comparative study between influence of rosiglitazone; a peroxisome proliferator-activated receptor gamma [PPARS] agonist, and corticosteroids on experimentally induced asthma in guinea pigs

Dugs used currently to treat asthma have limitations partly due to their undesired effects. PPARgamma agonists including rosiglitazone may offer additional therapeutic advantages to current treatment. The aim of the present study was to assess the anti-inflammatory potential of a PPARi agonist, rosiglitazone, locally delivered by means of nebulization in a guinea pig model of asthma, in comparison with that of the corticosteroid budesonide. Five groups of guinea pigs were used, five animals each. The first group was Sham -sensitized guinea pigs; the other four groups were sensitized by ovalbumin [OVA] by allergen solution containing 100 micrograms OVA and 100 mg Al [OH]3 per ml saline. 0.5 ml was injected intraperitoneally, while another 0.5 ml of the solution was divided over seven intracutaneous injection sites. The second group was OVA-sensitized and exposed to inhalation of saline. The third, fourth and fifth group were OVA albumin-sensetized. The third group was treated with vehicle inhalation, The fourth group was treated with rosiglitazone and the fifth group was treated with budesonide. Animals in the last 3 groups were exposed to allergen provocation procedure [Ag challenge] from weeks 4 to 5 after OVA sensitization. Assessment of asthma was done by studying the effect of rosiglitazone and budesonide on airway hyper responsiveness [AHR] to acetylcholine [Ach], inflammatory cellular changes in bronchoalveolar lavage and histopathological changes. The effect of rosiglitazone and budesonide pretreatment on histamine induced contraction of isolated OVA sensitized guinea pig tracheal spiral strips was also investigated. In addition, the direct effect of rosiglitazone and budesonide incubation on histamine induced contraction of isolated guinea pig tracheal spiral strips was examined. The results revealed that one week pre-treatment with rosiglitazone [20 minutes inhalation in a dose of 300 microg/ Kg/ day] and budesonide [20 minutes inhalation in a dose of 2mg/ Kg/ day] resulted in significant reduction in airway hyperreactivity to inhaled Ach, inflammatory cellular content in bronchoalveolar lavage fluid [BALF] and improvement in histopathological changes of asthmatic lung. There was no significant difference between both drugs as regard improvement of AHR, reduction in thickness of the interalveolar septum, decrease in total leucocytic count [TLC], count of lymphocytes and macrophages. However, budesonide caused significant reduction in eosinophils and macrophages count in comparison to rosiglitazone. In addition, rosiglitazone had a direct relaxant effect on airway smooth muscle. The results provided evidence for the therapeutic potential of inhaled PPARi agonist, rosiglitazone, in the treatment of airway asthmatic inflammation. In addition PPARgamma agonists had a direct relaxant effect on the isolated tracheal smooth muscle

Effect of thrombolytic therapy on QT dispersion in patients with acute myocardial infarction

QT dispersion is an important ECG feature fundamental for initiation of ventricular fibrillation and increased after myocardial infarction. to correlate site of infarction and QT dispersion and assess the effect of thrombolysis on it in patients with acute myocardial infarction [AMI]. The study include 100 patients with AMI were classified into 3 groups: 01: included 30 patients received streptokinase [SK] with successful reperfusion, 02: 30 patients received streptokinase with failed reperfusion and 03: included 40 patients not received SK due to contra-indications. all patients were subjected to resting 12 leads ECG at admission, 2 hours post SK [in G1 and G2] and predischarge. the following parameters were measured [QT interval, QRS interval, JT interval, PR interval, QT dispersion, JT dispersion, QRS dispersion, rate corrected QT, rate corrected JT, QTc dispersion and JTc dispersion]. The study reavles the QTd and JTd values significantly increased in patients < 50 years than pts > 50 years [p < 0.05]; QTd, JTd, QTcd and JTcd were significantly increased with anterior MI than inferior MI [p <0.001]. Among risk factors for coronary artery disease, QTcd and JTcd significantly increased in none obese pts [p < 0.05], QTd, QTcd, JTd, JTcd and QTc significantly increased in diabetics [p < 0.05], while in hypertensives, QTd, QTcd, JTd, JTcd and JTc are significantly increased [p <0.01]. The highest incidence of arrhythmia was in 01 and greater with anterior MI than inferior MI. QTd, JTd, QTcd and JTcd were longer in cases complicating arrhythmia and largest with ventricular fibrillation. In G1, QTd, JTd and QTcd were significantly increased at pre- discharge than at admission [p = 0.001] and than 2 hours after SK [p = 0.001] in G2, QTcd and JTcd significantly decreased 2 hrs after SK [p = 0.05], QTc, JTc, QTcd and JTcd decreased significantly at predischarge than at admission [p < 0.05], in G3, QTc and JTc significantly decreased at pre-discharge than at admission [p 0.001]. Conclusion The study concluded that QT dispersion is increased after myocardial infarction and showed significant rduction with successful thrombolysis. QTd is influenced by hypertension, diabetes mellitus, age and site of myocardial infarction. It could be used equally to QT for analysis

study on heart rate variability signals in healthy children and in patients with congenital heart disease

During the last decade the interest in the field of pediatric electrophysiology was progressing and attention towards pediatric arrhythmic mortality became of extreme concern. Analyses of heart rate variability [HRV] signals are one of the sensitive tools to study the autonomic control of the heart uming to solve the arrhythmic morbidity and mortality in the pediatric age group. Few studies had reported the normal values of HRV parameters in infants and children. As autonomic disturbances and arrhythmia are common features in patients with congenital heart disease, we tried to establish ranges for HRV parameters in normal individuals and in patients with congenital cardiac defects. One hundred and fifty infants and children were the study population. 50 patients had a cyanotic congenital heart diseases; 29 males and 21 females, with a mean age + SD of 88.75 +/- 139.8 months and 50 patients had cyanotic congenital, heart disease; 18 males and 32 females, with a mean age of 5.62 +/- 3.05 months. 50 subjects with no evidence of structural heart disease were included as controls; 24 males and 26 females, with a mean age of 6.33 +/- 3.65 months. For age matching between the study groups and controls, 50 normal subjects were compared with a cyanotics while only 36 of them were compared with cyanotics patients, The normal limits [mean +/- SD] of frequency domain HRV parameters for all the 50 controls were: LF ms[2] [388.7-509.5], LF-n.u [36.8-62.08], HF ms[2] [489.1-709.6] HF-n.u. [44.3-74.3] and LF/HF ratio [0.5-0.9]. The normal limits of HRV parameters for the 36 controls age-matched to the cyanotic group were LF ms[2] [386.5-514.1], LF-n.-u [39.5-61.9], HF ms[2] [515.0-693.4], HF-n.u [50.1-70.9], and LF/HF ratio [0.54-0.86]. There was a significant negative correlation between age and both LF n.u and HF n.u. with insignificant effect on LF/HF ratio. However, there were no gender variations in the studied HRV parameters of the control groups. We observed a significantly lower HF-n.u and higher LF ms[2], LF-n.u, HF ms[2] and LF/HF ratio in both acyanotics and cyanotics when compared to controls. We also noticed that high frequency bands HF m[2] and HF-n.u. were abnormally high in a large number of acyanotics and the LF/HF ratio was relatively higher in cyanotics, although the differences were statistically insignificant. The final results provided a basis for heart rate variability signals in children. Normal ranges for the various parameters were determined. Cyanotics express more sympathetic predominance than a cyanotics which might render them more susceptible to arrhythmias

Instent restenosis predictors of long coronary lesions

Balloon angioplasty of long coronary stenoses has been reported to be associated with a lower rate of acute clinical and procedural success and a higher rate of restenosis compared to short lesions. Intracoronary stenting has been shown to reduce restenosis, however, instent restenosis remains a major clinical problem despite improved stent flexibility and wall coverage and operator experience. The purpose of this study was to identify clinical, angiographic, and procedural predictors of restenosis after coronary stent placement in lesions longer than 15 millimeter. We analyzed the 6 month angiographic outcome of 378 patients [420 lesions]. All patients with successful coronary stent deployment and 6 month follow up were eligible for this study. Quantitative coronary coronary angiography [QCA] and intravascular ultrasound [IVUS] analyses were obtained immediately after stent deployment, and QCA at 6 months follow up. Restenosis was observed in 33.3% of lesions. By univariate analysis, stent length, number of stents per patient and per lesion, final IVUS lumen cross sectional area [CSA], and patients with multivessel disease were identified as the potential predictors of restenosis. Multivariate analysis identified final lumen CSA [OR= 0.85;95% CI=0.74-0.98, p=0.031] and stent length [OR=1.04;95% CI= 1.02-106, p=0.0001] as the only independent predictors of restenosis. Coronary stenting is associated with acceptable restenosis rate in this highly vulnerable cohort of lesions. Achieving an optimal final stent lumen CSA, and minimizing stent length as possible may help to reduce incidence of restenosis in this high risk group of lesions

Ventricular late potentials: pattern in normal and different cardiac congenital abnormalities

Pediatric mortality represents a major problem all over the world. During infancy, arrhythmia may be an important factor in the pathogenesis of some of these life-threate ling events. Congenital heart diseases increase the liability for many cardiac arrhythmias. Ventricular late potentials have shown to be markers for risk of ventricular arrhythmias. There is only limited data on normal reference values for signal- averaged electrocardiogram [SFECG] in pediatric population. In this sturdy, we tried to establish ranges for SAECG parameters in normal children and in patients with congenital cardiac defects. One hundred and fifty infant's and children were the study population. Fifty [50] children had congenital a cyanotic heart disease, 29 were males with a mean age +/- SD of 18.75 +/- 13.9 months and 50 children had congenital cyanotic heart diseases, 18 were males with a mean age of 5.62 +/- 3.0 months. 50 age- and sex- matched healthy individuals were served as controls. The SAECG parameters include QRS duration in milliseconds [msec], Root Mean Square voltage [RMS] in microvolts [micro v], Root Mean Square of the last 40 millisecond of the QRS comply [RMS 40] in micro V and the duration of low amplitude signal [< 40 micro V] at the terminal QRS [LAS] in msec. The results showed that, in normal subjects, the QRS duration ranged iron 80.5 to 100.5 msec, RMS voltage ranged from 158.6 to 240.0 micro V, RMS-4O voltage ranged from 44.5 to 126.1 micro V and the duration of LAS ranged from 2.7 to 10.3 msec. In acyanotics, the mean +/- SD for QRS duration was 101.2 +/- 85.2 msec, for RMS was 197.9 +/- 92.7 micro V, for RMS-40 was +/- 79.9 + 118.0 micro V and for LAS was 10.5 +/- 7.4 msec. In cyanotic, QRS duration was 127. +/- 11.8 msec, RMS was 128.5 +/- 60.1 micro V, RMS-40 was 35.34 + 2.4 micro V and LAS was 22.8 + 2.3 msec. Cyanotic patients had a significantly wide QRSD 8 LAS and significantly low RMS and RMS-40 than a cyanotic [p > 0.05]

Conclusion: our result; provide a basis for interpretation of SAECG in Children. Normal ranges for the various parameters were determined. In cyanotic, the late potentia3 are markedly abnormal in comparison to the little change in cyanotic rendering patients with cyanotic heart defects are highly susceptible for arrhythmia and arrhythmia-induced complications

Effect of hypertension on pulmonary function

Thirty hypertensives and ten normal control subjects were included in the study, all had a normal left ventricular systolic function, no clinical or radiological pulmonary disease, fifteen hypertensives had diastolic dysfunction. Echo-Doppler and ventilatory pulmonary function studies were done for all. There was a significant inverse relation between E/A ratio and both the age and level of BP in hypertensive, but a significant direct relation with EF. Hypertensives with normal diastolic function showed a significant decrease in F.E.V[1] and M.V.V. and a significant increase in F.E.V[1]/F.V.C. but still within the normal range. Hypertensives with diastolic dysfunction had a combined obstructive-restrictive ventilatory dysfunction as represented by a significant decrease in V. C, F.V. C, F.E.F and M.V.V. less than normal range. However the effect of hypertension on small airways was insignificant B.P = Blood Pressure E.F = Ejection Fraction F.E.V[1] = Forced Expiratory Volume at the first second M.V.V = Maximal Volantary Ventilation F.V.C. = Forced Vital Capacity. V.C. = Vital Capacity. P.E.F. = Peak Expiratory Flow

Extent and functional capacity of coronary collateral circulation in the hypertensive patients with atherosclerotic coronary artery disease

This study was an evaluation of coronary collateral circulation in relation to the presence of systemic hypertension and left ventricular hypertrophy. One hundred patients with significant coronary artery disease [>75%] were enrolled in the study. 35 hypertensive patients with left ventricular hypertrophy [LVH] were considered as group I, 35 hypertensive patients without LVH as group II and 30 normotensive patients as group III. Coronary angiography was done for all patients. Class 0: No collateral, class I: Partial filling and class II: Complete filling of collaterals were used as angiographically classified coronary collaterals. Echocardiography and graded exercise ECG test were done for all patients. From the results obtained, it was concluded that patients with systemic hypertension and coronary artery disease have an increase in coronary collateral circulation corresponding to the left ventricular hypertrophy and that functional capacity of the coronary collateral circulation is not augmented by left ventricular hypertrophy

Discrete versus diffuse coronary artery stenoses clinical angiographic and echo-doppler studies

Forty subjects were admitted to catheterization laboratory at Ain Shams University Hospital with typical and atypical chest pain. According to the coronary angiogram, 30 patients had coronary artery disease [CAD]. These patients were further classified into discrete CAD [19 patients] and diffuse CAD [11 patients]. There was no statistically significant difference between the two groups with regard to age, sex, duration of the disease, symptoms or functional class. The diffuse CAD group had significantly higher prevalence of diabetes mellitus [p < 0.01] than the discrete CAD group. On the other hand, the discrete CAD group had a significant prevalence of anterior myocardial infarction [p < 0.05]. Coronary angiographic data revealed that in the discrete CAD group lesions tended to occur more frequently in the proximal segments whereas diffuse CAD had both proximal and distal segment involvement and a higher significance [p < 0.01] of mean coronary severity score. Echocardiographic and Doppler data revealed that diffuse CAD group had a significantly [P < 0.05] higher wall motion score [WMS] and non significant difference in ejection fraction [EF] than the discrete group. The diastolic function was impaired in the CAD patients. The diffuse CAD group had a highly significant increase in A wave and A/E ratio [p < 0.01] and a significant lower acceleration and deceleration than discrete CAD group. So, our results indicated that the diastolic dysfunction is inter-related to the severity and extent of CAD lesions. Therefore, the diagnosis of diffuse rather than discrete CAD which is an angiographic diagnosis, could not be predicted from the clinical data alone. Moreover, CAD patients were not prone to more adverse effects on the ventricular function [LV] apart from some impairment of left ventricular diastolic function as detected by pulsed wave Doppler ultrasound