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

The role of Mg in cardiomyopathies of different etiologies is well known; however, relatively little is known about the changes in hepatic Mg levels following ischemia to the liver. The available information indicates that tissue and mitochondrial Mg levels are altered following global hepatic ischemia and reflow and that such alterations may be responsible for the depressed cellular function during those conditions. Administration of MgCl2 alone following ischemia was ineffective in improving tissue and mitochondrial Mg levels and cellular functions. ATP administration alone following ischemia was also ineffective. However, administration of ATP complexed with MgCl2 increased tissue and mitochondrial Mg levels, tissue ATP stores and cellular functions and proved beneficial for the survival of animals. The potential mechanisms of the beneficial effects of ATP-MgCl2 are discussed. A multicenter clinical trial of ATP-MgCl2 in patients with various adverse circulatory conditions is being initiated in this country.
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PMID:Use of magnesium-ATP following liver ischemia. 329 18

The development of optimal methods for preservation is important for the advancement of liver transplantation. This study compares hypothermic storage (HS) and hypothermic pulsatile perfusion (HPP) with various solutions, using an isolated normothermic perfusion model (LIPM). Canine livers were removed from mongrel dogs without warm ischemia and flushed with either heparinized Ringer's lactate (control and HPP-preserved groups) or the solution used for hypothermic storage (TP-V or modified Collins). The type of preservation and solution for each of the experimental groups was as follows: group I (n = 7), no preservation, fresh; group II (n = 7), 24-h HS with TP-V (a hyperosmolar colloid solution containing sucrose, dextrose, and ATP-MgCl2); group III (n = 7), 24-h HS with modified Collins (C-2), an intracellular crystalloid solution; group IV (n = 5), 24-h HP with TP-V; group V (n = 6), 24-h HPP with Belzer solution, containing ATP-MgCl2; group VI (n = 3), 24-h HPP with albumin. After the preservation period, livers were placed on HPP at 37 degrees C with albumin-mannitol solution for 3-h testing in an LIPM. Perfusate samples were taken at 1-h intervals to assess liver function. LDH, SGOT, alkaline phosphatase, lactic acid, LAP, GGT, pO2, pCO2, pH, osmolarity, AMP, ADP, and ATP were studied. Histologic studies were performed, as were representative HIDA scans. Using the LIPM, livers preserved by HS and HPP with TP-V solution appeared to be superior to those preserved with modified Collins, Belzer, and albumin solutions. In these non-TP-V groups, the greatest cellular and organ damage was observed. TP-V HPP appeared to give the best overall liver functional response and histologic results and is recommended as the preferred method for 24-h liver preservation.
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PMID:Liver preservation techniques for transplantation. 330 26

Although ATP-MgCl2 treatment after global hepatic ischemia has been shown to improve cell function, a recent report has failed to confirm this in a model of regional hepatic ischemia. To determine the reason for this, rats were anesthetized and blood vessels to the left and median lobes of the liver were occluded. After 90 min of ischemia, the ligature around those vessels was removed. In Model 1, blood flow to the right lobes of the liver was then occluded whereas in Model 2, flow to those lobes was left intact. In both models the rats received intravenously 1.0 ml of saline or ATP-MgCl2 (12.5 mumole each) after ischemia. One hour after reflow, hepatic blood flow in the right and/or left lobe was measured following which mitochondria from the respective lobes were isolated and their function measured. The results indicated that although ATP-MgCl2 infusion following hepatic ischemia significantly improved hepatic blood flow and mitochondrial function in Model 1 (in which the right lobes were ligated following release of the occlusion to the left and median lobes), it failed to do so in Model 2 (in which the right lobes were not occluded after release of the occlusion to the left and median lobes). These results emphasize the importance of the rapid restoration of blood flow following hepatic ischemia. In the presence of shunts such as occur in Model 2, it is unlikely that any therapeutic agent would be effective.
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PMID:Hepatic ischemia models for determining the effects of ATP-MgCl2 treatment. 348 94

Renal vasoconstriction is an important pathophysiological component of an ischemic acute renal injury. The postischemic infusion of ATP-MgCl2 enhances recovery of glomerular and tubular function, accelerates regeneration of sublethally injured tubular cells, and augments resynthesis of cellular nucleotides. Since both ATP and MgCl2 are vasoactive compounds, postischemic enhancement of renal blood flow (RBF) by a pharmacological agent, dopamine, was examined to study the possible contribution of vasodilation. At 2 h, the infusion of dopamine resulted in RBF (1.70 +/- 0.09 ml X min-1 X 100 g body wt-1 X kidney-1) and inulin clearance (CIn, 400 +/- 44 microliter X min-1 X 100 g body wt-1) similar to rats treated with ATP-MgCl2 (1.73 +/- 0.27 RBF, 404 +/- 38 CIn) and significantly (P less than 0.01) greater than saline-treated rats (0.80 +/- 0.04 RBF, 78 +/- 19 CIn; P less than 0.01). However, by 24 h CIn in dopamine animals had not continued to improve (460 +/- 25 microliter X min-1 X 100 g body wt-1) and was similar to normal saline rats (388 +/- 40). In contrast, CIn in ATP-MgCl2 animals showed sustained recovery (676 +/- 28 microliter X min-1 X 100 g body wt-1, P less than 0.01). These differences resulted from improved integrity of tubular epithelium as reflected by decreased cell swelling and necrosis. Moreover, the recovery of renal ATP levels, as assessed by 31P nuclear magnetic resonance, in animals given saline (63 +/- 3%) or dopamine (66 +/- 5%) was slow and incomplete by 120 min after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Postischemic hemodynamics and recovery of renal adenosine triphosphate. 349 Jan 85

The effect of the administration of ATP-MgCl2 and adenosine-MgCl2 on the volume density of necrosis occurring 24 hr following 60 min of ischemia in rat liver has been studied. The extent of necrosis in the lobes submitted to ischemia has been assayed by morphometric analysis of fresh liver slices incubated in tetranitro BT. The administration of ATP-MgCl2 (1.25 mumole of each solved in 0.5 ml 0.9% NaCl) reduced the volume density of necrotic areas in the liver of a fasted rat from about 15% to almost zero, provided that the compounds are given as a continuous infusion spread over a period of 15 min and the administration is started before the circulatory flow is restored following ischemia. However, the extent of necrosis was not reduced by ATP-MgCl2 administration when ischemia was induced in the liver of a fed rat which showed a more massive necrosis (about 30%). Increasing concentrations of ATP-MgCl2 to 5 mumole did not result in any improvement. Adenosine-MgCl2 reduced the extent of necrosis after ischemia in a fasted rat in the same way as ATP-MgCl2. The conclusion is drawn that ATP as a direct source of energy and adenosine as a substrate for ATP-synthesis can protect the liver against ischemic damage, whereas MgCl2 plays a supporting role.
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PMID:Quantitative analysis of the effect of ATP-MgCl2 and adenosine-MgCl2 on the extent of necrosis in rat liver after ischemia. 349 Jun

ATP-MgCl2 X administration had been shown to accelerate the recovery of renal function following warm ischemia. However, since the major breakdown product of ATP is adenosine, the relative contribution of ATP vs. adenosine in improving renal function following ischemia remains to be determined. To study this, kidneys were subjected to 45 min of normothermic ischemia and then perfused at 100 mmHg with oxygenated Krebs-HCO3 buffer containing albumin, [3H]inulin, substrates, and either 0.3 mM ATP-MgCl2 or adenosine-MgCl2 for 110 min. Perfusate and timed urine samples were collected and analyzed for radioactivity and [Na+]. The functional parameters indicated that although adenosine-MgCl2 treatment provided a transient improvement, it failed to provide a sustained improvement in renal function or attain control values compared with ATP-MgCl2 treatment. Thus, the salutary effects of ATP-MgCl2 following warm ischemia in the kidney are not mediated by adenosine.
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PMID:Comparison of effects of ATP-MgCl2 and adenosine-MgCl2 on renal function following ischemia. 349 30

This study was designed to test the hypothesis that infusion of ATP-MgCl2 during reperfusion following a prolonged period of hypothermic global ischemia would result in enhanced functional recovery of cardiac function. Two groups of dogs (n = 6 each) were placed on cardiopulmonary bypass (CP) with systemic hypothermia to 28 degrees C and subjected to 150 min of aortic cross-clamping. Crystalloid cardioplegia was infused every 20 min during ischemia. Reperfusion and rewarming were carried out for 20 min before discontinuation of CP bypass. During reperfusion, the experimental group received ATP-MgCl2(1.0 mg/kg/min ATP, 0.33 mg/kg/min magnesium). At 15 and 45 min following bypass, hemodynamic assessment was carried out for each animal by constructing Starling curves over a range of filling pressures at constant heart rate and comparing each animal to its own prebypass control level. The results indicated that ATP-treated animals exhibited complete functional recovery whereas control animals showed marked reduction in hemodynamic performance and myocardial compliance and had a higher myocardial water content (P less than 0.05). We conclude that infusion of ATP-MgCl2 during reperfusion following hypothermic ischemia may help ameliorate reperfusion injury.
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PMID:Reperfusion with ATP-MgCl2 following prolonged ischemia improves myocardial performance. 349 93

The reversible period of hypoxia and ischemia is a consequence of the function of numerous regulatory mechanisms which convert cells to a quiescent state. Thus, early changes in metabolism reflect regulatory events rather than pathological events. O2-dependent enzymes (oxidases and oxygenases) are the primary sensors for physiological responses to hypoxia, and failure of their functions are ultimately responsible for hypoxic and ischemic cell injury. At least 30 of these enzymes are known to occur in kidney, but only cytochrome oxidase has been extensively studied with regard to the above processes. Heterogeneity of subcellular oxygenation occurs as a result of the existence of clusters of mitochondria in the basolateral regions of proximal and distal tubule cells. This creates regions with very high O2 consumption rates, and results in diffusion limitations in O2 supply. Finally, dramatic progress has been made in protecting against ischemic injury through use of nonpermeant solutes to reduce cell swelling, addition of ATP-MgCl2 to stimulate recovery of cellular adenylates upon reoxygenation, use of a Ca2+ uptake blocker to prevent cellular loading of Ca2+, and addition of compounds to inhibit superoxide and H2O2 production or scavenge reactive O2 species. While the mechanistic details and complete description of metabolic effects are not yet available, the ability to alter cellular metabolism and delay or prevent irreversible injury marks a very important advance in renal physiology.
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PMID:Renal metabolism during normoxia, hypoxia, and ischemic injury. 351 18

Although much is known about the role of Mg in cardiomyopathies of different etiology, very little is known about the changes in hepatic Mg levels following hemorrhagic shock or ischemia to the liver. Information available indicates that tissue and mitochondrial Mg levels may be altered following shock and ischemia and that such alterations may be responsible for the depressed cellular function during those conditions. MgCl2 administration following shock or ischemia was ineffective in improving tissue and mitochondrial Mg levels and cellular functions. Administration of ATP complexed with MgCl2, however, increased tissue and mitochondrial Mg levels, tissue ATP stores and cellular functions and proved beneficial for the survival of animals. ATP-MgCl2 administration also increased cardiac output while decreasing myocardial as well as total body O2 consumption. The potential mechanisms of the beneficial effects of ATP-MgCl2 are discussed. ATP-MgCl2 can be given safely to humans and it decreases myocardial O2 consumption and increases cardiac output without producing hypotension. A clinical trial of ATP-MgCl2 in patients with various adverse circulatory conditions is underway at our institution.
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PMID:The role of ATP-magnesium in ischemia and shock. 352 59

Various modalities have been proposed to protect the liver from injury during the ischemic period or after reperfusion. Most of the drugs were administered before the onset of ischemia, but a beneficial effect of post-treatment was reported for MP, dopamine and ATP-MgCl2. Previous studies were mainly performed upon experimental animals, but hypothermia and steroids were used to protect the liver from ischemic injury in patients as well. However, no controlled clinical trials exist demonstrating the efficacy of any type of prevention or treatment in ischemia of the human liver.
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PMID:Prevention and treatment of ischemia of the liver. 354 77


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