Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue subjected to a period of ischemia undergoes functional and morphological damage that increases during the reperfusion phase. In this study, the protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit unilateral renal ischemia-reperfusion (I/R) model. New Zealand rabbits, weighing 1.5-2 kg, were randomized to receive either aprotinin 30.000 KIU x kg(-1) and 10.000 KIU x kg(-1) x h(-1) i.v. infusion (group I, n= 7) or equivalent volumes of 0.09% sodium chloride (SF) (group II, control, n= 7) i.v. 15 minutes before a 45 minutes interruption of left renal artery blood flow and then 45 minutes of reperfusion. Blood samples were obtained before and after the ischemia-reperfusion period for measurement of nitric oxide serum (NO) levels with the nitrite/nitrate colorimetric method. Histological changes were evaluated by quantitative measurements using a numerical score (0-4) and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) expression was determined. A Wilcoxon W -test was used for statistical analysis of biochemical measurements and mean values were expressed as +/-sd. Histological examination revealed the distinctive pattern of ischemic renal tissue injury with obvious signs of epithelial necrosis. The intensity of epithelial necrosis was more extensive in the SF group. Immunohistochemical analysis showed that there was severe immunostaining in the tubular epithelium in both cortical and medullary regions and iNOS expression was more intense in SF-only cases. The staining results for aprotinin cases did not differ much from the non-ischemic kidney. Biochemical analysis revealed an increase in serum NO levels in both groups (P< 0.05), but this was more evident in the SF group (mean NO levels were 38.63 +/- 19.03 micromol x L(-1) in group I, 50.63 +/- 24.28 micromol x L(-1) in group II). No statistically important difference was observed between the two groups. These results suggest that aprotinin may be beneficial in the prevention of systemic inflammation after transient renal ischemia.
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PMID:The effect of aprotinin on ischemia-reperfusion injury in the rabbit kidney. 1173 50

We tested the hypothesis that transtentorial herniation (TTH) represents a state of cerebral ischemia that can be reversed by hypertonic saline. Because of the high mortality associated with TTH, new therapeutic strategies need to be developed for rapid and effective reversal of this process. We produced TTH (defined by acute dilatation of one or both pupils) by creating supratentorial intracerebral hemorrhage with autologous blood injection in seven mongrel dogs anesthetized using intravenous pentobarbital and fentanyl. We measured serial rCBF (regional cerebral blood flow) using radiolabeled microspheres in regions around and distant to the hematoma. Cerebral oxygen extraction and oxygen consumption (CMRO2) were measured by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were continuously monitored. TTH was successfully reversed over a mean period of 25.7 +/- 4.9 minutes after intravenous administration of 23.4% sodium chloride (1.4 mL/kg) in all animals. All measurements were recorded 15, 30, 60, and 90 minutes after administration of 23.4% sodium chloride. Compared to prehematoma ICP (14.1 +/- 1.7 mm Hg, mean +/- SE), elevation in ICP was observed during TTH (36.2 +/- 7.2 mm Hg) with no change in cerebral perfusion pressure (CPP) (80.4 +/- 4.7 vs. 76.7 +/- 10.1 mm Hg) because of concomitant elevation in mean arterial pressure. Compared to baseline values, there was a reduction in rCBF (mL/100 gm/min +/- SE) in brainstem (12.1 +/- 2.0 vs. 21.4 +/- 1.4), gray matter (18.2 +/- 2.1 vs. 31.4 +/- 1.8), and white matter (8.6 +/- 1.7 vs.18.7 +/- 0.9) in the hemisphere contralateral to the hematoma; and gray matter (12.9 +/- 2.9 vs. 27.9 +/- 2.2) and white matter (8.3 +/- 2.0 vs.19.9 +/- 1.0) in the ipsilateral hemisphere distant from the hematoma. Administration of 23.4% sodium chloride resulted in reduced ICP at 15 minutes (12.7 +/- 1.4) and 30 minutes (15.6 +/- 3.1) after administration. RCBF values were restored in all regions studied after administration of 23.4% sodium chloride with an increase in CMRO2 (1.8 +/- 0.4 vs. 3.9 +/- 0.7 mL O2 /100 gm/min). Compared with baseline values, rCBF increased in the ipsilateral (31.7 +/- 2.5 vs. 63.4 +/- 11.7) and contralateral (28.7 +/- 1.9 vs. 45.5 +/- 5.7) thalamus at 15 minutes after administration of 23.4% sodium chloride. TTH represented a state of ischemia in brainstem and supratentorial gray and white matter in the presence of adequate CPP, suggesting mechanical compression of vessels at the level of tentorium. Hypertonic saline reversed TTH, and restored both rCBF and CMRO2, although hyperemia was observed immediately after reversal of TTH. Administration of hypertonic saline may preserve neurologic function during the interim period between TTH and surgical intervention.
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PMID:Treatment of transtentorial herniation unresponsive to hyperventilation using hypertonic saline in dogs: effect on cerebral blood flow and metabolism. 1177 19

A possible mechanism for D-cis-diltiazem (diltiazem)-mediated improvement of the contractile function of ischemic/reperfused hearts was examined. Thirty-five-min ischemia/60-min reperfusion recovered little the left ventricular developed pressure (LVDP) and decreased myocardial high-energy phosphates (HEPs). Ischemia induced an accumulation of tissue Na+ content, an increase in cytochrome c in the cytosolic fraction, and a decrease in the oxygen consumption rate (OCR) in perfused hearts. Treatment of the heart with 1 microM diltiazem for the last 3-min of pre-ischemia did not affect the decrease in HEPs during ischemia, whereas that with 3 microM partially attenuated the decrease in ATP, suggesting that 3 microM diltiazem exerted energy-sparing effect. Treatment with 1 microM diltiazem enhanced the post-ischemic recovery of LVDP associated with attenuation of the ischemia-induced accumulation of tissue Na+, increase in cytochrome c in the cytosolic fraction, and decrease in myocardial OCR, and restoration of the myocardial HEPs during reperfusion. Combined treatment with diltiazem and a Na+/H+ exchange inhibitor, but not a Na+ channel blocker, facilitated the attenuation of Na+ accumulation in the ischemic heart and the enhancement of the post-ischemic recovery of LVDP. Sodium lactate, a possible metabolite in ischemic hearts, and sodium chloride increased the Na+ concentration in mitochondria, released cytochrome c into incubation medium, and reduced the mitochondrial respiration. Treatment of isolated mitochondria with diltiazem failed to attenuate the sodium lactate- and sodium chloride-induced alterations. These results suggest that the cardioprotection of diltiazem may be exerted via attenuating cytosolic Na+ overload through Na+ channels in the ischemic heart, leading to preservation of mitochondrial functional ability during ischemia, followed by improvement of post-ischemic energy production and contractile recovery.
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PMID:Preservation of mitochondrial function during ischemia as a possible mechanism for cardioprotection of diltiazem against ischemia/reperfusion injury. 1503 8

Paraplegia, which develops after operation on aorta, represents a real catastrophe for the patient and for the surgeon. The aim of the present work was to investigate the light microscopy picture of this complication and consequently better understand related processes. Twenty one adult dogs, cross breeds of both sexes, weight 18-25 kg, were divided into four groups: 1. Controls (n = 3); 2.30-min ischemia induced by occlusion of thoracic aorta by a tourniquet, followed for 30 min survival (n = 6); 3.30-min ischemia and 72 h of survival (n = 6); 4) 30-min ischemia and 6 days of survival (n = 6). All these manipulations were made in sterile conditions under general anesthesia. As soon as the planned time of survival passed, the animals were flushed out, in deep pentobarbital anesthesia, with 3,000 ml of sodium chloride and fixed with 3,000 ml of 10% neutral formaldehyde. Sections, 30 microns thick, from L3-S1 medulla segments were processed in the laboratory of Neurobiological Institute by the method of Nauta for light microscopy examination. Neurohistological picture was characterized by a marked damage of the medulla neurons. The changes proved to be irreversible and resulted, in the course of six days of survival, to death of the cells, characterized by their disintegration. The results indicate that the only rational procedure in conditions of threatening ischemic-reperfusion injury of medulla is to prevent it.
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PMID:[Ischemic-reperfusion paraplegia in the dog and its light microscopy imaging]. 1508 24

Selective Kupffer cell blockade by gadolinium chloride (GdCl(3)) pretreatment of liver donors previously proved to be effective in reducing ischemia/reperfusion injury in rat liver transplants. Physiological mechanisms of this effect have not been specified so far. Vasoactive peptides are involved in liver blood flow regulation. We tested the hypothesis, that hepatic hemodynamic effects of GdCl(3) pretreatment are mediated by intrahepatic endothelin-1 (ET) secretion in a standardized porcine model of warm liver ischemia and reperfusion. Standardized warm hepatic ischemia (45 min) was induced after laparotomy in intubation narcoses (ITN) by Pringle-maneuver in pigs (n = 12). Animals were either pretreated with GdCl(3) (20 mg/kg i.v.) or sodium chloride 0.9% (control group) in a randomized manner 24 h before investigation. Relaparotomy was performed at day 7. Before, during ischemia and until 6 h after liver reperfusion, transhepatic blood flow (portal venous + hepatic artery flow) was defined by ultrasonic flow probes and hepatic parenchymous microcirculation evaluated by implanted thermodiffusion electrodes. ET plasma concentrations were analyzed (commercial RIA) at all time points in the hepatic veins after selective canulation. GdCl(3) pretreatment of animals markedly improved hepatic macro- and microperfusion before and particularly after warm ischemia. Mean ET plasma concentrations in the hepatic vein were significantly lower before, 6 h and 7 days after ischemia, compared with controls. Kupffer cell destruction by GdCl(3) pretreatment improves hepatic micro- and macroperfusion after warm ischemia, thus indicating reduced ischemia/reperfusion injury. Documented reduction of postischemic liver blood flow impairment after GdCl(3) pretreatment could be mediated by a decreased hepatic ET secretion, as hemodynamic effects were associated with significantly reduced ET plasma levels in hepatic veins.
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PMID:Gadolinium chloride-induced improvement of postischemic hepatic perfusion after warm ischemia is associated with reduced hepatic endothelin secretion. 1577 63

Neonatal rat hearts are more tolerant to ischemia compared to adult rat hearts. We hypothesized that opioid receptors and mitochondrial potassium channels are involved in the elevated ischemia tolerance of neonatal rats. Newborn rats were treated by an intraperitoneal injection with sodium chloride (placebo, Pla; n = 7), naloxone (Nal; n = 8), or K+ (ATP) channel blocker 5-hydroxydecanoate (HD; n = 8), or were left untreated (sham; n = 8). Thirty minutes after injection, the rats were sacrificed and hearts were arrested cardioplegically and fixed with aldehyde fixative 90 min after global ischemia at room temperature. For control, newborn rat hearts were fixed immediately after sacrifice. Ventricular tissue blocks were prepared for electron microscopy. Mitochondrial (volume-weighted mean volume of mitochondria) and cardiomyocyte volume (cellular edema index, CEI) were estimated to quantify the ischemic injury. Compared to control myocardium, CEI was increased by 244% +/- 39% in sham, 173% +/- 28% in Nal, 142% +/- 25% in HD, and 101% +/- 24% in Pla (P < 0.05 between groups). Volume-weighted mean volume of mitochondria was increased by 514% +/- 235% in sham, 341% +/- 110% in Nal, 458% +/- 149% in HD, and 175% +/- 70% in Pla. Differences between Pla and other groups were significant (P < 0.01 for all). No significant difference was observed between the other groups. Thus, ischemic injury was smallest with placebo, indicating a mechanism similar to preconditioning induced by the intraperitoneal injection. This response was attenuated by blockade of opioid receptors and mitochondrial potassium channels, suggesting their involvement in the elevated ischemia tolerance of newborn rat hearts.
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PMID:Myocardial ischemia tolerance in the newborn rat involving opioid receptors and mitochondrial K+ channels. 1645 73

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.
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PMID:Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke. 1687 31

Myocardial ischemia-reperfusion, including cardioplegic arrest (CA), has been associated with cardiac apoptosis induction. However, the time course of apoptosis activation and the trigger mechanisms are still unclear. Because apoptosis inhibition may represent a novel therapeutic strategy for long-term myocardial preservation, we sought to investigate the time course of apoptosis signal-pathway induction during CA. As to method, Sprague-Dawley rats (300-350 g) were anesthetized, intubated, and mechanically ventilated. CA was initiated by infusion of ice-cold crystalloid solution (Custodiol, 10 ml/kg) into the aortic root, and hearts were rapidly excised and stored for 0, 30, 60, and 120 min in 0.9% sodium chloride solution (28 degrees C). In controls, no CA was initiated before removal and storage at 28 degrees C. In another group, calcium-rich cardioplegia was used, and an additional group received a caspase-8 inhibitor before CA induction. Left ventricular cytosolic extracts were isolated and investigated for the activity of caspase-3 and -6 (effector caspases) and caspase-8 and -9 (involved in extrinsic and intrinsic pathways of apoptosis induction). Fluorometric activity assays were performed by using specific substrates. As a result, activities of all tested caspases were significantly increased immediately after CA induction compared with controls. Administration of the caspase-8 inhibitor significantly reduced activities of all caspases. With calcium-rich cardioplegia, caspase activities were significantly lower compared with low-calcium CA. Control hearts also showed an increase of caspase activities during cold-storage ischemia without CA but had significantly different time courses compared with hearts with CA. In conclusion, our data show rapid apoptosis signal-pathway induction immediately following CA exposure. Thus apoptosis signal-pathway inhibition as a potential strategy for improved myocardial preservation would have the greatest effect when applied before CA exposure.
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PMID:Induction of cardioplegic arrest immediately activates the myocardial apoptosis signal pathway. 1708 43

The present study was performed to assess the prophylactic effect of platonin, a cyanine photosensitizing dye and an inhibitor of proinflammatory cytokines, in an animal model of heatstroke. Anesthetized rats were immediately divided into 2 major groups after the start of heat stress and administered either isotonic sodium chloride solution (dose, 1 mL/kg of body weight i.v.) or platonin (dose, 12.5-50 microg/mL per kilogram of body weight i.v.). They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the isotonic sodium chloride solution-pretreated rats underwent heat stress, their survival time values were found to be from 20 to 24 min. Pretreatment with intravenous doses of platonin (12.5-50 microg/mL per kilogram of body weight) immediately after the start of heat exposure significantly improved survival time during heatstroke (duration, 63-185 min). As compared with normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of creatinine, serum urea nitrogen, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time and D-dimer in the plasma, cellular ischemia and injury markers in striatum, and intracranial pressure. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, brain Po2, and platelet count and protein C in the plasma. Immediately after the start of heat exposure, the previous administration of platonin significantly improved survival time by reducing the systemic inflammation, hypercoagulable state, and tissue ischemia and damage during heatstroke. The results demonstrate that platonin is effective for attenuation of heatstroke reactions.
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PMID:Platonin, a cyanine photosensitizing dye, is effective for attenuation of heatstroke in rats. 1711 36

Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. The present study was designed as a prospective and controlled laboratory experiment to assess the effects of continuous TEA on the mucosal microcirculation in a cecal ligation and perforation model of sepsis in rats. Anesthetized Sprague-Dawley rats underwent laparotomy and cecal ligation and perforation to induce sepsis. Subsequently, either bupivacaine 0.125% (n = 10) or isotonic sodium chloride solution (n = 9) was continuously infused via the thoracic epidural catheter for 24 h. In addition, a sham laparotomy was carried out in eight animals. Intravital videomicroscopy was then performed on six to ten villi of ileum mucosa. The capillary density was measured as areas encircled by perfused capillaries, that is, intercapillary areas. The TEA accomplished recruitment of microcirculatory units in the intestinal mucosa by decreasing total intercapillary areas (1,317 +/- 403 vs. 1,001 +/- 236 microm2) and continuously perfused intercapillary areas (1,937 +/- 512 vs. 1,311 +/- 678 microm2, each P < 0.05). Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.
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PMID:Continuous thoracic epidural anesthesia improves gut mucosal microcirculation in rats with sepsis. 1758 85


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