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BackgroundPostprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile.MethodsA randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 ± 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test.ResultsAlogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 ± 31 vs. 182 ± 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 ± 1.7 vs. 11.7 ± 1.1 μg h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 ± 3.2 vs. 17.6 ± 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in%FMD, from −4.2 ± 0.5% to −2.6 ± 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = −0.46, p = 0.03) and RLP-C (r = −0.45, p = 0.04).ConclusionAlogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent.

Abstract-Identifying patients at high risk for the occurrence of atrial fibrillation is one means by which subsequent thromboembolic complications may be prevented. Left atrial enlargement is associated with progression of atrial remodeling, which is a substrate for atrial fibrillation, but impaired atrial pump function is also another aspect of the remodeling. Our objective was to differentiate patients with a history of paroxysmal atrial fibrillation using echocardiography. We studied 280 hypertensive patients (age: 66Ϯ7 years; left ventricular ejection fraction: 65Ϯ8%), including 140 consecutive patients with paroxysmal atrial fibrillation and 140 age-and sex-matched control subjects. Left atrial volume was measured using the modified Simpson method at both left ventricular end systole and preatrial contraction and was indexed to body surface area. Peak late-diastolic mitral annular velocity was measured during atrial contraction using pulsed tissue Doppler imaging as an atrial pump function. Left atrial volume index measured at left ventricular end systole had a 74% diagnostic accuracy and a 71% positive predictive value for identifying patients with paroxysmal atrial fibrillation; these values for the ratio of left atrial volume index at left ventricular end systole to the peak late-diastolic mitral annular velocity were 82% and 81%, respectively, and those for the ratio of left atrial volume index at preatrial contraction to the peak late-diastolic mitral annular velocity were 86% and 90%, respectively. In conclusion, left atrial size combined with atrial pump function enabled a more accurate diagnosis of a history of paroxysmal atrial fibrillation than conventional parameters. (Hypertension. 2010;55:1150-1156.)Key Words: hypertension Ⅲ echocardiography Ⅲ atrial fibrillation Ⅲ left atrium Ⅲ remodeling A trial fibrillation (AF) is not generally life threatening but is considered to be the most common cause of ischemic stroke, which often yields serious complications because of acute occlusion of intracranial arteries without collateral circulation. The incidence of stroke is increased by Ϸ5-fold in the presence of nonvalvular AF. [1][2][3][4][5] Moreover, recent studies have demonstrated that stroke risk is no less in patients with paroxysmal AF (PAF) than in those with persistent AF. 6 Therefore, it is crucial to identify patients who have PAF in order to prevent subsequent thromboembolic complications, especially in patients with hypertension, which is a major etiologic factor associated with both AF and stroke. [7][8][9] Left atrial (LA) enlargement associated with the progression of atrial structural remodeling plays a key role in the initiation and maintenance of AF. 10,11 The most recent recommendations for echocardiographic chamber quantification indicate that LA volume (LAV) provides an accurate measurement of asymmetrical remodeling of the LA chamber. 12 LAV is increased in patients with PAF 13 and is also an important predictor of cardiovascular outcome, including the occurrence of AF, 14 supporti...

Intermittent arm ischemia before percutaneous coronary intervention induces remote ischemic preconditioning (RIPC) and attenuates myocardial injury in patients with myocardial infarction. Several studies have shown that intermittent arm ischemia increases coronary flow and is related to autonomic nerve system. The aim of this study was to determine whether intermittent arm ischemia induces vasodilatation of other arteries and to assess changes in the autonomic nerve system during intermittent arm ischemia in humans. We measured change in the right brachial artery diameter during intermittent left arm ischemia through three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood-pressure cuff using a 10-MHz linear array transducer probe in 20 healthy volunteers. We simultaneously performed power spectral analysis of heart rate. Ischemia-reperfusion of the left arm significantly dilated the right brachial artery time-dependently, resulting in a 3.2 ± 0.4% increase after the 3rd cycle. In the power spectral analysis of heart rate, the high-frequency domain (HF), which is a marker of parasympathetic activity, was significantly higher after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02). Intermittent arm ischemia was accompanied by vasodilatation of another artery and enhancement of parasympathetic activity. Those effects may play an important role in the mechanism of RIPC.

Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca2+ overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H2O2 and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca2+ overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca2+ overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure.

Acquired predisposing factors promoted repolarization abnormality (especially prolongation of QT and Tpe intervals), and the existence of fQRS had an important role in the development of TdP in patients with acquired LQTS.

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