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)

Whole excis ed rat hearts were treated with 5, 10, or 15% (v/v) dimethyl sulfoxide/glycerol and then some were frozen in liquid nitrogen while the balance remained unfrozen. Freezing and thawing rates were approximately 30degreesC/min. Ventricular tissue was examined for histological damage, glycogen depletion, and enzyme sites, using histological, histochemical, and electron microscopy techniques. Early signs of cellular degeneration and ischemia were observed in all unfrozen groups; depletion of glycogen reserves, fuchsinophilic staining, vacuolization and granulation of the sarcoplasm were noted. Results from frozen groups were similar, but ultrastructural damage was more severe and extensive. Alkaline phosphatase and succinic dehydrogenase sites were abundant in unfrozen specimens and absent or markedly reduced in frozen specimens which also exhibited widespread nonspecific staining throughout intercellular spaces.
 ...
PMID:Cryoprotectant-treated myocardium evaluation. 6 Nov 4

Pieces of liver (in vitro ischemia) and isolated microsomes were subjected to incubation at 4 degrees C and 37 degrees C for various time intervals. The effects on microsomal protein, phospholipids, and cholesterol and on microsomal phosphatases and electron transport enzymes were followed as a functional of time and temperature. NADH-cytochrome c reductase was very labile and was completely inactivated by 1 h, whereas G6Pase lost 50% of its activity after 2 h at 37 degrees C. IDPase and NADPH-cyt. c red. were of intermediate susceptibility whereas cytochromes b5 and P-450 were the most stable enzymes assayed. After 24 h of incubation of isolated microsomes at 37 degrees C there was no significant detachment of membrane components (protein, PLP or cholesterol), indicating that the inactivation of the enzymes was not primarily attributable to their solubilization. Instead, experiments with 14C-leucine and 14C-glycerol prelabeled microsomes demonstrated that the proteins detached from microsomes during incubation originated mainly from the intravesicular space due to repture of the microsomal membranes. The addition of a lysosomal extract during incubation did not alter either the rate of inactivation of the enzymes or the proportion of solubilized membrane components indicating that attack from the outside by proteolytic enzymes is not the mechanism for enzyme inactivation. There was no apparent correlation between the rates of inactivation of enzymes in vitro and their calculated half-lives in vivo or their postulated intramembranous localization. Ultrastructurally, enzyme inactivation was initially associated with alterations of the microsomal membranes, such as vesicle aggregation, membrane rupture, loss of unit membrane structure, and subsequently, thickening of membranes and transformation of the microsomes into nonrecognizable amorphous material.
 ...
PMID:Effect of storage and in vitro ischemia on the ultrasture of microsomal membranes and on microsomal enzymes. 18 24

The effect of repeated local ischemia and reperfusion on myocardial metabolism and ventricular performance was studied in 12 open-chested pigs fasted overnight. Myocardial ischemia was induced by reduction of the flow in the left anterior descending coronary artery to 40% of control during 30 min. After 35 min of reperfusion a second 30-min occlusion period was started, again followed by a 35-min reperfusion period. At the end of both reperfusion periods coronary flow and coronary resistance had returned to control values. During control there was lactate uptake, but no significant uptake of glucose, free fatty acids (FFA), triglycerdies, glycerol and inosine. During the first occlusion period the heart released lactate and inosine, and used glucose and FFA. At the end of the first reperfusion period lactate uptake approached control values, but inosine was still released by 10 of the 12 animals. In the second ischemic period, glucose and FFA were again taken up. Lactate and inosine were released, but the production was much smaller than during the first occlusion period. Depletion of myocardial glycogen and high-energy phosphates could be responsible for this quantitatively different response. Necrosis may have played a role, although enzyme release was minimal and only observed after the second occlusion period. Heart rate, peripheral resistance and ventricular filling pressure were virtually unchanged throughout the course of the experiments. Maximum rate of fall of left ventricular pressure (min LVdP/dt) decreased during ischemia and did not recover during reperfusion. Changes in min LVdP/dt and cardiac output were more closely related than changes in max LVdP/dt and cardiac output. This model cannot be used for the study of interventions during myocardial ischemia in which the animal serves as its own control.
 ...
PMID:Myocardial substrate utilization and hemodynamics following repeated coronary flow reduction in pigs. 52 55

The effects of whole heart ischemia on fatty acid metabolism were studied in the isolated, perfused rat heart. A reduction in coronary flow and oxygen consumption resulted in lower rates of palmitate uptake and oxidation to CO2. This decrease in metabolic rate was associated with increased tissue levels of long chain acyl coenzyme A and long chain acylcarnitine. Cellular levels of acetyl-CoA, acetylcarnitine, free CoA, and free carnitine decreased. These changes in CoA and its acyl derivatives indicate that beta oxidation became the limiting step in fatty acid metabolism. The rate of beta oxidation was probably limited by high levels of NADH and FADH2 secondary to a reduced supply of oxygen. Tissue levels of neutral lipids showed a slight increase durning ischemia, but incorporation of [U-14C]palmitate into lipid was not altered significantly. Although both substrates for lipid synthesis were present in higher concentrations during ischemia, compartmentalization of long chain acyl-CoA in the mitochondrial matrix and alpha-glycerol phosphate in the cytosol may have accounted for the relatively low rate of lipid synthesis.
 ...
PMID:Control of fatty acid metabolism in ischemic and hypoxic hearts. 65 17

With corticosteroids and diuretics, glycerol treatment may be an effective therapy of early edema accompanying focal brain ischemia. The suggested regimen for intravenous infusion is 500 ml of 10% glycerol solution during at least 2 h, twice a day, starting as soon as possible after stroke onset and continuing thereafter for 5--7 days.
 ...
PMID:Therapy of ischemic brain edema. 75 28

The measurement of lactate dehydrogenase (LDH) release into perfusates after hypothermic storage was found to be a reliable index of ischemic injury of rabbit kidneys. Kidneys were exposed to warm and cold ischemia for varying periods. Each kidney was perfused before and after storage at simple hypothermia with 25 ml of a modified Collins solution. The venous effuent was collected in 5 ml fractions. Total LDH activity was measured in the first fraction after storage and used as a measure of ischemic tissue damage. It was confirmed that increasing the period of cold ischemia result in significant increases in LDH activity. The release of LDH into perfusates was then used to compare kidney damage after preservation with various fluids. With this method, it was not possible to demonstrate any difference in the extent of tissue damage after preservation with sodium-rich vs. potassium-rich perfusion fluid. Addition of steroids, vitamins and essential amino acids did not prevent or reduce tissue damage, estimated in this way. The effects of adding cryoprotectants to the perfusion fluid varied; LDH release following addition of 5% DMSO was significantly greater, and after addition of 5% glycerol smaller than the release after perfusion with a modified Collins solution alone. Stepwise addition of DMSO up to 20% resulted in serious tissue damage with a large LDH release into the perfusate.
 ...
PMID:LDH release into perfusates of preserved kidneys. 78 32

Renal cortical blood flow of rats with postischemic, myohemoglobinuric, and mercury-induced acute renal failure was measured by the hydrogen washout technique using implanted platinum electrodes. Total renal blood flow was determined by venous cannulation in separate series of rats. The values obtained with the two methods were in excellent qualitative agreement (r=0.99, P less than 0.001), although venous cannulation gave values that were constantly lower than those calculated for whole kidney from the cortical flow rate and assumed cortical mass. Myohemoglobinuria produced by glycerol injection caused cortical blood flow to fall from a control value of 7.37+/-0.23 (SEM) ml/min X g of cortex to approximately one-half that value for four hours after injection (P less than 0.001). Flow rates 12 and 24 hr after glycerol injection were 85% (P less than 0.001) and 90% (P less than 0.05) of control, respectively. Cortical flow was reduced to 5.49+/-0.39 (SEM) ml/min X g of cortex four hours after release of one hour's total bilateral renal arterial occlusion (P less than 0.001), but rose to normal within 24 hr. Poisoning with 4.7 mg/kg of body wt of mercuric chloride produced a cortical blood flow value that was 30% higher than control 24 hr after injection (P less than 0.01), while a 12 mg/kg of body wt dose gave a normal flow value. Inulin clearance was severely depressed in all models at all study times. Thus, in contrast to human acute renal failure, marked renal cortical ischemia is not an essential feature of these different forms of murine acute renal failure.
 ...
PMID:Normal renocortical blood flow in experimental acute renal failure. 85 3

It is commonly assumed that the decrease in the effective circulatory volume (ECV) is the major event in acute renal failure (ARF) and the preferential ischemia of the cortex another major modification. Frusemide has been given to try to prevent this change in glycerol-induced ARF because of its effect in redistributing renal blood flow from medulla to cortex. Isontonic saline was also tried to avoid the ECV depletion. The pretreatment with frusemide not only fails to protect against the ARF but increases its severity. Isotonic saline adminstration and replacement of urinary losses almost prevent glycerol-induced ARF but when both isotonic saline frusemide are administered together their effect is only a slight increase in the excretion rate of urea and creatinine during the first days of the experiment. The importance of the changes in the ECV or a possible direct action of frusemide on the renin-angiotensin axis are discussed. There is a good correlation between plasma creatinine levels and interstitial oedema. The importance of the oedema in the maintenance of ARF is discussed.
 ...
PMID:Negative effect of frusemide pretreatment in glycerol induced acute renal failure. 87 19

The effect of intravenous infusion of 10 per cent glycerol on regional cerebral blood flow (using hydrogen bolus and Xenon-133 (133Xe) clearance methods) and metabolism was investigated in 57 patients with recent cerebral infarction. Hemispheric blood flow (HBF) increased, together with increase in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV), in foci of brain ischemia. Hemispheric oxygen consumption (HMIO2) decreased together with hemispheric respiratory quotient. Systemic blood levels of glucose, lactate, pyruvate, and triglycerides also increased after glycerol while free fatty acids (FFA) and inorganic phosphate (Pi) decreased. Hemispheric glucose consumption was unaltered after glycerol so that hemispheric glucose to oxygen ratio tended to rise. Pyruvate and lactate production by brain was unchanged. Glycerol moved across the blood brain barrier into brain and cerebrospinal fluid (CSF). Release of FFA and Pi from infarcted brain was reversed by glycerol. Total phosphate balance was maintained actoss brain both before and after glycerol infusion. Triglycerides increased in CSF after glycerol, originating either from cerebral blood or as a result of lipogenesis in cerebral tissue. The EEG Recording and neurological status of the patients improved despite decreased brain oxygen consumption. Results of this study suggest that after intravenous infusion of 10 per cent glycerol in patients with recent cerebral infarction, glycerol rapidly enters the CSF and brain compartments and favorably affects the stroke process in two ways: first, by redistribution of cerebral blood flow with increase in rCBF and rCBV in ischemic brain secondary to reduction in focal cerebral edema; and second glycerol may become an alternative source of energy either by being directly metabolized by the brain, or indirectly, by enhancing lipogenesis, or by both processes. Involvement of glycerol in lipogenesis with esterification to accumulated FFA might lead to improved coupling of oxidative phosphorylation, a hypothesis that fits the finding of improved neuronal function despite further decrease in cerebral hemispheric oxygen consumption.
 ...
PMID:Circulatory and metabolic effects of glycerol infusion in patients with recent cerebral infarction. 109 Mar 93

Metabolic and morphologic changes occurred in the kidneys of rats within 3 hours after inciting acute tubular necrosis by completely clamping the renal blood supply, by intramuscular injections of glycerol, and by subcutaneous injections of HgC12. Although the initial trend was for p-aminohippurate and tetraethylammonium transport to decrease and for oxygen consumption, ammonia production, and gluconeogenesis to increase after glycerol, all of these parameters changed in opposite directions after renal pedicle clamping and after subcutaneous HgC12 (4.7 mg. per kg;). In addition, early morphologic changes in glycerol-injected rats differed from those seen with pedicle clamping and low dose HgC12. With high dose HgC12 (25 mg. per kg.), the metabolic and morphologic changes were somewhere in between those seen with the other insults. Coinciding with early metabolic and morphologic changes, cardiac output and renal blood flow decreased soon after the glycerol was given. On the basis of our findings, we cannot ascribe all of the early metabolic and morphologic changes in the glycerol model to ischemia, and we postulate that the circulating heme proteins may be nephrotoxic to ischemic renal tissue.
 ...
PMID:Early events in various forms of experimental acute tubular necrosis in rats. 112 11


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