STEMI patients with greater residual thrombus burden after aspiration thrombectomy had worse microvascular dysfunction and greater myocardial damage compared with those with smaller residual thrombus burden.

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp s a treatment for acute myocardial infarction (AMI), thrombolytic therapy was started in the early 1980 s, 1 and now the best strategy is reperfusion of the occluded coronary artery and restoration of coronary blood flow with percutaneous coronary intervention (PCI) early after the onset of AMI. 2 Despite the fact that the outcome of AMI has improved with the reperfusion strategy, morbidity and mortality after AMI still remain significant. Editorial p 301Whether pharmacological interventions added to reperfusion therapy can further reduce myocardial damage or improve the prognosis has been investigated for the past 3 decades. 3 Many pharmacologic agents have been administered for cardiac protection, including KATP channel openers, human atrial natriuretic peptide, glucose-insulin-potassium infusion, sodiumhydrogen exchange inhibitors, adenosine receptor agonists, calcium-channel blockers, β-blockers and so on. Beta-blockers reduce myocardial oxygen consumption by decreasing the heart rate (HR) and myocardial contractility, which improves the oxygen supply/demand ratio. 4 It is well known that oral β-blocker therapy improves survival after AMI, especially in patients with reduced cardiac function. 5 However, it remains unclear whether intravenous administration of a β-blocker in the very acute phase of AMI is beneficial. In the pre-thrombolytic era, treatment with intravenous followed by oral administration of β-blocker improved survival and reduced infarct size. 6-8 In the thrombolytic era, early intravenous followed by oral administration of a β-blocker did not affect left ventricular Background: It is still controversial whether intravenous administration of β-blocker in the very acute phase of acute myocardial infarction (AMI) is beneficial. Landiolol is an ultra-short-acting β-blocker that has less effect on blood pressure, but little is known about its efficacy and safety for patients with AMI undergoing primary percutaneous coronary intervention (PCI).

The WCD use for the acute phase care of patients at high risk of VA can be safe and effective, and may be useful for evaluating indication of ICD implantation.

In male coupling factor 6 (CF6)-overexpressing transgenic (TG) mice, a high-salt diet induces hypertension and cardiac systolic dysfunction with excessive reactive oxygen species generation. However, the role of gender in CF6-mediated pathophysiology is unknown. We investigated the effects of ovariectomy and estrogen replacement on hypertension, cardiac dysfunction and Rac1 activity, which activates radical generation and the mineralocorticoid receptor, in female TG mice. Fifteen-week-old male and female TG and wild-type (WT) mice were fed a normal-or high-salt diet for 60 weeks. Systolic and diastolic blood pressures were higher in the TG mice fed a high-salt diet than in those fed a normal-salt diet at 20-60 weeks in males but only at 60 weeks in females. The blood pressure elevation under high-salt diet conditions was concomitant with a decrease in left ventricular fractional shortening. In the WT mice, neither blood pressure nor cardiac systolic function was influenced by a high-salt diet. In the female TG mice, bilateral ovariectomy induced hypertension with cardiac systolic dysfunction 8 weeks after the initiation of a high-salt diet. The ratios of Rac1 bound to guanosine triphosphate (Rac1-GTP) to total Rac1 in the heart and kidneys were increased in the ovariectomized TG mice, and estrogen replacement abolished the CF6-mediated pathophysiology induced under the high-salt diet conditions. The overexpression of CF6 induced salt-sensitive hypertension, complicated by systolic cardiac dysfunction, but its onset was delayed in females. Estrogen has an important role in the regulation of CF6-mediated pathophysiology, presumably via the downregulation of Rac1. Hypertension Research (2012) 35, 539-546; doi:10.1038/hr.2011.232; published online 19 January 2012Keywords: coupling factor 6; estrogen; heart failure; hypertension; salt INTRODUCTION Premenopausal women have a lower risk and incidence of hypertension and cardiovascular disease than age-matched men. However, this gender advantage gradually disappears after menopause. Although blood pressure is lower in premenopausal women than in men, after menopause, it increases to levels similar to or higher than those of agematched men. 1,2 The recent Nurse's Health Study 3 and WISE Study, 4 as well as others, 5 have demonstrated that compared with women with normal endogenous estrogen levels, young women undergoing early menopause owing to ovarian dysfunction or bilateral ovariectomy have an increased risk of cardiovascular disease. In animal models of cardiovascular disease, females exhibited lower mortality, less vascular injury, better preservation of cardiovascular function, and slower progression to decompensated heart failure than did males, although such differences were abolished after ovariectomy or induction of a deficiency in endogenous estrogen. 6,7-9 These findings clearly suggest that sex hormones have a cardioprotective role in women. Although randomized, prospective, primary or secondary prevention trials failed

Matrix metalloproteinase (MMP)-9 plays an important role in cardiovascular events. However, the mechanisms underlying in vivo activation of MMP-9 are largely unknown. We investigated the secretion and activation of MMP-9 under a cell-to-cell interaction, and the effects of hypoxia and cytokine. Human umbilical vein endothelial cell (HUVEC) and THP-1 (human monocyte cell line) were cultured individually, or cocultured under normoxic and hypoxic conditions. In a coculture of HUVEC and THP-1, proMMP-9 secretion was increased twofold compared with individual culture of HUVEC and THP-1, whereas MMP-2 secretion was unchanged. The increase in proMMP-9 secretion was suppressed by antiadhesion molecule antibodies and mitogen-activated protein kinase inhibitors, PD98059 (MAPK/ERK kinase1 inhibitor) and SP600125 (Jun N-terminal kinase inhibitor). ProMMP-9 secretion was increased by tumor necrosis factor (TNF)-α at 50 ng/ml (P < 0.05) but was not activated under normoxic (20%) conditions. ProMMP-9 in coculture was activated under hypoxic (<1%) conditions, and was potentiated by TNF-α (both P < 0.05). To further investigate the mechanism of hypoxia-induced MMP-9 activation, heat shock protein (Hsp)90, which was suggested to be related to MMP-9 activation, was measured by Western blot analysis. The ratio of Hsp90 to glyceraldehyde-3-phosphate dehydrogenase was increased in hypoxic (<1%) coculture conditions with TNF-α (P < 0.05). Treatment with geldanamycin and 17-DMAG (Hsp90 inhibitor) suppressed the active form of MMP-9. Cell-to-cell interaction between endothelial cells and monocytes promotes proMMP-9 synthesis and secretion. Hypoxia and inflammation are suggested to play an important role in activating proMMP-9, presumably via Hsp90.