Shoei K. Stephen Huang

Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca2+-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: An insight into the mechanism of atrial electrical remodeling

OBJECTIVES We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation. BACKGROUND Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear. METHODS A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. RESULTS The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation. CONCLUSIONS L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

Arrhythmias and conduction disturbances after coronary artery bypass graft surgery: Epidemiology, management, and prognosis

CABG is associated with many perioperative complications, including supraventricular and ventricular arrhythmias and conduction disturbances. Atrial fibrillation occurs in < or = 40% of patients after CABG and is especially common in older patients. Although it is often benign and self-limited, it can lead to complications such as stroke. Treatment consists primarily of control of the ventricular response rate; in some cases, antiarrhythmic drugs or electrical cardioversion are needed. Anticoagulation should be considered in appropriate cases of persistent (48 to 72 hours) atrial fibrillation after initial treatment. Prophylaxis, especially with beta-blocking agents, seems to be effective and should be considered in appropriate cases. Simple ventricular arrhythmias are common after CABG and do not affect the patients prognosis; however, sustained VT/VF occur infrequently (< 2% of patients) and carry a high mortality rate. Treatment is aimed at correcting precipitating factors (e.g., myocardial ischemia). Electrophysiologically guided drug therapy and implantation of an ICD should be considered in appropriate cases for patients who survive the initial events. Transient minor conduction disturbances are common after CABG; in some patients persistent AV block and sinus node dysfunction develop and may require treatment with permanent pacemaker.

Use of the Saline Infusion Electrode Catheter for Improved Energy Delivery and Increased Lesion Size in Radiofrequency Catheter Ablation

Although radiofrequency catheter ablation has undergone explosive growth as the treatment for a variety of arrhythmias, a limiting factor with the existing catheter delivery system has been the relatively small size of the lesions, which appears to be in part due to coagulum formation around the catheter tip, producing a rise in impedance and limiting energy delivery. In order to test the hypothesis that infusion of saline during radiofrequency current application can increase the lesion size and decrease the incidence of impedance rise, ten dogs were each given two radiofrequency ablation lesions to the left ventricular endocardium. One of these lesions was delivered with a standard 7 French quadripolar catheter with a 2‐mm tip, and the second was done with a 7 French Iuminal electrode catheter (also with a 2‐mm tip) for the infusion of normal saline during the delivery of radiofrequency energy. Energy was delivered for 60 seconds at either 10 or 20 watts at two distinct sites in the left ventricle for each animal. Four to 7 days following ablation, the animals were sacrificed for pathological examination. The lesions created with the saline infusion catheter were significantly bigger than those produced with a standard catheter (7.3 × 7.0 × 5.1 vs 5.2 × 4.9 × 3.5 mm, respectively, P < 0.001). At the lower energy level (10 W), none of the animals with the saline infusion catheter experienced an impedance rise versus 3 of 5 of the animals in whom the standard catheter was used. At the higher level (20 W), only 1 of 5 dogs had an impedance rise with the saline infusion catheter versus 5 of 5 with the standard catheter. We conclude that the use of a saline infusion catheter for radiofrequency energy delivery during catheter ablation produces a significantly larger lesion than that produced with a standard catheter and is effective in preventing impedance rise.

Reversal of deteriorated fractal behavior of heart rate variability by beta-blocker therapy in patients with advanced congestive heart failure

Beta‐Blocker Therapy and Heart Rate Variability. Introduction: The slope of the power spectrum in heart rate variability (HRV) reflects the fractal or scaling behavior in HR dynamics and recently was confirmed as an independent predictor of postmyocardial infarction survival. Whether or not the new measurement in HRV foresees the functional evolution in patients with advanced congestive heart failure treated by β blockers is unclear.

Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation.

Introduction: Functional and structural changes of atrial tissue occur during the natural course of atrial fibrillation (AF), and these changes may contribute to further AF. We investigated the changes in AF tissue using cDNA microarray and two‐dimensional protein electrophoresis techniques.

Measurement of Funny Current (If) Channel mRNA in Human Atrial Tissue: Correlation with Left Atrial Filling Pressure and Atrial Fibrillation

If in Human Atrial Tissue. Introduction: The funny current (If) contributes to phase IV spontaneous depolarization in cardiac pacemaker tissue. Enhanced If activity in myocardial tissue may lead to increased automatically and therefore tachyarrhythmia. We measured the amount of If, activity in the messenger ribonucleic acid (mRNA) in human atrial tissue and correlated the mRNA amount to left atrial filling pressure and atrial fibrillation (AF).

Cardiovascular complications after radiofrequency catheter ablation of supraventricular tachyarrhythmias

Abstract We report the incidence of cardiovascular complications in patients receiving RF catheter ablation for supraventricular tachyarrhythmias. To reduce the incidence of complications, a rigid guideline or policy for the personnel and facilities should be followed. A prospective, multicenter registry program may be needed to further define the complications associated with this procedure.

Changes in the mRNA levels of delayed rectifier potassium channels in human atrial fibrillation

Introduction: We measured mRNA levels of delayed rectifier potassium channels in human atrial tissue to investigate the mechanism of the shortening of the atrial effective refractory period and the loss of rate-adaptive shortening of the atrial effective refractory period in human atrial fibrillation. Methods and Results: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The mRNA amounts of KVLQT1 (IKs), minK (β-subunit of IKs), HERG (IKr), and KV1.5 (IKur) were measured by reverse transcription-polymerase chain reaction and normalized to the mRNA amount of GAPDH. We found that the mRNA levels of KV1.5, HERG and KVLQT1 were all significantly decreased in patients with persistent atrial fibrillation for more than 3 months. In contrast, the mRNA level of minK was significantly increased in patients with persistent atrial fibrillation for more than 3 months. We further showed that these changes were independent of the underlying cardiac disease, atrial filling pressure, gender and age. We also found that there was no spatial dispersion of mRNA levels among the four atrial sampling sites. Conclusions: Because the decrease in potassium currents results in a prolonged action potential, the shortening of the atrial effective refractory period in atrial fibrillation should be attributed to other factors. However, the decrease in IKs might contribute, at least in part, to the loss of rate-adaptive shortening of the atrial refractory period.

Downregulation of angiotensin converting enzyme II is associated with pacing-induced sustained atrial fibrillation

Atrial fibrillation (AF), the most common cardiac arrhythmia, is frequently accompanied by atrial interstitial fibrosis. Angiotensin II (Ang II) dependent signaling pathways have been implicated in interstitial fibrosis during the development of AF. However, Ang II could be further degraded by angiotensin converting enzyme II (ACE2). We examined expression of ACE2 in the fibrillating atria of pigs and its involvement in fibrotic pathogenesis during AF. Nine adult pigs underwent continuous rapid atrial pacing to induce sustained AF and six pigs were sham controls (i.e., sinus rhythm; SR). In the histological examinations, extensive accumulation of extracellular matrix in the interstitial space of the atria, as evidenced by Massons trichrome stain, were found in fibrillating atria. The relative amount of collagen type I in the atria with AF was significantly increased as compared with that in the SR. Local ACE activity in the fibrillating atria was also markedly higher than that in the SR subjects. ACE2 gene and protein expression in the AF subjects were significantly decreased compared with those in the SR subjects, whereas expression of mitogen‐activated/ERK kinase 1/2 (MEK1/2), extracellular signal‐regulated protein kinase 2 (ERK2), and activated ERK2 were significantly greater in the AF subjects. We propose that decreasing ACE2 expression during AF may affect the Ang II‐dependent signaling pathway. In addition, our results suggest that atrial fibrosis in AF may be induced by antagonistic regulation between ACE and ACE2 expression.

Electrophysiological effects of propofol on the normal cardiac conduction system.

To determine the electrophysiological effects of propofol and to explain the potential mechanism(s) whereby it causes bradyarrhythmias, 10 closed-chest pigs weighing 20-25 kg were studied. Each animal was premedicated by intramuscular administration of ketamine hydrochloride, intubated, and mechanically ventilated. Femoral arterial and venous catheters were placed, and a comprehensive electrophysiologic evaluation was performed at baseline and after two doses (1 mg/kg i.v. bolus and 0.1 mg/kg/min infusion and an extra 1- mg/kg i.v. bolus and 0.2 mg/kg/min infusion) of propofol. The electrophysiological effects obtained on low-and high-dose propofol were compared to baseline values. Propofol caused a dose-related decrease in sinus cycle length (baseline 565 +/- 36 ms, low-dose propofol 541 +/- 28, high-dose propofol 527 +/- 26 ms; p < 0.05), a prolongation of the corrected sinus node recovery time (baseline 119 +/- 35 ms, low-dose propofol 126 +/- 32, high-dose propofol 130 +/- 30 ms; p < 0.01), and an increase in the His-ventricular interval (baseline 33 +/- 4 ms, low-dose propofol 36 +/- 4, high-dose propofol 40 +/- 3 ms; p < 0.005). All other electrophysiological parameters remained unchanged, and there were no cases of spontaneous atrioventricular block or sinus pauses. We conclude that propofol causes dose-related depression of sinus node and His-Purkinje system functions, but has no effect on the atrioventricular node function and on the conduction properties of atrial and ventricular tissues in normal pig hearts.