Ziprasidone triggers inflammasome signaling via PI3K-Akt-mTOR pathway to promote atrial fibrillation.

BACKGROUND: Second-generation antipsychotics increase the risk of atrial fibrillation. This study explores whether the atypical antipsychotic ziprasidone triggers inflammasome signaling, leading to atrial arrhythmia. METHODS: Electromechanical and pharmacological assessments were conducted on the rabbit left atria (LA). The patch-clamp technique was used to measure ionic channel currents in single cardiomyocytes. Detection of cytosolic reactive oxygen species production was performed in atrial cardiomyocytes. RESULTS: The duration of action potentials at 50 % and 90 % repolarization was dose-dependently shortened in ziprasidone-treated LA. Diastolic tension in LA increased after ziprasidone treatment. Ziprasidone-treated LA showed rapid atrial pacing (RAP) triggered activity. PI3K inhibitor, Akt inhibitor and mTOR inhibitor abolished the triggered activity elicited by ziprasidone in LA. The NLRP3 inhibitor MCC950 suppressed the ziprasidone-induced post-RAP-triggered activity. MCC950 treatment reduced the reverse-mode Na+/Ca2+ exchanger current in ziprasidone-treated myocytes. Cytosolic reactive oxygen species production decreased in ziprasidone-treated atrial myocytes after MCC950 treatment. Protein levels of inflammasomes and proinflammatory cytokines, including NLRP3, caspase-1, IL-1ß, IL-18, and IL-6 were observed to be upregulated in myocytes treated with ziprasidone. CONCLUSIONS: Our findings suggest ziprasidone induces atrial arrhythmia, potentially through upregulation of the NLRP3 inflammasome and enhancement of reactive oxygen species production via the PI3K/Akt/mTOR pathway.

The Effect of Estrogen on Intracellular Ca2+ and Na+ Regulation in Heart Failure.

Contradictory findings of estrogen supplementation in cardiac disease highlight the need to investigate the involvement of estrogen in the progression of heart failure in an animal model that lacks traditional comorbidities. Heart failure was induced by aortic constriction (AC) in female guinea pigs. Selected AC animals were ovariectomized (ACOV), and a group of these received 17ß-estradiol supplementation (ACOV+E). One hundred-fifty days post-AC surgery, left-ventricular myocytes were isolated, and their electrophysiology and Ca2+ and Na+ regulation were examined. Long-term absence of ovarian hormones exacerbates the decline in cardiac function during the progression to heart failure. Estrogen supplementation reverses these aggravating effects.

Lemnalol Modulates the Electrophysiological Characteristics and Calcium Homeostasis of Atrial Myocytes.

Sepsis, an inflammatory response to infection provoked by lipopolysaccharide (LPS), is associated with high mortality, as well as ischemic stroke and new-onset atrial arrhythmia. Severe bacterial infections causing sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic multi-organ dysfunction and finally death. LPS challenge-induced inflammatory responses during sepsis may increase the likelihood of the arrhythmogenesis. Lemnalol is known to possess potent anti-inflammatory effects. This study examined whether Lemnalol (0.1 µM) could modulate the electrophysiological characteristics and calcium homeostasis of atrial myocytes under the influence of LPS (1µg/mL). Under challenge with LPS, Lemnalol-treated LA myocytes, had a longer AP duration at 20%, 50% and 90% repolarization of the amplitude, compared to the LPS-treated cells. LPS-challenged LA myocytes showed increased late sodium current, Na+-Ca2+ exchanger current, transient outward current, rapid component of delayed rectifier potassium current, tumor necrosis factor-α, NF-κB and increased phosphorylation of ryanodine receptor (RyR), but a lower L-type Ca2+ current than the control LA myocytes. Exposure to Lemnalol reversed the LPS-induced effects. The LPS-treated and control groups of LA myocytes, with or without the existence of Lemnalol. showed no apparent alterations in the sodium current amplitude or Cav1.2 expression. The expression of sarcoendoplasmic reticulum calcium transport ATPase (SERCA2) was reduced by LPS treatment, while Lemnalol ameliorated the LPS-induced alterations. The phosphorylation of RyR was enhanced by LPS treatment, while Lemnalol attenuated the LPS-induced alterations. In conclusion, Lemnalol modulates LPS-induced alterations of LA calcium homeostasis and blocks the NF-κB pathways, which may contribute to the attenuation of LPS-induced arrhythmogenesis.

The implication of seniority of supervising attending surgeon on the reexploration rate following elective coronary artery bypass grafting.

BACKGROUND AND AIMS: During coronary artery bypass graft (CABG) surgery, the residual hemostasis procedures, from weaning cardiopulmonary bypass to closing sternotomy, are always completed by residents and supervised by attending surgeons. We want to evaluate the teaching effectiveness for residents under the supervision of attending surgeons with different levels of seniority. MATERIALS AND METHODS: Between January 1st 2001 and December 31st 2010, 2279 consecutive CABG surgeries were performed in our medical center. In total, 83 patients underwent a reexploration for postoperative bleeding. All causes of bleeding were identified and recorded. Competent attending surgeons were defined as having >3 years' experience and young attending surgeons with ≦3 years' experience. We compared the reexploration rate and aimed to identify the common sources of bleeding by the two groups. We also assessed the impact of attending experience on the outcomes and major complications after reexploration. RESULTS: There were 36 surgical bleeding and 17 non-surgical bleeding in the young group and 16 surgical bleeding and 14 non-surgical bleeding in the competent group. The young group experienced more mediastinal drainage before a reexploration and a longer time interval to a reexploration. However, both are without statistical significance. Furthermore, the young group has a significant longer hospital stay. The most common intra-pericardium surgical bleeding included two-stage cannulation, side branch of the left internal mammary artery (LIMA), and side branch of vein grafts. The most common extra-pericardium surgical bleeding included a puncture hole by sternal wires, LIMA bed, and fragile sternum. CONCLUSION: Young attending surgeons indeed had both higher incidence of reexploration and surgical bleeding after a CABG. However, the supervisor experience only impacted hospital stay, not major complications or mortality after a reexploration. This might imply the competent attending surgeons provide higher teaching effectiveness for the hemostasis procedure after CABG.

Effect of ovariectomy on intracellular Ca2+ regulation in guinea pig cardiomyocytes.

This study addressed the hypothesis that long-term deficiency of ovarian hormones after ovariectomy (OVx) alters cellular Ca2+-handling mechanisms in the heart, resulting in the formation of a proarrhythmic substrate. It also tested whether estrogen supplementation to OVx animals reverses any alterations to cardiac Ca2+ handling and rescues proarrhythmic behavior. OVx or sham operations were performed on female guinea pigs using appropriate anesthetic and analgesic regimes. Pellets containing 17ß-estradiol (1 mg, 60-day release) were placed subcutaneously in selected OVx animals (OVx + E). Cardiac myocytes were enzymatically isolated, and electrophysiological measurements were conducted with a switch-clamp system. In fluo-4-loaded cells, Ca2+ transients were 20% larger, and fractional sarcoplasmic reticulum (SR) Ca2+ release was 7% greater in the OVx group compared with the sham group. Peak L-type Ca2+ current was 16% larger in OVx myocytes with channel inactivation shifting to more positive membrane potentials, creating a larger "window" current. SR Ca2+ stores were 22% greater in the OVx group, and these cells showed a higher frequency of Ca2+ sparks and waves and shorter wave-free intervals. OVx myocytes showed higher frequencies of early afterdepolarizations, and a greater percentage of these cells showed delayed afterdepolarizations after exposure to isoprenaline compared with sham myocytes. The altered Ca2+ regulation occurring in the OVx group was not observed in the OVx + E group. These findings suggest that long-term deprivation of ovarian hormones in guinea pigs lead to changes in myocyte Ca2+-handling mechanisms that are considered proarrhythmogenic. 17ß-Estradiol replacement prevented these adverse effects.NEW & NOTEWORTHY Ovariectomized guinea pig cardiomyocytes have higher frequencies of Ca2+ waves, and isoprenaline-challenged cells display more early afterdepolarizations, delayed afterdepolarizations, and extra beats compared with sham myocytes. These alterations to Ca2+ regulation were not observed in myocytes from ovariectomized guinea pigs supplemented with 17ß-estradiol, suggesting that ovarian hormone deficiency modifies cardiac Ca2+ regulation, potentially creating proarrhythmic substrates.

New vascular ring connectors in surgery for intramural haematoma of the abdominal aorta progressing to rupture.

Aortic intramural haematoma is similar to classic aortic dissection, which causes a life-threatening medical condition, and immediate diagnosis and treatment are crucial. The optimal therapy for intramural haematoma of the abdominal aorta remains controversial. Conservative medical management is usually the first choice of treatment for uncomplicated cases. Surgical intervention is usually required for complicated intramural haematomas of the abdominal aorta, including conventional open repair and endovascular treatment with stent-grafts. A new vascular ring connector that achieves a quick, blood-sealed and sutureless anastomosis has been designed for aortic dissection. We herein report a case of intramural haematoma of the abdominal aorta, progressing to rupture on day 14 after onset, which had successful aortic repair with the new vascular ring connector. The new vascular ring connector could be an alternative method for the treatment of complicated intramural haematomas of the abdominal aorta.

Two-stage resection for malignant colonic obstructions: the timing of early resection and possible predictive factors.

AIM: To study potential predictive factors for early radical resection in two-stage resection for left malignant colonic obstruction. METHODS: Thirty-eight cases of left-sided obstructive colon cancer undergoing two-stage operations were reviewed between January 1998 and August 2008. Patients were classified into two groups (n = 19 each): early radical resection (interval ≤ 10 d) and late radical resection (interval > 10 d). Baseline demographics, post-diversion outcome, perioperative data, tumor characteristics, outcome and complications were analyzed. RESULTS: The baseline demographics revealed no differences except for less pre-diversion sepsis in the early group (P < 0.001) and more obstruction days in the late group (P = 0.009). The mean intervals of early and late radical resections were 7.9 ± 1.3 d and 17.8 ± 5.5 d, respectively (P < 0.001). After diversion, the presence of bowel sounds, flatus, removal of the nasogastric tube and the resumption of oral feeding occurred earlier in the early group. The operation time and duration of hospital stay were both significant reduced in the early group. Complication rates did not differ between groups. CONCLUSION: The earlier recovery of bowel function seems to be predictive of early radical resection. In contrast, pre-diversion sepsis and more obstruction days were predictive of delayed radical resection.

Early recognition of an entrapped pulmonary artery catheter by blood leaking into the syringe and thermistor connector during cardiac surgery.

An 84-year-old male was scheduled for coronary artery bypass graft surgery under general anesthesia. During cardiopulmonary bypass, the leakage of blood into the syringe being used for balloon inflation and the thermistor connector of the pulmonary artery catheter (PAC) was detected. Resistance was encountered when trying to withdraw the PAC. A surgical suture of the right atrium cannulation was stitched to PAC and was immediately released. Early detection of surgical damage to PAC and recognition of the entrapped PAC by gently withdrawing it avoided possible life-threatening complications, including pulmonary air embolism, and the inevitable of resternotomy. Transesophageal echocardiography, chest radiography, and fluoroscopy can help confirm any postoperative surgical damage following closure of the sternum or while in the intensive care unit.

Left atrial appendage aneurysm with paroxysmal atrial fibrillation.

Aneurysm of the left atrial appendage is extremely rare, and afflicted patients most commonly present with atrial tachyarrhythmia or thromboembolism. For these patients, resection of the aneurysm is the recommended and preferred therapy. We present the case of a 57-year-old woman who was found incidentally to have a large aneurysm of the left atrial appendage presenting as atrial fibrillation. After surgical intervention with resection of the aneurysm and a Cox maze III procedure, the patient recovered and was discharged in sinus rhythm.

Efficacy and safety of transnasal butorphanol for pain relief after anal surgery.

AIM: To compare the analgesic properties and efficacy of transnasal butorphanol with intramuscular meperidine after anal surgery. METHODS: Sixty patients who underwent fistulectomy were enrolled in the study from January 2006 to December 2007. They were randomly divided into transnasal butorphanol (n = 30) or intramuscular meperidine (n = 30) treatment groups. Assessment of postoperative pain was made using a visual analogue scale (VAS). The VAS score was recorded 6 h after the completion of surgery, before receiving the first dose of analgesic, 60 min after analgesia and the next morning. Any adverse clinical effects such as somnolence, dizziness, nausea or vomiting were recorded. Satisfaction with narcotic efficacy, desire to use the particular analgesic in the future and any complaints were recorded by patients using questionnaires before being discharged. RESULTS: Forty-two men and eighteen women were included in the study. There were no significant differences in VAS scores between the groups within 24 h. Length of hospital stay and the incidence of adverse effects between the groups were similar. In addition, most patients were satisfied with butorphanol nasal spray and wished to receive this analgesic in the future, if needed. CONCLUSION: Butorphanol nasal spray is effective for the relief of pain after fistulectomy. However, it offered patients more convenient usage and would be suitable for outpatients.

Monotherapy with anti-CD20 monoclonal antibody in a heart transplant recipient with sick sinus syndrome and posttransplantation lymphoproliferative disorder: a case report.

Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with an incidence of 0.8% to 20% in heart transplant (HTx) recipients, and standard treatment may be too toxic in some cases. Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies and has been demonstrated effective in combination with chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Cardiotoxicity with CHOP remains a major concern for treating HTx recipients with PTLD, however. We present a case of an HTx recipient with sick sinus syndrome and PTLD who was successfully treated with rituximab alone, avoiding the cardiotoxicity of CHOP. The cardiotoxicity induced by CHOP should be kept in mind in HTx recipients with PTLD, especially when there is an existing heart problem in such recipients. Monotherapy with rituximab can be considered a safe choice.

Comparison of clinical effects between warm water spray and sitz bath in post-hemorrhoidectomy period.

BACKGROUND: Warm water sitz bath is advised for a variety of anorectal disorders. However, preparation of the sitz bath is sometimes difficult for patients. As an alternative to the sitz bath, we have adapted a water spray method. A randomized, controlled study was conducted to determine if the water spray method has similar effects to the sitz bath in the post-hemorrhoidectomy period and it is easy to carry out. METHODS: A total of 120 patients were randomly assigned to water spray or sitz bath groups. All patients received analgesics and a fiber-rich diet after hemorrhoidectomy. Clinical parameters including pain, irritation (burning or itching sensations), hygiene, convenience, and overall satisfaction were evaluated by a visual analog scale to assess treatment outcome in both groups. RESULTS: There was no obvious difference in age, gender distribution, body mass index, or duration of disease between groups. There were no significant difference in scores for postoperative pain (p = 0.23), irritation (p = 0.48), or hygiene (p = 0.725) between groups. However, the water spray group reported significantly greater convenience (p < 0.05) and higher overall satisfaction (p < 0.05) compared with the sitz bath group. At the end of the 4-week postoperative follow-up period, 90% of patients in the watery spray group and 93% of patients in the sitz bath group showed complete wound healing. There were no significant differences in postoperative complications between groups. CONCLUSION: Our results demonstrate that the water spray method could provide a safe and reliable alternative to the sitz bath for post-hemorrhoidectomy care. Furthermore, the water spray method could be used instead of the sitz bath as a more convenient and satisfactory form of treatment.