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)

After crystalloid cardioplegic arrest, cardiac-derived thromboxane A2 may be an important initiating mediator of no-reflow and hemodynamic deterioration during reperfusion because of its potent vasoactive properties. Although previous studies have already documented the increased release of cardiac thromboxane A2 after ischemia, none have studied the effects of cardiac thromboxane A2 on hemodynamics. We therefore tested the ability of cardiac thromboxane A2 to mediate deterioration of coronary flow and functional recovery during reperfusion after global ischemia. Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548. In eight of 15 hearts in each group, preischemic and postischemic aortic flow, coronary flow, cardiac output, heart rate, and stroke work were determined. In the remaining seven hearts in each group, preischemic and postischemic coronary effluent levels of the stable hydrolysis product of thromboxane A2 and thromboxane B2 were determined with radioimmunoassay through the use of nonrecirculating perfusate. At the completion of the experiment, water content was determined by wet weight/dry weight calculations. In a separate group (n = 7) preischemic myocardial water content was determined. Within the group protected by cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly decreased (p < 0.05) compared with preischemic values (aortic flow, 50.8 +/- 2.7 versus 29.4 +/- 3.3 ml/min; coronary flow, 13.2 +/- 1.3 versus 8.5 +/- 1.3 ml/min; cardiac output, 64.0 +/- 3.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.5 +/- 0.7 versus 7.1 +/- 0.8 cm H2O.ml). In relation to the group with cardioplegic solution alone, postischemic aortic flow, coronary flow, cardiac output, and stroke work were all significantly greater (p < 0.05) in the group with the receptor antagonist (aortic flow: 49.5 +/- 2.4 versus 29.4 +/- 3.3 ml/min; coronary flow; 12.4 +/- 1.2 versus 8.5 +/- 1.3 ml/min; cardiac output, 62.0 +/- 2.8 versus 38.0 +/- 4.4 ml/min; stroke work, 12.6 +/- 0.8 versus 7.1 +/- 0.8 cm H2O.ml). Overall, postischemic coronary effluent thromboxane B2 levels were greater than preischemic values (105.6 +/- 12.4 versus 69.6 +/- 9.8, p < 0.05) and treatment with the receptor antagonist did not significantly affect postischemic thromboxane B2 levels (92.0 +/- 7.3 versus 82.3 +/- 15.5, p = not significant). Neither ischemia nor treatment with the receptor antagonist significantly affected heart rate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury? 846 3

Thirty-five isolated rabbit hearts were subjected to 60 minutes of storage after cardiac arrest with high K+ crystalloid cardioplegic solution at 5 degrees C. They were divided into five groups (n = 7 per group) according to the preservative protocol: group I (simple immersion in 0 degrees C normal saline solution), group II (simple immersion in 30 degrees C blood cardioplegic solution), group III (immersion and perfusion in 30 degrees C blood cardioplegic solution), group IV (simple immersion in 10 degrees C blood cardioplegic solution), and group V (immersion and perfusion in 10 degrees C blood cardioplegic solution). After storage for 1 hour, cardiac function, tissue water content, and the number of hearts capable of ejecting against a 100 cm H2O column afterload were recorded and compared among the five groups. Cardiac function in group II was not different from group I. Aortic pulse pressure and left ventricular developed pressure were lower in group II than in group III, IV, or V. Aortic developed pressure was higher in groups III and V (p < 0.05). Tissue water content in group I was significantly higher than in groups II, III, and V (p < 0.05). All hearts in groups III and V could eject against a 100 cm H2O afterload after preservation (p < 0.05 versus groups I, II, and IV). Factorial analysis among the groups using blood cardioplegic solution showed that either hypothermia or perfusion alone or the combination was a protective factor in providing functional recovery of stored hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional recovery in rabbit heart after preservation with a blood cardioplegic solution and perfusion. 847

Transitory global cerebral ischaemia induced in rats by four vessel occlusion for 15 min produced substantial loss of CA1 cells in dorsal hippocampus, and minimal damage in other intra- and extrahippocampal forebrain regions examined. Ischaemic rats showed long-lasting deficits in spatial navigation in the water-maze, consisting of impaired learning to locate a hidden platform in a novel pool, a substantial increase in time spent searching close to the platform without finding it, and moderate deficits in matching to position in a working memory task. Groups of ischaemic rats were implanted with fetal tissue dissected from hippocampal CA1 field, containing glutamatergic CA1 pyramidal cells, from dentate gyrus, containing glutamatergic dentate granule cells, and from basal forebrain, containing cholinergic cells, with grafts sited in the alveus above the damaged CA1 region, for comparison with non-grafted ischaemic and non-ischaemic control groups, over a series of tests from four to 20 weeks after grafting. All ischaemic groups showed comparable acquisition deficits prior to transplantation, and similar loss of CA1 cells on post mortem examination. When tested in a familiar pool in retention and reversal learning of the original platform position, and a working memory task, all ischaemic rats performed better than in initial acquisition. However, rats receiving CA1 grafts showed the most consistent improvement relative to ischaemic controls. When tested in a second (i.e. novel) pool, ischaemic rats again showed marked impairment, whereas rats with CA1 grafts were significantly superior, and learned as rapidly as non-ischaemic controls. The performance of groups with dentate granule and basal forebrain grafts was similar to that of the non-grafted ischaemic control group throughout testing. These results suggest that ischaemic rats are impaired in the adaptive use of spatial information, as shown by acquisition and working memory deficits, but not in long- or short-term memory storage processes, and are also impaired in precise spatial localization. The effects of CA1 grafts in restoring spatial abilities, shown most clearly when rats were tested in a novel environment, suggest that these grafts may have assisted with repair to the damaged host circuit, rather than acted through the release of an appropriate neurotransmitter, since the glutamatergic dentate granule grafts were ineffective. However, CA1 grafts showed better survival and growth than the other types of transplant, so that functional recovery may have been related to graft viability rather than to the specific type of graft.
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PMID:Effects of fetal hippocampal field grafts on ischaemic-induced deficits in spatial navigation in the water maze. 851 47

We have previously shown that spatial memory changes following experimental traumatic brain injury (TBI) include long-term changes that are (1) 'overt': detected by routine behavioral assessments, or (2) 'covert': undetected in the absence of a secondary pharmacological challenge, such as by the cholinergic antagonist, scopolamine. Our objective in this study was to extend this finding by characterizing the time course of recovery of overt and covert spatial memory performance following two magnitudes of experimental TBI. The Morris water maze was used to assess cognitive performance. Rats received either moderate magnitude (6 m/s, 1.77 mm deformation) or low magnitude (6 m/s, 1 mm deformation) impacts through a lateral craniectomy under isoflurane anesthesia. Sham rats underwent identical surgical procedures but were not injured. To avoid motor deficits, water maze testing started two weeks post-injury. Rats were given four trials per day for seven consecutive days. For each trial, latency to find a hidden platform was timed. On the sixth, rats were injected (i.p.) with scopolamine (1 mg/kg) 15 min prior to maze testing. The next day, rats were retested. This testing regimen was repeated, beginning 4, 6, and 10 weeks post-TBI. Results showed that, while the low-magnitude injury produced no overt spatial memory deficits, the moderate-magnitude group exhibited overt deficits during the first test regimen. Also, while both injury magnitudes produced an enhanced sensitivity to spatial memory impairment by scopolamine at two weeks post-TBI, this covert deficit persisted only in the severe group at 4, 6, and 10 weeks post-TBI. Qualitative light microscopy showed that both injury groups had graded cortical necrosis. However, underlying subcortical structures such as the hippocampus appeared intact, with no overt cellular or parenchymal damage to the neuropil. These data suggest three distinct stages of functional recovery: (1) the initial period when overt deficits are present, (2) a period following recovery from overt deficits within which covert deficits can be reinstated by a pharmacological challenge, and (3) a period following recovery from both overt and covert deficits. Covert deficits can persist long after the recovery of overt deficits and, like other neurological deficits, the rate of recovery is dependent on the magnitude of TBI. Finally, spatial memory deficits can occur in the absence of light microscopic evidence of cell death in the hippocampus.
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PMID:Time course of increased vulnerability of cholinergic neurotransmission following traumatic brain injury in the rat. 856 3

Rat peroneal nerves were transected and entubulated with a Silastic channel. The experimental group was treated with hyperbaric oxygen to evaluate changes in acute edema, functional recovery, and histology. Hyperbaric oxygen was administered with 100% O2 at 2.5 atmospheres absolute for 90 minutes twice a day for 1 week and then four times a day for 1 week. Acute edema changes based on nerve water weight and transfascicular area measurements were greater in injured than in uninjured nerves but demonstrated no differences between hyperbaric oxygen-treated and -untreated groups 2, 8 and 16 days after surgery. Functional evaluation with gait analysis demonstrated significant changes between injured and uninjured group 1, 3, 7, and 13 weeks after injury but no differences between hyperbaric oxygen-treated and -untreated groups. Thirteen weeks after the initial injury, elicited muscle force measurements demonstrated no significant improvement from hyperbaric oxygen treatment of injured nerves. Histologic evaluation of nerve area, myelinated axon number, myelinated axon area, myelin thickness, and blood vessel number and area revealed no significant differences between hyperbaric oxygen-treated and -untreated groups. Hyperbaric oxygen was not associated with improvement of nerve regeneration with any of the outcome variables in this model.
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PMID:Hyperbaric oxygen treatment after rat peroneal nerve transection and entubulation. 864 77

We compared the efficacy of using histidine-tryptophan-ketoglurate (HTK) solution with that of University of Wisconsin (UW) solution for heart preservation in an isolated rat heart preparation. Nicorandil (NCR) exerts its action as an ATP-sensitive potassium channel opener at low extracellular potassium concentrations, and HTK solution has a low potassium concentration. Therefore, we also investigated the efficacy of using HTK solution with NCR following 12-hr preservation. Hearts isolated from male Wistar rats were mounted on a Langendorff apparatus to estimate baseline aortic flow (AF), coronary flow (CF), cardiac out-put (CO), heart rate (HR), systolic pressure (SP), aortic mean pressure, and the rate-pressure product (RPP). The hearts were divided into four groups: group 1, 8-hr storage in UW solution; groups 2 and 3, 8- or 12-hr storage in HTK solution, respectively; and group 4, 12-hr storage in HTK solution with NCR. They were arrested and stored at 4 degrees C in each preservation solution. Following storage, they were reperfused and postpreservative function was measured to assess cardiac functional recovery. Concentrations of creatine phosphokinase, troponin-T, and lactate in the coronary perfusate were measured. Frozen tissue samples from groups 3 and 4 were analyzed for adenylate content and cGMP. The myocardial water content was also measured. The recovery of AF, CF, CO, SP, and RPP in group 2 was significantly improved compared with that in group 1 (P<0.05). The recovery of AF, CF, CO and HR in group 4 was significantly better than that in group 3 (P<0.05). Creatine phosphokinase leakage in group 2 and troponin-T leakage in group 4 were significantly reduced (P<0.05 vs. groups 1 and 3, respectively). Total adenine nucleotides and the adenylate energy charge in group 4 were well sustained (P<0.05 vs. group 3). These results suggest that HTK solution is more effective than UW solution for cardiac preservation, and that NCR provides still better protection.
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PMID:Cardioprotective effect of nicorandil in histidine-tryptophan-ketoglurate solution during the cold storage of isolated hearts. 866 99

Nerve growth factor (NGF) stimulates functional recovery from cognitive impairments associated with aging, either when administered as a purified protein or by means of gene transfer to the basal forebrain. Because gene transfer procedures need to be tested in long-term experimental paradigms to assess their in vivo efficiency, we have used ex vivo experimental gene therapy to provide local delivery of NGF to the aged rat brain over a period of 2.5 months by transplanting immortalized central nervous system-derived neural stem cells genetically engineered to secrete NGF. By grafting them at two independent locations in the basal forebrain, medial septum and nucleus basalis magnocellularis, we show that functional recovery as assessed in the Morris water maze can be achieved by neurotrophic stimulation of any of these cholinergic cell groups. Moreover, the cholinergic neurons in the grafted regions showed a hypertrophic response resulting in a reversal of the age-associated atrophy seen in the learning-impaired aged control rats. Long-term expression of the transgene lead to an increased NGF tissue content (as determined by NGF-ELISA) in the transplanted regions up to at least 10 weeks after grafting. We conclude that the gene transfer procedure used here is efficient to provide the brain with a long-lasting local supply of exogenous NGF, induces long-term functional recovery of cognitive functions, and that independent trophic stimulation of the medial septum or nucleus basalis magnocellularis has similar consequences at the behavioral level.
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PMID:Long-term functional recovery from age-induced spatial memory impairments by nerve growth factor gene transfer to the rat basal forebrain. 869 19

Functional effects of fetal hippocampal field grafts were assessed in rats with spatial learning and memory impairments following global cerebral ischaemia. Experiment 1 examined effects of grafts dissected from fields CA1 and CA3 at embryonic day 19 and from the dentate gyrus at postnatal day 1. Cell suspensions (15,000 cells/site) were implanted bilaterally at two points above the dorsal CA1 area two weeks after four-vessel occlusion (electrocoagulation of the vertebral arteries followed the 24 h later by occlusion of the carotid arteries for 15 min). Histological examination showed that CA1 neuronal loss (60-70%) was equivalent in all ischaemic groups and that 80% of CA1 and 60% of CA3 grafts survived and were sited appropriately in the alveus or corpus callosum above the area of ischaemic CA1 damage in the host, but there was no survival of dentate grafts. Results from rats with poor pyramidal cell graft survival were excluded, but those from rats with non-surviving dentate grafts were retained as an additional control group. Acquisition in the water maze was examined nine and 25 weeks after transplantation, and spatial working memory was assessed in three-door runway and water maze matching-to-position tasks 19 and 28 weeks after grafting, respectively. For water maze acquisition rats were trained with two trails/day and a 10 min inter-trial interval for 10-12 days to locate a submerged platform. Ischaemic rats with CA1 grafts learned the platform position as rapidly as non-ischaemic controls, searched appropriately in the training quadrant and were accurate in heading towards the platform, but were initially impaired on recall of the precise platform position on probe trials with the platform removed. Performance of ischaemic controls and groups with CA3 and non-surviving dentate graft groups was significantly impaired relative to controls and to the CA1 grafted group. The CA1 grafted group was also as successful as controls in matching-to-position in the water maze and substantially superior to the other ischaemic groups, assessed using three trials/day, with a 30-s inter-trial interval and a different platform position on each day. In a more complex matching-to-position task in the three-door runway, the performance of the CA1 grafted group was significantly impaired relative to controls, although superior to that of the other ischaemic control and graft groups. Functional recovery with CA1, but not CA3, grafts in ischaemic rats was replicated in a second experiment which assessed water maze acquisition and working memory at 10 and 14 weeks after transplantation, in rats with 90% graft survival. These results indicate that long-lasting, task-dependent improvements can be seen in ischaemic rats with CA1 fetal grafts in both aversively and appetitively motivated spatial learning tasks. The findings suggest that functional recovery requires homotypic replacement of CA1 cells damaged by ischaemia, rather than provision of structurally similar glutamate-releasing CA3 pyramidal cells.
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PMID:Contrasting effects of fetal CA1 and CA3 hippocampal grafts on deficits in spatial learning and working memory induced by global cerebral ischaemia in rats. 873 23

We examined the effects of supplementation with eiosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids (PUFAs), on basal cardiac function and recovery of cardiac function of "donor hearts" from adults (30 week) rats following cold preservation and reperfusion (P/R). In groups 1, 2, 3, and 4, respectively, 30-week-old rats were fed a soybean oil diet, a high-cholesterol oil (HC) diet, an HC diet with EPA, or an HC diet with DHA for 5 weeks. After collecting blood to analyze plasma levels of fatty acids among each group, the heart was excised and perfused on a Langendorff apparatus. Following evaluation of each rat's cardiac function, each heart was stored in HTK solution for 8 hr at 4 degrees C. The heart was then reperfused and the coronary perfusate was collected to evaluate enzyme that had leaked. After cardiac functional recovery was estimated, myocardial fatty acids were measured. EPA supplementation significantly increases the plasma and cardiac levels of EPA as well as the ratio of EPA to arachidonic acid (AA). EPA supplementation also led to improved recovery of cardiac function following P/P, compared with that of rats who received soybean oil, high-cholesterol oil, and DHA. DHA supplementation significantly increased the plasma and cardiac levels of DHA as well as the ratio of DHA to AA--however, the cardiac functional recovery was almost identical to that of the rats who received high-cholesterol oil and was higher only than that of the rats who received soybean oil. There were no significant differences in enzyme that had leaked and myocardial water content among each group. These results suggest that alterations in the myocardial phospholipid composition by EPA supplementation may be profoundly responsible for attenuating myocardial I/R injuries. In contrast, DHA supplementation may not exert a cardioprotective effect following cold P/R. DHA supplementation alone may not increase the myocardial level of EPA enough to cause a protective effect against P/R injury. EPA supplementation to hyperlipidemic patients may be clinically warranted for increasing the potential number of donors.
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PMID:The effects of omega-3 polyunsaturated (correction of polyunsatulated) fatty acids on the recovery of cardiac function following cold preservation and reperfusion in hyperlipidemic rats. 882 69

The use of glutamate antagonists and GABA agonists may protect neurons from the effects of transient ischemia. Felbamate is a new antiepileptic drug with glutamate antagonist and GABA agonist properties. We tested the efficacy of felbamate in a gerbil model of transient forebrain ischemia. Damage assessment was done with silver staining at 7 and 28 days after 5 min of bilateral carotid occlusion. Cerebral cortex, hippocampus (CA1 and CA4), thalamus and striatum were evaluated on a 4-point scoring system. The animals sacrificed at 28 days were also tested in a water-maze task to assess recovery of function. The initial dose of felbamate (300 mg/kg) was given 30 min before the ischemic insult in one set of animals and 30 min after the insult in another set of animals. There were 8 animals tested per group (total: 48 animals). There was significant neuronal protection with the use of felbamate, both before and after ischemia in all regions of the brain. Protection was seen in animals sacrificed at 7 and 28 days. Protection was moderate when felbamate was used before ischemia. It was highly significant when felbamate was given 30 min after the insult. Behavioral studies however did not show any difference in the felbamate treated animals versus the saline treated controls. The structural protection with felbamate was very significant when used in the post-ischemic period. This window for protection merits further evaluation in relation to the clinical setting of stroke.
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PMID:Neuroprotection with felbamate: a 7- and 28-day study in transient forebrain ischemia in gerbils. 884 83


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