Chi-Woon Kong

Oxidative stress: an important phenomenon with pathogenetic significance in the progression of acute pancreatitis

Background—Reactive oxygen species and related oxidative damage have been implicated in the initiation of acute pancreatitis. Changes in these parameters during disease progression merit further investigation. Aims—To evaluate changes and the clinical relevance of superoxide radicals, endogenous antioxidants, and lipid peroxidation during the course of acute pancreatitis. Patients and methods—Superoxide radicals (measured as lucigenin amplified chemiluminescence), ascorbic acid, dehydroascorbic acid, α tocopherol, and lipid peroxidation (measured as thiobarbiturate reactive substances) were analysed in blood samples from 56 healthy subjects, 30 patients with mild acute pancreatitis, and 23 patients with severe acute pancreatitis. The association with grades of disease severity was analysed. Measurements were repeated one and two weeks after onset of pancreatitis. Results—In the blood from patients with acute pancreatitis, there were increased levels of the superoxide radical as well as lipid peroxides. There was notable depletion of ascorbic acid and an increased fraction of dehydroascorbic acid. Changes in α tocopherol were not great except in one case with poor prognosis. Differences between severe and mild acute pancreatitis were significant (p<0.01). Variable but significant correlations with disease severity scores were found for most of these markers. The normalisation of these indexes postdated clinical recovery one or two weeks after onset of disease. Conclusions—Heightened oxidative stress appears early in the course of acute pancreatitis and lasts longer than the clinical manifestations. The dependence of disease severity on the imbalance between oxidants and natural defences suggests that oxidative stress may have a pivotal role in the progression of pancreatitis and may provide a target for treatment.

Is the endogenous peroxyl-radical scavenging capacity of plasma protective in systemic inflammatory disorders in humans?

Systemic inflammatory response syndrome (SIRS) in humans is associated with heightened intravascular oxidative stress. The clinical significance of plasma endogenous antioxidative capability in SIRS remains undetermined. Time-sequence changes of plasma total radical-trapping antioxidant parameter (TRAP) and its components were measured in 135 patients with various clinical conditions leading to SIRS. The results were correlated with clinical parameters. Plasma TRAP significantly depressed upon diagnosis of SIRS (SIRS vs. healthy subjects (n = 50), 605.7 +/- 20.4 vs. 803.4 +/- 30.8 microM Trolox equivalent, p <.001). In survivors (n = 86), TRAP declined further during the course of SIRS, followed by a mild recovery at the end of follow-up. General linear mixed model analysis revealed that uric acid, vitamin C, vitamin E and unidentified antioxidants contributed to most of the changes in TRAP (each factor p <.001). In nonsurvivors (n = 49), TRAP increased steadily until death, and the increase was predominantly the result of the increased contribution of bilirubin (p <.01). Higher TRAP levels were not correlated with diminished blood oxidants formation (r = -0.13, p.05), lower intensity of lipid peroxidation (r = 0.261, p <.05) or lesser disease severity of SIRS. The results do not support the hypothesis that the endogenous peroxyl radical scavenging ability of plasma plays a protective role in the course of SIRS.

Prospective Randomized Study to Assess the Efficacy of Site and Rate of Atrial Pacing on Long-Term Progression of Atrial Fibrillation in Sick Sinus Syndrome

Background— Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. Methods and Results— We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79–1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79–1.74; P=0.69) did not prevent the development of persistent AF. Conclusions— In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00419640.

Prospective Randomized Study to Assess the Efficacy of Site and Rate of Atrial Pacing on Long-term Progression of Atrial Fibrillation in Sick Sinus Syndrome: Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) Study

Background— Atrial-based pacing is associated with lower risk of atrial fibrillation (AF) in sick sinus syndrome compared with ventricular pacing; nevertheless, the impact of site and rate of atrial pacing on progression of AF remains unclear. We evaluated whether long-term atrial pacing at the right atrial (RA) appendage versus the low RA septum with (ON) or without (OFF) a continuous atrial overdrive pacing algorithm can prevent the development of persistent AF. Methods and Results— We randomized 385 patients with paroxysmal AF and sick sinus syndrome in whom a pacemaker was indicated to pacing at RA appendage ON (n=98), RA appendage OFF (n=99), RA septum ON (n=92), or RA septum OFF (n=96). The primary outcome was the occurrence of persistent AF (AF documented at least 7 days apart or need for cardioversion). Demographic data were homogeneous across both pacing site (RA appendage/RA septum) and atrial overdrive pacing (ON/OFF). After a mean follow-up of 3.1 years, persistent AF occurred in 99 patients (25.8%; annual rate of persistent AF, 8.3%). Alternative site pacing at the RA septum versus conventional RA appendage (hazard ratio=1.18; 95% confidence interval, 0.79–1.75; P=0.65) or continuous atrial overdrive pacing ON versus OFF (hazard ratio=1.17; 95% confidence interval, 0.79–1.74; P=0.69) did not prevent the development of persistent AF. Conclusions— In patients with paroxysmal AF and sick sinus syndrome requiring pacemaker implantation, an alternative atrial pacing site at the RA septum or continuous atrial overdrive pacing did not prevent the development of persistent AF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00419640.

Influence of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, B vitamins and other factors on plasma homocysteine and risk of thromboembolic disease in Chinese

Background: Thromboembolic disease is a major cause of morbidity and mortality in many countries. Our previous study found that Chinese subjects carried the same polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene as described in Western studies. The aim of the present study was to determine the influence of MTHFR polymorphism, B vitamins and other factors on plasma homocysteine (Hcy) levels and risk of thromboembolic disease in Chinese. Methods: One hundred and six subjects were enrolled into the study. They were categorized into 4 groups: healthy individuals (n = 42); those with diabetes mellitus (n = 20); those with deep vein thrombosis (DVT) (n = 11); and those with coronary artery disease (CAD) (n = 33). Plasma levels of folic acid, vitamins B6 and B12, Hcy, and fasting blood sugar were measured; total cholesterol, triglycerides, complete blood count, and 677 C?T mutation in MTHFR were determined. Results: Plasma Hcy was lowest in the healthy subjects, higher in diabetics, followed by patients with DVT, and highest in patients with CAD (p < 0.001, ANOVA). MTHFR C677T polymorphism was the common factor affecting plasma logHcy levels in all 4 groups of subjects. Triglycerides affected plasma logHcy in the CAD patients. For the 4 groups as a whole, MTHFR polymorphism, triglycerides, and vitamin B12 were the most significant factors influencing plasma Hcy. Conclusion: We suggest that high plasma Hcy is an important risk factor for CAD. Other factors including MTHFR polymorphism, vitamin B12, triglycerides, total cholesterol, and gender might affect Hcy levels in different diseases and conditions.

Catheter ablation of accessory atrioventricular pathways in 114 symptomatic patients with Wolff-Parkinson-White syndrome—a comparative study of direct-current and radiofrequency ablation☆

To evaluate and compare the safety and efficacy of catheter-mediated direct-current and radiofrequency ablation in patients with Wolff-Parkinson-White syndrome, 114 patients with accessory pathway-mediated tachyarrhythmias underwent catheter ablation. Electrophysiologic parameters were similar in patients undergoing direct-current (group 1, 52 patients with 53 accessory pathways) and radiofrequency (group 2, 62 patients with 75 accessory pathways) ablation. Immediately after ablation, 50 of 53 accessory pathways (94%) were ablated successfully with direct current, but 2 of the 50 accessory pathways had early return of conduction and required a second ablation; 72 of 75 accessory pathways (96%) were ablated successfully with radiofrequency current. In the three accessory pathways in which radiofrequency ablation was unsuccessful, a later direct-current ablation was successful. During follow-up (group 1, 14 to 27 months; group 2, 8 to 13 months), none of the patients with successful ablation had a recurrence of tachycardia. Complications in direct-current ablation included transient hypotension (two patients), accidental atrioventricular block (one patient), and pulmonary air trapping (two patients); complications in radiofrequency ablation included cardiac tamponade (one patient) and suspicious aortic dissection (one patient). Myocardial injury and proarrhythmic effects were more severe in direct-current ablation. The length of the procedure and the radiation exposure time were significantly shorter in direct-current (3.5 +/- 0.2 hours, 30 +/- 4 minutes) than in radiofrequency (4.1 +/- 0.4 hours, 46 +/- 9 minutes) ablation. Findings in this study confirm the impression that radiofrequency ablation is associated with fewer complications than direct-current ablation and radiofrequency ablation with a large-tipped electrode catheter is an effective and relatively safe nonsurgical method for treatment of Wolff-Parkinson-White syndrome.

A Prospective Randomized Study to Assess the Efficacy of Rate and Site of Atrial Pacing on Long-Term Development of Atrial Fibrillation

The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is a single‐blinded, parallel randomized designed multicenter study in pacemaker indicated patients with paroxysmal atrial fibrillation (AF). The objective is to evaluate whether the site of atrial pacing–‐conventional right atrial appendage versus low atrial septal—with or without atrial overdrive pacing will influence the development of persistent AF. The study will provide a definitive answer to whether a different atrial pacing site or the use of AF suppression pacing or both can give incremental antiarrhythmic benefit when one is implanting a device for a patient with a history of paroxysmal AF.

Predictors of inappropriate atrial sensing in long-term VDD-pacing systems

AIMS The efficacy and stability of the atrial electrode sensing function is essential for maintaining atrioventricular (AV) synchrony. This study aimed to explore the long-term reliability and causes of the long-term sensing failure of VDD systems. METHODS AND RESULTS We enrolled all the patients with complete or high-degree AV block who received VDD pacemakers between August 1994 to January 2006 and who were followed up for more than 12 months. The interrogation parameters, including the atrial potentials (APs) and AV-synchrony ratio were acquired immediately post-implantation and at 3-6 month intervals thereafter. An inappropriate atrial sensing efficacy was defined as an AV-synchrony ratio of <90%. Totally 157 patients (70 +/- 12 years, 103 males) were enrolled into the study with a follow-up for 4.9 +/- 2.5 years. Twenty-six patients (16.6%) suffered from inappropriate atrial sensing. According to a Kaplan-Meier analysis, the incidence of inappropriate atrial sensing was higher in the patients with an age > or =72 years old (P = 0.047), mean AP during the implantation of <3.0 mV (P = 0.015), concomitant use of non-dihydropyridine calcium channel blockers (CCBs) (P = 0.003), and atrial fibrillation (AF) (P < 0.001). A Cox regression analysis showed that non-dihydropyridine CCBs (hazard ratio, 3.255; 95% confidence interval, 1.148-9.227, P = 0.026) and AF (hazard ratio, 6.507; 95% confidence interval, 2.478-17.104, P < 0.001) predicted inappropriate atrial sensing. CONCLUSION VDD pacing is a reliable pacing modality. However, we should monitor the pacemaker sensing function in the patients with the concomitant use of non-dihydropyridine CCBs and AF.

Leukocyte mitochondrial alterations after cardiac surgery involving cardiopulmonary bypass: clinical correlations.

Cardiac surgery with the use of cardiopulmonary bypass (CPB) is known to initiate systemic inflammatory responses that are associated with immune dysregulations, but the pathomechanisms underlying these changes remain elusive. Mitochondrial transmembrane potential (MTP) is an important determinant of leukocytic functions and viability, and may be altered as a part of the cellular responses to systemic inflammatory insults. Therefore, we examined MTP in three subsets of peripheral leukocytes in 18 patients receiving uncomplicated cardiac surgery involving CPB. The MTP of neutrophils and lymphocytes significantly increased, whereas that of monocytes significantly declined, after the surgery. The alterations in leukocytic MTP were transient, normalizing 3 days to 1 week after the surgery, and were accompanied by transient overproduction of intracellular oxidants, including nitric oxide and superoxide. Despite these perturbations, the viability status of leukocytes remained unaltered. Positive correlations were found between the changes of leukocyte MTP and various clinical parameters, implying that leukocyte mitochondrial alterations are parts of the systemic immune perturbations induced by the bypass surgery.

Acute Effects of Dual-chamber Pacing on the Left Ventricular Systolic Function and Relaxation in Patients with Advanced AV Block and Sick Sinus Syndrome

Background: Abnormal activation of the ventricles via right ventricular apical pacing deteriorates cardiac function, which may explain the increased mortality of patients with congestive heart failure receiving permanent pacemakers. We hypothesized that pacing at alternative sites may cause less detrimental effects on the cardiac function. Methods: Five symptomatic patients with either advanced AV block (n = 4) or sick sinus syndrome with normal left ventricular (LV) function (n = 1) were studied. During cardiac catheterization, LV pressure was recorded with a high‐fidelity catheter‐tipped transducer. Baseline rhythms were sinus rhythm or VVI pacing. Sequential VDD pacing with variable AV intervals was performed at the right ventricular apex (RVA), right ventricular septum (RVS), right ventricular outflow tract (RVOT) and coronary sinus (CS). LV systolic function was assessed by calculating dP/dtmax and LV diastolic function was indexed by calculating the exponential isovolumic relaxation constant (Tau). Percentage changes (mean ± SE) from baseline to pacing were measured. Results: RVA pacing reduced dP/dtmax (‐0.8 ± 8.4%) and prolonged Tau (7.0 ± 5.6%); RVS pacing enhanced dP/dtmax (20.7 ± 15.3%) and shortened Tau (‐10.4 ± 9%); RVOT pacing reduced dP/dtmax (‐8.0 ± 20.0%) and shortened Tau (‐6.0 ± 12.2%); CS pacing reduced dP/dtmax (‐11.7 ± 13.0%) and prolonged Tau (10.5 ± 11.9%). Our results demonstrated that different pacing sites have different effects on LV contractility and relaxation in patients with normal LV function. Conclusion: Since pacing at the RVS preferably increased LV dP/dtmax and shortened Tau, it may be a better alternative than the RVA.