Close Relationship Between Sympathetic Activation and Coronary Microvascular Dysfunction During Acute Hyperglycemia in Subjects With Atherosclerotic Risk Factors

Abstract

he Framingham offspring study has demonstrated that post-challenge hyperglycemia is an independent risk factor for cardiovascular disease, 1 and that stress hyperglycemia is one of the determinants of the outcome after myocardial infarction. 2,3 In this context, it is thought that coronary microvascular dysfunction related to stress hyperglycemia might be one of the possible reasons for the poor outcome in patients with acute myocardial infarction with stress hyperglycemia, and also for the improvement of epicardial coronary blood flow and outcome in these patients after nicorandil administration. 4 Thus, the association between acute hyperglycemia (AHG) and coronary microvascular function (ie, hyperemic response of coronary blood flow or coronary flow reserve) should be thoroughly examined. Although some studies have demonstrated that AHG may impair flow-mediated vasodilatation in the peripheral arteries, 5,6 which might be a predictor of future cardiovascular events, 7 the effect of AHG on coronary microvascular function has not been fully clarified. Increased oxidative stress 8 and/or sympathetic activation 9 have been demonstrated to contribute to impairment of coronary microvascular function, and both of these pathophysiological abnormalities are also observed during AHG.However, the influence of these abnormalities caused by AHG on coronary microvascular function has not been fully evaluated.Recently, transthoracic Doppler, which can be used to estimate coronary microvascular function in a non-invasive manner, has become feasible in the clinical setting. [10][11][12] Therefore, we chose to use it in the present study to evaluate the effects of AHG observed during the oral glucose tolerance test (OGTT) on coronary microvascular function, and the associations among changes in the hyperemic response of coronary blood flow velocity (CFV) or coronary flow velocity reserve (CFVR), oxidative stress, and increased sympathetic tone caused by AHG in subjects with atherosclerotic risk factors. Methods SubjectsTwenty-four patients receiving treatment for atherosclerotic risk factors (14 patients with hypertension, 6 with hypercholesterolemia, 3 with hypertension and hypercholesterolemia, and 1 patient with abnormal glucose intolerance) at Tokyo Medical University Hospital were enrolled in this study. None of the patients had any symptoms suggestive of coronary heart disease or changes on the electrocardiogram suggestive of myocardial ischemia. Furthermore, none of them showed any regional wall motion abnormality on echocardiography. Written informed consent was given by all the subjects prior to their participation and the study protocol was approved by the Ethics ComCirc J 2007; 71: 202 -206 (Received June 28, 2006; revised manuscript received September 12, 2006; accepted November 9, 2006) Background The effect of acute hyperglycemia (AHG) during the oral glucose tolerance test (OGTT) on coronary microvascular function was evaluated, as well as the associations among the changes in coronary microvascular functi...

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

“…27- 31 Others have shown that oxidative stress is increased in both type I and type II DM. 32, 33 Hyperglycemia induces oxidative stress through several pathways, 10-13, 34 including enhanced aldose reductase activity, 10 increased advanced glycation end-products, 11 altered protein kinase C activity 12 and mitochondrial overproduction of superoxide. 13 Matsushima et al found that glutathione peroxidase overexpression improved LV diastolic function, accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis and apoptosis, in mice with STZ-induced DM.…”

Direct Comparison of Takotsubo Cardiomyopathy between Japan and USA: 3-year Follow-up Study

“…In addition to an excess of catecholamines, vasospasm and myocarditis may also be related to the onset of TC, although the mechanism of TC is largely unknown. Sympathetic activation is closely related to coronary microvascular dysfunction (18). According to previous reports, left ventricular wall motion abnormalities in TC patients might be associated with coronary microvascular impair- (20).…”

Purinergic receptor P2Y, G-protein coupled, 2 (P2RY2) gene is associated with cerebral infarction in Japanese subjects

“…23 From a vascular biology perspective, the processes of cellular adhesion, monocyte and macrophage attachment, and transmigration of immune cells across the endothelium are crucial steps in early atherogenesis and in the later stages of mature plaque rupture. 24 Inflammatory cells express P2RY2 with multiple effects.…”