Endothelin receptor blockers reduce I/R-induced intestinal mucosal injury: role of blood flow

Abstract

The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability ((51)Cr-EDTA clearance) and tissue myeloperoxidase (MPO) activity were significantly increased after 30 min of ischemia followed by 30 min of reperfusion. The I/R-induced increases in mucosal permeability and polymorphonuclear leukocyte (PMN) infiltration were significantly attenuated by pretreatments with ET(A) (BQ-485) and/or ET(B) (BQ-788) receptor antagonists. Monoclonal antibody (MAb) directed against intercellular adhesion molecule-1 (ICAM-1; MAb 1A29) and superoxide dismutase (SOD) pretreatments significantly attenuated the increased mucosal permeability and PMN infiltration in a similar manner as with ET receptor antagonists. Superior mesenteric artery blood flow was significantly reduced during the reperfusion period. Both ET receptor antagonists caused a significant rise in blood flow compared with an untreated I/R group. In conclusion, our data suggest that ET(A) and/or ET(B) receptors, ICAM-1, and superoxide play an important role in I/R-induced mucosal dysfunction and PMN infiltration. Furthermore, ET is involved in the pathogenesis of post-reperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period.

Propofol attenuates intestinal mucosa injury induced by intestinal ischemia-reperfusion in the rat

“…Intracellular SOD has been shown to play a critical role in attenuating the intestinal inflammatory response. 26,17 Propofol is widely used as an anesthetic before and during cardiac surgery, and as a sedative postoperatively in the intensive care unit. Also, in the clinical setting, pre-treatment with a certain drug for diseases related to intestinal I/R injury occurs with a higher frequency compared to other regimens, but sometimes treatment may be initiated after the onset of ischemia or during reperfusion due to unexpected occurrence of I/R event.…”

“…Increased ET-1 activity is not only a causative factor to intestinal I/R injury, 17,36 but most importantly, elevated plasma ET-1 levels might be related to the size and extent of myocardial infarction and the mortality after myocardial infarction in patients, 37 a situation that is often accompanied with gastrointestinal complications. 38,39 Propofol attenuation of ET-1 production in the injured intestinal mucosa (Table) could potentially reduce its release to the circulation.…”

“…16,17 Therefore, the current study was undertaken to clarify whether propofol can prevent intestinal mucosa I/R injury, and to investigate its effects on NO, ET-1 release during intestinal I/R, in an in vivo rat model. The accumulation of lactic acid (LD), a product from glucose metabolism in anaerobic metabolism, was used as an indirect index of intestinal ischemia.…”

Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms

“…Slices (5 μm) were cut and stained with hematoxylin and eosin and were examined under a light microscope. For the histological assessment of intestinal injury, a 0-4 grading scale was used as follows [18] : 0=normal histology; 1=slight disruption of the surface epithelium; 2=epi-thelial cell loss injury at villus tip; 3=mucosal vasocongestion, hemorrhage, and focal necrosis with loss of less than one-half of the villi; and 4=damage extending to more than one-half of the villi. An observer who was unaware of the treatment performed all assessments of damage.…”

Ischemic Intestinal Injury during Cardiopulmonary Bypass Does Not Show an Association with Neutrophil Activation

“…Instead, in a model of brain I/R injury, a correlation between activation of leukocyte-endothelium interactions and the reduction of ischemic brain damage after global cerebral ischemia was found [22] . In contrast to the current CPB model, the one feature in common in these studies is total ischemia followed by 'true' reperfusion, when MPO activity typically increases several-fold [11,[13][14][15][16] . Thus, in most I/R models of gut ischemia, both the fundamental insult as well as its inflammatory consequences differ markedly from the CPB milieu [5,8,[23][24][25] .…”