Effect of Tocopheryl Acetate on Maternal Cigarette Smoke Exposed Swiss Albino Mice Inbred Fetus.

INTRODUCTION: Cigarette smoking is worldwide problem which can be correlated with teratogenicity. Tocopheryl acetate plays as an antioxidant against the oxidative stress evolved by cigarette smoke exposure during pregnancy. AIM: To study the effect of maternal exposure to cigarette smoke and Tocopheryl acetate on fetuses of mice. MATERIALS AND METHODS: Pregnant mice randomly assigned to different groups (Group I (control), Group II (Tocopheryl acetate), Group III(soyabean oil used as vehicle for Tocopheryl acetate), Group IV (Cigarette smoke Exposed), Group V (Cigarette smoke exposed plus Tocopheryl acetate) and Group VI(Cigarette smoke exposed plus soyabean oil) were exposed to cigarette smoke 3 times a day for 20 minutes each time and Tocopheryl acetate with dose of 200mg/kg/day in 0.3ml of soyabean oil as vehicle orally through oral gavage from the 5th day of gestation to 15th day. RESULTS: Cigarette smoke exposed mice showed significant fetal weight loss, resorption, placental anomalies, severe growth retardation, venous congestion, haemorrhage, limbs defects and enphalocele. Negligible abnormalities were seen among the control and Tocopheryl acetate group. Cigarette smoke exposed group with Tocopheryl acetate exhibited weight gain among the fetus as well as no gross abnormalities. The oxidative stress was significantly increased by increasing Malondialdehyde (MDA) 293±81.57 µmol/mg (p<0.0001) and decreasing Superoxide Dismutase (SOD) 1.43 ± 0.23mg/ml, (p<0.0001) Reduced Glutathione (GR) 0.017±0.002mg/ml, (p<0.01) and Catalase (CAT) 0.248±0.005mg/ml, (p<0.0001). Tocopheryl acetate induced group significantly maintained the oxidative stress with all p <0.0001. CONCLUSION: It can be concluded that Tocopheryl acetate may have an ameliorating effect on the cigarette smoke during pregnancy on fetus.

Direct thrombin inhibitors: novel antithrombotics on the horizon in the thromboprophylactic management of atrial fibrillation.

Antithrombotic agents have verified efficacy in reducing the thromboembolic risk associated with atrial fibrillation. This article focuses on the emergence of a new oral direct thrombin inhibitor, ximelagatran, into the arena of atrial fibrillation thromboprophylaxis. This review does not cover atrial fibrillation in the context of valvular heart disease. The efficacy of aspirin and warfarin will be discussed briefly.

Rate or rhythm control in persistent atrial fibrillation?

Atrial fibrillation (AF) is the most common sustained tachyarrhythmia encountered in clinical practice, with the majority of patients aged > 65 years. With an increasingly ageing population, the burden of AF in society continues to rise. One of the principal controversies in AF management is whether to control the ventricular rate and accept the underlying rhythm, or to attempt to achieve sinus rhythm. Until recently there were no clinical trial data directly comparing a rate versus rhythm strategy, and most physicians have opted for rhythm control, based on its theoretical benefits. We present an up-to-date evidence-based overview of the relative merits of rate versus rhythm control in AF, including data from five recent randomized trials. We draw conclusions from these studies and present evidence-based guidance on when to adopt which approach in routine clinical practice.

Higher energy monophasic DC cardioversion for persistent atrial fibrillation: is it time to start at 360 joules?

BACKGROUND: Electrical direct-current cardioversion (DCCV) has become a routine therapy for atrial fibrillation (AF), although some uncertainty remains regarding the optimal energy settings. AIMS: This study examines whether the use of a higher initial energy monophasic shock of 360 joules (J) for external DCCV, in patients with persistent AF would prove more effective, yet as safe, as the use of a lower initial energy 200 J shock. METHODS: A cohort of 107 patients with persistent AF was prospectively randomized to an initial synchronized DCCV shock of 360 J versus 200 J (n = 50 vs 57), followed by a similar shock sequence thereafter of four further shocks of 360 J for the two groups. In all patients the levels of troponin I (cTnI) were measured precardioversion and 18-20 hours later, the following day. In a subgroup of 36 patients in each group, the levels of creatine kinase (CK) and aspartate transaminase (AST) were measured pre- and 18-20 hours postcardioversion. RESULTS: The success rate for DCCV was significantly higher in the 360 J group compared to the 200 J group (96.0% vs 75.4%, P = 0.003). The mean CK IU/L levels (1137.5.0 vs 2411.8, P = 0.014) and AST levels (39.83 vs 52.86, P = 0.010) were significantly lower in the 360 J group compared to the 200 J group. There was no statistical rise in cTnI (microg/L) in either group (P = 1.00). The average number of shocks delivered (1.84 vs 2.56, P = 0.006) was significantly less in the 360 J group than in the 200 J group, although total energy requirements for DCCV were similar for the two groups (662.4 J vs 762.4 J, P = 0.67). CONCLUSION: For patients with persistent AF the use of a higher initial-energy monophasic shock of 360 J achieves a significantly greater success rate, with less skeletal muscle damage (and no cardiac muscle damage) as compared with the traditional starting energy of a 200 J DC shock.

Failed thrombolysis in myocardial infarction.

Prompt treatment with thrombolytic therapy in acute myocardial infarction has been proven to reduce infarct size and mortality. However, reperfusion fails to occur in 30-50% of patients, either due to impaired epicardial artery flow or microvascular occlusion, with these patients experiencing a higher morbidity and mortality. We review the diagnosis and management of failed thrombolysis in acute myocardial infarction.

Antiplatelet use in interventional cardiology.

Thrombosis within the target vessel is one of the most feared complications associated with coronary intervention, as it is often associated with severe adverse clinical sequelae. This thrombosis is mediated via the activation and aggregation of platelets and therefore considerable effort has been directed at ways of inhibiting platelet function. It is now mandatory to consider the use of two and often three different antiplatelet agents, particularly when intracoronary stents are inserted. Using these regimes, many of the adverse clinical outcomes associated with platelet activation can be reduced.

The role of coronary angioplasty and stenting in acute myocardial infarction.

Despite the improvements in the pharmacological treatment of acute myocardial infarction, it is recognised that thrombolysis fails to reproduce reperfusion in a significant proportion of patients. Coronary interventional techniques have been shown to offer an alternative reperfusion strategy. There is increasing evidence that mechanical reperfusion may offer significant advantages over established thrombolytic therapy.

Anticoagulation for cardioversion of atrial arrhythmias.

We would advocate 3 weeks of anticoagulation prior to, and 4 weeks post-cardioversion (either electrical or chemical) for patients in chronic atrial fibrillation or flutter. In selected cases it seems reasonable to use transoesophageal echocardiography to exclude preformed thrombus and negate the need for 3 weeks of prior anticoagulation. For patients presenting acutely with atrial fibrillation or flutter we suggest anticoagulating with heparin immediately on presentation and for those who do not spontaneously revert to sinus rhythm, using transoesophageal echocardiography to exclude atrial thrombi prior to cardioversion. Oral anticoagulation should be continued for 4 weeks post-procedure. If transoesophageal echocardiography is not readily available an alternative strategy would be to anticoagulate the patient for 3 weeks and thereafter readmit them for elective cardioversion, continuing the anticoagulation for a further 4 weeks after the procedure.

Aging-associated endothelial dysfunction in humans is reversed by L-arginine.

OBJECTIVES: This study investigated the hypothesis that aging selectively impairs endothelium-dependent function, which may be reversible by administration of L-arginine. BACKGROUND: An impaired response to acetylcholine with aging has been demonstrated in humans. However, the mechanisms underlying this impaired response of the coronary microvasculature remain to be determined. METHODS: We infused the endothelium-independent vasodilators papaverine and glyceryl trinitrate (GTN) and the endothelium-dependent vasodilator acetylcholine (1,3,10 and 30 micrograms/min) into the left coronary artery of 34 patients (27 to 73 years old) with atypical chest pain, negative exercise test results, completely normal findings on coronary angiography and no coronary risk factors. Coronary blood flow was measured with an intracoronary Doppler catheter. The papaverine and acetylcholine infusions were repeated in 14 patients (27 to 73 years old) after an intracoronary infusion of L-arginine (160 mumol/min for 20 min). RESULTS: There was a significant negative correlation between aging and the peak coronary blood flow response evoked by acetylcholine (r = -0.73, p < 0.0001). However, there was no correlation to papaverine (r = -0.04, p = 0.82) and GTN (r = -0.24, p = 0.17). The peak coronary blood flow response evoked by acetylcholine correlated significantly with aging before L-arginine infusion (r = -0.87, p < 0.0001), but this negative correlation was lost after L-arginine infusion (r = -0.37, p = 0.19). CONCLUSIONS: The results suggest that aging selectively impairs endothelium-dependent coronary microvascular function and that this impairment can be restored by administration of L-arginine, a precursor of nitric oxide.

Arrhythmogenic right ventricular dysplasia.

Right ventricular dysplasia is a primary disorder of the right ventricular myocardium characterised by a progressive replacement by adipose or fibrous tissue, proceeding from the epicardium towards the endocardium. Right ventricular dysplasia with the predominant clinical manifestation of an arrhythmia of right ventricular origin is defined as arrhythmogenic right ventricular dysplasia. There is, however, a wide spectrum of clinical presentation and physical findings owing to the polymorphism of the condition. The aetiology of right ventricular dysplasia remains unknown. Right ventricular angiography is currently regarded as the gold standard for the clinical diagnosis of right ventricular dysplasia Ventricular endomyocardial biopsy can be useful in confirming the diagnosis but a negative biopsy does not exclude the diagnosis of right ventricular dysplasia. There have been few electrophysiological studies and these, in general, have failed to help in risk stratification. Treatment is focused on the prevention of potentially lethal right ventricular electrical instability.

Anti-thrombotic therapy for non-rheumatic atrial fibrillation.

Recent randomized trials of antithrombotic therapy in non-rheumatic atrial fibrillation have helped to clarify the benefits of warfarin and aspirin. Low-risk patients (normotensives aged < 60 with normal left ventricular function) have a small risk of thromboembolic events and are unlikely to benefit significantly from anticoagulants, but may benefit from aspirin with little increase in risk of bleeding. High-risk patients (> 75 years, impaired left ventricular function, previous thromboembolism and/or associated conditions such as hypertension and diabetes mellitus) have an increased risk of thromboembolism, and benefit from long-term anticoagulant therapy to a greater degree than with aspirin, although at a risk of increased bleeding complications.

Angioplasty balloon compliance: can in vivo size be predicted from in vitro pressure profile measurements?

BACKGROUND AND HYPOTHESIS: This study was undertaken to determine whether the behavior of angioplasty balloons within coronary arteries may differ from that anticipated from data provided by the manufacturers. In particular, the in vitro pressure-diameter profiles may not truly represent in vivo sizes. METHODS: Thus, we assessed the degree of correlation of in vitro with in vivo measurements obtained during routine angioplasty practice. In vivo size of 2.5 mm compliant (n = 8) and 3 mm semicompliant (n = 8) balloons was assessed using quantitative angiography for first, second, and third inflations. RESULTS: In vivo size was less than expected from in vitro measurements. In general balloon diameter increased with inflation pressures up to 8 atmospheres, and some degree of elastic recoil was evident with both balloon types after the last inflation. CONCLUSION: In vivo balloon size may not be accurately predicted from manufacturers' published data. Size is more likely to be affected by factors such as lesion characteristics and elasticity of the vessel wall than by balloon material compliance characteristics.

Pulmonary embolism--the role of thrombolytic therapy in its management.

In massive pulmonary embolism where there may be evidence of right ventricular dysfunction and acute pulmonary hypertension, anticoagulation therapy alone may prove inadequate. In such situations use of thrombolytic agents produces an improvement in haemodynamics compared to anticoagulants alone, although studies to date have been too small to address the issue of mortality benefit. It would appear that all age groups gain benefit from the use of thrombolytics. Studies that have compared thrombolytic agents and anticoagulants are discussed. In addition, the issues of the choice of thrombolytic agent and the different modes of delivery of therapy are addressed.

Changes in vessel wall plasminogen activator activity and smooth muscle cell proliferation and activation after arterial injury.

OBJECTIVES: The aim was to examine changes in vessel wall fibrinolytic activity following angioplasty and to assess any relationship to changes in smooth muscle cell proliferation and activation. METHODS: Balloon angioplasty was performed to the iliac arteries of New Zealand White rabbits and vessel wall changes assessed at 2 h, 1 d, 7 d, 14 d, and 1 month postprocedure. Tissue-type (tPA) and urokinase-type (uPA) plasminogen activator activity was assessed using chromogenic substrate assays, while smooth muscle cell proliferation and activation was monitored using expression of proliferating cell nuclear antigen (PCNA) and of basic fibroblast growth factor (bFGF) respectively. RESULTS: Intimal thickening progressively increased up to 1 month. uPA activity increased at 2 h [1.94(SEM 0.19) v 1.59(0.05) U.mg-1 tissue for control vessels, P = 0.03], remained increased at 24 h, but by 7 d had decreased to below control levels and remained low. In contrast, tPA activity fell significantly at 2 h [0.9(0.3) v 1.96(0.13) micrograms.mg-1 tissue for control vessels, P = 0.03], remained low at 24 h, but by 7 d had reverted back to control levels [2.19(0.39) micrograms.mg-1]. PCNA positivity of the media increased at day 1, reached maximum on day 7 [16.9(5.1)% positively staining cells] before returning to baseline by 1 month. PCNA positivity of the intima first evident at day 7 [0.7(0.3)%], reached a maximum at day 14 [4.1(0.4)%]. bFGF expression increased early at 2 h [mean(SE) positively staining cells: 15.7(5.3)% v 11.2(4.8)% for control vessels] and continued to increase, reaching a maximum in the media at day 7 [59(8.6)%] and in the intima at day 14 [57.5(5.7)%]. CONCLUSIONS: Balloon injury produced an initial fall in tPA and rise in uPA activity. tPA increased back to control levels by 7 d, while uPA fell to below control levels at 7 d and 1 month. This would be compatible with a mechanism whereby acute injury suppressed tPA and upregulated uPA activity, with increased tPA activity acting as a marker for vessel repair.