysis. Due to heterogeneity, ALLHAT-LLT was excluded from some analyses. Statin therapy reduced major coronary events by 27% (95%CI 23, 30%), stroke by 18% (95%CI 10, 25%) and all-cause mortality by 15% (95%CI 8, 21%). There was a 4% (95%CI -10, 3%) nonsignificant reduction in noncardiovascular mortality. The reduction in major coronary events is independent of gender and presence of hypertension or diabetes. The risk reduction was greater in smokers (P < 0.05). Coronary events were reduced by 23% (95%CI 18, 29%) in pravastatin trials and 29% (95%CI 25, 33%) in five trials using other statins. Pravastatin reduced strokes by 12% (95%CI 1, 21%) whilst other statins reduced strokes by 24% (95%CI 16, 32%) (P = 0.04). CONCLUSIONS: Statins reduce coronary events, strokes and all-cause mortality without increasing noncoronary mortality. The benefits accrue in men and women, hypertensives and normotensives, diabetics and nondiabetics, and particularly in smokers. Pravastatin appears to have less impact on strokes.

Coronary Disease↗
PubMed2004

Methods for testing automatic mode switching in patients implanted with DDD(R) pacemakers.

The assessment of automatic mode switching (AMS) algorithms is impossible in vivo, due to a low chance of seeing the patient at the onset of a spontaneous episode of atrial fibrillation (AF). As the induction of AF to test AMS has clinical concerns, three alternative and non-invasive techniques may be proposed for this purpose: myopotentials, chest wall stimulation, and an external supraventricular arrhythmia simulator. The first method is simple and does not require additional equipment, even though in some patients adequate signals cannot be generated with a soft effort such as handgrip or hand compression. The main advantage of the chest wall stimulation method is the possibility that it be performed in every implanting center, since it is based on the use of standard devices for cardiac stimulation. The method based on the external supraventricular arrhythmia simulator allows the most detailed of the ECG traces, but it needs a dedicated electronic device.

Atrial Fibrillation↗
PubMed2003

Prevention of atrial fibrillation recurrence by statin therapy in patients with lone atrial fibrillation after successful cardioversion.

The aim of this study was to investigate the effect of statin therapy on arrhythmia recurrence in patients with lone atrial fibrillation (AF). From July 1998 to December 1999, 62 patients with lone persistent AF lasting >/=3 months underwent successful external cardioversion. After a mean follow-up of 44 months, 85% had recurrence of AF. The use of statins was associated with a significant decrease in the risk of arrhythmia recurrence after successful cardioversion of AF. The result of this retrospective study demonstrates that the use of statins in patients with lone AF was associated with a significant decrease in the risk of arrhythmia recurrence after successful cardioversion.

Aged↗
PubMed2003

Initial experience and safety in the treatment of chronic total coronary occlusions with a new optical coherent reflectometry-guided radiofrequency ablation guidewire.

The Safe-Cross wire system, which has optical coherence reflectometry technology for navigating and radiofrequency energy provided at its tip for crossing chronic total occlusions (CTOs), provides a promising means to treat hard, organized CTOs. Using this system, we report on a 60% success rate in patients who had long-standing coronary CTOs that had > or =1 failed attempt using conventional percutaneous coronary intervention.

Aged↗
PubMed2003

Pulmonary vein isolation using transvenous catheter cryoablation for treatment of atrial fibrillation without risk of pulmonary vein stenosis.

OBJECTIVES: We sought to evaluate the efficacy and safety of pulmonary vein (PV) isolation using transvenous cryoablation for the treatment of atrial fibrillation (AF). BACKGROUND: Although electrical isolation of PVs with radiofrequency energy for the treatment of AF is feasible, it is associated with a significant risk of PV stenosis. Cryoablation is a new alternative therapy allowing ablation of tissue while preserving its underlying architecture. METHODS: In 52 patients with paroxysmal (n = 45) or persistent (n = 7) AF, PV isolation using the CryoCor cryoablation system (CyroCor Inc., San Diego, California) with a 10F deflectable transvenous catheter was performed as guided by ostial PV potentials. Cryoablation was applied twice at each targeted site (2.5 to 5 min/application). Computed tomography (CT) of the thorax was performed at baseline and at 3 and 12 months to evaluate for PV stenosis. RESULTS: All targeted PVs were completely isolated in 49 (94%) of 52 of patients. Of 152 PVs targeted, 147 (97%) were successfully isolated (mean 3.0 PVs isolated per patient). After a mean period of 12.4 +/- 5.5 months of follow-up, 37 (71%) of 52 patients had no recurrence of AF or were clinically improved, including 29 patients (56%) who had no recurrence of AF with (n = 11) or without the use of anti-arrhythmic drugs. At 3 and 12 months, the CT scan showed no evidence of PV stenosis associated with cryoablation in any patients. CONCLUSIONS: Transvenous catheter cryoablation is an effective method to create PV electrical isolation for the treatment of AF. A clinically satisfactory result can be achieved in 71% of patients with AF, without the risk of PV stenosis.

Adult↗
PubMed2003

Calcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential.

OBJECTIVE: It is unknown whether 4-aminopyridine- (4-AP-) sensitive transient outward K(+) current (I(to1)) and/or Ca(2+)-activated transient outward Cl(-) current (I(Ca.Cl) or I(to2)) contribute(s) to phase 1 repolarization of pig ventricular action potential (AP). The purpose of the present study was to determine ionic contribution of the phase 1 repolarization of AP in pig ventricle. METHODS: We used whole-cell patch techniques to record APs and membrane currents, and Western immunoblotting analysis to detect expression of I(to1) protein (Kv4.2 or Kv4.3) in pig ventricular myocytes. RESULTS: A transient outward current (I(to)) was activated upon depolarization voltage steps to between -10 and +60 mV from -50 mV in pig ventricular cells, and the I(to) was resistant to 4-AP application, but sensitive to the inhibition by ryanodine (10 micromol/l) and the Ca(2+) channel blockade, and the Cl(-) channel blocker 4,4'-diisothiocyanostilben-2,2'disulfonic acid (DIDS, 150 micromol/l). The current was diminished by external Cl(-) (Cl(-)(o)) replacement and showed a 'bell-shaped' I-V relationship at room temperature, typical of I(to2). No difference in I(to2) was observed in the regional cells from epicardium, midmyocardium, and endocardium of left ventricle. APs showed significant phase 1 and 'spike and dome' in pig ventricular myocytes. The phase 1 and 'spike and dome' of APs were not affected by 4-AP (3 mmol/l), but abolished by replacing Cl(-)(o) and by application of 100 micromol/l DIDS, suggesting I(to2) contribution. Western immunoblotting analysis showed no evidence for the expression of 4-AP-sensitive I(to1) channel protein (Kv4.2 or Kv4.3) in pig ventricular cells. CONCLUSION: The results indicate that 4-AP-sensitive I(to1) is not expressed, and only Ca(2+)-activated I(to2) is present in pig cardiac cells, which contributes importantly to the phase 1 repolarization of ventricular APs in this species.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2003

Predictors of left ventricular reverse remodeling after cardiac resynchronization therapy for heart failure secondary to idiopathic dilated or ischemic cardiomyopathy.

Biventricular pacing results in left ventricular (LV) reverse remodeling in heart failure patients with wide QRS complexes. This study examines potential predictors of reverse remodeling. Echocardiography with tissue Doppler imaging was performed at baseline and 3 months after biventricular pacing in 30 patients (21 men and 9 women, mean age 62 +/- 14 years). There were 17 responders to reverse remodeling (defined as a reduction in LV end-systolic volume by >15%) and 13 nonresponders. Responders had significant improvement in 6-minute hall-walking distance (p = 0.006), metabolic equivalents (p = 0.02), peak oxygen uptake (p = 0.02), New York Heart Association functional class (p <0.001), and quality of life (p <0.001); an increase in the sphericity index (p = 0.007), ejection fraction (p <0.001), and diastolic filling time (p = 0.03); a decrease in myocardial performance index (p = 0.02), isovolumic relaxation time (p = 0.004), and mitral regurgitation (p = 0.007); and an improvement in systolic dyssynchrony (SD of the time to peak myocardial systolic contraction of the 12 LV segments as dyssynchrony index) (45.0 +/- 8.3 vs 32.5 +/- 14.5 ms, p = 0.003). In contrast, nonresponders only had a small degree of clinical improvement in New York Heart Association class (p = 0.03) and quality-of-life scores (p = 0.03), without any change in cardiac function, and worsening of systolic dyssynchrony (24.8 +/- 4.5 vs 34.1 +/- 13.5 ms, p = 0.02). When all the above factors were put into univariate and multivariate analyses models, systolic dyssynchrony was the only independent predictor of reverse remodeling (r = -0.76, p <0.001) (beta = -1.54, p = 0.007). A preimplant dyssynchrony index of 32.6 ms (+2 SDs from mean of 88 normal controls) was able to totally segregate responders from nonresponders of biventricular pacing. Thus, responders of LV reverse remodeling were associated with improvement in clinical status, cardiac function, and systolic synchronicity. Direct assessment of systolic synchronicity by tissue Doppler imaging is highly accurate in predicting responders to therapy.

Aged↗
PubMed2003

Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation.

Results of experimental studies have shown that intramyocardial implantation of bone marrow cells induces neovascularisation and improves heart function after myocardial infarction. Our aim was to test this notion in people. We implanted autologous mononuclear bone marrow cells into the ischaemic myocardium of eight patients with severe ischaemic heart disease as guided by electromechanical mapping with a percutaneous catheter procedure. After 3 months of follow-up, there was improvement in symptoms, myocardial perfusion, and function at the ischaemic region on MRI. Future randomised, controlled studies are required to validate this initial encouraging result.

Aged↗
PubMed2003

Percutaneous recanalization of chronic subclavian artery occlusion using optical coherence reflectometry-guided radiofrequency ablation guidewire.

Subclavian artery lesion that is associated with low complication rate could be treated by percutaneous intervention effectively. However, the success of endovascular therapy for occlusive lesion may be limited by failure to cross with a guidewire. We describe the use of a system using optical coherence reflectometry for navigation and radiofrequency ablation to enable wire passage through subclavian artery occlusion that could not be crossed by conventional guidewires.

Arterial Occlusive Diseases↗
PubMed2003

Effects of chromanol 293B on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes.

It is unclear whether chromanol 293B, a selective inhibitor of slow component of delayed rectifier K(+) current (I(Ks)), may affect other K(+) currents in human atrium. With whole-cell patch configuration, we evaluated effects of 293B on transient outward K(+) current (I(to1)) and ultra-rapid delayed rectifier K(+) current (I(Kur)) in isolated human atrial myocytes. It was found that 293B inhibited I(to1) and I(Kur) in a concentration-dependent manner. At 10 microM 293B suppressed I(to1) to 3.4 +/- 0.4 from 5.1 +/- 0.3 pA/pF (P < 0.01), and I(Kur) to 1.5 +/- 0.2 from 2.1 +/- 0.3 pA/pF (P < 0.01) at +50 mV. The inhibition of I(to1) and I(Kur) was independent of depolarizing voltage, and the concentration of 50% inhibition was 31.2 microM for I(to1), and 30.9 microM for I(Kur). 293B blocked I(to1) and I(Kur) with the same concentration range, and the significant effect was observed from the concentration of 1 microM. The maximum inhibitive effect was 88% for I(to1) and 96% for I(Kur) at 250 microM. Voltage dependence of activation and inactivation, and time-dependent recovery from inactivation of I(to1) were not altered by 293B; however, time to peak and time-dependent inactivation of I(to1) was significantly accelerated. The results indicate that 293B significantly inhibits the major repolarization K(+) currents I(to1) and I(Kur) in human atrial myocytes.

Adult↗
PubMed2003

Effect of left ventricular function on long-term left ventricular pacing and sensing threshold.

BACKGROUND: The effect of left ventricular (LV) systolic function on the long-term left ventricular pacing and sensing threshold is unclear. METHODS AND RESULTS: We studied the effect of LV ejection fraction (LVEF) on the LV pacing and sensing threshold in 56 patients (mean age: 70.2 +/- 10.5 years) underwent permanent LV pacing using a self-retaining coronary sinus lead (Model 1055 K, St Jude Medical, USA). In 49 patients, the LV lead was implanted for conventional pacemaker indication (sick sinus syndrome = 14, heart block = 26 or slow atrial fibrillation = 9). The remaining 7 patients were implanted for congestive heart failure. The LV pacing and sensing threshold, and lead impedance were compared between patients with LVEF <40% (Group 1, n = 28) and LVEF >40% (Group 2, n = 28) during implant and at 3-month follow up. The LV pacing lead was successfully implanted in all patients without any lead dislodgement on follow-up. At implant, Group 1 patients had a significant lower R wave amplitude, but similar LV pacing threshold and lead impedance as compared to Group 2. However, at 3-month follow-up, Group 1 patients had a significantly higher LV pacing threshold compared to Group 2 patients. There were no significant differences in the sensing threshold and lead impedance between the two groups. Furthermore, there was also a significant interval increase in LV pacing threshold in Group 1 patients (0.94 +/- 0.12 V) after 3 months, but not in Group 2 patients (0.16 +/- 0.08 V, p < 0.01). CONCLUSIONS: The results of this study suggest that the LV systolic function has a significant impact on the long-term LV pacing threshold. The long-term left ventricular pacing threshold in patients with left ventricular systolic dysfunction increased after implant and was higher than patients with normal left ventricular systolic function.

Aged↗
PubMed2003

Shortening of the sensed AV delay of a dual chamber pacemaker during normal sinus rhythm.

We studied the Medtronic Thera and Kappa 400 dual chamber pacemakers to determine the causes and mechanism of shortening of the sensed AV delay during normal sinus rhythm. When the sensed AV delay shortens to less than its programmed value, it lengthens gradually and returns to its programmed duration after a number of pacing cycles. This behavior is linked to the relatively slow automatic mode switching algorithm (AMS) and was observed when a transient increase in the sensed atrial rate failed to reach the point where AMS was activated and also upon exit from the AMS mode.

Cardiac Pacing, Artificial↗
PubMed2003

Advances in devices for cardiac resynchronization in heart failure.

Patients with advanced heart failure have a high mortality and morbidity despite medical therapy. Depending on the underlying heart disease and severity of heart failure, 3.7 to 52.8% of patients have a QRS complex > or =120 ms who may have interventricular and intraventricular dyssynchrony correctible by cardiac resynchronization therapy (CRT). The latter is usually achieved with biventricular pacing, with the left ventricular lead placed in a tributary of the coronary sinus (CS), with a reported success rate between 88-92%. The technical advances for implantation include preformed guide sheaths to cannulate the CS, over the wire leads with passive fixation mechanism, and surgical placement methods. Device-specific CRT features include optimizing heart failure through insurance of a high percentage of pacing, heart failure monitoring, atrioventricular and interventricular timing, and avoiding double ventricular sensing. Furthermore, arrhythmic co-morbidities of heart failure such as atrial fibrillation and ventricular tachyarrhythmias can also be managed. Recent prospective trials suggest that there is a 30% reduction in heart failure hospitalization with CRT, and preliminary results suggest a survival benefit with CRT and implantable cardioverter defibrillator over optimal medical therapy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Mechanisms of biatrial pacing for prevention of postoperative atrial fibrillation--insights from a clinical trial.

Atrial fibrillation (AF) occurs in a high proportion of patients after cardiac surgery and is associated with increased morbidity and longer hospital stay. Beta-blockers and amiodarone have been shown to reduce the incidence, but AF still occurs in up to 25% despite pre-treatment. The mechanisms of AF after cardiac surgery are presumably multifactorial. The transient nature of postoperative AF suggests a reversible trigger in patients with susceptible underlying electrophysiological substrates such as abnormal automaticity and conduction delay due to atrial incisions, ischemia and preexisting disease). These could result in atrial premature beats (APBs) and prolonged atrial activation causing lengthening of the P wave. Prophylactic atrial pacing (single- or multi-site) is reported to be effective in patients at high risk for postoperative AF. The mechanisms are probably a combination of preventing bradycardia-induced arrhythmias, overdrive suppression of APBs, eliminating compensatory pauses after APBs and reduction of dispersion of refractoriness. By reducing non-uniform and asynchronous activation resulting from anatomic or functional block, multi-site pacing could improve local excitability and reduce the window of opportunity for AF initiation. We found that the incidence of AF after coronary bypass surgery (CABG) was significantly reduced in patients who received prophylactic biatrial overdrive pacing (BiA) compared with single site left atrial (LA) or right atrial (RA) pacing or no pacing. (BiA 12.5% versus LA 36.4%; RA 33.3% or control 41.9%; P < 0.05). BiA pacing was associated with the greatest reduction of P wave dispersion compared with single site pacing or control (BiA 42 +/- 8%; LA 13 +/- 6%; RA 10 +/- 9%; P < 0.05). Prophylactic postoperative BiA pacing is thus a reasonable and attractive strategy for reducing the risk for postoperative AF.

Aged↗