OBJECTIVEThe investigated the effects of Dengzhan Xixin on brain water content, blood-brain barrier (BBB) permeability, T2-weighted imaging (T2WI), metabolites and the lesion ratio after cerebral ischemia-reperfusion injuries (IRI).

METHODThe 65 rats were randomly individed into three groups, the sham-operated group, the ischemia-reperfusion group and the Dengzhan Xixin treatment group. The models of ischemia-reperfusion of middle cerebral artery in rats were established by placing an intraluminal suture. The Dengzhan Xixin treatment group were injected 10% Dengzhan Xixin injection 22.5 mg kg(-1) after ischemia 1.5 h. The sh am-operated group (n=5) were sacrificed on 1 to measure brain water content and BBB permeability. The rats of the ischemia-reperfusion group (n=30) and the Dengzhan Xixin treatment group (n=30) were sacrificed at reperfusion for 6 h, 12 h, 1 d, 2 d, 4 d, 7 d, respectively, after ischemia 1.5 h. The additional 35 rats were individed into the same three groups. The changes of T2WI and metabolites in the brain were observed, and rats were sacrificed at reperfusion for 1 d, 2 d, 4 d after ischemia 1.5 h to determine the lesion ratio by TTC.

RESULTIn the ischemia-reperfusion group, brain water content(77.93+/-0.68)% and BBB permeability (3.77+/-0.28) increased after reperfusion for 6 h. The peak time of brain water content was at 4 d (83.82+/-0.49)% and BBB permeability was at 2 d (5.51+/-0.24)%. In the ischemia-reperfusion group and the Dengzhan Xixin treatment group, there were hyperintense signals in the injury region of T2WI. In the ischemia-reperfusion group after reperfusion for 1 d, the ratio of NAA/Cr decreased and Cho/Cr increased. In the Dengzhan Xixin treatment group, the ratio of NAA/Cr increased and Cho/Cr decreased. In the treatment group, the lesion ratio decreased by TTC was 16.78+/-1.45 and in the ischemia-reperfusion group was 21.27+/-1.73 at 2 d.

CONCLUSIONDengzhan Xixin may relieve cerebral ischemia-reperfusion injury by influencing the metabolites of brain, stabilizing BBB and decreasing brain edema.

Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain Ischemia ; complications ; metabolism ; pathology ; Flavonoids ; pharmacology ; Male ; Permeability ; drug effects ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; metabolism ; pathology ; Water ; metabolism

Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gut-origin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP's severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP's process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemic reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.
Acute Disease ; Animals ; Humans ; Intestinal Mucosa ; blood supply ; injuries ; metabolism ; Malnutrition ; pathology ; Microcirculation ; metabolism ; Pancreatitis ; complications ; metabolism ; pathology ; physiopathology ; Reperfusion Injury ; pathology

INTRODUCTIONReperfusion of acutely ischaemic tissue may, paradoxically, lead to systemic complications. This phenomenon is believed to be initiated by humoral factors that have accumulated in the ischaemic tissue. The ancient art of venesection may reduce the load of these mediators at the point of reperfusion. The aim of this study is to test if selective venesection, by removing the initial venous return from the ischaemic tissue, can attenuate the systemic effects of the ischaemic-reperfusion injury using a porcine model of acute limb ischaemia.

MATERIALS AND METHODSThe right femoral arteries of anaesthetised female pigs were clamped. Twelve pigs were divided into 2 groups (n = 6 per group). In the treatment group, 5% of blood volume was venesected from the ipsilateral femoral vein upon reperfusion; the other arm served as control. The animals were sacrifi ced after 4 days for histological examination. A pathologist, blinded to the experimental groups, graded the degree of microscopic injury.

RESULTSFor the control group, the kidneys showed glomeruli and tubular damage. The livers demonstrated architectural distortion with cellular oedema. There was pulmonary oedema as well as extensive capillary congestion and neutrophil infiltration. Such findings were absent or reduced in the venesected animals. Consequently, the injury scores for the kidney, lung, liver and heart were significantly less for the venesected animals.

CONCLUSIONSelective venesection reduces the remote organ injuries of the ischaemic-reperfusion phenomenon.

Animals ; Disease Models, Animal ; Female ; Hindlimb ; injuries ; Multiple Organ Failure ; etiology ; pathology ; prevention & control ; Phlebotomy ; Pulmonary Edema ; etiology ; pathology ; prevention & control ; Reperfusion Injury ; complications ; therapy ; Sus scrofa

Animals ; Carnosine ; pharmacology ; therapeutic use ; Liver ; drug effects ; pathology ; Male ; Rats ; Rats, Wistar ; Reperfusion Injury ; prevention & control ; Shock, Hemorrhagic ; complications ; pathology

AIMTo investigate the protective effect of exogenous carbon monoxide (CO) on the liver injury induced by ischemia/reperfusion (I/R) of hind limbs in rats.

METHODS100 SD rats were divided randomly into sham operated group (S), S+ CO group (SC), I/R group (I/R), I/ R+ CO group (RC). A rat model of ischemia in hind limbs and the reperfusion liver injury was established with the occlusion of the femoral arteries for 4 h and re-opening for 6 - 72 h, 10 d. The rats in SC and RC groups were exposed to air containing CO (the volume traction of CO: 0.05%) for 2 h before and after reperfusion or the corresponding control time point, while the other two groups were exposed to the routine air. The pathologic changes of liver tissue were morphologically observed by HE stain. Serum GPT activity was tested by Automatic Biochemical Analyzer. The percentage of apoptosis, expression levels of bax and bcl-2 protein in liver tissue were detected by Flow Cytometry.

RESULTSThere was no difference between S and SC groups. Compared with SC group: (1) Pathological changes in liver tissue were significant in I/R and RC groups. (2) The serum GPT activity of I/R and RC groups was obviously increased. (3) In IR and RC groups, the percentage of apoptosis in liver tissue was all significantly increased. (4) The bax expression level was significantly increased. Compared RC group with I/R group: (1) Pathological change was slight. (2) The serum GPT activity was depressed. (3) The percentage of apoptosis and expression level of bax protein in liver tissue were depressed. (4) The expression level of bcl-2 protein in liver tissue was increased.

CONCLUSIONExogenous CO could attenuate liver tissue injury induced by limbs I/R in rats.

Animals ; Carbon Monoxide ; pharmacology ; Extremities ; blood supply ; Female ; Liver ; blood supply ; pathology ; Liver Diseases ; etiology ; pathology ; prevention & control ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; prevention & control

OBJECTIVETo summarize the Chinese experience in pathologic diagnosis of liver biopsies after orthotopic liver transplantation (OLTx).

METHODS1123 post-transplant liver biopsies from 665 OLTx patients from the Shanghai Eastern Hepatobiliary Surgery Hospital, Tianjin First Central Hospital, Guangzhou Sun Yat-sen University and Chongqing Southwest Hospital were retrospectively analyzed. All liver biopsies were stained with hematoxylin and eosin. Immunohistochemical studies for cytomegalovirus, HBsAg, CK19, CD4 and CD8 were also performed in selected examples.

RESULTSIn the involved hospitals, 4 to 12 types of complications were encountered after OLTx. The number of liver biopsies performed for each patient ranged from 1 to 9 (mean = 2.2). The timing of these biopsies varied from the second to the 2877 th post-transplant day. The 5 most common complications were acute cellular rejection (35.6%), ischemic-reperfusion injury (13.4%), biliary stricture (5.6%), drug complication (5.0%) and chronic rejection (4.7%). The 5 earliest complications after OLTx were primary non-function (occurring at day 4.7 +/- 2.1), ischemic-reperfusion injury (occurring at day 14.0 +/- 4.0), acute cellular rejection (occurring at day 32.1 +/- 62.9), hepatic artery thrombosis / stricture (occurring at day 62.9 +/- 74.2) and cytomegalovirus infection (occurring at day 107.7 +/- 93.0).

CONCLUSIONSThis study has evaluated the types, incidence and timing of major complications occurring after OLTx. The most important issue is the distinction between rejection and non-rejection pathology. Thorough understanding of atypical pathologic features of these complications is necessary. The Banff Schema (rejection activity index) for grading liver allograft rejection is useful for monitoring anti-rejection therapy and should be used routinely.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy, Needle ; Child ; Child, Preschool ; Cholestasis, Intrahepatic ; pathology ; Female ; Graft Rejection ; pathology ; Hepatic Artery ; pathology ; Humans ; Infant ; Liver Transplantation ; pathology ; Male ; Middle Aged ; Postoperative Complications ; pathology ; Reperfusion Injury ; pathology ; Retrospective Studies ; Thrombosis ; pathology

OBJECTIVE: To investigate the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion MRI for the evaluation of femoral head ischemia. MATERIALS AND METHODS: Unilateral femoral head ischemia was induced by selective embolization of the medial circumflex femoral artery in 10 piglets. All MRIs were performed immediately (1 hour) and after embolization (1, 2, and 4 weeks). Apparent diffusion coefficients (ADCs) were calculated for the femoral head. The estimated pharmacokinetic parameters (Kep and Ve from two-compartment model) and semi-quantitative parameters including peak enhancement, time-to-peak (TTP), and contrast washout were evaluated. RESULTS: The epiphyseal ADC values of the ischemic hip decreased immediately (1 hour) after embolization. However, they increased rapidly at 1 week after embolization and remained elevated until 4 weeks after embolization. Perfusion MRI of ischemic hips showed decreased epiphyseal perfusion with decreased Kep immediately after embolization. Signal intensity-time curves showed delayed TTP with limited contrast washout immediately post-embolization. At 1-2 weeks after embolization, spontaneous reperfusion was observed in ischemic epiphyses. The change of ADC (p = 0.043) and Kep (p = 0.043) were significantly different between immediate (1 hour) after embolization and 1 week post-embolization. CONCLUSION: Diffusion MRI and pharmacokinetic model obtained from the DCE-MRI are useful in depicting early changes of perfusion and tissue damage using the model of femoral head ischemia in skeletally immature piglets.
Animals ; Arteries/physiopathology ; Diffusion Magnetic Resonance Imaging/*methods ; Disease Models, Animal ; Embolism/complications ; Epiphyses/*blood supply/*pathology ; Femur Head/*blood supply/*pathology ; Male ; Osteonecrosis/pathology ; Pelvic Bones/blood supply/pathology ; Reperfusion Injury/complications/*diagnosis ; Swine

To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in the lung injury as assessed by lung histology, polymorphonuclear count, malondialdehyde content and wet-to-dry weight ratio following ischemia-reperfusion (I/R) of hind limbs, zinc protoporphyrin (ZnPP), an inhibitor of HO activity, was used, and the lung HO activity and blood carboxyhemoglobin (COHb) level were measured. The results showed that HO activity and COHb level were increased significantly and lung injury occurred after limb I/R. After administration of ZnPP, the lung injury was further aggravated while the HO activity and COHb level were significantly decreased. These findings suggest that upregulation of HO activity followed by subsequent CO production attenuates the lung injury induced by limb I/R in rats.
Animals ; Carbon Monoxide ; physiology ; Carboxyhemoglobin ; analysis ; Heme Oxygenase (Decyclizing) ; analysis ; physiology ; Hindlimb ; Lung Diseases ; etiology ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; metabolism

AIMTo investigate the effects of ramipril on myocardial ischemia/reperfusion injury in diabetic rats, and to explore its mechanism according to the observation on myocardial ultrastructure.

METHODSStreptozotocin induced diabetic rats were divided randomly into three groups (n = 16): ischemia/reperfusion (I/R), ischemic preconditioning (IPC) and ramipril (RAM) group. Rats in RAM group were administered by RAM(1 mg x kg(-1) x d(-1)) orally for 4 weeks, the others were administered by normal saline. Then all rats were subjected to myocardial ischemia/ reperfusion injury. Rats in IPC group were preconditioned before ischemia. The ECG and the infarct size were examined. The changes of myocardial morphology were examined by light and electron microscopes.

RESULTSCompared with I/R group, the elevation of ST segment and the incidence of ventricular tachycardia and ventricular fibrillation during ischemia were significantly decreased, the infarct size at the end of reperfusion was remarkably reduced, the myocardial morphology were significantly improved, special structure of myofilaments and mitochondria remained clearly, blood vessels were unobstructed, injury of endothelium were decreased in PC and RAM groups.

CONCLUSIONRamipril administered for 4 weeks induces myocardial protection in diabetic rats, which is similar to that of IPC. The mechanism may be involved in protection of cardiocytes and mitochondria, and improvement of endothelial function.

Animals ; Cardiotonic Agents ; pharmacology ; Diabetes Mellitus, Experimental ; complications ; Ischemic Preconditioning, Myocardial ; methods ; Myocardial Reperfusion Injury ; pathology ; prevention & control ; Myocardium ; ultrastructure ; Ramipril ; pharmacology ; Rats

OBJECTIVETo investigate the effect of ischemia/reperfusion (I/R) on tumor metastasis in a experimental mouse model of hematogenous metastasis after I/R and to quantify expression of vascular cell adhesion molecule-1 (VCAM-1) during I/R.

METHODSAn experimental mouse model of metastasis after partial hepatic I/R was designed to determine the effects of I/R on tumor metastasis to liver. Tumor loads were valued 14 days after operation. In addition, the expressions of alanine transaminase (ALT), aspartate transaminase (AST), and VCAM-1 were detected.

RESULTSTwo hours after hepatic reperfusion, ALT and AST levels in ischemia 45-minute group and ischemia 30-minute group were significantly higher than in the sham group (all P < 0.05). Also, the changes of ALT and AST were more obvious in the ischemia 45-minute group than in ischemia 30-minute group (all P < 0.05). In the sham group, both ALT and AST slightly and transiently increased. ALT and AST in the ischemia 45-minute group and ischemia 30-minute group at 8 hours were both significantly higher than those at 2 hours reperfusion (P<0.05). The tumor load (valued by hepatic replacement area) and the expression of VCAM-1 in ischemic lobe were significantly larger in the ischemia 45-minute group than in the ischemia 30-minute group and sham group (P = 0.013, P = 0.007). However, there was no statistical difference on tumor load between the right lobe of sham operated mice and the right lobe (nonischemic lobes) of mice subjected to I/R (P = 0.089). Mouse survivals were significantly longer in the sham group than in the ischemia 30-minute group (P = 0.041) but were not significantly different between the ischemia 45-minute group and ischemia 30-minute group (P = 0.055). VCAM-1 expression in ischemia 45-minute group was significantly higher than in ischemia 30-minute group and sham group(P = 0.003, P < 0.001), and it was positively correlated with the hepatic replacement area (r = 0.491, P = 0.045).

CONCLUSIONHepatic I/R promotes liver hematogenic metastasis of hepatocellular carcinoma in mice and at least in part, through the induction of VCAM-1 expression.

Animals ; Liver ; blood supply ; Liver Neoplasms ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Reperfusion Injury ; complications ; Vascular Cell Adhesion Molecule-1 ; physiology