Reperfusion Injury In Rabbits Research Articles

Effect of an Airbag-selective Portal Vein Blood Arrester on the Liver after Hepatectomy: A New Technique for Selective Clamping of the Portal Vein.

A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions. Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels. Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group. Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy.

Model of Ischemia and Reperfusion Injury in Rabbits.

The protocol here provides a simple, highly replicable methodology to induce in situ acute regional myocardial ischemia in the rabbit for non-survival and survival experiments. New Zealand White adult rabbit is sedated with atropine, acepromazine, butorphanol, and isoflurane. The animal is intubated and placed on mechanical ventilation. An intravenous catheter is inserted into the marginal ear vein for the infusion of medications. The animal is pre-medicated with heparin, lidocaine, and lactated Ringer's solution. A carotid cut-down is performed to obtain arterial line access for blood pressure monitoring. Select physiologic and mechanical parameters are monitored and recorded by continuous real-time analysis. With the animal sedated and fully anesthetized, either a fourth intercostal space small left thoracotomy (survival) or midline sternotomy (non-survival) is performed. The pericardium is opened, and the left anterior descending (LAD) artery is located. A polypropylene suture is passed around the second or third diagonal branch of the LAD artery, and the polypropylene filament is threaded through a small vinyl tube, forming a snare. The animal is subjected to 30 min of regional ischemia, achieved by occluding the LAD by tightening the snare. Myocardial ischemia is confirmed visually by regional cyanosis of the epicardium. Following regional ischemia, the ligature is loosened, and the heart is allowed to re-perfuse. For both survival and non-survival experiments, the myocardial function can be assessed via an echocardiography (ECHO) measurement of the fractional shortening. For non-survival studies, data from sonomicrometry collected using three digital piezoelectric ultrasonic probes implanted within the ischemic area and the left ventricle developed pressure (LVDP) using an apically inserted left ventricle (LV) catheter can be continuously acquired for evaluating the regional and global myocardial function, respectively. For survival studies, the incision is closed, a left needle thoracentesis is performed for pleural air evacuation, and postoperative pain control is achieved.

Quantitative Evaluation of Renal Cortex Perfusion Using Contrast-Enhanced Ultrasound Imaging Parameters in Ischemia–Reperfusion Injury in Rabbits

The aim of this study was to evaluate blood perfusion of the renal cortex during ischemia–reperfusion (I/R) injury using quantitative contrast-enhanced ultrasound (CEUS) parameters. In this experiment, 24 rabbits were randomly divided into four groups (N = 6): sham-operated group, 24-h post-operation for I/R injury group (24-h I/R), 3-d post-operation for I/R injury group (3-d I/R) and 5 d post-operation for I/R injury group (5 d I/R). All quantitative CEUS parameters were monitored and included the gradient from the start frame to the peak frame (Grad), area under the curve (Area), time-to-peak (TTP), difference between B(intercept intensity at t=0) and A(the intensity attenuation t= 0) and arrival time (AT). Subsequently, we analyzed the changes in these parameters, as well as the correlation between changes in CEUS parameters and pathological parameters. AT and TTP values peaked 3 d after I/R surgery, which correlated with the most significant pathological changes at the same time point. These parameters (such as AT, TTP and Grad) may be useful in dynamically monitoring the severity of tissue damage at the early stage of I/R injury.

Quantitative Evaluation of Hepatic Microvascular Perfusion after Ischemia–Reperfusion Injury in Rabbits by Contrast-Enhanced Ultrasound Perfusion Imaging

The aim of this study was to evaluate microvascular perfusion after liver ischemia–reperfusion injury (IRI) in rabbits using the “flash-replenishment” method of contrast-enhanced ultrasound (CEUS) perfusion imaging. Twenty-eight rabbits underwent either 30, 60 or 90 min of ischemia and 120 min of reperfusion. CEUS perfusion imaging was performed using the “flash-replenishment” model, and hepatic microvascular perfusion parameters, including peak intensity (PI), area under the curve (AUC), and hepatic artery-to-vein transit time (HA-HVTT), were calculated. Prolonged ischemia upregulated intracellular adhesion molecule-1 (ICAM-1), alanine transaminase (ALT) and aspartate transaminase (AST) levels. Longer ischemia decreased PI and AUC, but increased HA-HVTT. The perfusion parameters were significantly correlated with Suzuki's pathology scores and ALT and AST levels. The “flash-replenishment” method of CEUS perfusion imaging is an accurate and non-invasive method for evaluating hepatic microvascular perfusion and provides a valuable experimental basis for early prediction of liver IRI damage after liver transplantation or liver resection.

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.

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.

Ginkgo biloba extract postconditioning reduces myocardial ischemia reperfusion injury.

We examined the protective effects of Ginkgo biloba extract (EGb761) postconditioning on myocardial ischemia reperfusion injury in rabbits. Four groups of 8 white rabbits were allocated to: pseudo surgery group: the left coronary was lined without blocking for 160 min after thoracotomy; ischemia and reperfusion group (IR): the left anterior descending coronary artery was blocked for 40 min and reperfused for 120 min; ischemic postconditioning group: the left anterior descending artery was ligated for 40 min, reopened for 30 s and ligated for 30 s, repeated three times, and then reperfused for 120 min; EGb761 postconditioning group (E): 100 mg/kg EGb761 was injected into a vein while the left coronary artery was opened for 1 min. The reperfusion took 120 min. Internal carotid arterial blood in each group was collected for cTnI measurement at five times: 20 min before occlusion of the left coronary artery, 20 min after left coronary artery occlusion, 40 min after left coronary artery occlusion, 1 h after myocardial reperfusion, and 2 h after myocardial reperfusion. Superoxide dismutase (SOD), malondialdehyde (MDA) in the centrifuged blood and myocardial infarction area were measured at the end of reperfusion. We found that the serum cTnI concentrations in the E group during reperfusion decreased significantly compared with those in the IR group. The infarction area was significantly lower in the E group than that in the IR group. The SOD activity in the E group was increased compared with that in the IR group; the MDA content decreased significantly in the E group compared with that in the IR group. We conclude that G. biloba extract postconditioning had myocardial protection effects by reducing the generation of oxygen-free radicals and increasing the antioxidant capacity of the myocardial cells.

The Effect of Safflower Yellow on Spinal Cord Ischemia Reperfusion Injury in Rabbits

Safflower yellow (SY) is the safflower extract and is the one of traditional Chinese medicine. The aim of the present work was to investigate the effect of SY on spinal cord ischemia reperfusion injury (SCIRI) in rabbits. The models of spinal cord ischemia reperfusion (SI/R) were constructed, and the degree of the post-ischemic injury was assessed by means of the neurological deficit scores and plasma levels of lipid peroxidation reactioin and neuronal morphologic changes. SCIRI remarkably affected the functional activities of the hind limbs and activated lipid peroxidation reaction. SY could attenuate apoptosis and SCIRI by enhancing Bcl-2 expression and inhibiting Bax and caspase-3 activation.

Beneficial effects of hydrogen gas against spinal cord ischemia–reperfusion injury in rabbits

Recently, hydrogen gas (H 2) is reported to be a new therapeutic agent in organ damage induced by ischemia–reperfusion (I/R). The present study was designed to investigate the beneficial effects of H 2 against spinal cord I/R injury and its associated mechanisms. Spinal cord ischemia was induced by infrarenal aortic occlusion for 20 min in male New Zealand white rabbits. Treatment with 1%, 2% or 4% H 2 inhalation was given from 10 min before reperfusion to 60 min after reperfusion (total 70 min). Here, we found that I/R-challenged animals showed significant spinal cord damage characterized by the decreased numbers of normal motor neurons and hind-limb motor dysfunction, which was significantly improved by 2% and 4 % H 2 treatment. Furthermore, we found that the beneficial effects of H 2 treatment against spinal cord I/R injury were associated with the decreased levels of oxidative products [8-iso-prostaglandin F2α (8-iso-PGF2α) and malondialdehyde (MDA)] and pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and high-mobility group box 1 (HMGB1)], as well as increased activities of antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] in serum and spinal cord. In addition, H 2 treatment reduced motor neuron apoptosis in the spinal cord of this model. Thus, H 2 inhalation may be an effective therapeutic strategy for spinal cord I/R damage.

Anti-apoptotic and neuroprotective effects of alpha-lipoic acid on spinal cord ischemia–reperfusion injury in rabbits

Radical oxygen species produced after injury counteracts antioxidant activity and frequently causes severe oxidative stress for the tissues. Alpha-lipoic acid is a powerful metabolic antioxidant with immunomodulatory effects which provides neuroprotection. The aim of this study is to investigate the neuroprotective and anti-apoptotic effects of alpha-lipoic acid on spinal cord ischemia-reperfusion. Twenty-four adult, male, New Zealand rabbits were divided into sham (n = 8), control (n = 8), and treatment groups (n = 8). The abdominal aorta was clamped for 30 min by an aneurysm clip, approximately 1 cm below the renal artery and 1 cm above the iliac bifurcation in control and treatment groups. Only laparotomy was performed in the sham group. Twenty-five cubic centimeters of saline in control group and 100 mg/kg lipoic acid were administered intraperitoneally in the treatment group after closure of the incision. The animals were killed 48 h later. Spinal cord segments between L2 and S1 were harvested for analysis. Levels of nitric oxide, glutathione, malondialdehyde, advanced oxidation protein products, and superoxide dismutase were analyzed as markers of oxidative stress and inflammation. Caspase-3 activity was analyzed to detect the effect of lipoic acid on apoptosis. In all measured parameters of oxidative stress, administration of lipoic acid significantly demonstrated favorable effects. Both plasma and tissue levels of nitric oxide, glutathione, malondialdehyde, and advanced oxidation protein products significantly changed in favor of antioxidant activity. There was no significant difference between the plasma superoxide dismutase levels of the groups. Histopathological evaluation of the tissues also demonstrated significant decrease in cellular degeneration and infiltration parameters after lipoic acid administration. However, lipoic acid has no effect on caspase-3 activity. Although further studies considering different dose regimens and time intervals are required, the results of the present study prove that alpha-lipoic acid has favorable effects on experimental spinal cord ischemia-reperfusion injury.

Effect of different programs of hyperbaric oxygen preconditioning on spinal cord ischemia- reperfusion injury in rabbits

Objective To investigate the effect of different programs of preconditioning with hyperbaric oxygen (HBO) on spinal cord ischemia-reperfusion injury (I/R) in rabbits. Methods Forty-five New Zealand rabbits aged 4-5 months weighing 2.0-2.5 kg were randomly divided into 5 groups: group S, sham operation ( n = 5);group IR, spinal cord I/R injury (n = 10);group H_(1～3) , the animals were pretreated with 100% O_2 at 2.5 ATA 1 h/d for 5 (group H_1 ), 10 (group H_2 ) , or 20 (group H_3 ) consecutive days respectively 24 h before spinal cord I/R. The animals were anesthetized with iv pentobarbital sodium 30 mg/kg. The artery in the ear and left femoral artery were cannulated for proximal and distal mean blood pressure monitoring. Spinal cord ischemia was produced by cross-clamping of abdominal aorta distal to renal artery for 20 min. Hind-limb motor function was assessed at 48 h after reperfusion according to the modified criteria established by Tarlov (0 = no spontaneous movement, 4= normal motor function) . The animals were then killed and the L_5 segment of the spinal cord was removed for detection of neuronal survival (by HE staining), apoptosis (by TUNEL) and degeneration (by Fluoro-Jade B staining). Results Preconditioning with 5 or 10 d of HBO improved the hind-limb motor function and preserved more normal neurons in the spinal cord after I/R injury. Both apoptotic and degenerative cell death were attenuated in H_1 and H_2 groups. There was no significant difference in hind-limb motor dysfunction and the number of normal neurons in the lumbar spinal cord between H_3 group and I/R group. Conclusion Preconditioning with 5 d or 10 d HBO induces tolerance against spinal cord I/R injury, whereas preconditioning with 20 d of HBO fails to protect the spinal cord from I/R injury. Key words: Hyperbaric oxygenation; Ischemic preconditioning; Reperfusion injury; Spinal cord

Evaluation of renal ischemia–reperfusion injury in rabbits using microbubbles targeted to activated neutrophils

ObjectiveThe objective of this study was to noninvasively evaluate the severity of renal ischemia–reperfusion (I–R) injury in rabbits with microbubbles targeted to activated neutrophils [phosphatidylserine-conjugated surfactant perfluoropropane-filled microbubbles (SPMB-PS)]. MethodsMicrobubbles targeted to activated neutrophils (SPMB-PS) were prepared by conjugating phosphatidylserine (PS) to self-assembling surfactant perfluoropropane-filled microbubbles (SPMB). Flow cytometry was performed to assess the presence of PS in SPMB. A renal I–R injury model was established in 18 rabbits for contrast-enhanced ultrasonography. Examination of ultrasonography with SPMB-PS and SPMB was performed on 12 rabbits before and after I–R injury. The time–intensity curve (TIC) was generated from a selected region of interest. Another six rabbits with renal I–R injury underwent contrast-enhanced ultrasonography for 15 min after intravenous injection of SPMB-PS. The renal tissues were immediately excised for immunohistochemical staining and myeloperoxidase (MPO) activity analysis. The correlation between MPO activity and echo intensity (VI) was analyzed. ResultsFlow cytometry demonstrated that PS was located on the surface of SPMB. TIC showed that the time at which the maximum VI was reached and the time needed for the microbubbles to wash out were the same in the normal kidneys injected with SPMB-PS or SPMB, while there was an obvious delay in emptying time with SPMB-PS compared with SPMB after I–R injury. Fifteen minutes after the injection of SPMB-PS and SPMB, VI was not remarkably different (P>.05) in the normal kidneys, while it was significantly higher (P<.01) in the I–R-injured kidneys. There was a strong correlation between MPO activity and VI 15 min after the injection of SPMB-PS (r=.933, P<.01). Immunohistochemistry showed that most of the inflammatory cells in the I–R-injured kidneys were neutrophils. ConclusionA delayed emptying phenomenon was observed during contrast-enhanced ultrasonography in the I–R-injured kidneys, with SPMB-PS targeted to activated neutrophils. Therefore, contrast-enhanced ultrasonography with SPMB-PS may noninvasively evaluate the severity of ischemia–reperfusion injury to the kidneys.

Preconditioning by desflurane reduces renal reperfusion injury in rabbits

Preconditioning by desflurane reduces renal reperfusion injury in rabbits

The effects of prophylactic zinc and melatonin application on experimental spinal cord ischemia–reperfusion injury in rabbits: experimental study

Experimental study. To determine the neuroprotective effects of zinc and melatonin on spinal cord ischemia-reperfusion (I/R) injuries of rabbits. The Experimental Research Centre of Selçuk University, Konya, Turkey. Twenty-four male rabbits underwent spinal cord ischemia by clamping the thoraco-abdominal aorta for 20 min. Twenty minutes before the aortic clamping, animals received zinc, melatonin or a combination of both. Neurological examination of the animals was performed three times during reperfusion period. The animals were killed 24 h after reperfusion. Spinal cord samples were taken for biochemical and histopathological evaluation. Pre-treated animals with zinc, melatonin or combination displayed better neurological outcomes than the I/R group (P<0.05). Zinc, melatonin and combined treatment prevented spinal cord injury by reducing apoptosis rate (P<0.05) and preserving intact ganglion cell numbers (P<0.05). Zinc pre-treatment protected spinal cord by preventing malondialdehyde (MDA) formation (P=0.002), increasing glutathione peroxidase (GPx) activity (P=0.002) and decreasing xanthine oxidase enzyme activity (P=0.026) at molecular level. Melatonin treatment also resulted with MDA formation (P=0.002), increased GPx activity (P=0.002) and decreased xanthine oxidase activity (P=0.026). The results of the study showed that prophylactic zinc and melatonin use in spinal cord I/R not only suppressed lipid peroxidation by activating antioxidant systems but also had significant neuroprotective effects by specifically improving the neurological and histopathological situation.

Protective Effects of Hyperoxygenated Solution Preconditioning on Intestinal Ischemia–Reperfusion Injury in Rabbits

The aim of this study was to investigate the protective effects of hyperoxygenated solution (HOS) preconditioning on intestinal ischemia-reperfusion (IR) injury in rabbits. Thirty-two rabbits were randomly divided into four groups as follows: (1) control group in which sham operation was performed (Sham group); (2) sham operation and HOS treatment group (sham+H group); (3) ischemia-reperfusion group (IR group); (4) ischemia-reperfusion and HOS treatment group (H group). Intestinal IR model was produced by clamping superior mesenteric artery with an atraumatic vascular clamp for 1 h, followed by reperfusion for 2 h. Animals in H group received intravenous HOS infusion (20 mL/kg) every day for 5 days before ischemia-reperfusion; animals in the sham+H group received the same amount of HOS before sham operation, and animals in IR group received the same amount of normal saline in the same way. At the end of reperfusion, histopathological changes of intestine were observed, and malondialdehyde (MDA) levels, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in intestinal tissues were also detected. Intestinal barrier function was assessed by blood d-lactate levels and bacterial translocation (BT). The H group showed significantly lower MDA levels and higher activities of SOD, CAT, and GSH-Px in the intestinal tissue compared with the IR group. Furthermore, the mean d-lactate levels and incidence of BT in the H group were significantly lower than those in the IR group. Histopathological analysis also indicated that there were significant histological improvements in the H group compared with the IR group. HOS preconditioning at an appropriate dose ameliorates the deleterious changes in intestinal mucosal injury and barrier function associated with IR by effectively preventing a decrease in the intestinal antioxidant defense system, which is another simple and effective measure to protect intestine from IR injury.

Resveratrol, a red wine polyphenol, protects spinal cord from ischemia-reperfusion injury

Clinical relevance Paraplegia that results from spinal cord ischemia is a catastrophic complication of thoracic and thoracoabdominal aorta surgical procedures. Despite several surgical modifications and pharmacologic approaches, paraplegia has not been totally eliminated. On clinical grounds, the efficiency of currently used pharmacologic agents to prevent spinal cord injury during thoracic and thoracoabdominal aorta surgery is very limited and their benefit is controversial. Preischemic infusion of resveratrol protects the spinal cord from ischemia reperfusion injury in rabbits. Following clarification of the underlying protective mechanism, optimal dose, and timing, resveratrol may used in humans as an adjunct to eliminate this catastrophic complication.

Effects of liposomal prostaglandin E(1) on myocardial reperfusion injury in rabbits

OBJECTIVE: To probe into the role of liposomal prostaglandin E(1) (Lipo-PGE(1)) on reperfusion injury in a rabbit ischemia-reperfusion model. METHODS: Twenty-four open-chest rebbits were randomized to receive a 10 min intravenous infusion of either liposome diluent, free PGE(1), or Lipo-PGE(1) after 60 min of left anterior desending (LAD) ligation just before reperfusion. Serum creatine phosphokinase (CPK), malodialdehyde (MDA), superoxide dismutase (SOD) were detected; infarct size and region at risk were measured. RESULTS: Infarct size as a ratio of weight of infarcted tissue to weight at risk (MI/RISK) was significantly reduced with Lipo-PGE(1) (32.20+/-4.70)% compared with PGE(1) (42.09+/-6.93)% or placebo (44.57+/-5.46)% infusion (P<0.01). The values of serum CPK, MDA during reperfusion in treatment of Lipo-PGE(1) group were significantly reduced than in treatment of PGE(1) group or control group (P<0.05), and the values of serum SOD were significantly increased (P<0.05). CONCLUSION: Lipo-PGE(1) can effectively decrease the serum CPK and MDA contents, elevate the SOD activity, and attenuate myocardial reperfusion injury.

Heparin reduces serum levels of endothelin-1 and hepatic ischemia reperfusion injury in rabbits.

Since the role of heparin in hepatic ischemia/reperfusion (I/R) injury is still not fully understood, we investigated the effects of heparin on hepatic I/R injury in rabbits. Heparin was injected into rabbits after inducing partial hepatic ischemia for 1 h. Thereafter, the serum levels of endothelin-1 (ET-1) and liver transaminase, and tissue levels of oxidized and deoxidized hemoglobin (oxHb, deoxHb) in the reperfused liver were analyzed. Microscopic examinations were also performed. The increased serum levels of ET-1 and liver transaminase after reperfusion were significantly reduced by heparin (P > 0.01). Hepatic ischemia reduced oxHb and increased deoxHb. Reperfusion with heparin immediately reduced deoxHb and increased oxHb, and thereafter the balance between the two kinds of Hb also recovered. However, reperfusion without heparin did not demonstrate any similar recovery, but instead gradually exacerbated the dissociation. Microscopically, heparin appeared to normalize I/R-induced activation of hepatic stellate cells which are the target cells for ET-1. These results suggest that heparin improves the hepatic I/R injury caused by sinusoidal microscirculatory disturbances partly via an inhibition of the ET-1 increase.

SB 211475, a metabolite of carvedilol, reduces infarct size after myocardial ischemic and reperfusion injury in rabbits

The aim of this study was to investigate the effect of SB 211475, a metabolite of carvedilol with weak α 1-adrenoceptor antagonism and antioxidant effect, on myocardial reperfusion injury and infarct size in anesthetized rabbits. The rabbits were subjected to 60 min of regional myocardial ischemia and 180 min of reperfusion. SB 211475 was administered either as 0.3, 1.0 or 3.0 mg/kg and compared to vehicle and carvedilol (1 mg/kg) treated animals. The lowest dose of SB 211475 (0.3 mg/kg) did not reduce infarct size compared to vehicle, whereas SB 211475 1.0 or 3.0 mg/kg reduced infarct size significantly compared to vehicle (41.2±2.2% and 40.5±2.8% vs. 59.1±3.9%, p<0.05). Carvedilol reduced infarct size significantly more than SB 211475 1.0 and 3.0 mg/kg (28.8±3.9% vs. 41.2±2.2% and 40.5±2.7%, p<0.05). Carvedilol and SB 211475 1.0 and 3.0 mg/kg reduced myeloperoxidase activity to the same extent, indicative of reduced inflammation. Rate-pressure product did not differ between doses of SB 211475. In conclusion, SB 211475 in the two highest doses reduced infarct size by protecting from reperfusion injury, possibly by reduced neutrophil accumulation. The superior cardiac protective effect of Carvedilol over SB 211475 are most likely due to its adrenergic pharmacology including non-selective β- and α 1-adrenoceptor antagonism.

Effect of the Extract from Salvia Miltiorrhiza Radix (SMR) on Skeletal Muscle Ischemia and Reperfusion Injury in Rabbits

The extract of salvia miltiorrhiza radix (SMR) is a well known Chinese herbal medicine known as danshen. It has been found in several experimental studies, published mostly in China, to have antioxidant properties. The purpose of this experiment was, therefore, to compare the effects of danshen injection with those of superoxide dismutase (SOD) and mannitol on skeletal muscle ischemia and reperfusion injury in rabbits. The authors used a rabbit limb replantation model subjected to 5 h of global ischemia. Immediately before reperfusion, the animals received SOD (16,000 U/kg), mannitol (1 g/kg) or danshen injection (2 g/kg) intravenously. Both danshen and mannitol significantly increased limb survival (P&lt;0.01). Increased limb survival was observed in the SOD-treated group compared with the saline-treated group (P&lt;0.05) but not with the ischemic group (P&gt;0.05). Light and transmission electron microscopy revealed that the pathologic and ultrastructural changes in skeletal muscles, which were subjected to 5 h of ischemia followed by 2 h of reperfusion, were reduced with SOD, mannitol and danshen injection. These results suggest that the hydroxyl radical seems to be the most important factor in ischemia and reperfusion injury to skeletal muscle and that danshen, like mannitol, may have a role in antioxidation as a hydroxyl radical scavenger.