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BACKGROUND: Spinal cord ischemia with resulting paraplegia remains one of the most common complications after repair of thoracoabdominal aortic aneurysms or dissection. Inducible nitric oxide synthase (iNOS) is known to have both neuroprotective and neurotoxic effects in the central nervous system. We investigated the possible relationship between the effect of pre-ischemic isoflurane exposure on mild spinal cord ischemia and the inducible nitric oxide synthase (iNOS) expression by using iNOS-specific antibody and pyrrolidinedithio carbamate (PDTC), NF-kappaB inhibitor, in the ventral horn of spinal cord in rats. METHODS: The animals were divided into five groups (n = 6 in each group): sham group, control group, PDTC-treated group, isoflurane-treated group, and PDTC/ isoflurane-treated group. In the PDTC-treated groups, 2% 100 mg/kg PDTC was administered intraperitoneally at 1 h before operation and at 24 h and 48 h after reperfusion. The rats in the isoflurane-treated groups received 30 min inhalation of 2.8% isoflurane at 24 h before spinal cord ischemia. Immunohistochemistry was performed to detect iNOS expression in the motor neuron of the ventral horn in spinal cord. RESULTS: Preconditioning with isoflurane increased the iNOS expression when compared to the control group (P < 0.05), whereas pre-treatment with both PDTC and isoflurane significantly decreased the iNOS expression compared to isoflurane-treated group (P < 0.05). CONCLUSIONS: Pre-ischemic isoflurane exposure was related with increase of the iNOS expression via a pathway modulated by NF-kappaB. iNOS may act as an important mediator of delayed preconditioning with isoflurane for the protective effect against spinal cord ischemia.
Subject(s)
Animals , Rats , Aortic Aneurysm, Thoracic , Central Nervous System , Control Groups , Horns , Immunohistochemistry , Inhalation , Isoflurane , Motor Neurons , NF-kappa B , Nitric Oxide , Nitric Oxide Synthase Type II , Paraplegia , Proline , Reperfusion , Salicylamides , Spinal Cord , Spinal Cord Ischemia , ThiocarbamatesABSTRACT
Objective To investigate the protective effect of adenosine A1 receptor agonist (2-chloro-N6-cyclopentyladenosine, CCPA) delayed preconditioning on myocardial ischemia reperfu-sion injury and the potential mechanism in rabbits. Methods Thirty New Zealand male white rabbits were randomly assigned to 3 groups:a control group, an I/R group, and a CCPA group. CCPA group was given CCPA 0.1 mg/kg before the myocardial ischemia. Twenty-four hours later I/R group and CCPA group underwent 40 min of coronary occlusion followed reperfusion for 2 h. At the end of the reperfusion, blood samples were taken from the arterial line for determining the plasma level of malondialdhyde and superoxide dismutase activity. The infarct size and area at risk were de-fined by Evans and TIC staining. The heart was harvested and levels of metallothionein (MT) were determined by Western blot, and ultrastructures were observed under the electron microscope. Results The MT level of CCPA group was significantly higher than that of the I/R group (P<0.05). CCPA significantly reduced the infarct size (22.1%±3.8% in the CCPA group) of the left yen-tricular area at risk as compared with the control (41.8%±4.3% in the I/R group,P<0.05). The injury of I/R group was worse than that of the CCPA group under the light microscope. CCPA group had higher superoxide dismutase and lower malondialdhyde than those of the I/R group. Con-clusion CCPA can increase the level of metallothionein during ischemia-reperfusion, which may be part of the molecular mechanism of CCPA delayed preconditioning on cardioprotection.
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Objective To explore the mechanism of the catdioprotection of isoflurane delayed preconditioning on myocardial ischemia reperfusion injury in rabbits.Method Thirty male New Zealand white rabbits,weighing 2.0 to 2.5 kg,were randomly divided into three groups(ten for each group):Control group(group C),I/R group(I/R group) ,2.0% isoflurane group(group S) .Group S was exposed to 2.0% isoflurane-100% oxygen for2 h.Group C and I/R group were exposed 2 h to 100% oxygen served as untreated controls.Twenty-four hours later I/R group and group S underwent 40 rain of coronary occlusion followed by 2 h of reperfusion.Blood samples were taken from arterial line at 20 min before occlusion(T1) ,20 rain after occlusion(T2) ,40 rain after occlusion(T3) ,1 h after reperfusion(T4) and 2 h after reperfusion(TS) for determination of plasma IL-10 levels and TNF-alevels by ELISA.At the end of the reperfusion,infarct size and area at risk were defined by Evans and TTC staining.The heart was harvested and levels of the nuclear factor kappa β(NF-κB)activity were determined by Western Blot,and ultrastructures were observed by electron microscopy.The data was expressed as,and were analyzed by using oneway ANOVA test with SPSS 13.0.P value less than 0.05 indicated statistical significance.Results The NF-κB activity of group S was significantly lower than that of group I/R(P<0.05).Group S significantly(P<0.05)reduced infarct size(19.7%±2.8% in group S) of the left ventricular area at risk as compared with control (37.8 %±1.7 % in I/R group).The injury of I/R group was worse than that of group S from the changes of the cellular structure under light microscope.Group S had a lower levels of TNF-α and also had a higher level of IL-10.Conclusions Isoflurane can inhibit NF-κB activity during myocardial ischemia reperfusion and modulate the cytokine expression,which may be one of molecular mechanisms of Isoflurane delayed preconditioning on cardioprotection.
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AIM: To explore the delayed protection of heme oxygenase-1 (HO-1) in the exercise preconditioning (EP) from the myocardial relative ischemia reperfusion injury (rI/R). METHODS: 40 Wistar Rats were divided into 5 groups randomly: control group (CN), rI/R group (IR), EP+rI/R group (EI), HO-1 inductor hemin+rI/R group (HE) and HO-1 inhibitor ZnPP+EP+rI/R group (EZ). The following indexes were detected, including the HO-1activity in myocardium, the cardiac function parameter-pressure-rate product (heart rate × left ventricular developed pressure, PRP) and the content of MDA in coronary effluent. RESULTS: After myocardial rI/R, HO-1 activity increased significantly. Moreover, EP or HO-1 inductor could enhance this effect manifestly. Nevertheless, when the HO-1 inhibitor was administered before EP,HO-1 activity decreased. In addition, there was no distinct difference in the HO-1 activity between EI group and HE group. At the 30 min point of reperfusion, the PRP recovery rate of EI group was higher clearly than that of IR group. However, there was reverse effect between the EZ group and the EI group. The MDA in coronary effluent of EI group, EZ group and HE group were lower obviously than that of IR group and there was significant difference between EI group and EZ group. CONCLUSION: EP could protect the heart from the rI/R injury occurring 24 hours later, which might be performed through activating the HO-1.
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Objective Investigate the relation between decrease of apoptosis caused by delayed preconditioning and expression of SMAC and XIAP.Methods Sprage-Dawleyt rats were divided into four groups: control,sham,I/R and IPC/SWOP.The rats in I/R group underwent ischemia for 1 hour by classic artery ligation and reperfusion for 1 hour.The rats in IPC/SWOP group underwent tree cycles of 5-minute ischemia and 5-minute reperfusion 24 hours prior to the index occlusion.Cell apoptosis was measured by flow cytometry,the activity of caspase-3 was also measured.The expression of SMAC and XIAP in cytosol of myocardial cell was measured by Western blot.Results Cell apoptosis rate,activity of caspase-3 and expression of SMAC significantly increased in I/R as compared with control(P
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Objective: To study the effect and mechanism of delayed preconditioning induced by adenosine A 1 receptor. Methods: Male Wistar rats in group A, C,D,K were preconditioned with CCPA, normal salt, Pyrrolidin diethyldi thiocarbamate(DDTC), DDTC +CCPA, respectively. The hearts were isolated and perfused with H-K buffer solution on the Langendorff apparatus 24 hours later,the isolate heart was perfused modified St.Thomas solution for 180 minutes at 4℃, and then reperfused with the H-K buffer for 60 minutes at 37℃. Results:The left ventricular function (+dp/dt max ,%) and myocardial ATP level in group A were better than those of C, D, K groups (P
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Adenosine receptor agonists can activate adenosine receptors A 1 and A 3, thus trigger delayed preconditioning signal pathway and induce high expression of protective proteins and some ionic channel opening in myocardial cells, which reduces myocardial ischemia/reperfusion injury.
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0 05). CONCLUSIONS: This study suggested that there might be a close relationship between delayed preconditioning mediated by adenosine A 1 receptor agonist R-PIA and myocardial nuclear factor-kappa B binding activity and Mn-SOD protein expression.
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Objective:To investigate the protection mechanism of adenosine A1 receptor agonist(2-chloro-N6-cyclopentyladenosine, CCPA)delayed preconditioning for rabbit myocardium during ischemia reperfusion.Methods:Thirty New Zealand male white rabbits were randomly assigned to Sham group,I/R group and CCPA group,with ten in each.Group CCPA was given CCPA 0.1 mg/kg before myocardial ischemia.Twenty-four hours later the I/R and CCPA underwent 40 min of coronary occlusion followed by 2 h of reperfusion.Blood samples were taken from arterial line at 20 min before occlusion(T)1,20 min after occlusion(T2),40 min after occlusion(T)3,1 h after reperfusion(T)4and 2 h after reperfusion(T)5for determination of the plasma levels of IL-10.At the end of the reperfusion,infarct size(IS)and area at risk(AAR)were defined by Evans blue and TTC staining.The heart was harvested and levels of the HSP70 were determined by Western blot analysis,and ultrastructures were observed under the electron microscopy.Results:The IL-10 and HSP70 levels of group CCPA was higher than those of group I/R.The CCPA(P