Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up

Purpose

Brugada syndrome is a hereditary disease linked with an increased risk of sudden death that may require an implantable cardioverter-defibrillator (ICD) in order to halt the arrhythmic events. The aim of this study was to identify possible triggers for appropriate ICD therapies in patients with Brugada syndrome, focusing on their past and current therapeutic profiles.

Methods

Thirty patients with high-risk Brugada syndrome, with ICD implanted at the Coimbra Hospital and University Center, were enrolled. Patients were questioned about their Brugada syndrome history, previous cardiac events, comorbidities, present and past medications, and physical activity. Patients were followed up during 5.8?±?5.3 years. The ICD was interrogated, and arrhythmic events and device therapies were recorded. The cohort who received appropriate ICD therapies was compared with the remaining patients to determine the potential link between clinical variables and potentially fatal arrhythmic events.

Results

More than half of the patients (53.3%) took at least one non-recommended drug, and 16.7% received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was a tendency for more appropriate ICD therapies in patients who took unsafe drugs (85.7 versus 45.5%, p?=?0.062), and the mean time between unsafe drug intake and appropriate ICD therapies was 3.8?±?7.5 days.

Conclusions

This study revealed that the medical community is still unaware of the pharmacological restrictions imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have a higher risk of ventricular arrhythmic events.

     

Exercise and Doxorubicin Treatment Modulate Cardiac Mitochondrial Quality Control Signaling

The cross-tolerance effect of exercise against heart mitochondrial-mediated quality control, remodeling and death-related mechanisms associated with sub-chronic Doxorubicin (DOX) treatment is yet unknown. We therefore analyzed the effects of two distinct chronic exercise models (endurance treadmill training—TM and voluntary free wheel activity—FW) performed during the course of the sub-chronic DOX treatment on mitochondrial susceptibility to permeability transition pore (mPTP), apoptotic and autophagic signaling and mitochondrial dynamics. Male Sprague–Dawley rats were divided into six groups (n = 6 per group): saline sedentary (SAL + SED), SAL + TM (12-weeks treadmill), SAL + FW (12-weeks voluntary free-wheel), DOX + SED [7-weeks sub-chronic DOX treatment (2 mg kg^?1 week^?1)], DOX + TM and DOX + FW. Apoptotic signaling and mPTP regulation were followed by measuring caspase 3, 8 and 9 activities, Bax, Bcl2, CypD, ANT, and cophilin expression. Mitochondrial dynamics (Mfn1, Mfn2, OPA1 and DRP1) and auto(mito)phagy (LC3, Beclin1, Pink1, Parkin and p62)-related proteins were semi-quantified. DOX treatment results in augmented mPTP susceptibility and apoptotic signaling (caspases 3, 8 and 9 and Bax/Bcl2 ratio). Moreover, DOX decreased the expression of fusion-related proteins (Mfn1, Mfn2, OPA1), increased DRP1 and the activation of auto(mito)phagy signaling. TM and FW prevented DOX-increased mPTP susceptibility and apoptotic signaling, alterations in mitochondrial dynamics and inhibits DOX-induced increases in auto(mito)phagy signaling. Collectively, our results suggest that both used chronic exercise models performed before and during the course of sub-chronic DOX treatment limit cardiac mitochondrial-driven apoptotic signaling and regulate alterations in mitochondrial dynamics and auto(mito)phagy in DOX-treated animals.     

Effect of verapamil on regional coronary and myocardial perfusion during acute coronary occlusion

To elucidate the mechanism of action of the calcium antagonist verapamil, S-T segment mapping, retrograde coronary flow and regional coronary resistance were studied in 28 dogs subjected to acute coronary occlusion. Retrograde coronary flow was measured directly through catheterization of the distal occluded coronary artery. Regional coronary resistance was calculated by dividing mean distal coronary pressure by coronary flow. Verapamil (0.8 mg/kg) administered intravenously to eight dogs 30 minutes before coronary occlusion significantly reduced S-T segment elevation as compared with occlusion alone (p < 0.025); heart rate and diastolic pressure were also reduced (p < 0.05) but systolic pressure remained essentially unchanged. When verapamil was given to seven dogs within 30 minutes after coronary occlusion, there was a significant increase in retrograde coronary flow (p < 0.05) and a decrease in regional coronary resistance (p < 0.05). Simultaneously, heart rate and heart rate-blood pressure product declined significantly (p < 0.05), suggesting a reduction in myocardial oxygen consumption. Systolic blood pressure was unaltered, and diastolic pressure decreased only transiently. In 13 control dogs there was no significant change in any of these variables during the observation period. Thus, verapamil during acute coronary occlusion protects the ischemic myocardium by both increasing perfusion and reducing myocardial oxygen consumption.     

Congenital Horner’s Syndrome Associated with Unilateral Agenesis of the Internal Carotid Artery and Unusual Aortic Arch Anomaly

Unilateral congenital agenesis of the internal carotid artery (ICA) is a very rare vascular anomaly. Rarely, congenital Horners syndrome has been associated with agenesis of the ICA. This article describes a rare case of congenital Horners syndrome in a patient with ICA agenesis and very unusual aortic arch anomaly. This study was done at Zonguldak Karaelmas University, Faculty of Medicine, No financial support was required for this study.     

Rectovaginal septum endometriosis: a disease with specific diagnosis and treatment

BACKGROUND: The involvement of the rectovaginal septum, of rectum and sigmoid by endometriosis leads to intense symptoms as dysmenorrhea, pelvic pain, deep dyspareunia, tenesmus and hematochezia in young and middle aged women during periods. The diagnosis can be made by tipycal history and vaginal examination, rectal examination, barium enema, proctoscopy and so on. The indications of operation include severe clinic symptoms and failed conservative therapy. The treatment of choice for this type of endometriosis is the surgical resection of affected tissue, in order to relieve patient symptoms, and avoid disease progression. The correct assessment as to the presence and extension of the endometriosis-affected sites such as the rectum, uterosacral ligaments and rectovaginal septum is extremely important to provide better results with the surgical treatment of endometriosis. AIM: To describe the main aspects related to rectovaginal septum endometriosis and offer the general surgeon some information about this enigmatic disease. CONCLUSION: Rectovaginal septum endometriosis is a frequent disease, with specific diagnosis and treatment.     

Serum level of beta-chemokine RANTES in patients with coronary artery disease

Chronic inflammatory process plays an important, as still not clear, role in pathophysiology of coronary artery disease (CAD), especially in acute coronary syndromes. Chemokines are present in atherosclerotic plaques and are essential factors in the recruitment of leukocytes and stabilization of atherosclerotic lesions. The aim of the study was the evaluation of RANTES serum level in patients with stabile CAD and seeking for correlations between RANTES serum level and progression of atherosclerotic lesions. The study included 83 patients from 22 to 87 years old, 41 women (mean age 61,2 +/- 12,5) and 42 men (mean age 58,8 +/- 15,4), who were admitted to the Cardiology Department for coronarography. After coronarography the patients were separated in 4 groups according to the presence of atherosclerotic lesions. Patients with atherosclerotic lesions were also divided depending on the severity of anginal pains to CCS II or CCS III classes. Blood samples for the measurement of RANTES serum level were taken at baseline conditions on the day after the admittance to the hospital. RANTES serum level was measured by enzyme-linked immunoabsorbent assay (ELISA) kit system (Endogen, MA, USA). There was not statistically significant differance in RANTES serum level between patients with CAD and subjects without atherosclerotic lesions in coronary arteries with or without arterial hypertension. Significantly higher levels of RANTES were observed in patients with atherosclerotic lesions in coronary arteries and anginal pains in CCS II class, than in patients with atherosclerotic lesions in coronary arteries and anginal pains in CCS II class, as well as in subjects without atherosclerotic lesions (respectively 58.5 vs 42.1 pg/ml and 54.5 vs 41.9 pg/ml, p<0.01). Significant positive corellations were found in patients with CAD between RANTES serum level and systolic blood pressure (r Pearson 0,291, p<0.05), and cholesterol (R Spearman 0.289, p<0.05). In all patients analysis of regression found significant correlation between RANTES serum level and systolic blood pressure (p 0.296, B 0.391, p<0.007). These results may indicate the active implication of chemokines in the pathophysiology of atherosclerotic lesions.     

Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice

BACKGROUND & AIMS: Sterol carrier protein 2 (SCP-2) enhances sterol cycling and facilitates cholesterol translocation between intracellular organelles and plasma membrane in cultured cells, including hepatocytes. We examined the role of SCP-2 in hepatic cholesterol and lipid trafficking through the sinusoidal and canalicular secretory pathways of the liver in vivo. METHODS: Recombinant adenovirus-mediated SCP-2 gene transfer was used to obtain hepatic overexpression of SCP-2 in C57BL/6 mice. RESULTS: SCP-2 overexpression in the mouse liver resulted in an 8-fold increase of SCP-2 protein levels and determined various effects on lipid metabolism. It decreased high-density lipoprotein cholesterol and increased low-density lipoprotein (LDL) cholesterol concentrations. The expressions of hepatic LDL receptor, apolipoprotein (apo) A-I, apoB, and apoE were decreased. SCP-2 overexpression also increased hepatic cholesterol concentration, associated with decreased cholesterol neosynthesis. Increased biliary cholesterol and bile acid secretion, bile acid pool size, and intestinal cholesterol absorption were also observed. CONCLUSIONS: These results indicate that modulation of SCP-2 expression in the liver determines important modifications on lipoprotein metabolism, hepatic cholesterol synthesis and storage, biliary lipid secretion, bile acid metabolism, and intestinal cholesterol absorption.