Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia.
نویسندگان
چکیده
Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 microg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml x kg-1 x h(-1) fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 4]. Luminal gut lactate concentrations and PCO2 gap increased in groups IV and V (P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called "cytopathic hypoxia."
منابع مشابه
The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock.
BACKGROUND Endothelin-1, the most potent vasoconstrictor known, is produced in septic states and may be involved in the pathophysiology of the deteriorated splanchnic circulation seen in septic shock. AIMS To elucidate the capability of bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in en...
متن کاملTissue Post Cardiac Arrest
Hypoperfusion to the gut during cardiac arrest is an important clinical problem. The inability to control pH during metabolic stress, e.g. ischemia, leads to the disruption or halting of processes vital to balancing cellular metabolism. Alterations in cellular pH have been linked to changes in intramucosal permeability, which may result in the leakage of inflammatory mediators or bacteria, or b...
متن کاملDexmedetomidine ameliorates gut lactate production and impairment of exogenous lactate clearance in an endotoxic sheep model
Introduction The mechanisms of persistent hyperlactemia during endotoxic shock are probably multifactorial. Both hypoperfusion-related anaerobic production and adrenergic-driven aerobic generation have been implicated. More recently an early and severe impairment in exogenous lactate clearance has also been described [1]. Theoretically, an excessive adrenergic response could influence all these...
متن کاملAttenuation by l-thyroxine of oxidant-induced gut epithelial damage
Objective(s): Severe injuries are often associated with tissue hypothyroidism, elevated damaging mediators in circulation, and broken gut epithelial barrier. However, the relationships between the hypothyroid state and gut epithelial damage are largely unknown. Therefore, in this study, we investigated the effects of L-thyroxine (T4) on in vitro models of intact and ...
متن کاملAlteration of complement hemolytic activity in different trauma and sepsis models
Complement activation is involved in various diseases in which innate immunity plays a crucial role. However, its pathophysiological relevance is not clearly understood. Experimental models have been widely used to characterize the role of complement activation under different pathological conditions, such as hypoxemia, ischemia and reperfusion, tissue damage, and polymicrobial invasion. Screen...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of applied physiology
دوره 95 5 شماره
صفحات -
تاریخ انتشار 2003