• Journal of Veterinary Clinics
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• v.25 no.3
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• pp.165-169
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• 2008

Renal ischemia-reperfusion (I/R) injury is great clinical important because viability of the organ depends on the tolerance to ischemia-reperfusion injury, an inevitable processing during surgery. The purpose of this study was to investigate the effects of premedicated ascorbic acid alone in I/R injury model induced by cross-clamping of renal vessels. In the rabbit models, 2-4 kg New Zealand white rabbits were subjected to 30 minutes of warm unilateral renal ischemia followed by removal of contralateral kidney and then divided into five groups, control (2) arid treatment groups (3). In control group 1, the rabbits only received right nephrectomy. In control group 2, the rabbits received I/R on left kidney after the right nephrectomy. In treatment group 1, the rabbits received ascorbic acid 50 mg/kg IV before the operation. In treatment group 2, the rabbits received ascorbic acid 100 mg/kg IV before the operation. In treatment group 3, the rabbits received ascorbic acid 200 mg/kg IV before the operation. Blood samples were collected from these rabbits for measurement of kidney function tests at the 0, 1 st, 3rd and 7th day and antioxidant enzyme( SOD, GSHPx, CAT) at 24 hours. Kidney function tests (serum creatinine and BUN) showed a significant difference between group 2 and group 4, 5. Activity of antioxidant enzymes in plasma were significant decrease in group 4, 5 compare to group 2. The result of this study suggested that the exogenous ascorbic acid had a role of attenuation of renal I/R injury in rabbit model.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.4
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• pp.323-331
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• 2001

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of rutin, a flavonoid having antiprostanoid, anti-inflammatory, antithrombotic, antioxidant effect, were investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state resulted in a fatal outcome within 120 min of reperfusion in many rats. Rutin was given as a bolus (1.28 mg/kg) 10 min prior to reperfusion. Administration of rutin significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p＜0.05). Rutin treatment also resulted in a significant attenuation in the increase in plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. These results suggest that rutin provides beneficial effects in part by preserving endothelial function and attenuating neutrophil accumulation in the ischemic reperfused splanchnic circulation.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.3
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• pp.181-187
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• 2009

Intestinal ischemia/reperfusion (I/R) is one of common causes of acute lung injury (ALI). Early and accurate diagnosis of patients who are like to develop serious acute respiratory distress syndrome (ARDS) would give a therapeutic advantage. Ferritin and heme oxygenase-1 (HO-1) are increased by oxidative stress and are potential candidates as a predictive biomarker of ARDS. However, the mechanisms responsible for the increases of ferritin and HO-1, and their relationship to ALI, are unclear. In order to elucidate the interactions between ferritin and HO-1, we studied the changes in ferritin and HO-1 levels in serum and bronchoalveolar lavage (BAL) fluid after intestinal I/R injury in rats. Leukocyte number and protein contents in BAL fluid were elevated following I/R, and the increases were attenuated by mepacrine pretreatment. Both serum ferritin and HO-1 concentrations were progressively elevated throughout the 3 h observation period. Mepacrine pretreatment attenuated the increase of serum and BAL fluid ferritin concentrations, but did not suppress the increase of serum HO-1. Moreover, BAL fluid HO-1 levels did not change after I/R or after mepacrine pretreated I/R compared with sham rats. Unlike ferritin, HO-1 levels are not exactly matched with the ALI. Therefore, there might be a different mechanism between the changes of ferritin and HO-1 in intestinal I/R-induced ALI model.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.4
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• pp.187-191
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• 2006

Serum ferritin levels are increased in subjects at-risk for or with acute lung injury (ALI), and there are observations to suggest that increases in serum ferritin levels may help predict the development of ALI in at-risk individuals. To deepen our understanding of increases of serum ferritin and their relationship to the development of ALI, we measured serum ferritin levels before and after intestinal ischemia/reperfusion (I/R) injury in rats, and found that serum ferritin levels increased significantly following I/R. Increases in serum and lavage ferritin levels paralleled increases in lung inflammation (lavage leukocyte numbers and tissue myeloperoxidase activities) and lung leak (lavage protein levels). In contrast, pre-treatment of rats with mepacrine (60 mg/kg, i.p.), a phospholipase $A_2$ inhibitor, attenuated not only I/R-induced serum and lavage ferritin increases, but also the development of ALI. These findings indicate that, besides of human subjects with ALI, serum ferritin levels increase early on also in an animal model of ALI. Therefore, serum and lavage ferritin can be a candidate for early biomarker of ALI.

• Journal of Chest Surgery
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• v.33 no.3
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• pp.213-220
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• 2000

Background: Adhesion of leukocytes to myocardium or vascular endothelium has been known as an importation initial step in the ischemia-reperfusion injury which may affect the cardiac function. Therefore, leukocyte-depleted reperfusion may inhibit ischemia-reperfusion induced functional and ultrastructural deterioration. In this study, we quantified the time-dependent expression of the vascular cell adhesion molecule-1(VCMA-1) on piglet myocardium and demonstrated its relation to functional recovery using isolated piglet heart perfusion model. Material and Method: Neonatal(1 to 3 day old) piglet heart was harvested with 4$^{\circ}C$ University of Wisconsin solution (UWS) and presrved in the same solution for 12 hours. Ex vivo model of an isolated working neonatal piglet heart perfusion consisting of membrane oxygenator and roller-pump was used (Fig. 1). Hearts were grouped into leukocyte-non-depleted (group A, n=8) and leukocyte-depleted group(group B, n=8). In group B, hearts were reperfused with leukocyte-depleted blood using a leukocyte filter (Sepacell R, Asahi Medical, Japan). Segments of right atrium were taken before and after 1, 2, 3, and 4 hours of reperfusion for the evaluation of expression of VCAM-1. The intensity of immunohistochyemical satining of the VCAM-1 on the myocardium were graded semiquantitatively (0 to 4). For the evaluation of myocardial stroke work indices were calculated as well at the same time-points. Result: Mean expressins of VCAM-1 on the myocardium at 0, 1, 2, 3, adn 4 hours of reperfusion were 0.63, 1.44, 1.64, 2.65, and 3.34 in group A, while 0.56, 1.40, 1.50, 1.88 and 2.14 in group B (Fig. 3). Mean stroke work indices at 0.5, 1, 2, 3, and 4 hours after reperfusion were 1.35$\times$104, 1.32$\times$104, 1.14$\times$104, 0.81$\times$104, 0.68$\times$104 erg/gm in group A, while 1.40$\times$104, 1.43$\times$104, 1.43$\times$104, 1.28$\times$104, and 1.12$\times$104 erg/em in group B(Fig. 4). Conclusion : In this study, we demonstrated that leukocyte-depletion attenuated the expression of VCAM-1 during reperfusion and the time-dependent functional deterioration of the myocardium was well correlated with the degree of VCAM-1 expression.

• Journal of Veterinary Clinics
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• v.25 no.4
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• pp.257-262
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• 2008

Renal ischemia-reperfusion injury is great clinical important because viability of the transplanted organ depends on the tolerance of the graft to ischemia-reperfusion injury, an inevitable processing during surgery. The purpose of this study was to investigate the effects of irrigation-aspiration in ischemia-reperfusion injury model induced by cross-clamping of renal vessels. Blood samples were collected from these dogs for measurement of kidney function and antioxidant enzyme activity, and RI at the intrarenal artery was measured at different time intervals. And the kidneys were taken for histopathologic evaluation at day 14. Kidney function (Cr and BUN) showed a significant increasing in untreated group compared to treated group. Resistive index of intrarenal artery was no significant difference among the groups. Activity of antioxidant enzymes in plasma was significant decrease in untreated group compare to control group while in treated group was no significant difference compared to control group. In histopathologic finding, treated group was showed less damage than that of untreated group. This result suggests that the processing of irrigation-aspiration is useful to reducing ischemia-reperfusion injury.

• Advances in pediatric surgery
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• v.3 no.2
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• pp.98-107
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• 1997

To determine whether bile juice exclusion can prevent the mucosal damage, and Insulin-like growth factor-I can promote mucosal regeneration in ischemia-reperfusion injury of the bowel, 39 weanling rats with 10 cm of Thiry-Vella loop were studied. Animal groups were; Control, BL(common bile duct ligation), IGF{insulin-like growth factor-I(IGF-I) infusion} and IGF-BL(combined treatment). IGF-I(1.5 mg/kg/day) was continuously delivered through a subcutaneously implanted miniosmotic pump. After 15 minutes of superior mesenteric artery clamping, a tissue specimen(P) was taken after 30 minutes of reperfusion. Intestinal continuity was restored to allow oral feeding. A specimen of main tract(M) and another of the Thiry-Vella loop(T) were collected for histomorphometry after 48 hours of reperfusion and free feeding. Villus size ratio(VSR), crypt depth(CD), crypt-depth/villus-height ratio(CVR) and injury score(IS) were measured in 15 consecutive villi. The postoperative mortalities of bile duct ligation groups(BL and IGF-BL) were higher than those of other groups. In control group, VSR of M was lower(P<0.05) than P or T, but not in the other groups. VSR of M in control was lower than those in other groups. CD of T in control, IGF and IGF-BL group were higher than those of M. CD of M and T showed gradual increments from control, IGF and IGF-BL group, respectively. CVR of M and T in IGF group were higher than those in control. CVR in IGF-BL group, T was higher than M, and M was higher than P. About IS, M of BL($20.1{\pm}2.5$) and IGF-BL($20.9{\pm}3.3$) groups were significantly lower than that of control($32.4{\pm}2.5$). These results suggest that the exclusion of bile juice reduces the severity of the reperfusion injury of the mucosa, by inability to activate pancreatic enzymes and IGF-I stimulates mucosal regeneration in injured bowel, and the effect is potentiated by bile juice exclusion.

• Journal of Chest Surgery
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• v.31 no.6
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• pp.567-575
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• 1998

Panax Ginseng C.A. Meyer has been known for hundreds of years as the most valuable drug having mysterious effects among all the herbal medicines and plants in Korea. Also, many experimental studies have been performed recently that the various effects were identified and applied clinically. So we attempted an experimental study on the effect of ginsenoside Rg1 mixtures in an isolated rat heart with the use of the Langendorff model. The objective of this study was to determine whether this ginsenoside Rg1 mixtures would protect the myocardial injury after ischemic arrest and reperfusion. Isolated rat hearts were allowed to equilibrate for 20 minutes and were then subjected to 15 minutes of normothermic ischemia. After this ischemic period, isolated rat hearts were allowed to reperfusion for 10 minutes(Ischemic Group). In other group , isolated rat hearts were perfused for 60 minutes continuously with normothermia( Normothermic Group). Hemodynamic and biochemical parameters such as heart rate, left ventricular pressure, +dp/dt max, coronary blood flow and cardiac enzymes were measured during initial perfusion, ischemia, reperfusion period (Ischemic group) and 20, 40 and 60 minutes after continuous perfusion(Normothermic group). After completion of the experiment, this data was evaluated and the following results were obtained. 1. Heart rates showed an increase in both ischemic and normothermic experimental groups, but statistically significant differences were not identified. 2. LVP(Left Ventricular Pressure) showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.005, p<0.01). 3. +dp/dt max showed statistically significant differences in both ischemic and normothermic experimental groups(p<0.01, p<0.01). 4. There were no statistically significant differences in coronary blood flow and cardiac cenzymes in all groups, but experimental groups seemed to have better protection and recovery. These results suggest that ginsenoside Rg1 mixtures has a protective effect on the myocardial injury after ischemia and reperfusion.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.67-72
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• 2014

To investigate the alteration of c-Jun N-terminal kinase (JNK) activity after myocardial ischemia reperfusion injury (MIRI) and further explore the effect of naloxone postconditioning on MIRI. Forty male Sprague Dawley rats were randomly divided into five groups: sham operation (sham, n=8); ischemia reperfusion (IR, n=8); IR+naloxone 0.5 mg/kg (Nal L, n=8); IR+naloxone 1.0 mg/kg (Nal M, n=8); IR+naloxone 2.0 mg/kg (Nal H, n=8). Pathological changes of myocardial tissue were visualized by HE staining. The expression of p-JNK, and the apoptosis of cardiomyocytes were investigated with Western blotting and the TUNEL assay, respectively. Irregular arrangement and aberrant structure of myocardial fibers, cardiomyocytes with granular or vacuolar degeneration, and inflammatory cells infiltrating the myocardial interstitial regions characterized MIRI in the IR group. Signs of myocardial injury and inflammatory infiltration were less prominent in the Nal-treated groups. The expression of p-JNK in the sham group and in all Nal-treated groups was significantly lower than that in the IR group (p<0.01). The apoptosis index of cardiomyocytes in the IR group was significantly higher than in the sham group (p<0.01). The apoptosis indices of cardiomyocytes in all Nal-treated groups were significantly reduced to 55.4%, 26.2%, and 27.6%, respectively, of the IR group (p<0.01). This study revealed that Naloxone postconditioning before reperfusion inhibits p-JNK expression and decreases cell apoptosis, thus alleviating MIRI.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.901-913
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• 1989

This study was investigated under the postulation that activation of intracellular calcium- calmodulin complex during ischemia-reperfusion leads to myocardial injury. The protective effects of calcium channel blocker, diltiazem and calmodulin inhibitors, trifluoperazine, flunarizine and calmidazolium from ischemic injury in rat hearts were observed by using Langendorff apparatus when the antagonists were infused for 3 min in the beginning of ischemia. Thereby, an increase in resting tension developed during 30-min ischemia was analyzed with regard to [1] the degree of cardiac functional recovery following 60-min reperfusion, [2] changes in biochemical variables evoked during 30-min ischemia. The results obtained were as follows: l. In the ischemic group, the resting tension was increased by 4.1*0.2 g at 30-min ischemia. However, the increase in resting tension was markedly reduced not only by pretreatment with diltiazem [3.3 p M] but also with calmodulin inhibitors, trifluoperazine [3.3 p M], flunarizine [0.5 p M] and calmidazolium [0.5 p M], respectively. 2. Recovery of myocardial contractility, +dF /dt and coronary flow were much reduced when evoked by reperfusion in the ischemic group. These variables were significantly improved either by pretreatment with diltiazem or with calmodulin inhibitors. 3. The resting tension increment evoked during ischemia was significantly inversely correlated with the degree of cardiac function recovered during reperfusion. 4. Following 30-min ischemia, the production of malondialdehyde and release of lysosomal enzyme were much increased in association with a decrease in creatine kinase activity. 5. The increases in malondialdehyde production and release of free lysosomal enzyme were suppressed by pretreatment with calmodulin inhibitors as well as diltiazem. Likewise, the decrease of creatine kinase activities was prevented by these calcium antagonists. With these results, it is indicated that a increase in resting tension observed during ischemia has an inverse relationship to the cardiac function recovered following reperfusion, and further, the later may be significantly dependent on the degree of biochemical alterations occurred during ischemia such as decrease in creatine kinase activity, increased production of malondialdehyde and increased release of free lysosomal enzyme. Thus it is concluded that calmodulin plays a pivotal role in the process of ischemic injury.