Ischemia-reperfusion Injury In Rabbits Research Articles

Protective effects of ginkgo leaf extracts on neurons in spinal cord after ischemia-reperfusion injury in rabbits

To observe the protective effects of ginkgo leaf extracts on spinal cord after ischemia-reperfusion (IR) injury in rabbits and to find out its possible mechanism. Twenty-seven New Zealand white rabbits were randomly divided into three groups, which were sham-operation group, untreated group and ginkgo leaf extracts-treated group. The locomotor scores of hindlimbs in rabbits after 24 and 48 h of reperfusion were evaluated, and the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in ischemia spinal cord were examined. The apoptotic index (AI) of neurons in spinal cord was detected by terminal deoxyribonucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method. The expressions of Bcl-2 and Bax proteins were examined by streptavidin-biotin peroxidase method. The locomotor scores of hindlimbs in rabbits after 24 and 48 h of reperfusion in the ginkgo leaf extracts-treated group were obviously elevated as compared with those in the untreated group (P<0.05). The activity of SOD was higher and the level of MDA was lower in ischemia spinal cord in the ginkgo leaf extracts-treated group than those in the untreated group (P<0.01). The decreased neuron AI and the expressions of up-regulated Bcl-2 protein and down-regulated Bax protein were also observed in the ginkgo leaf extracts-treated group. The protective effects of the ginkgo leaf extracts against spinal cord injury induced by IR may be related to scavenging oxygen free radicals, reducing lipid peroxidation injury and inhibiting apoptosis.

Effect of desflurane-induced preconditioning following ischemia-reperfusion on nitric oxide release in rabbits

Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial infarction. Desflurane produces anesthetic preconditioning to protect the myocardium against infarction. In the model of myocardial ischemia-reperfusion injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long lasting left anterior descending coronary artery (LAD) occlusion and three hours (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into four groups for preconditioning treatment (eight for each group). The control group did not receive any preconditioning treatment. The desflurane group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar concentration) for 30 min that was followed by a 15 min washout period. The L-NAME-desflurane group received L-NAME (N G-nitro-L-arginine methyl ester; non-selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0 MAC inhaled desflurane for 30 min. The L-NAME group received L-NAME 1 mg/kg IV. Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH), creatine kinase (CK) activity and myocardial perfusion were recorded simultaneously. We have found that hemodynamic values of the coronary blood flow before, during, and after LAD occlusion were not significantly different among these four groups. For the myocardial ischemia-reperfusion injury animals, the infarction size (mean ± SEM) in the desflurane group was significantly reduced to 18 ± 3% in the area at risk as compared with 42 ± 7% in the control group, 35 ± 6 in the L-NAME group, and 34 ± 4% in the L-NAME-desflurane group. The plasma LDH, CK levels, and duration of ventricular arrhythmia were also significantly decreased in the desflurane group during ischemia-reperfusion injury. Our results indicate that desflurane is an anesthetic preconditioning agent, which could protect the myocardium against the ischemia-reperfusion injury. This beneficial effect of desflurane on the ischemic preconditioning is probably through NO release since L-NAME abrogates the desflurane preconditioning effect.

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.

Novel small molecule inhibitor of C1s exerts cardioprotective effects in ischemia-reperfusion injury in rabbits.

Myocardial ischemia-reperfusion injury can be related to complement activation with generation of chemotactic agents, adhesion molecule expression, release of cytokines and oxygen-derived free radicals, and subsequent neutrophil accumulation. In the present study the cardioprotective effects of a novel highly selective small molecule C1s inhibitor (C1s-INH-248, Knoll) were examined in a rabbit model of myocardial ischemia (I) and reperfusion (R; i.e., 60 min I + 180 min R). In in vitro tests (enzyme activity and SRBC lysis) C1s-INH-248 demonstrated profound inhibitory potency. In vivo C1s-INH-248 (1 mg/kg body weight) administered 5 min before reperfusion significantly attenuated myocardial injury (31.9 +/- 2.5 vs 8.9 +/- 1.6% necrosis/area at risk; p < 0.01). The cardioprotective effect was dose dependent. The reduction of myocardial injury was also observed as diminished plasma creatine kinase activity in C1s-INH-248-treated animals (70.7 +/- 6.8 vs 45.1 +/- 3.9 U/g protein after 3 h of reperfusion, p < 0.05). Further, cardiac myeloperoxidase activity (i.e., a marker of PMN accumulation) in the ischemic and necrotic area was significantly reduced following C1s-INH-248 treatment (1.31 +/- 0.23 vs 0.4 +/- 0.05 U/100 mg tissue in necrotic area, p < 0.01). Thus, blocking the classical complement pathway with a highly specific and potent synthetic inhibitor of the activated C1 complex appears to be an effective mean to preserve ischemic myocardium from injury following reperfusion.

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.