Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0599766 (functional recovery)
 13,441 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of nucleoside uptake in the enhanced metabolic recovery seen with postischemic ATP.MgCl2 was assessed by determining the effect of S-(p-nitrobenzyl)-6-thioinosine (NBTI) on postischemic ATP recovery in rats given normal saline (NS), ATP.MgCl2, or adenosine after 45 min of bilateral renal ischemia. In NS-infused animals, postischemic administration of NBTI (250 nmol) had no significant effect on the pattern of ATP recovery. In animals given 50 mumol ATP.MgCl2, coinfusion of NBTI significantly reduced the renal ATP content 2 h after reperfusion but blocked only one-half of the enhancement in renal ATP content compared with animals given ATP.MgCl2 alone. In animals postischemically infused with [2,5,8-3H]ATP.MgCl2 (50 mumol) there was significant labeling of nucleotides, nucleosides, and bases after 2 h of reperfusion. The specific activity of the adenosine pool was consistent with significant label uptake in the form of adenosine. Coinfusion of NBTI led to a significant reduction in label incorporation into renal ATP and total adenine nucleotide pools. These data are consistent with an important role for an NBTI-sensitive nucleoside uptake mechanism in the enhanced metabolic and functional recovery observed in ischemically injured kidney treated by postischemic infusion of ATP.MgCl2.
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PMID:Role of nucleoside uptake in renal postischemic ATP synthesis. 162 13

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

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control (10 min), normoxic cardioplegia (10 min), intermittent global ischemic arrest (two 15-min periods separated by 2 min infusion of the normoxic cardioplegic perfusate), and normoxic postischemic control reperfusion (60 min). Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl2, and 20 mM MgCl2 with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of 31P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P less than 0.01) that persisted throughout the first 50 min of postischemic reperfusion. Diltiazem in combination with magnesium cardioplegia was detrimental to postischemic functional recovery, despite a rapid restoration of high-energy phosphate stores. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically. The mechanistic basis and drug specificity of this response require further clarification. The present findings appear to exclude ATP and PCr production, and structural causes as the basis for the observed aberrant functional recovery from global ischemia of magnesium plus diltiazem-arrested hearts.
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PMID:Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia. 371 20

Spontaneously beating isolated rat atria were subjected to 1 h of anoxia at 37 degrees C in various cardioplegic solutions. Contraction continued for different times upon initiation of anoxia, depending on the nature of the cardioplegic solution. Two hundred micromolar P1,P5-di(adenosine-5')pentaphosphate (Ap5A) stopped atrial function in less than 30 s of anoxia in contrast to 50 s in the case of Hearse's cardioplegic solution (16 mM MgCl2, 16 mM KCl, 1 mM Procaine), and 20 min in the case of controls. The stopping time was also prolonged from 30 to approximately 50-55 seconds if a lower concentration of Ap5A (100 microM) was used. Function, adenine nucleotides (AN), and phosphocreatine (PCr) were then measured 20 min after reoxygenation. The recovery of both function and AN was most rapid and complete with 200 microM Ap5A (97% recovery in ATP and 100% in function) and least complete in control (50% recovery in ATP and 78% in function). A positive correlation between recovery of ATP, or total adenine nucleotides, and recovery of function was observed in all cases. The higher the level of ATP remaining at the end of 1 h of anoxia and the more recovered after 20 min of reoxygenation, the more complete the recovery of function. The PCr returned to normal or even higher than normal values in all cases, even though function returned only in proportion to ATP. Since PCr is mitochondrial in origin, it appears that loss of a portion of the AN localized at the energy-utilizing sites occurred before serious mitochondrial damage and was responsible for the incomplete postanoxic functional recovery.
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PMID:Recovery of isolated rat atrial function related to ATP under different anoxic conditions. 372 10

The effect of ATP-MgCl2 treatment was investigated on the biochemical changes of preserved kidneys and on the functional recovery of hypoxically damaged and autotransplanted canine kidneys. We observed that ATP-MgCl2 administered before or during simple hypothermic storage did not protect the integrity of preserved kidney cells, as measured by enzyme wash-out (LDH and NAG) or by lactate release. If the compound was administered after 120 min or 180 min clamping of the renal artery, the solitary kidney showed a faster regeneration as measured by changes in serum creatinine level. The survival rates were significantly higher in the treated groups. Without warm ischemia of the kidney all of the autotransplanted dogs survived after surgery. After 60 min of warm ischemia the mortality rate was 100%, and the mean survival time in average 5 days. If ATP-MgCl2 was administered after the 60 min of warm ischemia, an improved recovery of the graft function was observed
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PMID:Effect of ATP-MgCl2 treatment on kidney preservation and on recovery of graft function. 701 Apr 79

The ability of a solution of low-vanadium-content (less than 1 ppm) adenosine triphosphate and magnesium chloride (ATP/MgCl2) versus normal saline to improve recovery of function and reduce necrosis of skeletal muscle after severe ischemia was investigated in an in situ autoperfused canine hind limb model. The study consisted of 12 dogs divided into 3 study groups: nonischemic control (NIL) (n = 7 limbs), ischemic (IL) (n = 7 limbs), and ischemic ATP/MgCl2-treated (IATP) (n = 7 limbs). In groups IL and IATP, the limb was reperfused for 3 hours following 4 hours of complete ischemia. In IATP limbs, 200 mumol/kg of ATP/MgCl2 was infused upon reperfusion of the limbs, whereas IL limbs received a similar volume of normal saline at the time of reperfusion. Function was determined by stimulating the deep peroneal nerve and anterior tibial muscle and measuring the resultant isometric twitch contractile force of paw dorsiflexion. Muscle necrosis was evaluated by photographic analysis of sectioned anterior tibial muscle stained with nitroblue tetrazolium dye. ATP/MgCl2 significantly increased functional recovery (p < 0.01) and significantly reduced skeletal muscle necrosis (p < 0.01). This study suggests that ATP/MgCl2 may be useful in reducing the clinical sequelae of severe limb ischemia and reperfusion.
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PMID:Allastair B. Karmody Award. Improved recovery of limb function with ATP/MgCl2 in an ischemic canine hind limb. 835 98

The mechanism by which preconditioning (brief intermittent periods of ischemia and reflow) improves recovery of function and reduces enzyme release after a subsequent 30-minute period of ischemia was investigated in perfused rat hearts. Specifically, it was hypothesized that ischemia after preconditioning would result in a decreased production of H+ and therefore a smaller rise in [Na+]i and [Ca2+]i via Na(+)-H+ and Na(+)-Ca2+ exchange. To test this hypothesis we measured pHi, [Na+]i, [Ca2+]i, and cell high-energy phosphates during ischemia and reflow, and we correlated this with recovery of contractile function and release of creatine kinase during reflow. 31P nuclear magnetic resonance (NMR) was used to measure pHi and cell phosphates. [Na+]i was measured by 23Na NMR using the shift reagent thulium 1,4,7,10-tetraazacyclododecane-N,N,'N",N"'-tetramethylenephosph onate to distinguish intracellular from extracellular sodium. [Ca2+]i was measured by 19F NMR using hearts loaded with 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid, termed 5F-BAPTA. Basal time-averaged levels of pHi, [Na+]i, and [Ca2+]i were 7.07 +/- 0.08, 9.4 +/- 0.8 mM, and 715 +/- 31 nM, respectively. After 30 minutes of ischemia, in preconditioned hearts, pHi was 6.5 +/- 0.06, [Na+]i was 2.09 +/- 4.4 mM, [Ca2+]i was 2.1 +/- 0.4 microM, and ATP was negligible. In untreated hearts, after 30 minutes of ischemia, pHi was 6.3 +/- 0.08, [Na+]i was 26.7 +/- 3.8 mM, [Ca2+]i was 3.2 +/- 0.6 microM, and ATP was undetectable. During reperfusion after 30 minutes of ischemia, preconditioned hearts had significantly better recovery of contractile function than untreated hearts (71 +/- 9% versus 36 +/- 8% initial left ventricular developed pressure), and after 60 minutes of ischemia, preconditioned hearts had significantly less release of the intracellular enzyme creatine kinase (102 +/- 12 versus 164 +/- 17 IU/g dry wt). We also found that unpreconditioned hearts arrested with 16 mM MgCl2 (to inhibit calcium entry via calcium channels and Na(+)-Ca2+ exchange) before 30 minutes of ischemia recover function on reflow to the same extent as preconditioned hearts with or without magnesium arrest. Thus, preconditioning has no additional benefit in addition to magnesium arrest. In addition, in hearts that received 16 mM MgCl2 just before the 30-minute period of ischemia, preconditioning had no effect on the rise in [Ca2+]i during the 30-minute period of ischemia. These data support the hypothesis that preconditioning attenuates the increase in [Ca2+]i, [Na+]i, and [H+]i during ischemia, most likely because of reduced stimulation of Na(+)-H+ and Na(+)-Ca2+ exchange.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of preconditioning. Ionic alterations. 838 Feb 59

Magnesium has been shown to be involved with the processes associated with brain injury and its use in animal models of brain injury has received considerable attention. The present paper reviews the use of MgCl2 therapy to facilitate behavioral recovery and to reduce subcortical degeneration in an electrolytic lesion model of cortical injury in the rat. Several studies were performed which compared the effectiveness of MgCl2 to other established neuroprotective agents, examined the preoperative administration of MgCl2, and examined the effectiveness of MgCl2 in a lesion model that produces chronic behavioral impairments. The results from these studies indicate that MgCl2 therapy is effective in facilitating recovery of function and limiting subcortical degeneration, is as effective as other neuroprotective agents, and can induce recovery of function in a chronic lesion model. These results suggest that MgCl2 therapy is effective in facilitating recovery of function in an electrolytic lesion model of cortical injury.
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PMID:The behavioral and anatomical effects of MgCl2 therapy in an electrolytic lesion model of cortical injury in the rat. 1130 Jun 22

The present study was conducted to establish the window of opportunity for the administration of a regimen of MgCl2 pharmacotherapy following focal injury to the brain. Rats were subjected to unilateral electrolytic lesions of the sensorimotor cortex (SMC) and administered a regimen of MgCl2 (1.0 mmol/kg) or 0.9% saline (1.0 ml/kg) beginning either 15 min, 8 h or 24 h after injury. Subsequent injections were administered 24 and 72 h after the initial treatment. Behavioral testing assessed recovery of function on several sensorimotor behaviors for 24 days following injury. The results of the present study suggest that treatment with a regimen of MgCl2 significantly facilitated recovery of function on the forelimb-->forelimb and vibrissae-->forelimb placing tests when administered 15 min, 8 h or 24 h after injury compared with saline-treated rats. Recovery of locomotor placing was significantly facilitated at 15 min and 8 h but not at 24 h compared with saline-treated rats. In addition, the ability of MgCl2 to limit neuronal loss in the ipsilateral ventral posterior lateral (VPL) nucleus of the thalamus was seen at only the 15-min treatment interval. These results suggest that the window of opportunity for MgCl2 pharmacotherapy is 24 h, task dependent and is much shorter for protecting neurons in the VPL.
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PMID:The window of opportunity for administration of magnesium therapy following focal brain injury is 24 h but is task dependent in the rat. 1204

Many studies have examined the preclinical efficacy of Mg2+ therapy in models of traumatic brain injury. However, more of these studies have examined sensorimotor and motor performance than cognitive performance following injury. The present paper reviews the use of Mg2+ therapy to facilitate cognitive recovery in several models of cortical injury in the rodent. The first study examined the ability of daily injections of MgCl2 (1 or 2 mmol) to impair acquisition of a reference memory task in the Morris Water Maze. Additional studies examined the ability of MgCl2 to improve cognitive function following bilateral anterior medial cortex ablations, bilateral frontal cortex contusions, and unilateral frontal contusions. The results from these studies indicate that MgCl2 therapy is biologically active and readily crosses the blood-brain barrier because daily injections of MgCl2 impaired learning of a reference memory task in intact rats. Mg2+ therapy for brain injury revealed that administration of post-injury MgCl2 effectively improved recovery of cognitive deficits following injury. These results suggest that Mg2+ therapy is effective in facilitating cognitive recovery of function following brain injury; however, there are task and dose-dependent aspects to this recovery.
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PMID:Assessment of cognitive function following magnesium therapy in the traumatically injured brain. 1827 92


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