The effects of nicotine and cigarette smoking on cardiac electrophysiology.

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in vivo effects of nicotine and non-nicotine constituents of cigarette smoking on cardiac ion channels, (b) the direct and indirect effects of the autonomic nervous system on cardiac electrophysiology, and (c) studies of acute and chronic effects of cigarette smoking in humans. Chapter 2 consists of two studies in which we used cotinine levels to investigate the differences in baseline cardiac electrocardiogram between chronic smokers and non-smokers, and to define smoking status and its burden. We also explored the relationship between urinary catecholamines, cotinine, and electrocardiographic changes. Chapter 3 features the 2 x 2 factorial experimental study designed to compare the acute effects of cigarette smoking and nicotine, with and without a β-blocker (propranolol). We found that chronic cigarette smoking was associated with a shortened PR segment at baseline, and that dopamine possibly mediates this effect. There was also (corrected) QT interval shortening with increased cotinine levels. This experimental study revealed that the non-nicotine constituents in cigarette smoking were mainly responsible for PR segment shortening, through β-adrenoreceptors. Other evidence revealed that, although nicotine in cigarette smoke is primarily responsible for sympathetic activation and (corrected) QT interval shortening, it is the non-nicotine constituents that depress the ST segment. Collectively, acute and chronic exposure studies indicate that smoking may promote cardiac arrhythmia, primarily via β-adrenoreceptors, causing acceleration of dromotropy and ischemia (non-nicotine mediated), and ventricular repolarization (nicotine-mediated). This research elucidated a major physiological mechanism driving the effect of cigarette smoking and nicotine on cardiac electrophysiology. Consequently, these findings will inform U.S. Food and Drug Administration of tobacco and nicotine-containing products’ impact on the human cardiac electrical system, and potentially help regulate alternative forms of nicotine delivery and protect public health

Presence of multiple coronary angiographic characteristics for the diagnosis of acute coronary thrombus

Background: Coronary angiography is frequently employed to aid in the diagnosis of acute coronary thrombosis, but there is limited data to support its efficacy. The aim of the study was to evaluate sensitivity and specificity of five commonly used angiographic characteristics for diagnosis of acute coronary thrombosis: Ambrose complex lesion morphology; spherical, ovoid, or irregular filling defect; abrupt vessel cutoff; intraluminal staining; and any coronary filling defect. Methods: Coronary angiography of 80 acute myocardial infarction or stable coronary artery disease subjects were assessed in blinded fashion, for the presence or absence of five angiographic characteristics. Only lesions of ≥ 10% stenosis were included in the analysis. Presence or absence of each angiographic characteristic was compared between lesions with or without the following study defined outcomes: 1) histologically confirmed thrombus, 2) highly probable thrombus, and 3) highly unlikely thrombus. Results: A total of 323 lesions were evaluated. All studied angiographic characteristics were associated with histologically confirmed and highly probable thrombotic lesions vs. lesions not meeting criteria for these outcomes (p < 0.03), except for complex Ambrose morphology which was not associated with any of the study outcomes (p > 0.05). Specificity for identifying histologically confirmed or highly probable thrombotic lesion was high (92–100%), especially for spherical, ovoid, or irregular filling defect (99–100%) and intraluminal staining (99%). Sensitivity for identification of histologically confirmed or highly probable thrombotic lesions was low for all tested angiographic characteristics (17–60%). Conclusions: The presence of spherical, ovoid, or irregular filling defect or intraluminal staining was highly suggestive of coronary thrombus. However, none of the evaluated angiographic characteristics were useful for ruling out the presence of coronary thrombus. If confirmed in an independent cohort, these angiographic characteristic will be of significant value in confirming the diagnosis of acute coronary thrombosis.

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study

Objective Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes