Burns ; complications ; metabolism ; therapy ; Fluid Therapy ; Humans ; Hypoxia ; etiology ; metabolism ; prevention & control ; Ischemia ; etiology ; metabolism ; prevention & control

Myocardial damage and decrease in blood-pumping function, which occur immediately after severe burns, not only lead to cardiac insufficiency, but also induce or exacerbate burn shock, constituting one of the initiating factors for visceral ischemic/hypoxic damage. Therefore, prompt and effective prevention and treatment of myocardial damage are important for resuscitation of burn patients with severe burns, especially in those whose hospitalization is delayed. In this review, the potential clinical strategies including angiotensin-converting enzyme inhibitors, modulation of beta-AR-mediated signal transduction and the "molecular switch Gsalpha/Gialpha", modulation of ion channels, the control of NO donor, the use of anti-inflammatory agents, and antioxidants, and energy metabolic modulation are introduced in details.
Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Burns ; complications ; metabolism ; Humans ; Hypoxia ; etiology ; metabolism ; prevention & control ; Myocardial Ischemia ; etiology ; metabolism ; prevention & control ; Myocardium ; metabolism ; Signal Transduction

OBJECTIVETo investigate the effect of second messengers protein kinase C (PKC) and inositol (1,4,5)-trisphosphate (IP(3)) during hypoxic-ischemic brain injury in neonatal rats.

METHODSThe protein concentration was determined by Lowry's method. PKC activity was measured by the incorporation of [gamma-32P] into a specific substrate peptide in the cytosol and particulate fraction, respectively. IP(3) was determined by the radioreceptor binding assay.

RESULTSCompared with the control, PKC activities in the particulate fractions in both the cerebral cortex and hippocampus decreased, while increased in the cytosol in cerebral cortex and remained within the normal range in the cytosol in the hippocampus at 0, 4, 12, 24, 48, 72 h, 7, and 14 d after hypoxic-ischemia for 20 min. All these changes restored to normal levels at 21 d post hypoxic-ischemia. Similarly, a decrease in IP(3) in the cerebral cortex and hippocampus and an increase in IP(3) in the thalamus after hypoxic-ischemia were noted, respectively. Changes in cytosolic PKC activity were not related to those of IP(3), as evaluated statistically.

CONCLUSIONHypoxia-ischemia induces disturbance of the second messengers IP(3) and PKC, which may play important roles in the pathogenesis of hypoxic-ischemic brain injury.

Animals ; Animals, Newborn ; Brain Ischemia ; etiology ; metabolism ; Female ; Hypoxia, Brain ; etiology ; metabolism ; Inositol 1,4,5-Trisphosphate ; physiology ; Male ; Protein Kinase C ; physiology ; Rats ; Rats, Wistar

OBJECTIVESTo investigate the effects of astilbin on the expressions of TNF alpha and IL-10 during liver warm ischemia-reperfusion injury.

METHODSC57BL/ 6 mice were randomly divided into 4 groups (n = 8): sham-operated group (Sham), model control group(I/R), low dosage of astilbin treatment group (10 mg/kg) and high dosage of astilbin (40 mg/kg) treatment group. The treatment group mice were intraperitoneally injected with 10 or 40 mg/kg astilbin 24 hours and one hour before Ischemia, the hepatic ischemia-reperfusion model were thus established. After jn90 of min ischemia and 6 h reperfusion of the partial hepatic lobe, the expressions of TNF alpha and IL-10 in liver tissues collected from the experimental groups were detected by Western blot and semiquantitative RT-PCR.

RESULTSThe expression of TNF alpha protein in liver tissues gradually decreased in treatment groups (low and high dosages of astilbin treatment groups) as compared to the I/R model control group. Similar results were observed in the mRNA expressions of these genes as determined by semiquantitative RT-PCR (P less than 0.05 for low dosage group; P less than 0.01 for high dosage group). Compared with the I/R model control group, the expression of IL-10 was increased in both treatment groups (low dosage group P less than 0.05; large dosage group P less than 0.01).

CONCLUSIONTreatment with astilbin decreases TNF alpha expression but induces IL-10 expression in liver during warm ischemia-reperfusion injury.

Animals ; Flavonols ; pharmacology ; Interleukin-10 ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; etiology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Warm Ischemia

OBJECTIVETo inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis (2-DE) map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome.

METHODSAmeroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome.

RESULTSThe preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDITOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 (NAD+) alpha, NADH dehydrogenase (NAD) Fe-S protein 1, chain A (crystal structure of aldose reductase by binding domain reveals a new Nadph), heat shock protein 27 (HSP27), oxidoreductase (NAD-binding protein), antioxidant protein isoform, cardiac troponin T (cTnT), myosin (myosin light polypeptide), cardiac alpha tropomyosin, apolipoprotein A-I and albumin.

CONCLUSIONDown-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker(s) for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine.

Animals ; Blood Coagulation Disorders ; complications ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; physiology ; Metabolic Diseases ; etiology ; metabolism ; Myocardial Ischemia ; complications ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism ; Proteomics ; methods ; Qi ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Swine ; Swine, Miniature ; Syndrome

Animals ; Blood Gas Analysis ; Brain Ischemia ; complications ; metabolism ; physiopathology ; Lung Injury ; etiology ; metabolism ; physiopathology ; Male ; Pyrazines ; pharmacology ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; metabolism ; physiopathology

PURPOSE: To evaluate the expression of the Na(+)-K(+)-2Cl(-)-cotransporter 2 (NKCC2) in the ischemic rat retina. METHODS: Retinal ischemia was induced by pressures 90 to 120 mmHg, above systemic systolic pressure. Immunohistochemistry and western blot analysis were performed. RESULTS: NKCC2 is expressed in the normal retina and its expression is increased by ischemia caused by intraocular pressure elevation. NKCC2 immunoreactivity was observed mainly in axon bundles of ganglion cells and horizontal cell processes in the retina. NKCC2 expression continuously increased with a peak value 3 days (to 415% of normal levels) after ischemic injury, and then gradually decreased to 314% of controls until 2 weeks post injury. The mean density of NKCC2-labeled ganglion cells per mm2 changed from 1,255 +/- 109 in normal retinas to 391 +/- 49 and 185 +/- 37 at 3 days and 2 weeks after ischemia, respectively (p < 0.05), implying cell death of ganglion cells labeled with NKCC2. CONCLUSIONS: Taken together, these results suggest that NKCC2, which is expressed in retinal ganglion and horizontal cells, may contribute to cell death by ischemic injury in the retina, although the molecular mechanisms involved remain to be clarified.
Animals ; Blotting, Western ; Disease Models, Animal ; Immunohistochemistry ; Intraocular Pressure ; Ischemia/etiology/*metabolism ; Male ; Microscopy, Confocal ; Ocular Hypertension/*complications/metabolism/physiopathology ; Rats ; Rats, Sprague-Dawley ; Retinal Diseases/etiology/*metabolism ; Retinal Ganglion Cells/*metabolism/pathology ; Sodium-Potassium-Chloride Symporters/*biosynthesis

AIMIn order to study the effects of pituitary adenylate cyclase activating polypeptide(PACAP) on brain edema induced by ischemia in rats and its underlying receptor mechanism.

METHODSBrain ischemia model in rats was established by ligaturing four--vessels. The percentage ratio of wet over dry tissue weight, sodium and potassium contents of dry brain tissue were measured by weighing and enzymatic analysis methods.

RESULTSThe brain water contents significantly increased after rats exposed to 1 h of reperfusion following 30 - minute ischemia. Furthermore, sodium contents in brain tissue increased and potassium contents decreased following perfusion. Changes of brain water contents, sodium and potassium contents were relieved by lateral ventricular injection of PACAP in the concentration of 1 x 10(-9), 1 x 10(-10) or 1 x 10(-11) mol respectively before ischemia. The effect of PACAP could be blocked by MCAP6 - 38 (specific type I PACAP receptor antagonist) lateral ventricular injection prior to PACAP administration.

CONCLUSIONExogenous PACAP may act as a protective effect in brain edema induced by ischemia in rats, which is mediated by type I receptor.

Animals ; Brain ; metabolism ; physiopathology ; Brain Edema ; etiology ; metabolism ; prevention & control ; Brain Ischemia ; complications ; metabolism ; Male ; Neuropeptides ; metabolism ; Pituitary Adenylate Cyclase-Activating Polypeptide ; pharmacology ; Potassium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium ; metabolism

OBJECTIVETo investigate the protective effect of progesterone against high intraocular pressure-induced ischemia-reperfusion (IR) injury.

METHODSTwenty-four SD rats were randomly divided into normal control, IR model, dimethyl sulfoxide (DMSO) solvent treatment group, and progesterone treatment group. In the latter 3 groups, retinal IR injury was induced by intraocular injection of saline. In the progesterone group, intraperitoneal injections of 4 mg/kg progesterone were administered 30 min before and 2 h after ischemia, and an equivalent volume of DMSO was used in the DMSO group. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured by spectrophotometer after the treatment, and the pathological changes of the retina were observed by transmission electron microscope and light microscope.

RESULTSSix hours after reperfusion, the content of MDA in the model group was significantly higher than that in the normal control group (P<0.01), but lower than that in progesterone treatment group (P<0.01); reverse changes in SOD activity was observed. In the model group, the inner nuclear layer and nerve fiber layer became thinner with obvious cellular pathologies including nuclear condensation, mitochondria vacuolization and endocytoplasmic reticulum swelling. Progesterone treatment markedly alleviated these pathologies in the inner nuclear layer and nerve fiber layer of the retina.

CONCLUSIONProgesterone offers protection of the retina against IR injury in SD rats by increasing SOD activity and decreasing MDA content in the retina.

Animals ; Dimethyl Sulfoxide ; Female ; Ischemia ; etiology ; pathology ; Male ; Malondialdehyde ; metabolism ; Ocular Hypertension ; complications ; Progesterone ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; prevention & control ; Retina ; metabolism ; Retinal Vessels ; physiopathology ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the effects of Xuezhikang and simvastatin on cerebral ischemia/reperfusion injury in rat, as well as the influences after intervention with L-NAME.

METHODRats were given orally with Xuezhikang and simvastatin or vehicle for 2 weeks, and then subjected to middle cerebral artery occlusion for 120 min using intraluminal filament model. L-NAME were injected into the lateral ventricles in half of the rats treated with Xuezhikang and simvastatin 45 min before the ischemia. The neurological deficits examinations were performed at 2, 24, 48 h after reperfusion. After the last examination the animals were sacrificed, the infarct volumes were determined by TTC staining, and MDA levels were also measured.

RESULTXuezhikang and simvastatin both significantly reduced the infarct volume and improved the functional recovery when compared to vehicle. Xuezhikang and simvastatin both significantly decreased the MDA accumulation after reperfusion. L-NAME partially inhibited the protective effect of Xuezhikang but nearly completely abolished the protective effect of simvastatin.

CONCLUSIONXuezhikang has protective effects on ischemic brain damage in rats, which the beneficial effects are partly due to the statins components. The other components in Xuezhikang may also account for the neuroprotective effects, which is worth further investigations.

Animals ; Brain ; pathology ; Brain Ischemia ; etiology ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Infarction, Middle Cerebral Artery ; complications ; Male ; Malondialdehyde ; metabolism ; NG-Nitroarginine Methyl Ester ; pharmacology ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; metabolism ; pathology ; Simvastatin ; pharmacology