BACKGROUND: Lipid-emulsion propofol (LP) has cardioprotective effects against ischemia-reperfusion injury, but it has lipid-related side effects. Microemulsion propofol (MP) is a lipid-free propofol emulsified with 10% purified poloxamer 188 (PP188). PP188 is a nonionic surfactant and has cardioprotective effects. However, some reports have suggested that reduced cardioprotective effects were observed when the cardioprotective agents were used in combination even though each cardioprotective agent has cardioprotective effects. The aims of this study were to examine and compare the cardioprotective effects of MP and LP. METHODS: 50 isolated rat hearts were perfused with modified Kreb's solution. They were divided into 4 groups and underwent 30 minutes of ischemia and 60 minutes of reperfusion. Control group: ischemia-reperfusion was performed without treatment. LP, MP and PP groups: LP, MP and PP188 were infused during the pre-ischemic and reperfusion period, respectively. Hemodynamic parameters and coronary effluent flow rate (CEFR) were measured. Infarct size was determined using triphenyl-tetrazolium staining. RESULTS: In the MP group, systolic pressure was maintained near baseline, the systolic pressure was higher than that in the other groups and HR was lower than that in the other groups during reperfusion. Diastolic pressure was transiently increased in the PP group after treatment and at 5 minutes after reperfusion compared with that in the control group and in the the LP group. There were no differences in dP/dtmax and CEFR between groups. Infarct size in the LP, MP and PP groups was smaller than that in the control group, but there were no significant differences between these three groups. CONCLUSIONS: MP has cardioprotective effects similar to those of LP. MP can be used for cardiac anesthesia in cases with ischemia-reperfusion injury to avoid the lipid-related side effects of LP.
Anesthesia ; Animals ; Blood Pressure ; Cardiotonic Agents ; Heart ; Hemodynamics ; Ischemia ; Poloxamer ; Propofol ; Rats ; Reperfusion ; Reperfusion Injury

OBJECTIVETo investigate the role of plasma tissue factor (TF) and tissue factor pathway inhibitor-1 (TFPI-1) level and to observe the effect of extrinsic TFPI-1 on no-reflow (NR) in a rabbit model of ischemia/reperfusion.

METHODSRabbits were randomized into four groups (n = 10 each): ischemic- reperfusion group (IR, subjected to 120 minutes of coronary artery occlusion and followed by 60 minutes of reperfusion); ischemic- reperfusion TFPI-1 group (100 ng/kg bolus and 1 ng x kg(-1) x min(-1) infusion during reperfusion); ischemic group (subjected to 180 minutes of coronary artery occlusion) and sham group. The NR area and ischemic area were determined by thioflavin S and Evan's blue staining in vivo. Plasma TF and TFPI-1 levels were measured before operation, before and at 120 minutes post coronary artery ligation, 10 and 60 minutes after reperfusion by ELISA.

RESULTSPlasma TF and TFPI-1 levels before and at 120 minutes post coronary artery ligation were similar among the four groups (all P > 0.05). At 10 and 60 minutes after reperfusion, the plasma TF levels in the IR group was significantly higher than those in ischemic group and sham group [10 minutes: (20.7 + or - 4.1) pg/ml vs. (13.9 + or - 2.2) pg/ml (P < 0.001), (20.7 + or - 4.1) pg/ml vs. (13.2 + or - 2.6) pg/ml (P < 0.001); 60 minutes: (15.8 + or - 2.6) pg/ml vs. (13.5 + or - 1.6) pg/ml (P < 0.05), (15.8 + or - 2.6) pg/ml vs. (12.1 + or - 0.7) pg/ml (P < 0.001)] while the plasma TFPI-1 levels were similar among IR, ischemic and sham groups at 10 minutes after reperfusion and at 60 minutes after reperfusion (all P > 0.05). TFPI-1 level [(9.7 + or - 1.6) ng/ml] was significantly lower in the IR group than in the ischemic group [(11.6 + or - 1.6) ng/ml, P < 0.05] and sham group [(10.1 + or - 1.3) ng/ml, P < 0.01]. TF mRNA expression in the NR area in IR group was significantly up-regulated compared to the ischemic group (P < 0.05) and sham group (P < 0.001) while TFPI-1 mRNA expression was similar between IR group and ischemic group (P > 0.05). NR severity in the ischemic-reperfusion TFPI-1 group was significantly attenuated compared to IR group (0.39 + or - 0.11 vs. 0.54 + or - 0.06, P < 0.01).

CONCLUSIONUpregulated TF mRNA expression in the NR area and increased plasma TF level during reperfusion period, reduced plasma TFPI-1 level during reperfusion period as well as attenuated NR severity by extrinsic application of human rTFPI-1 in this model suggested an important role in the pathogenesis of the NR phenomenon.

Animals ; Blood Proteins ; metabolism ; Lipoproteins ; blood ; Myocardial Reperfusion Injury ; blood ; Rabbits ; Thromboplastin ; metabolism

The relationship between the hepatic ischemia/reperfusion (I/R) injury and the balance of nitric oxide/endothelins (NO/ET) was studied. The changes of the ratio of NO/ET and the hepatic injury were observed in a rat hepatic I/R model pretreated with several tool drugs. In the acute phase of hepatic I/R injury, the ratio of plasma NO/ET was reduced from 1.58 +/- 0.20 to 0.29 +/- 0.05 (P < 0.01) and the hepatic damage deteriorated. NO donor L-Arg and ET receptor antagonist TAK-044 could alleviate the hepatic I/R injury to some degree, whereas NO synthase inhibitor L-NAME aggravated the damage. It was concluded that the hepatic I/R injury might be related with the disturbance of the NO/ET balance. Regulation of this balance might have an effect on the I/R injury.
Arginine ; Endothelins/*blood ; Liver/*blood supply ; NG-Nitroarginine Methyl Ester ; Nitric Oxide/*blood ; Receptors, Endothelin/antagonists & inhibitors ; Reperfusion Injury/*blood

BACKGROUND: Among the various mechanisms of Myocardial reperfusion injuries, neutrophil is thought to be one of them. Endogenous coronary vasodilator adenosine is known to have myocardial protective effect through variable pharmacologic action, influencing the function of several cell types involved in the pathogenesis of myocardial reperfusion injury. This study was designed to determine the beneficial effect of adenosine on the left ventricular function during reperfusion and whether this effect is due to the adenosine on the role of neutrophil. METHODS: 27 open-chest cats were randomly divided into 3 groups. 6 cats received ischemic injury without reperfusion(group 1). 21 cats were subjected to 60 minutes of proximal left anterior descending coronary artery occlusion followed by a 60-minute reperfusion. 11 of 21 cats received intravenous adenosine(0.15mg/Kg/min) infusion starting 5 minutes before reperfusion throughout the entire period(group 3). 10 cats received equal volume of saline instead of adenosine(group 2). RESULTS: 1) During the experimental period, significant decrease of heart rate, blood pressure, RPI, negative dP/dT and increase of LVEDP were noted in group 2 and 3 with no difference between the two groups. The reduction of positve dP/dT was more significant in group 2 at 30 and 60 minute of reperfusion than the preocclusion value(1404+/-111, 1631+/-161 vs 1832+/-169mmHg/sec at baseline, p<0.05). In contrast, positive dP/dT in group 3 at 30 and 60 minute of reperfusion were similar to baseline values(1890+/-92, 2052+/-112 vs 2025+/-227mmHg/sec at baseline, p=NS). These were significantly higher(p<0.05) than untreated group 2. 2) Infarct size was significantly reduced in adenosine-treated group 3, when expressed as a percentage of the area at risk(28.4+/-3.3% vs 44.5+/-3.2% of group 2, p<0.05). The significant increase in myeloperoxidase activity observed after reperfusion was not detected in adenosine treated group 3.(0.18+/-0.05 vs 0.46+/-0.09 unit/100mg wet tissue weight, p<0.05). A significant correlation was present between infarct size (% of left ventricle) and myeloperoxidase activity(r=0.72, p<0.01). 3) Light microscopic examination demonstrated the decreased acute interstitial and intra vascular inflammatory infiltration and capillary plugging together with decreased tendency of incidence of contraction band necrosis in adenosine treated group 3. CONCLUSION: These findings suggest that intravenous administration of adenosine during the early reperfusion period significantly reduces infarct size, improving the early recovery of global ventricular function. The probable cause is the effect of adenosine on neutrophil as one of the various protective mechanisms of adenosine in feline heart model subjected to coronary occlusion and reperfusion, 60 minutes each.
Adenosine* ; Administration, Intravenous ; Animals ; Blood Pressure ; Capillaries ; Cats ; Coronary Occlusion ; Coronary Vessels ; Heart Rate ; Heart* ; Incidence ; Myocardial Reperfusion Injury* ; Myocardial Reperfusion* ; Necrosis ; Neutrophils ; Peroxidase ; Reperfusion ; Reperfusion Injury ; Ventricular Function ; Ventricular Function, Left

Humans ; Kidney ; blood supply ; Nephrectomy ; methods ; Reperfusion Injury ; prevention & control ; Time Factors ; Warm Ischemia

AIMTo establish a model of ischemia/reperfusion injury on L-6TG cell.

METHODSCultured L-6TG cells were divided into 2 groups: control group (C), ischemia/reperfusion group (I/R), LDH in culture fluid, SOD, XOD, free calcium in L-6TG cell and mitochondria respiration were evaluated in each group, the micromorphologic changes were observed with microscope.

RESULTSCompared with control group, after L-6TG cell suffered ischemia 4 hours and reperfusion 4 hours, LDH in culture fluid, XOD, free calcium in L-6TG cell all increased significantly, while SOD in L-6TG cell and mitochondrial respiration decreased, structural damage to L-6TG cell was severe.

CONCLUSIONUsing mimicking ischemic solution and mimicking reperfusion solution can successfully establish a model of ischemia/reperfusion injury on L-6TG cell.

Animals ; Cells, Cultured ; Colorimetry ; L-Lactate Dehydrogenase ; analysis ; Muscle, Skeletal ; blood supply ; Rats ; Reperfusion Injury

In order to provide us new clues to induce some endogenous protective molecular mechanisms, the changes in gene expression profile induced by ischemia-reperfusion in pulmonary tissues of rats were investigated and the dynamic mechanism of pulmonary ischemia-reperfusion injury was elucidated. Thirty male Wistar rats were randomly divided into 6 groups: 5 ischemia-reperfusion (I/R) groups (I/R 0-h, I/R 1-h, I/R 3-h, I/R 6-h, I/R 24-h) and control group (n=5 in each). An in situ ischemia-reperfusion lung injury rat model was established by occluded hilus of lung. The RatRef-12 Expression Beadchip (22 226 gene probes per array) was used to analyze the pattern of gene expression in all groups. The results showed that 648, 340, 711, 1279 and 641 genes were differentially expressed in I/R 0-, 1-, 3-, 6-and 24-h groups respectively. The differentially expressed genes were classified as following 7 functional categories: cytokine, adhesion molecule, growth factor and apoptosis-related factor, oxidation and antioxidation molecule, metabolic enzyme, ion channel and aquaporin, signal transduction molecule. It was suggested that gene chip technology was an effective and quick method for screening differentially expressed genes. Many differentially expressed genes with different functions interacted each other to result in pulmonary ischemia-reperfusion injury.
Gene Expression Profiling ; Lung/*blood supply ; Random Allocation ; Rats, Wistar ; Reperfusion Injury/*genetics

OBJECTIVETo investigate the mechanism of plasma bilirubin level increase after hepatic ischemia-reperfusion in rats.

METHODSRats were divided into a sham operation group (A group), a 20 min ischemia-reperfusion group (B group) and a 35 min ischemia-reperfusion group (C group). Study time points were 6 hours and 1, 3, and 5 days after the reperfusion. Pathological changes in the livers were studied with histological slides stained with hematoxilin and eosin. Routine biochemistry methods were used to detect the bilirubin level of blood plasma and the bile drained from the ischemic hepatic lobes. RT-PCR was used to analyze the expression of the multidrug resistance-associated protein 2 (MRP2) and mRNA. Immunohistochemistry was used to analyze the localization of MRP2 in the canalicular membrane.

RESULTSB and C groups showed a mild inflammatory reaction without hepatocyte necrosis. At 6 h and 1 day after reperfusion, there was a significant increase of the plasma bilirubin level and a decrease of the bilirubin level of the drained bile in B group. These changes lasted to the day 3 and day 5 in C group. MRP2 mRNA down-regulation was found at 6 h only in the B and C groups. No localization of MRP2 in the canalicular membrane was found but it appeared in "esicules" under the canalicular membrane in C group.

CONCLUSIONSAbsence of MRP2 localization in the canalicular membrane could be the cause of the blood plasma bilirubin level increase after liver ischemia-reperfusion.

Animals ; Bilirubin ; blood ; Liver Diseases ; blood ; Male ; Multidrug Resistance-Associated Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood

Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Additional control rat hearts were perfused with 75 X 106 PMNs, with 75 X 106 platelets, or with 75 X 106 PMNs+75 X 106 platelets over a five minute perfusion followed by a 75 min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of 5 ~ 10% (p < 0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50 to 60% in all measurements of cardiac function (p < 0.01). These dual cell perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiaodynamic effects as well as PMN accumulation and P-selectin expression were markedly attenuated by a recombinant soluble PSGL-1 which inhibits selectin mediated cell adhesion. These results provide evidence that platelets and PMNs act synergistically in provoking post-reperfusion cardiac dysfunction, and that this may be largely due to cell to cell interactions mediated by P-selectin. These results also demonstrate that a recombinant soluble PSGL-1 reduces myocardial reperfusion injury by platelet and PMNs interaction.
Animals ; Blood Cells ; Blood Platelets* ; Cell Adhesion ; Cell Communication ; Endothelium ; Glycoproteins* ; Heart ; Ischemia* ; Myocardial Reperfusion Injury ; Neutrophils* ; P-Selectin* ; Perfusion ; Peroxidase ; Rats ; Reperfusion*

OBJECTIVETo investigate the protective role of ischemic preconditioning (IPC) during lung ischemia-reperfusion (I/R) injury and its influence on inflammatory cytokine production.

METHODSIn vivo I/R injury of rabbit was induced by blocking hilum of the left lung. The wet/dry ratio of the lung, lung permeability index and neutrophils percentage in bronchoalveolar lavage fluid (BALF) were detected as indexes of the lung injury. Serum levels of tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) were also detected using enzyme-linked immunosorbent assay. The protective role of IPC and its influence on inflammatory cytokine production were observed.

RESULTSThe wet/dry ratio of the lung, lung permeability index and neutrophils percentage in BALF of I/R group were 9.73 +/- 1.14, (41.62 +/- 5.77) x 10(-4) and (58.1 +/- 10.0)% respectively. The IPC group indexes were 6.23 +/- 0.69, (20.31 +/- 4.03) x 10(-4) and (23.8 +/- 5.2)% respectively. There was a significant difference between the two groups (P < 0.01). Serum levels of TNFalpha, IL-6 and IL-8 of I/R group were (0.9078 +/- 0.1062), (0.2137 +/- 0.0598) and (0.7211 +/- 0.0979) ng/ml respectively. The IPC group indexes were (0.7478 +/- 0.0843), (0.1271 +/- 0.0089) and (0.5903 +/- 0.0746) ng/ml respectively, significantly lower than that of I/R group (P < 0.01).

CONCLUSIONSLung IPC has a marked protection effect against I/R injury. The effect was related to its inhibition of inflammatory cytokines such as TNFalpha, IL-6 and IL-8, thus reducing activation and infiltration of neutrophils.

Animals ; Cytokines ; blood ; Disease Models, Animal ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Ischemic Preconditioning ; Lung ; blood supply ; Rabbits ; Random Allocation ; Reperfusion Injury ; blood ; Tumor Necrosis Factor-alpha ; blood