Cardiotonic pills, a compound Chinese medicine, protects ischemia-reperfusion-induced microcirculatory disturbance and myocardial damage in rats

2010 ◽  
Vol 298 (4) ◽  
pp. H1166-H1176 ◽  
Author(s):  
Na Zhao ◽  
Yu-Ying Liu ◽  
Fang Wang ◽  
Bai-He Hu ◽  
Kai Sun ◽  
...  
Keyword(s):  
Blood Flow ◽  
Chinese Medicine ◽  
Coronary Blood Flow ◽  
Adhesion Molecule ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Microcirculatory Disturbance ◽  
Albumin Leakage

Cardiotonic pills (CP) is a compound Chinese medicine widely used in China, as well as other countries, for the treatment of cardiovascular disease. However, limited data are available regarding the mechanism of action of CP on myocardial function during ischemia-reperfusion (I/R) injury. In this study, we examined the effect of CP on I/R-induced coronary microcirculatory disturbance and myocardial damage. Male Sprague-Dawley rats were subjected to left coronary anterior descending branch occlusion for 30 min followed by reperfusion with or without pretreatment with CP (0.1, 0.4, or 0.8 g/kg). Coronary blood flow, vascular diameter, velocity of red blood cells, and albumin leakage were evaluated in vivo after reperfusion. Neutrophil expression of CD18, malondialdehyde, inhibitor-κBα, myocardial infarction, endothelial expression of intercellular adhesion molecule 1, apoptosis-related proteins, and histological and ultrastructural evidence of myocardial damage were assessed after reperfusion. Pretreatment with CP (0.8 g/kg) significantly attenuated the I/R-induced myocardial microcirculatory disturbance, including decreased coronary blood flow and red blood cell velocity in arterioles, increased expression of CD18 on neutrophils and intercellular adhesion molecule 1 on endothelial cells, and albumin leakage from venules. In addition, the drug significantly ameliorated the I/R-induced myocardial damage and apoptosis indicated by increased malondialdehyde, infarct size, myocardial ultrastructural changes, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive myocardial cells, inhibitor-κBα degradation, and expression of Bcl-2, Bax, and caspase-3 in myocardial tissues. The results provide evidence for the potential role of CP in preventing microcirculatory disturbance and myocardial damage following I/R injury.

scholarly journals Ischemia-reperfusion induced microvascular responses in LDL-receptor −/− mice

1999 ◽  
Vol 276 (5) ◽  
pp. H1647-H1654 ◽  
Author(s):  
Naoharu Mori ◽  
Yoshinori Horie ◽  
Mary E. Gerritsen ◽  
D. Neil Granger
Keyword(s):  
Adhesion Molecule ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Normal Diet ◽  
Intercellular Adhesion Molecule ◽  
High Cholesterol Diet ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1 ◽  
Rolling Velocity ◽  
Albumin Leakage

The objective of this study was to determine whether the microvascular responses to ischemia and reperfusion (I/R) are altered in an animal model of atherosclerosis, the low-density lipoprotein-receptor knockout (LDLr −/−) mouse. Intravital video microscopy was used to monitor venular wall shear rate, leukocytes rolling velocity, the number of rolling, adherent and emigrated leukocytes, and albumin leakage in cremasteric postcapillary venules of wild-type (B6129) and LDLr −/− mice exposed to 60 min of ischemia and 60 min of reperfusion. The postcapillary venules of LDLr −/− mice exhibited two- to threefold larger increments in the number of adherent leukocytes and a more profound albumin leakage response to I/R than venules in wild-type mice. The exaggerated inflammatory responses noted in LDLr −/− mice placed on a normal diet were not exacerbated by a high-cholesterol diet. Treatment of LDLr −/− mice with either a platelet-activating factor (PAF) receptor antagonist (WEB-2086) or a monoclonal antibody (YN-1) against the endothelial cell adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), markedly attenuated the I/R-induced leukocyte adherence and albumin leakage. These findings indicate that atherogenic mice are more vulnerable to the deleterious microvascular effects of I/R and that PAF-mediated, ICAM-1-dependent leukocyte adhesion contributes to this exaggerated response to I/R.

Effects of NF-κB inhibition on mesenteric ischemia-reperfusion injury

2003 ◽  
Vol 284 (4) ◽  
pp. G713-G721 ◽  
Author(s):  
Lei Zou ◽  
Bashir Attuwaybi ◽  
Bruce C. Kone
Keyword(s):  
Reperfusion Injury ◽  
Tyrosine Phosphorylation ◽  
Adhesion Molecule ◽  
Interleukin 6 ◽  
Mesenteric Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

Mesenteric ischemia-reperfusion injury is a serious complication of shock. Because activation of nuclear factor-κB (NF-κB) has been implicated in this process, we treated rats with vehicle or the IκB-α inhibitor BAY 11-7085 (25 mg/kg ip) 1 h before mesenteric ischemia-reperfusion (45 min of ischemia followed by reperfusion at 30 min or 6 h) and examined the ileal injury response. Vehicle-treated rats subjected to ischemia-reperfusion exhibited severe mucosal injury, increased myeloperoxidase (MPO) activity, increased expression of interleukin-6 and intercellular adhesion molecule 1 protein, and a biphasic peak of NF-κB DNA-binding activity during the 30-min and 6-h reperfusion courses. In contrast, BAY 11-7085-pretreated rats subjected to ischemia-reperfusion exhibited less histological injury and less interleukin-6 and intercellular adhesion molecule 1 protein expression at 30 min of reperfusion but more histological injury at 6 h of reperfusion than vehicle-treated rats subjected to ischemia-reperfusion. Studies with phosphorylation site-specific antibodies demonstrated that IκB-α phosphorylation at Ser32,Ser36 was induced at 30 min of reperfusion, whereas tyrosine phosphorylation of IκB-α was induced at 6 h of reperfusion. BAY 11-7085 inhibited the former, but not the latter, phosphorylation pathway, whereas α-melanocyte-stimulating hormone, which is effective in limiting late ischemia-reperfusion injury to the intestine, inhibited tyrosine phosphorylation of IκB-α. Thus NF-κB appears to play an important role in the generation and resolution of intestinal ischemia-reperfusion injury through different activation pathways.

scholarly journals O-linked β-N-acetylglucosamine During Hyperglycemia Exerts Both Anti-Inflammatory and Pro-Oxidative Properties in the Endothelial System

2009 ◽  
Vol 2 (3) ◽  
pp. 172-175 ◽  
Author(s):  
Angana Gupta Rajapakse ◽  
Xiu-Fen Ming ◽  
João M. Carvas ◽  
Zhihong Yang
Keyword(s):  
Oxidative Stress ◽  
Adhesion Molecule ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiovascular Complications ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Anti Inflammatory ◽  
Vascular Adhesion

Elevated cellular levels of proteinO-linked β-N-acetylglucosamine (O-GlcNAc) through hexosamine biosynthesis pathway (HBP) are suggested to contribute to cardiovascular adverse effects under chronic hyperglycemic condition associated with oxidative stress and inflammation. Conversely, enhancingO-GlcNAc levels have also been demonstrated being protective against myocardial ischemia/reperfusion injury. We recently demonstrated that hyperglycemia increases oxidative stress and HBP flux in endothelial cells and enhances endothelial expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in response to tumor necrosis factor-α (TNFα) through oxidative stress rather than HBP pathway. Here we present further complementary data showing that enhancingO-GlcNAc levels by glucosamine does not mimic hyperglycemia's effect on TNFα-induced endothelial VCAM-1 and ICAM-1 expression. Glucosamine however inhibits ICAM-1 (not VCAM-1) expression and induces superoxide generation in the cells. The results further suggest that increasedO-GlcNAc levels do not mediate the enhancing effect of hyperglycemia on the endothelial inflammatory responses to TNFα. In contrast, it exerts certain anti-inflammatory effects accompanied by pro-oxidative properties. Further work should delineate the exact role of HPB pathway in different aspects of cardiovascular functions, especially those of diabetic cardiovascular complications.

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