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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have attempted to reconstruct in vitro the events that may occur in vivo during reperfusion injury after ischemia in the central nervous system. The phenomenon is induced by previous exposure to low calcium solutions ("calcium paradox") before the reperfusion episode. Intracellular calcium alterations during reperfusion of human astrocytoma U1242MG cells have been investigated with microspectrofluorimetry using the calcium-sensitive dye fura-2. Cells were perfused in calcium-free buffer solution for 30 min and then re-exposed to the control buffer solution (1.5 mM CaCl2). [Ca2+]i increased up to 3.5 times control levels during the reperfusion period. The mechanism of the increase was also investigated. Addition of TTX (2 microM) or choline chloride sodium substitution during perfusion with low calcium prevented the [Ca2+]i increase during reperfusion. Reperfusion increases in [Ca2+]i were exacerbated by low potassium in the perfusion medium, but unaltered by the calcium channel blockers cadmium (100 microM) and nickel (100 microM). In a similar manner, flunarizine (10 microM) and cadmium (100 microM) were unable to modify reperfusion [Ca2+]i alterations. Low sodium in the reperfusion medium produced significant increases in [Ca2+]i if preceded by low potassium and calcium perfusion. The viability of cells after 24 h of incubation after the insult produced by exposure to Ca(2+)-free media for 30 min was also investigated. Compared with control groups, the groups treated with Ca(2+)-free media for 30 min had a decreased number of surviving cells and morphological alterations indicative of cell pathology. The relative number of cytotoxic cells was increased by maneuvers (low potassium perfusion) that presumably blocked the Na/KATPase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reperfusion paradox: a novel mode of glial cell injury. 153 10

The isolated working rabbit heart preparation was used to study whether the "contractile machinery" remains unchanged in globally stunned myocardium. The function of the heart has been measured in nonischemic and postischemic conditions. The effect of isoprenaline or calcium chloride administration in both conditions was also studied. Myocardial contractile function was significantly depressed after 20-min global ischemia and returned to normal after CaCl2 and supranormal values after isoprenaline administration. From hearts used in experiments myofibrils were prepared and their ATPase activity was determined. It was observed that myofibrils prepared from "stunned" myocardium showed about 50% increase in ATPase activity in the presence of CaCl2. Subjection of the heart to ischemia caused a decrease in calcium sensitivity of the myofibrillar ATPase. Myofibrils obtained from ischemic hearts but subjected to isoprenaline or CaCl2 administration exhibited increased calcium sensitivity over that of control heart. These effects were accompanied by changes in the extent of phosphorylation of troponin I (TNI) and myosin light chains. The modification of contractile apparatus in the postischemic period described in this paper may contribute to the overall mechanism of myocardial stunning.
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PMID:Contractile proteins in globally "stunned" rabbit myocardium. 183 10

The activity of phospholipase C acting against [3H]-inositol-phosphatidylinositol (PI) and the activity of arachidonic acid (AA) release from [1-14C]arachidonoyl-phosphatidylinositol by enzyme(s) located in synaptic vesicles (SV) isolated from normoxic and ischemic brains was investigated. Brain ischemia significantly activated phospholipase C (PhLC) by about 90% and AA release by about 50%. PhLC and AA release in SV isolated from brain submitted to ischemia were not further activated by 2 mM CaCl2 contrary to the enzymes from normoxic brain. The activation of PhLC and PhLA2 may produce conformational changes and rearrangement of the SV membranes leading to vesicle-membrane fusion and subsequently to massive neurotransmitter release known to occur during ischemia.
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PMID:Synaptic vesicle-bound phospholipase(s) acting on phosphatidylinositol exhibit(s) high susceptibility to brain ischemia. 211 86

The effect of diltiazem (d-cis-diltiazem) on the ischemic myocardium was compared with that of l-cis-diltiazem, an optical isomer having less potent calcium channel-blocking action, in the isolated, perfused working rat heart. Ischemia decreased mechanical function and tissue levels of ATP and creatine phosphate, and increased tissue levels of nonesterified fatty acids (NEFA), AMP and lactate. Reperfusion did not restore mechanical function, but restored incompletely the levels of metabolites (except NEFA) that had been altered by ischemia. The ischemia-induced changes in NEFA were prevented by d-cis-diltiazem completely and by l-cis-diltiazem incompletely. Other metabolic changes induced by ischemia were attenuated by d-cis-diltiazem but not by l-cis-diltiazem. In heart pretreated with d-cis- or l-cis-diltiazem, both the mechanical function and the levels of metabolites recovered during reperfusion, the degree of recovery with both drugs being similar. These results indicate that not only d-cis-diltiazem but also l-cis-diltiazem has an anti-ischemic action probably due to inhibition of the tissue NEFA accumulation. These results also suggest that the mechanism of the protective effect of d-cis-diltiazem on the ischemic myocardium is not entirely due to the calcium channel-blocking action. Treatment with low Ca2+ (1.0 mM CaCl2) also attenuated the ischemia-induced changes. The interval between reoxygenation and start of function in the reperfused heart that had been treated with low Ca2+ was significantly longer than that with d-cis- or l-cis-diltiazem. The effect of these isomers to shorten this interval may contribute to their common anti-ischemic action.
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PMID:Both d-cis- and l-cis-diltiazem have anti-ischemic action in the isolated, perfused working rat heart. 224 48

The effect of high concentration of magnesium on both mechanical dysfunction and metabolic damage after ischaemia-reperfusion was studied in isolated rat hearts. The heart was perfused by the Langendorff's technique at a constant flow (10 ml/min) with modified Krebs-Henseleit solution and driven at 300 beats/min. The heart was made ischaemic by reducing the flow to 0 ml/min for 25 min, and then reperfused at the constant flow for 15 min. MgSO4 was added to the perfusate for 5 min before the onset of ischaemia, or after the end of ischaemia (after the onset of reperfusion). Ischaemia-reperfusion produced both mechanical dysfunction (as evidenced by an increase in the left ventricular end diastolic pressure and a decrease in the left ventricular developed pressure) and metabolic damage [as evidenced by a decrease in the myocardial adenosine triphosphate (ATP)]. When 15 mmol/l MgSO4 was given before ischaemia, there was no appreciable recovery of mechanical function, whereas when given after ischaemia (during reperfusion), there was a marked recovery of mechanical function. Lower concentrations (10 or 5 mmol/l) of MgSO4 given after ischaemia recovered the mechanical function concentration-dependently. The beneficial effect of 15 mmol/l MgSO4 was minimized by the coexistence of 4.5 mmol/l CaCl2 in the reperfusion solution. The decrease in the myocardial level of ATP induced by ischaemia-reperfusion was attenuated by 15 mmol/l MgSO4 given in the reperfusion solution. These results suggest that high Mg2+ is effective in attenuating both functional and metabolic damage of the post-ischaemic heart, provided it is given after ischaemia.
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PMID:Beneficial effect of magnesium on the isolated perfused rat heart during reperfusion after ischaemia: comparison between pre-ischaemic and post-ischaemic administration of magnesium. 240 98

This study was performed to determine if cardiodepression can be dissociated from cardioprotection with calcium antagonists and which one (diltiazem, nifedipine, or verapamil) can maximally protect ischemic myocardium at a given level of cardiodepression. Isolated rat hearts were subjected to 0.1, 0.5, or 1.0 microM diltiazem, verapamil, or nifedipine 10 min before global ischemia. Ischemia was maintained for 25 min, at which time reperfusion was instituted for 30 min. Pre- and postischemia function, flow, and lactate dehydrogenase (LDH) release were measured. All three drugs reduced preischemic function and improved postischemic function and reflow in a dose-dependent fashion. LDH release and contracture were also mitigated with all drugs. When the efficacy of these drugs was expressed as the ratio of LDH release versus preischemic, postdrug function (ability of drug to reduce LDH release at a given level of cardiodepression), diltiazem had a significantly lower ratio as compared with verapamil or nifedipine. When similar experiments were performed with various concentrations of calcium in the perfusion buffer (2.50, 1.25, 0.75, 0.50, 0.41 mM CaCl2) administered 10 min before ischemia and reperfusion with normal (1.25 mM) buffer, preischemic function was reduced in a concentration-dependent fashion. Despite severe reductions in function at the concentration of 0.50 mM CaCl2, LDH release was not reduced. The concentration of 0.41 mM CaCl2, which depressed function to the same degree as 0.50 mM CaCl2, reduced LDH release. This reduction in LDH release, however, was not as great as that which occurred with the high dose of the calcium antagonists. Reperfusion with 0.41 mM calcium buffer, however, nearly abolished LDH release. Thus, although all three calcium antagonists reduced the severity of ischemia, diltiazem reduces it with the lowest cost in cardiac function. Reduction in extracellular calcium reduces cardiac function, but reductions in severity of ischemia, as measured by LDH release, do not parallel these changes.
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PMID:Dissociation of cardiodepression from cardioprotection with calcium antagonists: diltiazem protects ischemic rat myocardium with a lower functional cost as compared with verapamil or nifedipine. 247 10

The effect of 10 min ischemia on the activity of phospholipase C acting against [3H]inositol-phosphatidylinositol (PI) and [3H]inositol-phosphatidylinositol 4,5-bisphosphate (PIP2) in the brain subsynaptosomal fractions was investigated. In the presence of endogenous CaCl2, specific activity of phospholipase C acting on phosphatidylinositol was as follows: synaptic cytosol (SC) greater than synaptic vesicles (SV) greater than synaptic plasma membrane SPM). Brain ischemia activated phospholipase C acting on PI by about 60% and 40% in SV and SPM, respectively. The enzyme of synaptic cytosol was not affected by ischemic insult. Phospholipase C acting against PIP2 in the presence of endogenous calcium expressed the specific activity in the following order: SV greater than SPM greater than SC. After 10 min of brain ischemia, activity of phospholipase C acting on PIP2 was significantly suppressed in all subsynaptosomal fractions by about 50-60%. These results indicate that prolonged ischemia produced activation exclusively of phospholipase C acting against phosphatidylinositol.
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PMID:Prolonged ischemia differently affects phospholipase C acting against phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate in brain subsynaptosomal fraction. 255 83

Both Mg2+ and Ca2+ have been implicated as having roles in the pathomechanisms of cerebral ischemia. To further study the effects of these ions on postischemic histologic outcome, fasted rats were given one of three intravenous infusions: 5.0 mmol/kg MgCl2, 5.0 mmol/kg MgCl2 + 0.035 units/kg regular insulin, or 1.0 mmol/kg CaCl2. This resulted in elevated plasma Mg2+ or Ca2+ concentrations in the corresponding groups. A fourth group received 0.9% NaCl (saline). Preinfusion plasma glucose concentration was similar for all groups and was unchanged after infusion in rats receiving either saline or MgCl2 + insulin. In contrast, postinfusion glucose concentration was increased in the MgCl2 group (p less than 0.001) and decreased in the CaCl2 group (p less than 0.001) relative to saline-treated rats. Following respective infusions, all rats underwent 10 minutes of reversible forebrain ischemia (bilateral carotid artery occlusion and systemic hypotension) followed by 7 days' recovery. Six of 12 CaCl2-treated rats died 2-3 days after ischemia; all other rats remained neurologically indistinguishable, without gross neurologic deficits. Histologic injury in the neocortex and caudate was moderate in all groups. In the hippocampus, MgCl2 + insulin resulted in 66 +/- 6% (mean +/- SD) dead CA1 pyramidal cells, which was similar to the amount in saline-treated rats (68 +/- 10%). Injury was increased in the MgCl2 group (79 +/- 4% dead cells), while in surviving CaCl2-treated rats, injury was decreased (54 +/- 13%). We conclude that the increased injury in MgCl2-treated rats and the decreased injury noted in surviving rats receiving CaCl2 are due to the plasma glucose concentrations present prior to ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of elevated plasma magnesium versus calcium on cerebral ischemic injury in rats. 264 53

The efficiency of transferring the total energy generated by ventricular contraction (pressure-volume area, PVA) to external work (EW) and internal work (IW) and the myocardial oxygen consumption (MVO2) at zero PVA were determined during volume loading on right heart bypass before and after a 50% augmentation (CaCl2, 0.03 mEq/kg/min, n = 7) or depression (20 minutes of 37 degrees C ischemia with 30 minutes of reperfusion, n = 7) of the contractile state. An increased EW efficiency (64% +/- 7% vs. 81% +/- 6%, p less than 0.01) with reciprocally decreased IW efficiency (36% +/- 7% vs. 19% +/- 6%, p less than 0.01) occurs with calcium chloride-augmented contractility. A reversible ischemia and reperfusion insult has the converse effect on these relative efficiencies (EW, 73% +/- 4% vs. 49% +/- 4%; IW, 27% +/- 4% vs. 51% +/- 4%; each p less than 0.01). Calcium chloride increases the oxygen requirements of both basal metabolism (28 +/- 2 vs. 67 +/- 9 ml O2/beat/100 gm LV, p less than 0.01) and fiber shortening (11 +/- 5 vs. 62 +/- 11 ml O2/beat/100 gm LV, p less than 0.01). The postischemic heart has a decreased oxygen need for shortening (20 +/- 2 vs. 3 +/- 4 ml O2/beat/100 gm LV, p less than 0.01), paralleling the depressed inotropic state. This new model of compartmentalized chemomechanical transduction may allow specific modulation of the energetic derangements attendant to the surgically treated heart.
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PMID:Compartmentalizing chemomechanical transduction in the ejecting heart. 276 28

Preincubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) in Ca2+-free Krebs buffer resulted in a 27% inhibition of synaptosomal gamma-aminobutyric acid (GABA) uptake. Addition of 1.5 mM CaCl2 increased the inhibition with X/XO to 46%, and inhibition was essentially complete when the calcium ionophore A23187 also was included. In other studies, preincubation of purified rat brain mitochondria with the combination of X/XO and 4 microM CaCl2 produced a significant (38%) decrease in state 3 respiration with glutamate/malate as substrate that was not seen with either X/XO or Ca2+ alone. Similar results were obtained using cultured mouse spinal cord neurons in which incubation with X/XO/ADP/FeCl2 and A23187 produced membrane damage as assessed by a 32% reduction of neuronal Na+, K+-ATPase activity. Neither X/XO/ADP/FeCl2 nor A23187 alone caused detectable inhibition. These results demonstrate the synergistic damaging effect of free radicals and Ca2+ on membrane function. In addition, they suggest that free radical-induced peroxidation of membrane lipid, occurring focally during complete or nearly complete ischemia in vivo, could result in intense cellular perturbation when coupled with increased intracellular Ca2+.
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PMID:Calcium enhances in vitro free radical-induced damage to brain synaptosomes, mitochondria, and cultured spinal cord neurons. 299 23


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