Open Access Research Article Seki, et al., Vasc Med Surg 2015, 3:2 DOI: 10.4172/2329-6925.1000193 Volume 3 • Issue 2 • 1000193 J Vasc Med Surg ISSN: 2329-6925 JVMS, an open access journal *Corresponding author: Taro Mizutani, Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, Tel: +81-29-853- 3210/3081; Fax: +81-29-853-5984; E-mail: mizutani@md.tsukuba.ac.jp Received January 22, 2015; Accepted March 14, 2015; Published March 16, 2015 Citation: Seki Y, Jesmin S, Islam M, Ogura Y, Oki M, et al. (2015) Landiolol Hydrochloride Normalizes Diminished Levels of Cardiac Vascular Endothelial Growth Factor (VEGF) Signaling System Components in Lipopolysaccharide- Induced Sepsis Independent of Infammatory Markers. J Vasc Med Surg 3: 193. doi:10.4172/2329-6925.1000193 Copyright: © 2015 Seki Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Landiolol Hydrochloride Normalizes Diminished Levels of Cardiac Vascular Endothelial Growth Factor (VEGF) Signaling System Components in Lipopolysaccharide-Induced Sepsis Independent of Inflammatory Markers Yoshimoto Seki, Subrina Jesmin, Majedul Islam, Yoshiyasu Ogura, Masami Oki, Nobutake Shimojo, Tanzila Khatun, Hideaki Sakuramoto, Satoru Kawano and Taro Mizutani* Department of Emergency and Critical Care Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan Keywords: Heart; Landiolol hydrochloride; VEGF; Sepsis; Rat model Introduction Sepsis is considered as a systemic infammatory response to infection. Due to the recent increase in the aging of the population and the wider use of immunosuppressive agents, as well as invasive procedures, the morbidity and mortality associated with sepsis has increased lately [1]. Because sepsis is associated with widespread injury of the vascular endothelia, multiple organs become dysfunctional, including cardiac failure, ARDS (acute respiratory distress syndrome), acute kidney injury and coagulation disorder. Also, since the cardiovascular system plays a key homeostatic role, sepsis-induced myocardial depression is commonly associated with increased morbidity and mortality. Although sepsis-induced myocardial depression has not yet been clearly defned, it is known to involve both the lef and right sides of the heart, and is thus global or systemic [2]. Sepsis-induced cardiac dysfunction has been shown to occur very early in sepsis, including the hyperdynamic phase of septic shock, and the underlying pathogenesis may be related to mitochondrial dysfunction, as well as levels of nitric oxide, complements and cytokines [3]. However, the pathogenesis of this condition (septic myocardial depression) is so complex that there is no single efective treatment for it. Terefore, additional studies are necessary in order to improve our understanding of the disease, develop reliable diagnostic procedures, as well as efective therapeutic interventions for this disorder [4]. Vascular endothelial growth factor (VEGF) is an endothelial cell- specifc mitogen that plays an important role in neovascularization Abstract Aim: Myocardial dysfunction is one of the complications associated with sepsis during its (sepsis) pathogenesis. To date, very few studies have investigated whether angiogenic factors in the heart, such as vascular endothelial growth factor (VEGF) and components of its signaling system are involved in myocardial dysfunction during the early phases of sepsis. Therefore, the present study aims to examine: 1) the expression pattern of VEGF and its signaling molecules in the heart during the early hours of LPS-induced sepsis and 2) whether landiolol hydrochloride, an ultrashort-acting beta- blocker, can ameliorate alterations in the expression of cardiac VEGF signaling system components in the rats under these (sepsis) conditions. Method: Eight (8)-week-old male Wistar rats were administered for three hours with either LPS only once, or continuously with LPS plus landiolol. Result: At 3 h after LPS (only) administration, circulatory levels of tumor necrosis factor (TNF)-α, IL-6, iNOS, lactate concentration and percentage of fractional shortening of the heart were signifcantly increased. However, levels of cardiac VEGF and its downstream signaling components were signifcantly down regulated. Treatment of LPS-administered rats with landiolol for 3 h normalized LPS-induced blood lactate levels, cardiac functional compensatory events, as well as VEGF and its signaling molecules, but did not alter levels of plasma TNF-α, IL-6 and iNOS. Conclusion: Taken together, these data led us to conclude that landiolol may be cardio-protective in septic rats by normalizing coronary microcirculation through blockage of sepsis-induced decrease in expression of VEGF signaling system but independent of infammatory cytokines. under both physiological and pathological conditions [5]. VEGF possibly exerts these biological processes through three mechanisms of action, namely by: (1) increasing blood fow to the tissue via vasodilation, (2) reducing the distance between the cells and the nearest blood vessel by stimulating angiogenesis and (3) increasing the permeability of the blood vessels to plasma, small solutes and macromolecules. VEGF is a crucial molecule in that it is up regulated in all known physiological and pathological forms of angiogenesis and is known to stimulate angiogenesis directly [6]. Although growth of new blood vessels is normally rare in the heart, chronic ischemia can stimulate VEGF synthesis, which subsequently leads to angiogenesis and coronary collateral formation [7,8]. Other functions of VEGF, Journal of Vascular Medicine & Surgery J ou r n a l o f V a s c u l a r M e d i c i n e & S u r g e r y ISSN: 2329-6925