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)

Heart muscle mitochondria with satisfactory functional parameters of oxidative phosphorylation and with morphologically intact structure were isolated from canine myocardium employing a modified KEA-medium (0.18 M KCl, 10 mM EDTA, 0.5% bovine serum albumin, pH 7.1) according to Sordahl and Schwartz (1). The functional behaviour of mitochondria was investigated after different durations of in situ ischemia (cardioplegia, 15 degrees C) and correlated with metabolic findings. During ischemia the following changes were seen: 1. Successive reduction of electron flow. 2. Relatively small impairment of phosphorylation efficiency. 3. Less damage of FAD- than NAD-catalyzed oxidative phosphorylation. 4. A marked increase of electron flow and thus recovery of phosphorylation rate even after longer ischemic periods by addition of cytochrome c. As important factors of accelerating mitochondrial impairment during ischemia the myocardial ATP decrease, the lactate and H+-activity increase are discussed.
 ...
PMID:Functional behaviour of isolated heart muscle mitochondria after in situ ischemia. Polarographic analysis of mitochondrial oxidative phosphorylation. 20 84

This study determines the effect of ischemia and reperfusion on energy-linked Ca2+ uptake by myocardial mitochondria. The left anterior descending coronary artery was occluded in 14 mature pigs for 2 hr. In seven animals the ligature was released and the ischemic zone reperfused for 2 additional hours. After sacrifice, mitochondrial function was measured in normal and reperfused or ischemic areas of the left ventricle, using a polarographic method. Mitochondria were prepared without EDTA by standard procedures and Ca2+ uptake measured by 45Ca2+ isotope tracer. Uptake of Ca2+ by mitochondria derived from ischemic myocardium is markedly impaired with or without phosphate. Reperfusion may accentuate this impairment. The presence of exogenous Ca2+ inhibits the ability of ischemic or reperfused mitochondria to phosphorylate ADP.
 ...
PMID:Alteration in calcium metabolism in mitochondria isolated from ischemic and reperfused myocardium. 103 50

Capsaicin (10 microM), KCl (80 mM) or superfusion with a low pH medium (pH 5 or 6) produced a significant increase of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) outflow from the superfused rat isolated soleus muscle. CGRP-LI outflow produced by capsaicin or pH 5 medium was totally abolished in a calcium free medium containing EDTA (1 mM) and the effect of pH 5 medium was prevented by a previous application of capsaicin. Ruthenium red (10 microM) produced a marked inhibition of CGRP-LI release produced by capsaicin or pH 5 medium (69 and 84%, resp.), without affecting that evoked by KCl. These findings demonstrate that protons activate capsaicin-sensitive primary afferents in rat skeletal muscle through a Ruthenium red-sensitive mechanism. Proton-induced CGRP-LI release in skeletal muscle could be of relevance during exercise and/or skeletal muscle ischemia.
 ...
PMID:Release of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity from rat isolated soleus muscle by low pH, capsaicin and potassium. 127 75

The intracellular cation contents were determined in isolated perfused rat heart using cobaltic EDTA as a marker of the extracellular space. In hearts in which Na+ accumulation was induced with monensin, a Na+ ionophore, during 20 min-ischemia which otherwise did not result in accumulation of Na+, the levels of Na+ and Ca2+ were significantly higher after reperfusion with a significant decrease in K+. While the recovery of the cardiac mechanical function (CMF) was complete after reperfusion in control hearts, the recovery was incomplete in monensin-hearts. Dichlorobenzamil (DCB), the most specific inhibitor of Na(+)-Ca2+ exchanger, infused for 10 min before induction of ischemia in a dose of 10(-5) M, which produced a definite suppression of CMF (over 80%), inhibited the accumulation of Ca2+ and Na+ and the loss of K+ and ATP after 40 min-ischemia and reperfusion. The same dose of DCB given for 3 min before induction of ischemia and after reperfusion, which produced a less than 20% inhibition of CMF, failed to prevent the Ca2+ accumulation after 40 min-ischemia and reperfusion. These findings are at variance with the idea that the accumulation of Na+ during ischemia and the consequent augmented operation of Na(+)-Ca2+ exchange is responsible for accumulation of Ca2+ after reperfusion.
 ...
PMID:Myocardial Na+ during ischemia and accumulation of Ca2+ after reperfusion: a study with monensin and dichlorobenzamil. 143 15

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis. The present study was undertaken to determine whether these changes are mediated by local or systemic factors. In 6-week-old weanling rats, the ileum was divided into two isolated loops with separate vascular supplies. The mesentery of the proximal loop was occluded for 30 minutes, following which the bowel was reperfused; permeability to 51Cr EDTA was then assessed in the distal loop 30 minutes after reperfusion. In control groups, the distal loop was subjected to 30-minute IRI ("positive" control) or 30-minute sham operation ("negative" control). Permeability in the distal loop was increased only with IRI to the distal bowel (15.4 +/- 3 counts/min/standard), and not with IRI to the proximal bowel (5.1 +/- 1) or with sham operation (8.5 +/- 2). To determine whether a mild "priming" injury might be necessary for systemic factors to have an effect, the distal loop was subjected to 2-minute IRI and the proximal to 30-minute IRI or sham. Permeability was not increased in the distal loop in either of these groups (5.7 +/- 1 and 7.8 +/- 2, respectively). Thirty-minute IRI in the proximal loop did not increase permeability in the distal loop, with or without a priming injury. Only direct IRI in the distal loop resulted in a significant increase in permeability. We conclude that the permeability changes in this model are mediated through local tissue effects, rather than by systemic factors.
 ...
PMID:Increased mucosal permeability after intestinal ischemia-reperfusion injury is mediated by local tissue factors. 150 Oct 6

The three-vessel occlusion model of Kameyama et al. (Kameyama, M., Suzuki, J., Shirane, R. and Ogawa, A. (1985) Stroke 16, 489-493) was adapted with modifications to induce complete reversible rat forebrain ischemia. A fast and simple procedure for the isolation and purification of rat brain mitochondria, which provides high yield, is described. Mitochondria isolated from ischemic brain (12-30 min ischemia) exhibited decreases in State 3 respiratory rates of approx. 70% with NAD-linked respiratory substrates. Less effect was observed with succinate and rotenone. The State 4 respiratory activity remained near control levels except at 15 min of ischemia (25% increase) with NAD-linked substrates. Similarly, with succinate and rotenone, an approx. 30% increase in State 4 activity was observed at 20 min of ischemia. Consequently, the respiratory control indices (RCIs) were decreased. Both the respiratory rates and RCIs could be restored to near control levels upon the addition of EGTA(EDTA) or ruthenium red to the assay mixture. Analysis employing fura-2 as a Ca2+ probe, indicated a great decrease in the first order rate constant for Ca2+ uptake of ischemic mitochondria and a significant increase in Ca2+ homeostasis with an increase in the cytosolic Ca2+ concentration which results in excessive association of Ca2+ on the mitochondrial membrane and an inhibition of the respiratory chain-linked oxidative phosphorylation and Ca(2+)-transport activity of forebrain mitochondria. These deficits are proportional to the duration of ischemia.
 ...
PMID:Ischemic injury to rat forebrain mitochondria and cellular calcium homeostasis. 155 46

Disturbances in intestinal circulation for even short periods of time can produce mucosal injury, translocation of gut bacteria, and multiple organ failure. We recently reported a model of intestinal ischemia that included occlusion of the superior mesenteric artery (SMA) and interruption of collateral arcades from the right colic and jejunal arteries for 20 min. This present study was designed to characterize further our model of intestinal ischemia by quantitatively assessing changes in intestinal permeability (plasma to luminal clearance of 51Cr-labeled EDTA) and intestinal blood flow (IBF) (microspheres). A total of 89 rats were included for study; mean arterial blood pressure and acid-base balance were not significantly altered by intestinal ischemia or reperfusion. Baseline measurements of 51Cr-labeled EDTA were not significantly different among the experimental animals, and clearance did not change throughout the experimental period in the sham-ischemic group (N = 14). Clearance of 51Cr-labeled EDTA at the end of 20 min of intestinal ischemia (0.194 +/- 0.057 ml/min/100 gm, N = 17) was significantly greater than that measured at control (0.079 +/- 0.006 ml/min/100 gm, P less than 0.05). In addition, clearance measurements during reperfusion (20 min, 0.362 +/- 0.051; 60 min, 0.267 +/- 0.084 ml/min/gm) were significantly higher than those measured at the end of ischemia. Baseline IBF was similar in all rats (N = 42); SMA occlusion reduced IBF by 99% from baseline (from 1.4 +/- 0.27 to 0.014 +/- 0.001 ml/min/gm, N = 20). Removal of the SMA clip returned intestinal perfusion to baseline values (1.72 +/- 0.51 ml/min/g).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alterations in intestinal permeability and blood flow in a new model of mesenteric ischemia. 158 4

The ATP dependence of the Na-Ca exchanger was investigated in isolated adult rat heart cells to evaluate the extent to which ATP depletion after a period of ischemia plus reperfusion in whole hearts could limit calcium uptake by Na-Ca exchange. A standard state for measurement of Na-Ca exchange activity that could be used with cells depleted of ATP to different degrees was defined. This was a state of zero sarcolemmal gradient for sodium, potassium, and pH and was achieved by incubation of the cells for 5 minutes with EDTA, EGTA, ouabain, and nigericin. Heterogeneity of cell ATP levels was minimized by using a protocol of total ATP depletion by incubation under conditions similar to ischemia, followed by reoxygenation to give partial restoration of ATP levels. No ATP was regenerated when cells were reoxygenated in the presence of rotenone, and such cells showed a very low rate of calcium uptake. Without rotenone, cells showed an almost complete restoration of Na-Ca exchange activity, in spite of a restoration of ATP levels to only one third of control values. Thus, the dependence of calcium uptake on ATP was highly nonlinear under these conditions. The calculated Km for ATP was no more than 10% of normal ATP levels. We conclude that ATP depletion after ischemia plus reperfusion is unlikely to limit the rate of calcium uptake through Na-Ca exchange in the whole heart if at least one quarter of the ATP is restored. In addition, we measured the apparent ATP dependence of calcium uptake by Na-Ca exchange in cells under conditions in which we previously had concluded that cell ATP distributions were very heterogeneous: when cells undergo contracture during incubation with oligomycin and without glucose. A linear relation between calcium uptake rate and ATP was observed at all ATP levels. This can be understood if cells in contracture that are incubated with oligomycin cannot take up calcium because of low ATP, whereas rod-shaped cells are able to retain a full uptake capability. This result further supports our conclusion that the ATP level declines catastrophically to near zero in these oligomycin-incubated cells just before contracture.
 ...
PMID:ATP dependence of calcium uptake by the Na-Ca exchanger of adult heart cells. 160 63

We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of [51Cr]EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loops receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in [51Cr]EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.
 ...
PMID:Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis. 169 96

This study assesses the effect of the superoxide anion scavenger superoxide dismutase on myocardial capillary permeability-surface area (PS) products for small hydrophilic molecules after ischemia and reperfusion. Open-chest dogs underwent a 20-minute occlusion of the left anterior descending coronary artery followed by 1 hour of reperfusion. Myocardial plasma flow rate and capillary extraction of chromium 51-labeled EDTA or technetium 99m-labeled diethylenetriaminepentaacetic acid were measured by the single-injection, residue-detection method before ischemia and 5 and 60 minutes after the start of reperfusion. In 13 dogs, no scavenger treatment was given (nonprotected control group), whereas eight dogs were treated systemically with 15,000 units/kg superoxide dismutase during 1 hour, starting 20 minutes before ischemia. In the control group, three dogs developed reperfusion ventricular fibrillation in contrast to none in the superoxide dismutase group. Before ischemia, plasma flow rate, myocardial capillary extraction fraction, and PS values were similar in the two groups. Five minutes after the start of reperfusion, plasma flow rate increased significantly (p less than 0.01) in both groups. In the control group, capillary extraction fraction increased by 12% (p = NS) in spite of the higher plasma flow; these increases in capillary extraction fraction and plasma flow induced a 69% increase in PS (p less than 0.01). In the superoxide dismutase-treated group, capillary extraction fraction decreased by 32% (p less than 0.05) in accordance with the increased plasma flow rate, resulting in an unchanged PS (p = NS). Sixty minutes after reperfusion, plasma flow rate, capillary extraction fraction, and PS returned to preocclusion values in both groups (p = NS). The increased capillary extraction fraction and PS values seen in the control group suggest an increased capillary permeability after ischemia and reperfusion. Superoxide anions seem to participate, directly or indirectly, in this response.
 ...
PMID:Myocardial capillary permeability after regional ischemia and reperfusion in the in vivo canine heart. Effect of superoxide dismutase. 198 59


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