Pulmonary delivery of flecainide causes a rate-dependent predominant effect on atrial compared with ventricular depolarization duration revealed by intracardiac recordings in an intact porcine model.

BACKGROUND: Pulmonary delivery of flecainide results in the rapid conversion of atrial fibrillation (AF) to normal sinus rhythm in large-animal models and is safe and well-tolerated by normal human volunteers. OBJECTIVE: We investigated the effects of pulmonary delivery of flecainide on atrial and ventricular depolarization and repolarization duration. METHODS: Intratracheal instillation (1.5 mg/kg, rapid push) of flecainide or sterile water (placebo) was performed in 12 closed-chest, anesthetized Yorkshire pigs with a catheter positioned at the bifurcation of the main bronchi. High-resolution electrograms obtained from catheters fluoroscopically positioned in the right atrium and left ventricle circumvented measurement errors due to the fusion of P and T waves in surface leads when rapid heart rates shortened the TP interval. Pacing was achieved using electrical stimuli delivered via right atrial catheter electrodes. RESULTS: During sinus rhythm (98 ± 4.7 beats/min), intratracheal flecainide caused comparable (P = 0.56) increases in atrial depolarization (P a ) duration by 22% (39.8 ± 3.2 to 48.7 ± 3.3 milliseconds) and left ventricular (LV) QRS complex duration by 20% (47.9 ± 1.6 to 57.3 ± 1.8 milliseconds) at peak effect at 2 minutes post-dosing. During right atrial pacing at 180 beats/min, Pa duration increased by 55% (37.0 ± 2.0 to 57.2 ± 1.6 milliseconds; P < 0.0001). The atrial response was greater (p = 0.001) than the 30% increase in LV QRS complex duration (46.6 ± 1.7 to 60.6 ± 2.5 milliseconds; P = 0.005). Pa duration and QRS complex duration were unchanged by placebo independent of pacing (P ≥ 0.4 for both). Atrial repolarization duration (PTa ; P = 0.46) and QTc interval (P = 0.49) remained unchanged. CONCLUSION: Intratracheal flecainide exerts a rate-dependent, predominant effect on atrial compared with ventricular depolarization duration. Pulmonary delivery of flecainide could facilitate AF conversion to sinus rhythm with reduced ventricular proarrhythmia risk.

Total dissolved iron and hydrogen peroxide determination using the PhotoMetrixPRO application: A portable colorimetric analysis tool for controlling important conditions in the solar photo-Fenton process.

The use of the solar photo-Fenton process for water treatment requires monitoring of the main conditions, especially the total dissolved iron concentration and the consumption of hydrogen peroxide. In this study, a new methodology using the PhotoMetrixPRO application was validated for rapid monitoring of total dissolved iron and hydrogen peroxide concentrations, and was tested in the solar photo-Fenton process. A comparison was made between the results obtained using a reference spectrophotometric method and the PhotoMetrixPRO application employing a portable device. Both methods were validated in terms of linearity, sensitivity, precision, robustness, and matrix effects. The degree of dispersion between the series of measurements obtained using UV-vis and portable device tool was low and was in compliance with the established Brazilian and ICH validation criteria. Additionally, PhotoMetrixPRO enabled the use of a smaller sample volume. The total volume generated of each sample is 1 mL, reducing 6 and 10 times the wastes produced in different validated methods. These results evidencing that the miniaturization can provide positive advantages in terms of simplicity, cost effectiveness, and less environmental impact. PhotoMetrixPRO offers significant advantages including rapid analysis, smaller sample volumes, and greater portability and accessibility.

Optimizing flecainide plasma concentration profile for atrial fibrillation conversion while minimizing adverse ventricular effects by rapid, low-dose intratracheal or intravenous administration.

BACKGROUND: We investigated whether rapid administration of a low dose of flecainide, either intratracheally or intravenously (IV), could accelerate conversion of atrial fibrillation (AF) while reducing adverse ventricular effects. METHODS: Flecainide was delivered via intratracheal administration at 1.5 mg/kg bolus and compared to IV infusion at 1.0 mg/kg over 2 min (lower-dose, rapid) and 2.0 mg/kg over 10 min (ESC guideline) in closed-chest, anesthetized Yorkshire pigs. Catheters were fluoroscopically positioned in right atrium to measure atrial depolarization (Pa) duration and left ventricle (LV) to measure QRS complex duration and contractility (LV dP/dt) during atrial pacing at 140 beats/min. Flecainide was delivered intratracheally via a catheter positioned at the bifurcation of the main bronchi. AF was induced by intrapericardial administration of acetylcholine followed by burst pacing. RESULTS: Flecainide reduced AF duration similarly by intratracheal and IV delivery. Peak plasma levels were comparable but Tmax differed and coincided with peaks in Pa prolongation. The area under the curve indicating sustained plasma levels was greater for higher-dose, slow IV flecainide than for either intratracheal instillation (by 32%) or lower-dose, rapid IV infusion (by 88%). As a result, higher-dose, slow IV flecainide caused 58% (p < 0.03) and 48% (p < 0.006) greater increases in QRS complex duration and 61% and 96% (both, p < 0.02) greater reductions in contractility compared to intratracheal and lower-dose, rapid IV flecainide, respectively. CONCLUSION: Lower-dose, rapid flecainide, delivered either intratracheally or IV, optimizes the plasma concentration profile for effective conversion of AF while minimizing adverse effects on QRS complex duration and LV contractility.

Accelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary delivery of flecainide acetate in a porcine model.

BACKGROUND: Pulmonary delivery of antiarrhythmic agents has the potential to increase rapidly targeted drug concentrations in pulmonary veins and left atrium to terminate atrial fibrillation (AF). OBJECTIVE: We evaluated the efficacy of flecainide administered via intratracheal instillation in terminating AF in a reliable preclinical model. METHODS: In 11 closed-chest anesthetized Yorkshire pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of 102.5 mM solution) followed by burst pacing and allowed to continue for 2 minutes before intratracheal flecainide (0.4 or 0.75 mg/kg) administration. RESULTS: Both the 0.4- and 0.75-mg/kg doses of intratracheal flecainide significantly reduced AF duration by 35% (P = .02) and 54% (P = .001), respectively, compared to no-drug baseline. There was a strong inverse correlation (r2 = 0.87; P = .03) between the duration of AF and the change in atrial depolarization duration in response to intratracheal flecainide. Induction of AF resulted in a marked increase in ventricular rate and corresponding reduction in mean arterial pressure, which returned to baseline levels within 5 minutes after conversion. CONCLUSION: Intratracheal flecainide instillation is effective in rapidly converting AF to normal sinus rhythm and restoring mean arterial pressure and heart rate to baseline values. The basis for this efficacy is likely rapid absorption of the drug through the lungs and delivery as a first-pass bolus to the left atrial and ventricular chambers and then to the coronary arterial circulation. The anti-AF effect of flecainide is inversely correlated with the drug's prolongation of atrial depolarization, implicating slowing of intra-atrial conduction as an important mechanism underlying conversion of AF to normal sinus rhythm.

Circulating catecholamines are associated with biobehavioral factors and anxiety symptoms in head and neck cancer patients.

Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamine secretion profiles in head and neck cancer patients. The present study investigated plasma norepinephrine and epinephrine levels in head and neck squamous cell carcinoma (HNSCC) patients and patients with oral leukoplakia, as well as their association with clinicopathological and biobehavioral variables and anxiety symptoms. A total of 93 patients with HNSCC and 32 patients with oral leukoplakia were included. Plasma norepinephrine and epinephrine levels were measured by high performance liquid chromatography with electrochemical detection (HPLC-ED), and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Plasma norepinephrine and epinephrine concentrations were significantly higher in patients with oral and oropharyngeal squamous cell carcinoma (SCC) compared to non-cancer patients. Oral SCC patients displayed plasma norepinephrine levels about six times higher than oropharyngeal SCC patients, and nine times higher than oral leukoplakia patients (p < .001). Plasma epinephrine levels in oral SCC patients were higher compared to the oropharyngeal SCC (p = .0097) and leukoplakia (p < .0001) patients. Oropharyngeal SCC patients had higher plasma norepinephrine (p = .0382) and epinephrine levels (p = .045) than patients with oral leukoplakia. Multiple regression analyses showed that a history of high alcohol consumption was predictive for reduced plasma norepinephrine levels in the oral SCC group (p < .001). Anxiety symptom of "hand tremor" measured by the BAI was an independent predictor for higher plasma norepinephrine levels in HNSCC patients (ß = 157.5, p = .0377), while the "heart pounding/racing" symptom was independently associated with higher plasma epinephrine levels in the oropharyngeal SCC group (ß = 15.8, p = .0441). In oral leukoplakia patients, sleep deprivation and worse sleep quality were independent predictors for higher plasma norepinephrine levels, while severe tobacco consumption and higher anxiety levels were factors for higher plasma epinephrine levels. These findings suggest that head and neck cancer patients display sympathetic nervous system hyperactivity, and that changes in circulating catecholamines may be associated with alcohol consumption, as well as withdrawal-related anxiety symptoms.

Natural occurrence of fumonisins and characteristics of pamonhas sweet type from Southern Brazil.

Fresh and frozen pamonhas, a native Brazilian food made with sweet corn (Zea mays L.), similar to the Mexican tamal, which has been incorporated into the country's diet, were investigated for fumonisins (FBs: FB1 and FB2) contamination and product characteristics. The laboratory conditions of the applied fumonisins method with liquid chromatography and fluorescence detection were validated. Five out of the total samples showed FBs contamination above the national maximum level of 1000-1500 µg/kg. Despite this, in 59.6% (31) of the samples FB1 and in 23.1% (12) FB2 could be detected. The pamonhas characteristics did not show uniformity among the brands surveyed. The moisture content of 59.4% and water activity of 0.97 for both (fresh and frozen) samples showed to be suitable conditions for fungal growth. One sample had a quite high pH. It is essential to establish guidance criteria for pamonha production by the regulatory agencies.

Comparison between two functional mobility scales for Parkinson's disease directly applied to physical therapy practice: cross-cultural adaptation and measurement properties.

BACKGROUND: The Modified Parkinson Activity Scale (PASm) and Lindop Parkinson's Disease Mobility Assessment (LPA) scales were developed to assess the functional mobility in patients with Parkinson's disease (PD) being directly applied to physical therapy practice. AIM: To translate and perform the cross-cultural adaptation of PASm and LPA scales to Portuguese-Brazil, and to analyze some psychometric properties. DESIGN: Cross-cultural validation study. SETTING: Clinical environment. POPULATION: Thirty-two Brazilian subjects with Parkinson's disease. METHODS: The study consisted of two stages: 1) cross-cultural adaptation process; 2) evaluation of psychometric properties. RESULTS: Considering the total score, the interrater and test-retest reliabilities showed a coefficient of intra-class correlation that ranged between 0.97 and 0.98. Both scales showed excellent internal consistency (α=0.83 and 0.94). Positive correlations were obtained between the Brazilian versions of the LPA and PASm and PAS (ρ=0.63 and 0.92). The concurrent validity between scales and part III of UPDRS, established a moderate negative correlation, (ρ=-0.54 and -0.65). The one way ANOVA showed that LPA-Brazil discriminates the individual with PD between all stages according HY, and the PASm- Brazil between mild and severe stages, and moderate and severe. The MDC of scales ranging from 1 to 2 points. There was Ceiling effect only for the LPA-Brazil. CONCLUSIONS: Brazilian versions of PASm and LPA are valid and reliable instruments to assess the functional mobility in patients with PD, being directly applied to physical therapy clinical practice. CLINICAL REHABILITATION IMPACT: The major goal of physical therapy in PD is to maintain functional mobility and independence of the patient. The results of study are relevant and could improve the physical therapy practice in Brazil, since it provides the Brazilian version of two mobility scales (one of them recommended by the European Guidelines for Physical Therapy Practice in patients with Parkinson disease).

Parkinson Activity Scale: cross-cultural adaptation and reliability of the Brazilian version.

AIM: Following the substantial growth of the elderly population in Brazil, there has been an increase in cases of Parkinson's disease (PD), which raises the need for reliable and culturally adapted scales specific to the disease. The Parkinson Activity Scale (PAS) was developed in order to assess the activity level of people with PD through tasks related to mobility. The aims of the present study were to translate the cross-cultural adaptation of the PAS into Brazilian Portuguese and analyze its reliability during the "on" phase of PD. METHODS: A total of 25 patients with PD participated in the study. The intrarater reliability was evaluated using a test-retest design with a 1-week interval. RESULTS: The interrater reliability was tested twice on the same day by two different raters. The intraclass correlation coefficient (ICC), and the Bland and Altman plots were calculated to examine the test-retest and interrater reliabilities for total score of the PAS, whereas the weighted Kappa (Wk) was used to assess interrater agreement. The interrater ICC was 0.89 and Wk was 0.65 for the total score. For intrarater reliability, the total score ICC was 0.88. CONCLUSIONS: The present study suggests that the Brazilian version of the PAS is a reliable instrument for the assessment of mobility in elderly patients with PD.