Glycaemic, insulin and ghrelin responses to traditional South Asian flatbreads in diabetic and healthy subjects.

In the South-East Asian subcontinent, flatbreads contribute the main portion of carbohydrate to a meal. There are no specific data on the effect of different flatbreads on satiety and recurrent hunger, as indicated by the duration of ghrelin suppression after a meal. The present study was designed to examine the glycaemic, insulin and ghrelin responses to traditional subcontinental breads in type 2 diabetic subjects and healthy volunteers. For this purpose, twelve normoglycaemic healthy volunteers and ten type 2 diabetic patients, in the fasting state, consumed one of five common flatbreads on consecutive days. Capillary blood glucose was examined in the fasting state and serially for 5 h after a meal. Serum insulin and ghrelin levels were determined at hourly intervals for 5 h after the consumption of bran and plain chapatti flatbreads. The incremental area under the curve (iAUC) was calculated for glycaemic and insulin responses, while the net AUC was used to assess the ghrelin response. The results showed that glycaemic and insulin iAUC were lowest for bran chapatti, and highest for plain chapatti. Furthermore, bran chapatti showed maximum ghrelin suppression in both normal and diabetic groups. In conclusion, the low-glycaemic index bran chapatti flatbread had a lower postprandial glycaemic excursion and insulin response, and a more prolonged suppression of ghrelin levels, compared with the plain chapatti flatbread, and in each case, the difference was greater for the diabetic subjects than for the normal subjects. The inclusion of these flatbreads in the diabetic/weight-reducing diet may help weight loss by promoting satiety and reducing hyperinsulinaemia.

Pharmacological prevention and termination of focal atrial fibrillation.

AIMS: Patients undergo ablation for focal atrial fibrillation (AF) as a result of failure of anti-arrhythmic drugs. Our basic studies have implicated cholinergic and adrenergic neurotransmitter release as the underlying mechanism for focal AF. Therefore, we tested the efficacy of a combination of sodium channel-blocking agents with additional vagolytic properties and a ß-blocker to terminate and prevent focal AF. METHODS AND RESULTS: In 18 Na-pentobarbital-anaesthetized dogs, after a right or left thoracotomy, acetylcholine (Ach, 0.5 cc, 100 mM) was injected into a fat pad containing ganglionated plexi (GP) or applied on an atrial appendage (AA) to induce focal firing at the pulmonary veins (PVs) or AA, respectively. Disopyramide (2-4 mg/kg, n= 6) or quinidine (3-6 mg/kg, n= 12) combined with esmolol or propranolol (1 mg/kg, n= 13 and 5, respectively) were slowly injected to terminate (Group I, n= 12) or prevent (Group II, n= 6) Ach-induced sustained focal AF. In another four dogs, only the sodium channel-blocking agents with additional vagolytic properties or only the ß-blocker was injected prior to or after the initiation of focal AF. At baseline, the mean duration of AF induced by Ach was 26 ± 4 min. Group I: After drugs, Ach-induced AF duration was 3 ± 1 min (P< 0.001). Group II: Prior to drugs, Ach-induced AF lasted for 19 ± 3 min. With the drug combination the duration of Ach-induced AF, decreased to 6 ± 1/min, P< 0.001. Either quinidine or propranolol alone did not change the duration of Ach-induced AF, mean 25 ± 10 min compared with Ach alone, 28 ± 16 min, P= 0.2. CONCLUSIONS: Type IA (cholinergic antagonist) plus Type II (ß-adrenergic antagonist) provides significant prevention and suppression of focal AF arising at PV and non-PV sites.

Prediction model for determining important factors of success of external cephalic version.

BACKGROUND: The External cephalic version (ECV) is a skill as well as an art that could be easily acquired. It has become a valuable option in the management of breech foetus at term. Aims of this study were to determining those factors that were significantly associated with success of external cephalic version (ECV) procedure. METHOD: This prospective interventional study was conducted at Department of Obstetrics and Gynaecology, Unit-III, Services Hospital, Lahore, Pakistan from July 2007 to December 2009. Total of 56 patients who had undergone ECV was analysed descriptively and analytically. Univariate and multivariate data analysis was performed. Pre-procedural factors (gravidity, gestational age, amniotic fluid index, placental location, type of breech, maternal obesity, foetal weight), and factors associated with the procedure itself (abdominal wall musculature tone, uterine tone, maternal anxiety, maternal threshold for pain, engagement of breech, number of attempts) were assessed. RESULTS: Thirty-three patients were successfully converted to vertex presentation. In multivariate analysis, placenta, type of breach, station of breach and number of attempts (< or = 2 times) were significantly associated factors with ECV procedure. CONCLUSION: ECV is most likely to succeed when the patient has already one pregnancy and child birth, the breech is not engaged, and is flexed. Procedure is usually successful within one or two attempts, whereas ongoing attempts lead to increased maternal anxiety, lesser cooperation and ending in failure.

A new approach for estimation of body mass index using waist and hip circumference in type 2 diabetes patients.

BACKGROUND: Body mass index (BMI), derived by dividing weight (Kg) by the square of height (m), is a useful anthropometric parameter, with multiple applications. It is dependent upon accurate measurement of its component parameters. Where measurement of height and weight with calibrated instruments is not possible, other objective parameters are required to maintain accuracy. OBJECTIVES: We aimed to propose an alternate prediction model for the estimation of BMI based on statistical linear regression equation using hip and waist circumferences. Our objective was to ascertain the accuracy of estimated BMI when compared with observed BMI of patients, and to propose a model for BMI prediction which would overcome problems encountered in the prediction of body mass index of critically ill or immobile patients, needed for applications such as BMI based calculations in ventilation protocols in ICUs. METHODS: This cross sectional survey was done by reviewing hospital records of adult subjects of both genders (n=24,485; 10,687 males and 13,798 females), aged 20 years and above, who were diagnosed with type 2 diabetes. Two different prediction models were designed for males and females keeping morphological and physiological differences in gender. The measured waist and hip circumference values were used to estimate BMI. RESULTS: Data analysis revealed a significant linear relationship between BMI, waist and hip circumference in all categories [waist circumference (r=0.795, p=0.000), hip circumference (r=0.838, p=0.000)]. Estimated regression models for males and females were BMI=-10.71+0.212 (hip cir)+0.170 (waist circumference); and BMI=-15.168+0.143 (hip circumference)+0.30 (waist circumference) respectively. CONCLUSION: Estimation of BMI using this prediction model based upon measured waist and hip circumferences, is an alternate and reliable method for the calculation of BMI.

Comparison of atrial fibrillation inducibility by electrical stimulation of either the extrinsic or the intrinsic autonomic nervous systems.

OBJECTIVES: To study the effects of bilateral vagosympathetic nerve stimulation (VNS) and ganglionated plexi stimulation (GPS) on atrial refractoriness and inducibility of atrial fibrillation (AF). METHODS: Studies were performed in fourteen adult mongrel dogs anesthetized with Na-pentobarbital, 30 mg/kg. VNS was achieved by insertion of wires into the left and right VN trunks. An octapolar catheter was attached to contact the right superior pulmonary vein (RSPV) and other octapolar catheter electrodes were sutured to the right atrial (RA) free wall and appendage (RAA). GPS was performed via a plaque electrode sutured to the fat pad containing the anterior right (AR) GP. VNS and GPS were matched to decrease heart rate by approximately 50%. Programmed stimulation delivered from the RSPV or RAA at 2x, 4x and 10x threshold (TH) allowed the determination of atrial refractory period (ARP) and the AF inducibility. The latter was quantitated by the cumulative window of vulnerability (WOV), i.e., the longest minus the shortest coupling interval during which AF was induced at 2x, 4x, 10x, TH combined. RESULTS: Programmed electrical stimulation at the RSPV showed that the ARP was significantly shorter for both VNS and GPS than baseline (baseline, 113 +/- 22 ms; VNS, 94 +/- 26 ms; GPS, 85 +/- 31 ms) but there was no significant difference in ARP between VNS and GPS. In contrast, the cumulative WOV was significantly wider with GPS (39 +/- 36 ms) than either the baseline state (1 +/- 1 ms) or with VNS (14 +/- 26 ms), p < 0.05. Moreover, pacing from RAA showed a significantly greater cumulative WOV for VNS (33 +/- 36 ms) vs both baseline and GPS (1 +/- 4 ms and 15 +/- 26 ms, respectively, p < 0.05). The heart rate slowing caused by GPS and VNS was not significantly different, 82 +/- 11/min vs 82 +/- 7/min. CONCLUSIONS: These data indicate a distinct functional separation of autonomic nerve innervation to the atria from the extrinsic and intrinsic nervous systems. AF is more liable to occur due to intrinsic nerve stimulation at the PVs whereas peripheral atrial sites are more readily inducible for AF due to the extrinsic neural input.

Identification of epidemiological risk factors for hepatitis C in Punjab, Pakistan.

BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV) is one of the major health issues in Punjab, Pakistan. About 3% of the world population have been infected by hepatitis C virus. The objective of this study was to find out significantly associated factors with Hepatitis C in the region. Demographic, socio-economic and clinical factors were taken in consideration to determine the predictive strength of these associated factors by the logistic regression model approach. METHODS: This was a hospital based case-control study of 400 patients; out of which 119 were controlled patients (HCV negative) while 281 were cases (HCV positive). Patients admitted in gastroenterology wards of Jinnah, Shaikh Zayed, and Mayo hospitals in Lahore city were interviewed to gather risk factors information. Data was collected in six months starting from April 2006 to September 2006. RESULTS: results from multiple linear logistic regression model for overall data showed that age (OR = 1.035, p = 0.001), history of blood transfusion (OR = 9.204, p = 0.004), history of hospitalization (OR = 2.979, p = 0.043), Tattooing (OR = 27.484, p = 0.013), family history of hepatitis (OR = 4.069, p = 0.000), surgical operation (OR = 4.290, p = 0.030) were found to have significant and positively association with Hepatitis C. CONCLUSION: Hence our estimated logit model can be used to predict the chance of hepatitis C under the presence or absence of certain significant factors.

An acute model for atrial fibrillation arising from a peripheral atrial site: evidence for primary and secondary triggers.

BACKGROUND: We previously demonstrated that acetylcholine (Ach) injected into cardiac ganglionated plexi (GP) causes pulmonary vein (PV) ectopy initiating atrial fibrillation (AF). OBJECTIVE: To determine the effects of Ach applied at non-PV sites. METHODS: Overall, 54 dogs were anesthetized with Na-pentobarbital. A right and left thoracotomy allowed the placement of multielectrode catheters to record from the superior PVs, mid portion of the atrium and the atrial appendages (AA). A monophasic action potential (MAP) was recorded from the AA. Ach (1, 10, 100 mM) was applied sequentially to the AA. RESULTS: In 19 of 26 animals, Ach 100 mM on the right (n = 15) or left (n = 4) AA induced focal, sustained AF (>or=10 minutes) with rapid regular firing (cycle length = 37 +/- 7 ms) at the AA. A clamp with teeth placed across the AA caused arrest in the AA. However, AF was sustained only when PV sites adjacent to the GP manifested complex fractionated atrial electrograms (CFAE). Clamping the AA prior to Ach (100 mM) application resulted in focal AF arising at the PVs but not at the AA. When a clamp without teeth was applied prior to Ach application, no AF at either AA or PV site could be induced. CONCLUSION: Isolation of the focal AF at the AA (primary trigger) by clamping caused cessation of activity in the AA, but AF continued due to secondary triggers arising from PVs. The possible mechanism(s) responsible for these findings are discussed, and various ancillary experiments (n = 28) were added to help elucidate mechanisms.

Autonomic mechanism for complex fractionated atrial electrograms: evidence by fast fourier transform analysis.

INTRODUCTION: The mechanism(s) underlying complex fractionated atrial electrograms (CFAE) is not well understood. We hypothesized that CFAE may be caused by enhanced activity of the intrinsic cardiac autonomic nervous system. METHODS AND RESULTS: In 35 anesthetized dogs, via a right or left thoracotomy, sustained atrial fibrillation was induced by local application of acetylcholine (ACh; 10, 100 mM) to the surface of the atrial appendage (AA) or by injection of ACh (10 mM) into the ganglionated plexi (GP). Fast Fourier transform analysis was performed from recordings at AA, atrial sites near the AA, mid portion of the atrium, atrial sites near the GP, and the pulmonary veins. After AF was induced with ACh either by topical application to the AA or by direct injection into the GP, CFAE exhibited a significant gradient of progressively decreasing dominant frequency and incidence of CFAE (CFAE%) from the GP toward distant sites, while regularity index progressively decreased in the opposite direction. Ablation of GP markedly attenuated CFAE and eliminated these gradients. CONCLUSIONS: These results suggest CFAE may result from activation of the intrinsic cardiac autonomic nervous system in these animal models of sustained AF. Ablation of GP attenuates CFAE and eliminates the DF gradient.

The role of ganglionated plexi in apnea-related atrial fibrillation.

OBJECTIVES: This study was conducted to simulate sleep apnea-induced atrial fibrillation (AF) in an experimental model and to determine whether neural ablation will prevent AF. BACKGROUND: An increasing number of clinical reports have associated sleep apnea and AF, and many possible mechanisms responsible for this relationship have been proposed. METHODS: Thirty dogs anesthetized with Na-pentobarbital were ventilated by a positive pressure respirator. Protocol 1 (n = 14): After a right thoracotomy, atrial and pulmonary vein programmed pacing at 2x and 4x threshold determined the shortest atrial refractory period. Obstructive apnea was induced by turning off the respirator during end expiration for 2 min. During apnea, programmed pacing was performed with S1-S2 = 5 to 10 ms earlier than the atrial refractory period. Neural activity was monitored from the ganglionated plexi (GP) adjacent to the right pulmonary veins. Protocol 2 (n = 16): Electrical stimulation identified the GP at the right pulmonary artery (RPA). Programmed pacing was again instituted, below atrial refractory period, during 2 min of apnea. After radiofrequency ablation of the RPA GP, continuous programmed pacing was again repeated during 2 min of apnea. In 5 dogs, blood gases were determined at baseline and at 2 min of apnea. RESULTS: Protocol 1: During apnea, S1-S2 induced AF within 85 +/- 38 s (9 of 10). In 1 case, AF occurred spontaneously at 1 min 36 s of apnea. Recorded GP neural activity progressively increased before AF onset. Systolic but not diastolic blood pressure rose significantly before AF (149 +/- 26 mm Hg to 193 +/- 38 mm Hg, p < 0.05). In 4 dogs, autonomic blockade prevented apnea-induced AF. Protocol 2: AF induced by pacing occurred in 8 of 11 dogs within the 2-min period of apnea, before neural ablation. After ablation, 0 of 6 showed AF during 2 min of apnea (p = 0.009). CONCLUSIONS: This experimental model of apnea shows a reproducible incidence of AF. After neural ablation of the RPA GP or autonomic blockade, AF inducibility was significantly inhibited.

Low-level vagosympathetic stimulation: a paradox and potential new modality for the treatment of focal atrial fibrillation.

BACKGROUND: We used high-frequency stimulation delivered during the refractory period of the atrium and pulmonary veins (PVs) to induce focal firing and atrial fibrillation (AF). This study was designed to demonstrate that bilateral low-level vagosympathetic nerve stimulation (LL-VNS) could suppress high-frequency stimulation-induced focal AF at atrial and PV sites. METHODS AND RESULTS: In 23 dogs anesthetized with Na-pentobarbital, electrodes in the vagosympathetic trunks allowed LL-VNS at 1 V below that which slowed the sinus rate or atrioventricular conduction. Multielectrode catheters were fixed at the right and left superior and inferior PVs and both atrial appendages. LL-VNS continued for 3 hours. At the end of each hour, the high-frequency stimulation algorithm consisting of a 40-ms train of stimuli (200 Hz; stimulus duration, 0.1 to 1.0 ms) was delivered 2 ms after the atrial pacing stimulus during the refractory period at each PV and atrial appendages site. The lowest voltage of high-frequency stimulation that induced AF was defined as the AF threshold. Five dogs without LL-VNS served as sham controls. Six dogs underwent LL-VNS after transection of bilateral vagosympathetic trunks. LL-VNS induced a progressive increase in AF threshold at all PV and atrial appendages sites, particularly significant (P<0.05) at the right superior PV, right inferior PV, left superior PV, and right atrial appendage. Bilateral vagosympathetic transection did not significantly alter the previous findings, and the 5 sham control dogs did not show changes in AF threshold at any site over a period of 3 hours. CONCLUSIONS: LL-VNS may prevent episodic AF caused by rapid PV and non-PV firing.

An acute experimental model demonstrating 2 different forms of sustained atrial tachyarrhythmias.

BACKGROUND: The objective of this study was to develop an acute experimental model showing both focal and macroreentrant sustained atrial fibrillation (AF). METHODS AND RESULTS: In 31 anesthetized dogs, bilateral thoracotomies allowed the attachment of electrode catheters at the right and left superior pulmonary veins, atrial free walls, and atrial appendages. Acetylcholine, 100 mmol/L, was applied topically to either appendage. Sequential radiofrequency ablation was achieved for the ganglionated plexi (GP), found adjacent to the 4 pulmonary veins. In 12 separate studies, a propafenone bolus, 2 mg/kg, was given before and after GP ablations at the start of acetylcholine-induced AF. Acetylcholine caused abrupt onset of AF (n=22) or induced AF by burst pacing (n=9) that lasted > or = 10 minutes. Rapid, regular, or fractionated atrial electrograms were consistently seen (average cycle length, 37+/-7 ms) at the appendages versus cycle lengths of 114+/-23 ms at other atrial sites. After ablations of GP, AF abruptly terminated (n=25). In 6 dogs, sustained atrial tachyarrhythmias continued. Pacing at specific atrial sites organized electrograms of one atrium or also captured the other atrium. The latter resulted in termination when pacing was stopped in 4 of these 6 experiments. Propafenone did not change the duration of focal AF before GP ablation (17+/-9 versus 14+/-8 minutes; control, P=0.6) but terminated reentrant atrial tachyarrhythmias (12+/-3 versus 2+/-1 minutes, P=0.0009). CONCLUSIONS: Before GP ablation, acetylcholine (100 mmol/L) induced sustained AF characterized by rapid, focal firing. GP ablations were associated with loss of focal firing and regularization of electrograms in both atria before termination. Propafenone failed to terminate focal AF but rapidly terminated entrainable macroreentrant atrial tachyarrhythmias.

Atrial fibrillation begets atrial fibrillation: autonomic mechanism for atrial electrical remodeling induced by short-term rapid atrial pacing.

BACKGROUND: The mechanism(s) for acute changes in electrophysiological properties of the atria during rapid pacing induced atrial fibrillation (AF) is not completely understood. We sought to evaluate the contribution of the intrinsic cardiac autonomic nervous system in acute atrial electrical remodeling and AF induced by 6-hour rapid atrial pacing. METHODS AND RESULTS: Continuous rapid pacing (1200 bpm, 2x threshold [TH]) was performed at the left atrial appendage. Group 1 (n=7) underwent 6-hour pacing immediately followed by ganglionated plexi (GP) ablation; group 2 (n=7) underwent GP ablation immediately followed by 6-hour pacing; and group 3 (n=4) underwent administration of autonomic blockers, atropine (1 mg/kg), and propranolol (0.6 mg/kg) immediately followed by 6-hour pacing. The effective refractory period (ERP) and window of vulnerability (WOV, in milliseconds), ie, the difference between the longest and the shortest coupling interval of the premature stimulus that induced AF, were measured at 2xTH and 10xTH at the left atrium, right atrium, and pulmonary veins every hour before and after GP ablation or autonomic blockade. In group 1, ERP was markedly shortened in the first 2 hours and then stabilized both at 2xTH and 10xTH; however, WOV was progressively widened throughout the 6-hour period. After GP ablation, ERP was significantly longer than before ablation and AF could not be induced (WOV=0) at either 2xTH or 10xTH. In groups 2 and 3, rapid atrial pacing failed to shorten the ERP. AF could not be induced in 6 of 7 dogs in group 2 and all 4 dogs in group 3 during the 6-hour pacing period. CONCLUSIONS: The intrinsic cardiac autonomic nervous system plays a crucial role in the acute stages of atrial electrical remodeling induced by rapid atrial pacing.