Ischemia-reperfusion Injury In Rabbits Research Articles

Renal ischemia-reperfusion injury in rabbits evaluated with quantitative susceptibility mapping: an animal study.

There were no effective noninvasive methods to diagnose renal ischemia-reperfusion injury (IRI), which is a major clinical problem. The objective of this study was to explore the feasibility of the quantitative susceptibility mapping (QSM) technique in evaluating the dynamic changes in the renal IRI process. A total of 36 New Zealand rabbits were randomly assigned to the IRI group (n=30) and the sham group (n=6). All rabbits underwent magnetic resonance imaging (MRI) examination, including T2-weighted imaging and QSM before the operation (pre-IRI) and 1, 12, 24, and 48 h after the operation (IRI-1h, IRI-12h, IRI-24h, and IRI-48h, respectively). Regions of interest were manually delineated in the outer medulla. All specimens were stained with hematoxylin and eosin (HE) and glutathione peroxidase 4 (GPX4). The pathological score of renal injury and the average optical density value of GPX4 were calculated. The repeated measurement analysis of variance (ANOVA) and Spearman correlation analysis were used to compare the differences between the susceptibility values and determine the correlation. In the IRI group, the susceptibility values of the outer medulla at the pre-IRI, IRI-1h, IRI-12h, IRI-24h, and IRI-48h time points were (42.83±7.83)×10-3, (-5.33±6.28)×10-3, (6.50±3.94)×10-3, (12.00±3.74)×10-3, and (22.00±6.81)×10-3 ppm, respectively. The susceptibility values significantly differed among the different time points (P<0.001). The susceptibility values had a negative correlation with the scores of cell edema (ρ=-0.61; P=0.002) and the average optical density value of GPX4 (ρ=-0.70; P<0.001). The susceptibility values had a positive correlation with iron content (ρ=0.79; P<0.001), the scores of cell necrosis (ρ=0.71; P<0.001), interstitial inflammation (ρ=0.60; P=0.002), cast (ρ=0.75; P<0.001), and the total pathological score of renal injury (ρ=0.51; P=0.01). QSM can be used as a noninvasive method to assess the dynamic changes of the outer medulla in the early stage of renal IRI in rabbits.

The effect of retrograde venous renal reperfusion on ischemia-reperfusion injury in rabbits

The effect of retrograde venous renal reperfusion on ischemia-reperfusion injury in rabbits

Can R2 ' mapping evaluate hypoxia in renal ischemia reperfusion injury quantitatively? An experimental study.

To explore if R2 ' mapping can assess renal hypoxia in rabbits with ischemia reperfusion injury (IRI). Forty rabbits were randomly divided into 4 groups according to the clipping time: the sham group and 45 min, 60 min, and 75 min for the mild, moderate, and severe groups (with n = 10 each group), respectively. Intravenous furosemide (FU) was administered 24 h after IRI. All rabbits were performed 5 times (IRIpre , IRI24h , FU5min , FU12min , and FU24min ) with a 3.0 Tesla MR. The R2 ' values and the hypoxic scores were then recorded. The repeated measurement analysis of variance and Spearman correlation analysis was used for statistical analysis. Compared to the baseline, the medullary R2 ' values increased significantly 24 h after the IRI (baseline 19.31 ± 1.21 s-1 , mild group 20.05 ± 1.26 s-1 , moderate group 25.38 ± 1.38 s-1 , and severe group 25.79 ± 1.10 s-1 ; each P < .001). FU led to a significant decrease in the medullary R2 ' value (sham group 11.17 ± 4.33 s-1 , mild group 7.80 ± 0.74 s-1 , moderate group 3.92 ± 0.28 s-1 , and severe group 3.82 ± 0.23 s-1 ; each P < .05). Quantitative hypoxic scores revealed significant differences among the 4 groups in the outer medulla (P < .001 each). The medullary R2 ' differences (before and after intravenous FU) were significantly correlated with the hypoxic scores, respectively (P < .001). R2 ' mapping can evaluate the renal hypoxia in the procession of IRI in rabbits and might serve as a quantitative biomarker for IRI.

Administration of Dexmedetomidine Does Not Produce Long-Term Protective Effect on Testicular Damage Post Testicular Ischemia-Reperfusion Injury.

BackgroundAfter surgical correction of testicular torsion, up to 68% of ipsilateral testes undergo atrophy due to ischemia-reperfusion injury (IRI). Recent studies have shown that dexmedetomidine (Dex) alleviates IRI in various vital organs. However, those studies evaluated its protective effect on short-term reperfusion.PurposeWe aimed to investigate whether Dex has a long-term protective effect against testicular injury after IRI.Materials and MethodsA total of 24 New Zealand white rabbits were randomly divided into three groups (n = 8/group): the control group (saline-infused rabbits without IRI), the IRI group (saline-injected rabbits with IRI), and the Dex group (Dex-injected rabbits with IRI). The spermatic cord of rabbits in IRI and Dex groups was ligated for 4 h, and 1 h before reperfusion, Dex was administered intraperitoneally at a dose of 50 μg/kg body weight in group Dex, whereas saline was administered at the same dose to the IRI and control groups. Rabbits were kept alive for 4 weeks post reperfusion, then the testes were harvested, and the rabbits were euthanized.ResultsFour weeks post reperfusion, testicular volumes of the affected side decreased considerably in the IRI and Dex groups compared to the control group, with no significant difference between the IRI and Dex groups. Compared to the control group, the Johnson score and the mean seminiferous tubular diameters were significantly decreased in the IRI and Dex groups, but no significant differences were observed after administration of Dex. There were no significant differences in malondialdehyde and superoxide dismutase levels between the groups treated with and without Dex.ConclusionDex administration 3 h after ischemia and 1 h before reperfusion did not demonstrate a significant protective effect against testicular injury 4 weeks after IRI in rabbits. Further research is needed to confirm the potential therapeutic effects of Dex by varying the experimental conditions.

Anti-high mobility group box-1 (HMGB1) antibody therapy for spinal cord ischemia-reperfusion injury in rabbits

Anti-high mobility group box-1 (HMGB1) antibody therapy for spinal cord ischemia-reperfusion injury in rabbits

Transplantation of chicken egg white extract-induced rabbit PBMCs as a treatment for renal ischemia-reperfusion injury in rabbits.

Ischemia-reperfusion injury is an important contributor to acute kidney injury and a major factor affecting early functional recovery after kidney transplantation. We conducted this experiment to investigate the protective effect of induced multipotent stem cell transplantation on renal ischemia-reperfusion injury. Forty rabbits were divided into four groups of 10 rabbits each. Thirty rabbits were used to establish the renal ischemia-reperfusion injury model, and ten rabbits served as the model group and were not treated. Among the 30 rabbits with renal ischemia-reperfusion injury, 10 rabbits were treated with induced peripheral blood mononuclear cells (PBMCs), and 10 other rabbits were treated with noninduced PBMCs. After three weekly treatments, the serum creatinine levels, urea nitrogen levels and urine protein concentrations were quantified. The kidneys were stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS) and Masson's trichrome and then sent for commercial metabolomic testing. The kidneys of the rabbits in the model group showed different degrees of pathological changes, and the recovery of renal function was observed in the group treated with induced cells. The results indicate that PBMCs differentiate into multipotent stem cells after induction and exert a therapeutic effect on renal ischemia-reperfusion injury.

Perfusion imaging with 320-slice spiral computed tomography and color-coded digital subtraction angiography for assessing acute skeletal muscle ischemia-reperfusion injury in a rabbit model

BackgroundIn recent years, skeletal muscle-related ischemia-reperfusion injury (IRI) has become more common. IRI can lead to severe limb injuries, multiple organ failure, and even death in some cases. However, there is still a lack of rapid and sensitive detection methods for IRI in skeletal muscle. This study aims to explore the value of computed tomography perfusion imaging (CTPI) and color-coded digital subtraction angiography (DSA) in assessing acute IRI of skeletal muscle in a rabbit model.MethodsFifty New Zealand white rabbits were randomly assigned to the ischemia-reperfusion (IR) group (n = 40) or sham group (n = 10). After 3 h of surgically-induced hindlimb ischemia, the IR group underwent reperfusion and CTPI and color-coded DSA were taken to assess the skeletal muscle at 0, 6, 12, or 24 h post-reperfusion. The data from CTPI and DSA in the right and left hindlimbs, blood flow (AF-R/L), blood volume (BV-R/L), contrast clearance rate (C-R/L) and the maximum contrast enhancement values (peak-R/L) were obtained. Serum superoxide dismutase (SOD), creatine kinase (CK), lactic dehydrogenase (LDH) and malondialdehyde (MDA) were measured. The statistical correlation between the above parameters (CTPI, color-coded DSA, and biochemical markers) was analyzed.ResultsThe mean value of AF-R/L, BV-R/L, C-R/L and peak-R/L decreased linearly from 1.07 ± 0.08 to 0.75 ± 0.11, 1.03 ± 0.06 to 0.85 ± 0.14, 0.93 ± 0.15 to 0.71 ± 0.18, and 1.07 ± 0.01 to 0.47 ± 0.04, respectively. The correlation coefficients between AF-R/L and SOD, CK, LDH and MDA were 0.57, − 0.44, − 0.60, and − 0.62, respectively (p < 0.001). The correlation coefficients between Peak-R/L and SOD, CK, LDH, MDA were 0.59, 0.68, 0.71 and 0.66, respectively (p < 0.001). The correlation coefficient between AF-R/L and Peak-R/L was 0.70 (p < 0.001).ConclusionBoth CTPI and color-coded DSA could dynamically assess skeletal muscle IRI in rabbits.

Protective effect of tongfu xiere method on hepatic ischemia reperfusion injury in rabbits

Objective To investigate the protective effect of Tongfu Xiere method on hepatic ischemia reperfusion injury in rabbits by examining the changes in the serum tumor necrosis factor (TNF)-α and interleukin (IL)-6. Methods The rabbit hepatic ischemia reperfusion model was established (n=30). The animals were randomly divided into three groups: Chinese medicine group (n=10), pseudo operation group (n=10) and control group (n=10). The blood serum of each group was collected separately before operation, during operation and 5 days after operation. The serum levels of TNF-α and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). Results Before operation, during operation and 5 days after operation, the TNF-α levels were as follows: Chinese medicine group [(203.05±36.52), (452.56±29.29) and (195.00±35.86) ng/L]; control group [(219.18±41.03), (462.45±62.17) and (322.77±70.19) ng/L]; and pseudo operation group [(203.63±21.32), (210.77±58.83) and (205.19±60.39) ng/L], and those of IL-6 were as follows: Chinese medicine group [(423.56±64.27), (1 325.55±97.02) and (223.69±62.72) ng/L]; control group [(428.08±110.75), (1 221.99±101.21) and (851.07±58.84) ng/L], and pseudo operation group [(411.02±57.02), (377.28±168.33) and (382.92±81.07) ng/L]. There was no statistically significant difference among three groups in TNF-α and IL-6 before operation (TNF-α: t=-0.929, -0.044, 1.064, P>0.05; IL-6: t=-0.112, 0.462, 0.433, P>0.05). But there was statistical significance (TNF-α: t=21.549, 19.720, P<0.05; IL-6: t=21.506, 18.761, P<0.05)with Chinese medicine group and control group during operation in which the contents of these two groups were higher. Five days after operation the figures of all groups back to normal, but the Chinese medicine group are lower than the control group with statistical significance (t=-23.069, P<0.05). Conclusion Tongfu Xiere method may significantly reduce the TNF-α and IL-6 levels in the rabbit hepatic ischemia reperfusion model and alleviate the inflammatory reaction of hepatic ischemia reperfusion injury. Thus, it may protect the liver function of the rabbit after hepatic ischemia reperfusion. Key words: Hepatic ischemia reperfusion injury; Tongfu xiere method; Tumor necrosis factor-α; Iinterleukin-6; Rabbit

Time-course Study on Left Ventricular Function in a Rabbit Model of Ischemia-reperfusion Injury With Morphine Preconditioning.

To analyze the left ventricular longitudinal function in a rabbit model of myocardial ischemia reperfusion with morphine preconditioning through strain rate imaging and to evaluate the effect of morphine preconditioning. A myocardial ischemia-reperfusion model was induced by occlusion and recanalization of the coronary artery in 40 male New Zealand white rabbits, which were divided into a sham group, morphine group, and vehicle control group. Routine echocardiography data were recorded 1 day before and within 28 days after the operation. Dynamic images were also collected and analyzed off-line using Doppler tissue imaging software. On the first day after the operation, the global and regional systolic functions of the left ventricle in the morphine and vehicle control groups were lower than those in the sham group. After ischemia reperfusion, some of the values of the above-mentioned parameters decreased over time, which was more obvious in the vehicle control group at each examined time point. The current study revealed that detection of changes in regional myocardial function after myocardial ischemia reperfusion by strain rate imaging is objective and accurate. In addition, our results indicated that morphine preconditioning significantly attenuates myocardial ischemia-reperfusion injury in rabbits.

Antioxidative and Antiapoptotic Effects of Delta-Opioid Peptide [D-Ala2, D-Leu5] Enkephalin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits.

Background: In our previous study, we found that regional administration of delta-opioid peptide [D-Ala2, D-Leu5] enkephalin (DADLE) could provide dose-dependent protection on spinal cord ischemia-reperfusion (I/R) injury in rabbits. However, the relative protective molecular mechanisms underlying this neuroprotection remain unclear. The purpose of this study was to investigate whether DADLE provided the protection in spinal cord I/R injury through its antioxidant property by decreasing malondialdehyde (MDA) and nitric oxide (NO) levels and increasing glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels and through its antiapoptotic capacity by inhibiting caspase-3 and p53 expression.Methods: The rabbits were divided into three groups. The animals in Group NS and Group DADLE were administered with normal saline (NS) or DADLE via aorta during 30 min of ischemia respectively, while the one in Group Sham received no intervention. During the period of reperfusion, the rabbit's blood samples were collected for enzyme-linked immunoabsorbent assay (ELISA) examinations of MDA, NO, GSH-Px and SOD. At 48 h after reperfusion, the lumbar spinal cords were harvested for immunohistochemical, real-time polymerase chain reaction (PCR) and western blot studies to detect the caspase-3 and p53 expressions.Results: The activities of serum MDA and NO showed significant reductions in the DADLE group as compared with the control group. By contrast, the levels of serum GSH-Px and SOD were significantly higher in the DADLE group than those in the NS group. In addition, caspase-3 and p53 expression were significantly increased in the NS group, while DADLE mitigated these changes.Conclusions: The protective effects of DADLE at the dosage of 0.05 mg/kg may be related to its antioxidant and antiapoptosis properties in the rabbit model of spinal cord I/R injury.

Cardioprotective Effects of HSP72 Administration on Ischemia-Reperfusion Injury

BackgroundAlthough early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress. ObjectivesThis study investigated the cardioprotective effects of a single intravenous dose of heat shock protein-72 (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes. MethodsA left coronary artery occlusion (40 min) reperfusion (3 h) model was used in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate-buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular function before and after reperfusion. Micro–single-photon emission computed tomography imaging of 99mTc-labeled annexin-V was performed with micro–computed tomography scanning to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue and sequential cardiac troponin I measurements were also undertaken. ResultsMyocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72–treated rabbits compared with control animals receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic left ventricular ejection fraction 27% higher in the Fv-HSP72–treated group compared with control animals. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared with control rabbits. ConclusionsSingle-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis by almost one-half and improved left ventricular functional recovery after myocardial ischemia-reperfusion injury in rabbits. It might have potential to serve as an adjunct to early reperfusion in the management of myocardial infarction.

The transplantation of Akt-overexpressing amniotic fluid-derived mesenchymal stem cells protects the heart against ischemia-reperfusion injury in rabbits.

Amniotic fluid-derived mesenchymal stem cells (AFMSCs) are an attractive cell source for applications in regenerative medicine, due to characteristics such as proliferative capacity and multipotency. In addition, Akt, a serine-threonine kinase, maintains stem cells by promoting viability and proliferation. Whether the transplantation of Akt-overexpressing AFMSCs protects the heart against ischemia-reperfusion (I/R) injury has yet to be elucidated. Accordingly, the Akt gene was overexpressed in AFMSCs using lentiviral transduction, and Akt-AFMSCs were transplanted into the ischemic myocardium of rabbits prior to reperfusion. Any protective effects resulting from this procedure were subsequently sought after three weeks later. A histological examination revealed that there was a decrease in intramyocardial inflammation and ultrastructural damage, and an increase in capillary density and in the levels of GATA binding protein 4, connexin 43 and cardiac troponin T in the Akt-AFMSC group compared with the control group. A significant decrease in cardiomyocyte apoptosis, accompanying an increase in phosphorylated Akt and B-cell lymphoma 2 (Bcl-2) and a decrease in caspase-3, was also observed. Furthermore, the left ventricular function was markedly augmented in the Akt-AFMSC group compared with the control group. These observations suggested that the protective effect of AFMSCs may be due to the delivery of secreted cytokines, promotion of neoangiogenesis, prevention of cardiomyocyte apoptosis, transdifferentiation into cardiomyocytes and promotion of the viability of AFMSCs, which are assisted by Akt gene modification. Taken together, the results of the present study have indicated that transplantation of Akt-AFMSCs is able to alleviate myocardial I/R injury and improve cardiac function.

Monitoring of renal ischemia reperfusion injury in rabbits by ultrasonic contrast and its relationship with expression of VEGF in renal tissue

To evaluate the renal ischemia reperfusion injury (IRI) in rabbits using the ultrasonic contrast technique and discuss the clinical value of ultrasonic contrast technique in the diagnosis of renal IRI by comparing the time-intensity curve of renal cortex and the expression of vascular endothelial growth factor (VEGF) of renal tissue. Twenty 3-month-old New Zealand rabbits were randomly divided into 4 groups, namely Ctrl group, IRI-12h, IRI-24h and IRI-48h groups. The two dimensional gray-scale ultrasonography was employed to determine and mark the position of rabbit kidney. Rabbits were given the intraperitoneal anesthesia with 20% urethane with the dosage of 5mL/kg. The aseptic operation was performed after the local skin disinfection in the area of both kidneys. The right kidney of animals in the control group was excised without any treatment for the left kidney. After excising the right kidney of animals in groups of IRI-12h, IRI-24h and IRI-48h, the aneurysm clip was used to clip the renal pedicle vessel of left kidney, in order to simulate the ischemia. Because of the tissue ischemia, it could be seen that the color of kidney was changed from bright red to dark red, which indicated the successful modeling of ischemia. The aneurysm clip was released after one hour of maintaining the ischemia. Then the kidney turned out to be bright red from dark red, which indicated that the reperfusion was completed. Taking this moment as the time of ischemia reperfusion, the wound was stitched up. A total of 12, 24 and 36h after the operation, the two-dimensional and color Doppler flow imaging and ultrasonic contrast were employed for the examination. The dynamic changes of ultrasonic contrast were recorded. The quantitative analysis software (QontraXt) was adopted to analyze the time-intensity curve of echo at different positions of renal cortex. After the ultrasonic contrast testing, rabbits were put to death. The renal cortex tissue was isolated and the tissue RNA and total protein were extracted respectively. Real-time PCR and western blotting were used to detect the VEGF and the Pearson product moment correlation coefficient was used to measure the linear relationship between these two variables. The ultrasonic contrast could clearly reflect the process of IRI. The results of testing at mRNA and protein level indicated that the expression of VEGF in IRI groups was significantly increased (P<0.05) and the expression of VEGF was also increased by the time of reperfusion. There is the certain correlation between the expression of VEGF and process of IRI. The correlation coefficient between the ultrasonic contrast parameters of AT and TTP and the relative expression of VEGF is over 0.9, which indicates the relatively high correlation. But there is no significant difference in the change of perfusion peak intensity between groups, which has no correlation with the expression of VEGF.

Effects of Atorvastatin on Experimental Spinal Cord Ischemia-Reperfusion Injury in Rabbits.

Extent of secondary injury is the determinant of tissue destruction and functional worsening after primary spinal cord injury (SCI). Data have accumulated on alleviation of secondary injury in SCI from many studies on the subject. Besides its cholesterol lowering effects, statins are known to have anti-inflammatory and anti-oxidant effects which are the main targets of spinal cord research. This study aims to evaluate the effects of atorvastatin on experimental spinal cord ischemia-reperfusion injury. Thirty adult male New Zealand rabbits were allocated into control, ischemia-reperfusion (I/R) and treatment groups. Treatment group received 5 mg/kg of atorvastatin via lavage for the preceding 14 days. Other groups received placebo during the same time period. After two weeks, animals in the I/R and treatment groups underwent abdominal temporary aorta occlusion for 30 minutes. Neurological condition of the animals was recorded during the 48 hours of observation. Afterwards, animals were sacrificed and levels of malondialdehyde, glutathione and nitric oxide in spinal cord tissue and plasma and the histopathological tissue changes were determined. Animals in the treatment groups demonstrated significantly better results than the I/R group regarding biochemical markers. Neurological evaluation using the Tarlov scale demonstrated significantly better results at the 48th hour in treatment group. Histopathological results were also better in the treatment groups. Results of this study demonstrate the neuroprotective effects of atorvastatin. Atorvastatin has favorable effects on biochemical markers of oxidative stress in SCI. Further studies with larger cohorts and different time periods are also needed.

An experimental study on protective effect of meglumine adenosine cyclosphosp on cerebral ischemia reperfusion injury in rabbits

Objective To investigate the protective effect of meglumine adenosine cyclosphosp (MAC) on the cerebral ischemia-reperfusion (I/R) injury in rabbits. Methods Twenty four healthy rabbits were randomly divided into control group (n=6), I/R group (n=6), MAC pretreated group (n=6), and MAC treated group (n=6). Cerebral ischemia-reperfusion injury model was made by separating and electrocoagulating vertebral arteries and clipping common carotid arteries in the latter 3 groups after anesthesia. The sham-operated group underwent vessel separation without clipping. I/R group was administered with nothing, while MAC pretreated group with MAC before ischemia, and MAC treated group with MAC just after ischemia. Blood was gathered from jugular vein before ischemia, and 30 min, 1 h, and 2 h after reperfusion for testing IL-8, superoxide dismutase (SOD) and malondialdehyde (MDA). The brain tissue slice was observed by optical microscope. Results Compared to control group and before ischemia, the levels of IL-8 and SOD in serum were significantly increased and decreased, and the levels of MDA was significantly increased at 30 min after reperfusion in I/R group; the levels of IL-8 and MDA in serum were significantly increased, and the levels of SOD in serum was significantly decreased at 1 h and 2 h after reperfusion in I/R group. The levels of IL-8 in serum was less at 30 min and 1 h and 2 h after reperfusion in MAC pretreated group than in I/R group.At 1 h and 2 h after reperfusion, the levels of MDA in serum was less and the levels of SOD in serum was higher in MAC pretreated group than in I/R group. At 1 h and 2 h after reperfusion, the levels of IL-8 in serum were less and the levels of SOD in serum were higher in MAC treated group than in I/R group. The levels of MDA in serum were less at 2 h after reperfusion in MAC treated group than in I/R group. Compared to I/R group, pathological change was lighter in the MAC pretreated and MAC treated group. Conclusions MAC has a fine cerebral-protective effect and has no side effect. Key words: Cyclic AMP/PD; Brain ischemia/DT; Reperfusion injury/DT

Evaluation of effect of adenosine triphosphate postconditioning on myocardial ischemia reperfusion injury in rabbits using ultrasound speckle tracking imaging

Objective To evaluate the effect of adenosine triphosphate postconditioning on myocardial ischemia reperfusion injury in rabbits by ultrasound speckle tracking imaging(STI). Methods Forty-two healthy rabbits were randomly divided into three groups averagely: ischemia-reperfusion(IR) group, ischemia postconditioning(IPost) group, ATP-pharmacological postconditioning(PPost) group. The model of myocardial ischemia reperfusion was established. Echocardiography examinations were conducted before the coronary artery ligatured, after 45 min later and at the end of reperfusion. Pathological examinations were applied to detect the change of which two rabbits randomly selected from each group after the coronary artery ligatured 45 minutes later and the rests after reperfusion of 120 min. Results ①Ischemic and infarct changes could find in the six rabbits which were sacrificed after the coronary artery ligatured 45 minutes later. The same changes also could be found in the three groups after reperfusion, and the damage in IR group was the most significant. ②After block of coronary artery, left ventricular ejection fraction(LVEF) decreased in all groups (P<0.05) and STI index decreased in all groups (P<0.01). ③After reperfusion of 120 min later, global longitudinal systolic strain rate(GLSrsys), global longitudinal systolic strain(GLSsys) increased in IPost group and GLSrsys increased in ATP-PPost group, and longitudinal systolic strain rate(SrLsys), longitudinal diastolic strain rate(SrLd), longitudinal systolic strain(SLsys) increased both in IPost group and ATP-PPost group(P<0.05 or P<0.01). Compared in groups, GLSsys, SrLsys, SLsys in IPost group and ATP-PPost group all higher than those in IR group (P<0.05). Conclusions STI can evaluate exactly the global and regional myocardial function of rabbit myocardial infarct-reperfusion model and local index is better than overall index. STI can also detect correctly the protect effects on myocardial reperfusion injury of ATP. Key words: Echocardiography; Myocardial ischemia; Reperfusion injury; Postconditioning; Adenosine; Speckle tracking imaging

Neuroprotective Effects of Rosuvastatin in Spinal Cord Ischemia-Reperfusion Injury in Rabbits

Background: This experimental study was performed to investigate the neuroprotective effects of rosuvastatin in a rabbit model of spinal cord ischemia-reperfusion injury. Materials and Methods: Rabbits were randomized into 3 groups of 6 animals each: group 1 (control), group 2 (ischemia), and group 3 (rosuvastatin 5 mg/kg/d). Spinal cord ischemia was produced in rabbits by a 30-minute occlusion of the aorta by clamping with aneurysm clips; just caudal to renal artery divison and above the aortic bifurcation. Rosuvastatin was administered intraperitoneally before onset of occlusion, for 3 days. At 48 hours after ischemia, neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor rating scale before they were killed. Levels of malondialdehyde (MDA), glutathione, advanced oxidation protein products (AOPP), superoxide dismutase, catalase, nitrite/nitrate, and tumor necrosis factor-α were measured in the spinal cord tissue and plasma. Histopatologic evaluation of the tissues and activation of caspase 3 were also studied. Results: Basso, Beattie, and Bresnahan scores for rosuvastatin group were significantly higher. MDA, AOPP, and nitrite/nitrate levels in the ischemia group were significantly higher than those for control and rosuvastatin groups (P<0.05). There were no significant differences in MDA, AOPP, and nitrite/nitrate levels between rosuvastatin and control groups. In rosuvastatin group, spinal cord tissue and plasma superoxide dismutase, glutathione, and catalase levels were significantly increased compared with the ischemia group. The gross histopathologic examination demonstrated decrease in axonal damage, neuronal degeneration, and glial cell infiltration after rosuvastatin treatment. Conclusions: Rosuvastatin may protect the spinal cord tissue against ischemic damage, by its anti-inflammation and antiapoptotic effect. Although further studies including different dose regimens and time intervals are required, this drug may therefore be a good candidate for clinical use during surgical procedures on the thoracoabdominal aorta.

The role of mitochondrial permeability transition pore in ischemic post-conditioning for counteracting small intestinal ischemia-reperfusion injury in rabbits

Objective To investigate the role of mitochondrial permeability transition pore (mPTP)in ischemic post-conditioning for counteracting small intestinal ischemia-reperfusion(I/ R)injury in rabbits. Methods Forty New Zealand rabbits were randomly divided into sham-operated group(Sham group), I/R group,ischemic post-conditioning group(IPO group), mPTP inhibitor cyclosporine A group(Cs A group), and IPO+ mPTP agonist atraotydin group(IPO+ Atr group).Parts of small intestine tissues were collected from each group of rabbits after intervention for hematoxylin-eosin(HE) staining. Malondialdehyde(MDA) activity in small intestine tissue was measured by the relevant kit.The mitochondria were isolated and mPTP opening was detected by relevant kits.Intestinal mucosal injury was observed by Chiu's grade 6 scoring method.The apoptosis of intestinal epithelial cells was examined by Td T-mediated d UTP nick end labeling(TUNEL) assay. Results As compared with Sham group, mPTP opening in I/R group was significantly increased(3. 53±0. 36 vs. 1. 37±0. 16, P< 0. 05); MDA activity was significantly increased[(0. 98±0. 14) nmol/mg vs. (0. 34±0. 03) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly increased(4. 66± 0. 41 vs.0. 92±0. 58, P< 0. 05); apoptosis index of intestinal cells was significantly increased [(60. 34±6. 02)% vs.(4. 65±1. 68)%, P< 0. 05].As compared with I/R group, mPTP openings in IPO group and Cs A group were significantly decreased(2. 32±0. 23 and 2. 62±0. 18 vs.3. 53± 0. 36, P< 0. 05); MDA activity was significantly decreased[(0. 55±0. 04) and(0. 62±0. 06) nmol/mg vs.(0. 98±0. 14) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly decreased(3. 25±0. 27 and 3. 52±0. 55 vs.4. 66±0. 41, P< 0. 05); apoptosis of intestinal cells was significantly decreased[(28. 33±3. 20)% and(20. 49±4. 10)% vs.(60. 34±6. 02)%, P< 0. 05]. As compared with IPO group, mPTP openings in IPo+ Atr group were significantly increased(2. 32 ±0. 23 vs.1. 05±0. 16, P< 0. 05); MDA activity was significantly increased[(1. 08±0. 18) vs. (0. 55±0. 04) nmol/mg, P< 0. 05]; intestinal mucosa score was significantly increased(4. 57± 0. 32 vs.3. 25±0. 27, P< 0. 05); apoptosis index of intestinal cells was significantly increased [(40. 35±2. 18)% vs.(28. 33±3. 20)%,P< 0. 05]. Conclusion The mechanism of ischemic post-conditioning for counteracting intestinal ischemia-reperfusion injury in rabbits may be associated with the inhibition of mitochondrial permeability transition pore opening. Key words: Mitochondrial permeability transition pore; Ischemic post-conditioning; Intestine ischemia; Reperfusion injury

Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans.

Background. Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. Methods and Results. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. Conclusion. A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation.

Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits.

Ulinastatin (UTI), a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties.