Tao Yeuan Wang

Dexmedetomidine–ketamine combination mitigates acute lung injury in haemorrhagic shock rats

AIM OF THE STUDY Upregulation of pulmonary inflammatory molecules is crucial in mediating the development of acute lung injury induced by haemorrhagic shock. Dexmedetomidine and ketamine possess potent anti-inflammatory capacity. We sought to elucidate whether dexmedetomidine, ketamine, or dexmedetomidine-ketamine combination could mitigate acute lung injury in haemorrhagic shock rats. METHODS Fifty adult male Sprague-Dawley rats were randomized to the sham-instrumented, haemorrhagic shock (HS), HS plus dexmedetomidine (HS-D), HS plus ketamine (HS-K), or HS plus dexmedetomidine-ketamine (HS-D+K) group (n=10 in each group). Haemorrhagic shock was induced by blood withdrawing and the mean blood pressure was maintained at 40-45mmHg for 120min. Resuscitation was then performed by infusion of shed blood/saline mixtures. After monitoring for another 8h, rats were sacrificed. RESULTS Histology findings and lung injury score analysis revealed moderate lung injury in rats of the HS, HS-D, and HS-K groups, whereas those of the HS-D+K group revealed mild lung injury. The effects of haemorrhagic shock on increasing cell number and protein concentration in bronchoalveolar lavage fluid as well as water content, leukocyte infiltration, and myeloperoxidase activity of lung tissues were significantly attenuated by dexmedetomidine-ketamine combination but not by dexmedetomidine or ketamine alone. Dexmedetomidine-ketamine combination, but not dexmedetomidine or ketamine alone, also significantly inhibited haemorrhagic shock-induced upregulation of pulmonary inflammatory molecules, including nitric oxide, prostaglandin E(2), chemokine (e.g., macrophage inflammatory protein-2), and cytokines [e.g., interleukin (IL)-1beta, and IL-6]. CONCLUSIONS Dexmedetomidine-ketamine combination mitigates acute lung injury in haemorrhagic shock rats.

Protective Effects of Dexmedetomidine-Ketamine Combination Against Ventilator-Induced Lung Injury in Endotoxemia Rats

BACKGROUND Pulmonary inflammatory response is crucial in mediating the development of ventilator-induced lung injury (VILI) in animals experiencing endotoxemia. Dexmedetomidine and ketamine are two sedative agents with potent anti-inflammatory capacity. We sought to elucidate the anti-inflammatory effects of dexmedetomidine-ketamine combination against VILI in endotoxemia rats. MATERIALS AND METHODS Eighty-four adult male rats were allocated to receive normal saline, VILI, VILI plus dexmedetomidine-ketamine combination (D+K), lipopolysaccharide (LPS), LPS plus D+K, LPS plus VILI, or LPS plus VILI plus D+K (designated as the NS, V, V-D+K, LPS, LPS-D+K, LPS/V, and LPS/V-D+K group, respectively; n = 12 in each group). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 50 breath/min; FiO(2) 21%). After being mechanically ventilated for 4 h, rats were sacrificed and the levels of pulmonary inflammatory response were evaluated. RESULTS Histologic findings revealed severe, moderate, and mild inflammation in lung tissues of the LPS/V, LPS, and V groups, respectively, whereas those of the LPS/V-D+K, LPS-D+K, and V-D+K groups revealed moderate, mild, and normal to minimal inflammation, respectively. Moreover, the total cell number and the concentrations of macrophage inflammatory protein-2 and interleukin-1β in bronchoalveolar lavage fluid as well as the lung water content, leukocyte infiltration, myeloperoxidase activity, and the concentrations of inducible nitric oxide synthase/nitric oxide, and cyclooxygenase 2/prostaglandin E(2) in lung tissues of the LPS/V, LPS, and V groups were significantly higher than those of the LPS/V-D+K, LPS-D+K, and V-D+K groups, respectively. CONCLUSIONS Dexmedetomidine-ketamine combination could mitigate pulmonary inflammatory response induced by VILI in endotoxemia rats.

Acupuncture stimulation of ST36 (Zusanli) attenuates acute renal but not hepatic injury in lipopolysaccharide-stimulated rats.

BACKGROUND:We sought to determine the effects of ST36 acupuncture on sepsis-induced kidney and liver injuries. METHODS:A total of 120 rats were randomized into 10 groups: 1) lipopolysaccharide (LPS), 2) normal saline (N/S), 3) LPS + ST36, 4) ST36, 5) LPS + P-ST36, 6) P-ST36, 7) LPS + Sham, 8) Sham, 9) LPS + P-Sham, and 10) P-Sham groups. Rats in the LPS + ST36, ST36, LPS +Sham, and Sham groups received ST36 (designated as “ST36”) or a nonacupoint (designated as “Sham”) acupuncture for 30 min followed by LPS or N/S injection. Rats in the LPS + P-ST36, P-ST36, LPS + P-Sham, and P-Sham groups received LPS or N/S injection for 3 h followed by a 30 min of ST36 or a “nonacupoint” acupuncture. Rats were killed at 6 h after LPS injection. RESULTS:LPS caused prominent kidney and liver injuries. The renal and hepatic nitric oxide (NO) concentrations and inducible NO synthase (iNOS) expression were also increased by LPS. ST36 acupuncture pretreatment significantly attenuated the LPS-induced kidney injury and the increases in renal NO concentration and iNOS expression. However, ST36 acupuncture pretreatment did not affect the LPS-induced liver injury and increases in hepatic NO concentration or iNOS expression. Furthermore, ST36 acupuncture performed after LPS did not affect the LPS-induced organ injuries or increases in NO concentration and iNOS expression. CONCLUSIONS:ST36 acupuncture pretreatment significantly attenuated sepsis-induced kidney, but not liver, injury in rats, whereas ST36 acupuncture performed after sepsis induction had no protective effects against sepsis-induced organ injuries.

Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats

BACKGROUND Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO(4)) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO(4) could mitigate I/R-induced lung injury. As MgSO(4) is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated. MATERIALS AND METHODS Adult male rats were allocated to receive I/R, I/R plus MgSO(4) (10, 50, or 100 mg/kg), or I/R plus MgSO(4) (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 μg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined. RESULTS Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E(2) concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO(4), at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO(4). CONCLUSIONS MgSO(4) mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels.

High-lipid enteral nutrition could partially mitigate inflammation but not lung injury in hemorrhagic shock rats

BACKGROUND Loss of gut barrier function is crucial in mediating lung injury induced by hemorrhagic shock/resuscitation (HS). High-lipid enteral nutrition (HL) can preserve gut barrier function. We hypothesized that HL could also mitigate HS-induced lung injury. MATERIALS AND METHODS Forty-eight adult male rats were randomly assigned to one of four experimental groups: HS; HS-HL; Sham; Sham-HL. HS was induced by blood drawing and mean blood pressure was maintained at 40-45 mmHg for 120 min followed by resuscitation with re-infusion of exsanguinated blood/saline mixtures. HL gavage was performed at 45 min before blood drawing and at the end of resuscitation. RESULTS Intestinal permeability of the HS group was significantly higher than that of the Sham group (P < 0.001). Pulmonary concentrations of malondialdehyde (lipid peroxidation) and inflammatory molecules, including prostaglandin E2, tumor necrosis factor-α, interleukin-6, and macrophage inflammatory protein-2, of the HS group were significantly higher than those of the Sham group. Histologic analyses, including histopathology, wet/dry weight ratio, and neutrophil infiltration revealed moderate lung injury in the HS group. In contrast, intestinal permeability (P < 0.001) and pulmonary concentrations of tumor necrosis factor-α and macrophage inflammatory protein-2 (P = 0.021 and 0.01) of the HS-HL group were significantly lower than those of the HS group. However, pulmonary concentrations of malondialdehyde, prostaglandin E2, and interleukin-6 of the HS-HL and HS groups were comparable. Moreover, histologic analyses also revealed moderate lung injury in the HS-HL group. CONCLUSIONS High-lipid enteral nutrition significantly mitigated gut barrier loss and partially mitigated lung inflammation but not oxidation and lung injury in hemorrhagic shock/resuscitation rats.

Simvastatin attenuates testicular injury induced by torsion-detorsion

PURPOSE The lipid lowering agent simvastatin has potent anti-oxidation capacity. We elucidated the potential of simvastatin to attenuate testicular injury induced by testicular torsion-detorsion. We also investigated simvastatin effects on nuclear factor-kappaB expression. MATERIALS AND METHODS We allocated 60 adult male Sprague-Dawley(R) rats to testicular torsion-detorsion, torsion-detorsion plus simvastatin (1 or 5 mg/kg), sham operation or sham operation plus simvastatin (5 mg/kg). There were 12 rats per group. Simvastatin was administered immediately after detorsion or immediately after sham operation. Testes were harvested 30 minutes and 24 hours after detorsion to facilitate the evaluation of nuclear factor-kappaB and testicular injury, respectively. RESULTS Histological findings revealed severe injury in testes of the torsion-detorsion and torsion-detorsion-simvastatin (1 mg/kg) groups while testes in the torsion-detorsion-simvastatin (5 mg/kg) group showed moderate injury. Myeloperoxidase activity, and cytokines, nitric oxide and malondialdehyde in testes in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. Testicular concentrations of nuclear factor-kappaB in nuclear extracts and phosphorylated inhibitor-kappaB in cytosolic extracts in the torsion-detorsion-simvastatin (5 mg/kg) group were significantly lower than in the torsion-detorsion group. Values were comparable in the torsion-detorsion-simvastatin (1 mg/kg) and torsion-detorsion groups. CONCLUSIONS Simvastatin protected testes from torsion-detorsion injury in a dose dependent manner. Mechanisms may involve attenuating nuclear factor-kappaB activation and decreasing oxidative stress induced by torsion-detorsion.

Platonin mitigates acute lung injury induced by bilateral lower limb ischemia-reperfusion in rats.

BACKGROUND Oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by bilateral lower limb ischemia-reperfusion (I/R). Platonin, a potent antioxidant, possesses anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury induced by lower limb I/R. MATERIALS AND METHODS Forty-eight adult male rats were allocated to receive I/R, I/R plus platonin (100 μg/kg intravenous injection immediately after reperfusion), sham instrumentation, or sham instrumentation plus platonin (denoted as the I/R, I/R-platonin, Sham, or Sham-platonin group, respectively; n = 12 in each group). Bilateral hind limb I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After sacrifice, the degree of lung injury was determined. RESULTS Histologic findings revealed moderate inflammation in lung tissues of the I/R group and mild inflammation in those of the I/R-platonin group. Total cell number and protein concentration in bronchoalveolar lavage fluid as well as the leukocyte infiltration and myeloperoxidase activity in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. The pulmonary concentrations of macrophage inflammatory protein-2, interleukin-6, and prostaglandin E(2) of the I/R group were significantly higher than those of the I/R-platonin group. Moreover, the plasma nitric oxide concentration as well as the nitric oxide and malondialdehyde concentrations in lung tissues of the I/R group were significantly higher than those of the I/R-platonin group. CONCLUSIONS Platonin mitigates acute lung injury induced by bilateral lower limb I/R in rats.

FTY720 mitigates torsion/detorsion-induced testicular injury in rats

BACKGROUND FTY720, a sphingosine-1-phosphate (S1P) receptor agonist, possesses potent anti-inflammation capacity. We evaluated the therapeutic potentials of FTY720 against testicular injury induced by testicular torsion and/or detorsion (T/D). MATERIALS AND METHODS Young adult male Sprague-Dawley rats were allocated to receive T/D (the T/D group) and T/D plus FTY720 (4 mg/kg, the T/D-FTY group, n = 6 in each group). To investigate the possible roles of the S1P receptors, another group of rats received T/D plus FTY720 plus the potent S1P receptor antagonist VPC23019 (1 mg/kg, the T/D-FTY-VPC group, n = 6). FTY720 was administered immediately before testicular detorsion, and VPC23019 was administered 30 min before FTY720. Another set of rats that received sham operation, immediately followed by injection of normal saline, FTY720, or FTY720 plus VPC23019, served as control groups. Sham control groups were run simultaneously. After euthanization, levels of testicular injury were measured. RESULTS Histologic findings revealed severe testicular injury changes in both the T/D and T/D-FTY-VPC groups and moderate testicular injury changes in the T/D-FTY group. In addition, malondialdehyde activity (oxidative status), concentration of interleukin-1β (inflammation index), myeloperoxidase activity (neutrophil infiltration index), and wet-to-dry weight ratio (tissue edema index) of both the T/D and T/D-FTY-VPC groups were significantly higher than those of the T/D-FTY group. These data confirmed the protective effects of FTY720 against testicular T/D. Moreover, antagonizing the S1P receptors could reverse the protective effects of FTY720. CONCLUSIONS FTY720 significantly mitigated testicular injury induced by testicular T/D. The mechanisms may involve activating the S1P receptors.

Platonin mitigates acute lung injury in haemorrhagic shock rats

AIM OF THE STUDY Enhanced oxidative stress and inflammatory response are crucial in mediating the development of acute lung injury induced by haemorrhagic shock with resuscitation. Platonin, a potent antioxidant, possesses potent anti-inflammation capacity. We sought to elucidate whether platonin could mitigate acute lung injury in haemorrhagic shock/resuscitation rats. METHODS Seventy-two adult male rats were randomized to receive haemorrhagic shock/resuscitation (HS), HS plus platonin (10, 50, or 100μg/kg intravenous injection immediately after resuscitation), sham instrumentation (Sham), or Sham plus platonin (100μg/kg) (n=12 in each group). Haemorrhagic shock was induced by blood drawing and mean blood pressure was maintained at 40-45mmHg for 120min. Then, resuscitation was achieved by shed blood/saline mixtures re-infusion. After monitoring for another 8h, rats were sacrificed. RESULTS Arterial blood gas and histological findings, in concert with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that haemorrhagic shock/resuscitation caused significant lung injury. Significant increases in concentrations of inflammatory molecules (chemokine, cytokine, and prostaglandin E(2)) as well as nitric oxide and malondialdehyde in lung tissues confirmed that haemorrhagic shock/resuscitation elicited inflammatory response and imposed oxidative stress in rats. Platonin at the dosages of 50 and 100μg/kg, but not 10μg/kg, significantly attenuated the inflammatory response and oxidative stress induced by haemorrhagic shock/resuscitation. Most important, platonin at the dosages of 50 and 100μg/kg, but not 10μg/kg, significantly mitigated the lung injury induced by haemorrhagic shock/resuscitation. CONCLUSIONS Platonin mitigates acute lung injury in haemorrhagic shock/resuscitation rats.