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

Abdominal aorta constriction was performed in 10-week-old Lewis rats (Aoband). Ten weeks later the hearts were isolated and attached to a non-recirculating perfusion apparatus. The hearts could eject against a diastolic aortic pressure of either 60 or 100 mmHg. The functional recovery was compared with that of hearts of sham-operated (Sham) rats. After 45 min of global ischemia, Sham hearts regained cardiac output up to 75% and 70% of the pre-ischemic levels at 60 and 100 mmHg, respectively. At 60 mmHg Aoband hearts showed a minor recovery of ejection function. However, at 100 mmHg the recovery of Aoband hearts was completely comparable with that of Sham hearts. At 60 mmHg but not at 100 mmHg, the pre-ischemic and post-ischemic coronary flow was lower in Aoband than in Sham hearts (P less than or equal to 0.05). During the initial reperfusion phase Sham hearts, perfused at 60 mmHg, released more degradation products of adenine nucleotides and lactate dehydrogenase (LDH) than Aoband hearts (P less than or equal to 0.05), while the Aoband hearts lost more degradation products and LDH than the Sham hearts later during the reperfusion phase (P less than or equal to 0.05). In the groups perfused at 60 mmHg, higher tissue levels of ATP were found in Sham than in Aoband hearts at the end of the reperfusion period (P less than or equal to 0.05). However, at 100 mmHg comparable levels were found in the Sham and Aoband hearts. It is concluded that the height of the coronary perfusion pressure is of critical importance for the post-ischemic functional recovery of the compensated hypertrophied heart. At sufficiently high perfusion pressure levels, the functional and biochemical recovery of the hypertrophied heart is at least as good as in the non-hypertrophied heart. However, in the hypertrophied heart a coronary perfusion pressure which is too low leads to relative underperfusion during the initial reperfusion period which is associated with severely depressed cardiac performance and delayed wash-out of metabolites and intracellular enzymes.
 ...
PMID:The effects of global ischemia and reperfusion on compensated hypertrophied rat hearts. 215 Sep 72

Reduction of extracellular pH from 7.4 to 6.5 attenuated glutamate neurotoxicity in murine cortical neuronal and glial cultures, but if maintained for 24 h, resulted in morphological evidence of selective glial injury. Acid-induced gliotoxicity was examined quantitatively in cortical astrocyte cultures, using lactate dehydrogenase efflux as an index of cell damage. An exposure time of 9 h to pH 6.4 was sufficient to destroy about one third of the glia, whether or not 25 mM lactate was present. Furthermore, such acidosis increased the vulnerability of glia to injury by combined oxygen and glucose deprivation. These observations support the suggestion that the acidosis which accompanies ischemia in vivo may contribute to glial injury.
 ...
PMID:Selective vulnerability of cultured cortical glia to injury by extracellular acidosis. 217 14

The alterations of several small-intestinal mucosal enzymes have been examined in cats that underwent different periods (1-4 hr) of occlusion of the superior mesenteric artery, followed by 4 hr of reperfusion. The damage progressed during ischemia and reperfusion from the villus tips to the crypts: first, there was a rapid decrease in the activity of maltase, a brush-border enzyme; a slower decline occurred in two cytoplasmic enzymes, aldolase A (with preferential location in feline villus cells) and lactate dehydrogenase (with an ubiquitous distribution); a lag preceded the decrease in aldolase B (a cytoplasmic enzyme shown to occur mainly in feline crypt cells). For all these enzymes, the initial period of reperfusion was associated with a greater decrease in enzyme activity than persisting ischemia. By determination of the unsedimentable proportion of glutamate dehydrogenase (a mitochondrial matrix enzyme) and of acid phosphatase (a lysosomal enzyme) it was demonstrated that ischemia caused important mitochondrial damage before the cells were lost, whereas no lysosomal damage was observed in any condition. These sensitive parameters of cell damage can serve as a criterion for an adequate evaluation of potential cytoprotective agents.
 ...
PMID:Influences of ischemia and reperfusion on the feline small-intestinal mucosa. 219 34

Oxygen-derived free radicals have been implicated in causing degradation of myocardial membrane phospholipids associated with ischemia and reperfusion. Since iron is known to catalyze the hydroxyl radical formation responsible for cellular injury, this study was designed to relate the role of iron with phospholipid breakdown in ischemic-reperfused heart. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 30 min of reperfusion. The experimental group received 0.6 mM deferoxamine, an iron chelator, before reperfusion of ischemic myocardium. Deacylation and reacylation of membrane phospholipids were monitored by using [14C]arachidonic acid (AA), whereas the de novo phospholipid synthesis was evaluated by using [3H]glycerol in the perfusate. In the deferoxamine group, the loss of [14C]phosphatidylcholine (PC) and the corresponding accumulation of isotopic lysophosphoglycerides as well as AA was significantly lower compared with the control. The incorporation of radioactivity for [14C]AA and [3H]glycerol into phospholipids was significantly increased in the treated group compared with the untreated group. In addition, decreased malonaldehyde formation and lactate dehydrogenase release, a higher recovery of high-energy phosphate compounds, and myocardial contractility were noticed in the deferoxamine-treated hearts. These results indicated that postischemic administration of an iron chelator such as deferoxamine can preserve membrane phospholipids and reduce myocardial dysfunction associated with reperfusion of ischemic heart.
 ...
PMID:Role of iron on membrane phospholipid breakdown in ischemic-reperfused rat heart. 222 Nov 18

In normoxic hearts a limited number of multilamellar vesicles was found in both endothelial cells and myocytes. The total number of multilamellar vesicles observed in myocytes, particularly those extruded from mitochondria, significantly increased in hearts rendered ischemic for at least 60 mins. The number of multilamellar vesicles extruded from sarcolemma was increased in hearts reperfused after this period of ischemia. The number of multilamellar vesicles in or adjacent to lipid droplets was independent of the duration of ischemia. Multilamellar vesicles were similar in size and periodicity of the lamellae. It is proposed that the number of multilamellar vesicles can be used to quantitate ischemic membrane injury. The formation of multilamellar vesicles was significantly related in time to (a) the accumulation of arachidonic acid and total fatty acids; (b) a decrease in the tissue content of ATP and (c) the release of lactate dehydrogenase (LDH). No significant alterations in the total tissue content of triacylglycerols and phospholipids were detected. The amount of arachidonic acid accumulated in the hearts reflects the degradation of only a minor fraction of the phospholipid pool. Assuming a close relationship between phospholipid degradation, induction of multilamellar vesicles and loss of cellular integrity, the present findings might indicate that the loss of a small part of phospholipids might have serious pathophysiological consequences, as indicated by the morphological changes in cellular membranes and the release of cytoplasmic macromolecules.
 ...
PMID:Ischemia and reperfusion induced multilamellar vesicles in isolated rabbit hearts: time correlation between morphometric data and metabolic alterations. 223 35

Considerable evidence suggests that free radicals engendered by redox-active metals, particularly iron and copper, are causative agents in reperfusion injury following ischemia. This study demonstrates that perfusion of the isolated rat heart with a buffer containing zinc, a non-redox active metal similar to copper in its coordination chemistry, inhibits the development of ventricular arrhythmias during reperfusion. Zinc was employed as the bishistidine complex, Zn--His2, to maintain solubility and permeability. Zn--His2 exerted an antiarrhythmic activity as hearts spent a longer time in normal sinus rhythm and a shorter time in ventricular fibrillation during reperfusion following 10 min of regional ischemia. However, Zn--His2 also produced a negative inotropic and chronotropic effect, evident during equilibration and ischemia. In the course of experiments which began in Israel and continued in the U.S. it was necessary to use two different sources of rats. Hearts from the two sources manifested different sensitivities to the concentrations of Zn--His2, although their physiological effects were similar. Differential activity responses were noted for antiarrhythmic activity, negative inotropic and chronotropic properties, and toxicity. In both groups of untreated hearts the incidence of ventricular fibrillation after ischemia was 100%. Ventricular fibrillation was reduced to 17% at 37.5 microM Zn--His2 in the U.S.-bred rat hearts and to 9% at 200 microM Zn--His2 in those from Israel. These changes in Zn--His2 treated animals were accompanied by a decrease in lactate dehydrogenase release from the myocardium during reperfusion. None of the protective effects was due to histidine alone. These results indicate that zinc prevents ventricular arrhythmias during reperfusion following regional ischemia and may prevent membrane damage, possibly, by reduction of free radical formation.
 ...
PMID:The effect of zinc on reperfusion arrhythmias in the isolated perfused rat heart. 232 82

The influence of neutrophils on peritubular capillary permeability and intravascular red blood cell (RBC) aggregation after renal ischemia was studied in anesthetized Sprague-Dawley rats. Intraperitoneal administration of antineutrophil serum (ANS) reduced the number of neutrophils in the blood to 3% of normal. The control group received an equal volume of inactive serum. Renal macromolecular capillary permeability was studied from 1) extravasation of albumin and 2) plasma to lymph transport of plasma proteins and of neutral and negatively charged lactate dehydrogenase (LDH). The net driving force (NDF) for fluid transfer over the peritubular capillary membrane was determined by the micropuncture technique. The intrarenal distributions of neutrophils and RBC were measured by a histochemical method and 51Cr-labeled RBC, respectively. Under preischemic control conditions neither macromolecular permeability nor renal clearance of inulin was affected by ANS. However, the steep increase in the macromolecular transport from plasma to lymph resulting from 45 min of ischemia and reperfusion was blunted by ANS, and preischemic control values were restored after 1 h of recirculation. In the control group the mass transport of plasma proteins increased twofold and that of both neutral and negatively charged LDH fourfold. NDF was equal in the two groups. In the ANS-treated animals the intrarenal neutrophil content was only 2% of the control. Neutrophils were found mainly in the cortex, whereas RBC aggregation was observed only in the renal medulla. It is concluded that neutrophils mediate postischemic capillary leakage. It is suggested that this leakage underlies RBC aggregation and incomplete return of blood flow in the renal medulla after ischemia.
 ...
PMID:Peritubular capillary permeability and intravascular RBC aggregation after ischemia: effects of neutrophils. 233 Sep 69

A comparison was made of the anti-ischemic effects of dihydropyridine calcium antagonists in isolated globally ischemic rat hearts. Pretreatment with amlodipine, nifedipine, nitredipine, or nisoldipine reduced reperfusion enzyme (lactate dehydrogenase) release and contracture after 25 min of global ischemia and 30 min of reperfusion. Increasing concentrations of all compounds resulted in proportionally smaller reductions in the severity of ischemia, with larger decreases in nonischemic tissue contractility occurring. Reperfusion function was significantly improved at 30 min with nifedipine only; however, at 60 min reperfusion function was significantly improved for all except nisoldipine. Washout data from nonischemic hearts (rate of disappearance of cardiodepressant effects) showed that the dihydropyridines washed out in the following order (fastest to slowest): nifedipine greater than nitrendipine greater than nisoldipine greater than amlodipine. Thus, these dihydropyridines are anti-ischemic, though at higher concentrations cardiodepressant effects increase disproportionately. Differences in washout also effect the ability of these compounds to improve reperfusion function.
 ...
PMID:Comparative anti-ischemic effects of dihydropyridine calcium antagonists in isolated perfused rat hearts: relationship of cardiodepression and cardioprotection. 233 20

We examined the effects of two degrees of hypothermia on hepatic oxygen delivery and uptake, hepatic lactate uptake as a marker of hepatic function, and the effect of hypothermia on ischemia-reperfusion injury in the liver in miniature pigs (n = 18, 21-30 kg body wt). Hepatic arterial and portal venous blood flows were measured while hepatic oxygen delivery was progressively decreased without venous congestion in the preportal area. With decreases in hepatic blood and oxygen supply, oxygen extraction gradually increased from 50 to 90% in the normothermic group and from 25 to 70 and 84% in the hypothermic (30. and 34 degrees C, respectively) groups. The values of critical hepatic oxygen delivery were between 7.3 and 11.9 ml O2.min-1.100 g-1 without significant differences among the groups. During reperfusion after ischemic insult, hepatic oxygen uptake returned to base-line values in both hypothermic groups but remained substantially below base-line values in normothermic groups of animals. Hepatic enzyme concentrations (lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and alcohol dehydrogenase) were substantially increased (up to 30-fold) in normothermic animals, but the concentrations did not increase in either of the hypothermic groups. These results demonstrated that hypothermia per se does not affect hepatic oxygen delivery but decreases hepatic oxygen demand and uptake, provides an effective protection from hepatic oxygen deprivation, and lessens reperfusion injury.
 ...
PMID:Hypothermia, hepatic oxygen supply-demand, and ischemia-reperfusion injury in pigs. 236 Jun 37

Innate biochemical responses of rabbit renal proximal convoluted (PCT) and straight (PST) segments following in vitro exposure to anoxia or hypoxia were investigated to delineate the mechanisms responsible for segment-selective injury in vivo. After bulk isolation, suspensions (1 mg/ml) enriched in either PCT or PST were preincubated in Dulbecco's modified Eagle's-Ham's F-12 medium for 1 h before being exposed to either 40 min of anoxia (N2) or 120 min of hypoxia (1% O2) and 1 h of recovery under air-CO2 conditions. After recovery from anoxia, the percent of control values for each viability indicator in PCT and PST, respectively, were as follows: O2 consumption (QO2), 30/50; ATP content, 22/49; K+ content, 60/70; and percent lactate dehydrogenase (LDH) release, 66/45. Likewise, following recovery from hypoxia, the percent of control values for PCT and PST, respectively, were as follows: QO2, 50/90; ATP, 16/57; K+, 52/79; LDH, 45/17. These differential responses indicate that PCT segments were innately more susceptible to anoxic and hypoxic injury than PST segments. Because ATP content was significantly higher in PST segments immediately after anoxia and hypoxia, we investigated glucose-dependent responses during anoxia by exposing these segments to 30 min of anoxia in nutrient buffer with or without glucose. Results from these experiments demonstrate that the PST protection from anoxia was glucose dependent because removal of glucose from the nutrient buffers during anoxia abolishes the differential responses between PCT and PST. The in vitro PCT sensitivity observed here contrasts with the PST sensitivity observed following in vivo ischemia, suggesting that hemodynamic factors present in vivo may ultimately determine the overall susceptibility of PST segments in situ.
 ...
PMID:Bulk isolation of renal PCT and PST. II. Differential responses to anoxia or hypoxia. 237 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>