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 significantly increased. However, levels of cardiac VEGF and its downstream signaling components were significantly 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 inflammatory cytokines.
Highlights
Sepsis is considered as a systemic inflammatory response to infection
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 Vascular Endothelial Growth Factor (VEGF) signaling system but independent of inflammatory cytokines
The important findings revealed by the present study are that: (1) landiolol dramatically improved the survival ratio of septic rats, as much as 80% compared to treated with LPS only, (2) landiolol normalized the hyperdynamic state of sepsis rats at 3 h, and prevented both the decrease in arterial oxygenation, as well as elevation in levels of blood lactate, which was noted within 3 h, for animals were not treated with landiolol, (3) VEGF levels were significantly down regulated within 3 h after LPS administration and treatment with landiolol attenuated this decrease in VEGF levels, (4) Akt and eNOS, the downstream effecters of VEGF significantly decreased in septic rats and landiolol normalized levels of these molecules
Summary
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. Since the cardiovascular system plays a key homeostatic role, sepsis-induced myocardial depression is commonly associated with increased morbidity and mortality. Sepsis-induced myocardial depression has not yet been clearly defined, it is known to involve both the left and right sides of the heart, and is global or systemic [2]. The pathogenesis of this condition (septic myocardial depression) is so complex that there is no single effective treatment for it. Additional studies are necessary in order to improve our understanding of the disease, develop reliable diagnostic procedures, as well as effective therapeutic interventions for this disorder [4]
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