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

Perfusion of isolated, nondiabetic rat hearts with high concentrations of regular insulin (10 mU/ml) produced earlier onset of myocardial contracture during ischemia than control perfusions without insulin. High insulin concentrations also increased total myocardial calcium content (p less than .001) and myocardial Ca-45 uptake postischemia (p less than .05). Insulin perfusion before ischemia did not enhance calcium uptake. These results support the hypothesis that insulin may increase calcium movement across myocardial cell membranes, which may lead to increased ischemic contracture. Insulin-aggravated myocardial ischemia in cardiothoracic surgery and cardiac resuscitation deserves further investigation.
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PMID:Calcium uptake during insulin-aggravated ischemic myocardial contracture in the rat heart. 351 79

The effects of ischemia at varying temperatures on the survival of fetal islet endocrine cells was investigated by placing 17-day-old fetal mouse pancreata in organ culture after 2, 4, or 6 h at either 4 degrees C, 22 degrees C, or 37 degrees C. Insulin secretion by the cells in vitro, the content of insulin in the cultured pancreata, and the ability of the cultured islets to reverse diabetes in syngeneic streptozotocin-diabetic mice were assessed. Fetal pancreas subjected to 2-6 h of ischemia at either 4 degrees C or 22 degrees C showed neither loss of insulin secretory capacity in vitro nor loss of ability to produce large functional grafts, and behaved identically to tissue not subjected to deliberate ischemia. In contrast, after 2 h of ischemia at 37 degrees C, although some grafts functioned, their insulin content was reduced despite apparently normal prior insulin production in vitro, but 4 or 6 h at 37 degrees C resulted in total loss of functional islet tissue. However, despite retention of functional capacity and the ability to produce large grafts with high insulin content after cold or room temperature ischemia, some loss of insulin storage capacity in vitro was noted by islets subjected to ischemic periods longer than 2 h even at 4 degrees C. Thus, fetal pancreas can withstand prolonged periods of ischemia provided its temperature is reduced, and functional recovery can be demonstrated after transplantation.
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PMID:Effect of ischemia and temperature on fetal mouse pancreas. Insulin production in vitro, and function after isotransplantation. 642 31

Insulin treatment of hearts during aerobic reperfusion following transient ischemia in the working rat heart preparation significantly improved the recovery of myocardial function. This improvement was reflected both by a shorter time required for the heart to resume beating, and to increase heart rate and peak systolic pressure after resumption of beating. The beneficial effects of insulin may be related to improved energy metabolism secondary to small increases in pyruvate production during the early phase of reperfusion. It was also associated with an increased rate of restoration of cellular K+. Pyruvate addition to the perfusate also improved resumption of spontaneous beating of the heart and restoration of normal rate and pressure development. This effect of pyruvate was also associated with increased cellular levels of K+. Both insulin and pyruvate may improve ATP production during the first few minutes of reperfusion when glycolysis and oxidation of fatty acids are inhibited, but ATP levels were not increased after 30 min of reperfusion.
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PMID:Energy metabolism during reperfusion following ischemia. 701 2

Insulin has recently been shown to ameliorate damage in models of global brain ischemia. To determine whether insulin is also neuroprotective in focal ischemia, 20 rats were given 2 to 3 IU/kg insulin and 10 did not receive treatment prior to normothermic transient middle cerebral artery occlusion for 2 hours at a blood pressure of 60 mm Hg. To further elucidate whether infarction volume is influenced by variations in blood glucose levels within the physiological range, blood glucose was raised in 10 of the insulin-treated animals to levels comparable with the untreated controls. At 1-week survival, damage was assessed using quantitative neuropathological examination of 25 coronal planes. It was found that preischemic insulin lowered the mean intraischemic blood glucose level from 8.4 +/- 0.2 mM (mu +/- standard error of the mean) in the control group to 3.4 +/- 0.2 mM and reduced total damage (atrophy plus cortical and striatal necrosis), expressed as the percentage of the normal hemisphere, from a control of 28.5% +/- 2.9% to 14.5% +/- 1.6% (p < 0.005). Coadministration of glucose and insulin resulted in a mean intraischemic blood glucose level of 10.1 +/- 0.5 mM, with 27.0% +/- 2.4% total damage (p = 0.96, compared with control). Total ischemic damage showed an independent correlation with blood glucose levels (r = 0.67, p = 0.0018). The findings indicate that insulin benefits transient focal ischemia and that reducing the blood glucose from 8 to 9 mM to the low-normal range of 3 to 4 mM with insulin dramatically reduces subsequent infarction. The data suggest that the neuroprotective mechanism of insulin action in focal middle cerebral artery occlusion is mediated predominantly via alterations in blood glucose levels. In comparison to global ischemia, focal ischemia appears to show only a minor direct central nervous system effect of insulin. In clinical situations in which transient focal ischemia to the hemisphere can be anticipated, insulin-induced hypoglycemia of a mild degree may be beneficial.
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PMID:Insulin reduction of cerebral infarction due to transient focal ischemia. 861 24

This report describes high performance liquid chromatographic analysis of transplanted pancreatic islets. A reversed phase ODS column made it possible to measure rat insulin I, II, rat C-peptide I, II and glucagon simultaneously in isolated rat islets without using radioisotopes. Freshly isolated islets contained 118.0 +/- 9.7 ng (mean +/- SE, n = 6) insulin and 3.01 +/- 0.60 ng glucagon per islet. The insulin I/II ratio was 1.22 +/- 0.03. Isolated islets were then cultured in vitro or transplanted into mice under the renal capsule. Transplantation induced mild hypoglycemia in the recipients. The graft mean survival time was 7.2 +/- 0.4 days (n = 5). Both cultured (n = 7) and transplanted (n = 6) islets showed similar alterations of polypeptide hormones on day 4. Insulin decreased to one third and glucagon remained unchanged. The insulin I/II ratio increased twofold. In conclusion, it was suggested that the general fate of isolated islets was caused by ischemia and denervation. Relatively, ischemia may not damage alpha cells but may damage beta cells because alpha cells are peripherally located. Denervation may release beta cells from a resting state under neural tonic inhibition. Mild hypoglycemia and an increased insulin I/II ratio were related to the accelerated insulin synthesis in the isolated islets.
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PMID:High performance liquid chromatographic analysis of polypeptide hormones in transplanted rat islets. 788 34

Studies were carried out to investigate the effects of prostaglandin E1 (PGE1) pretreatment on normothermic liver ischemia. Mixed-breed dogs were divided into three groups: a control group, a group with induced liver ischemia, and a group pretreated with PGE1 followed by induced liver ischemia. Liver ischemia was induced by the Pringle procedure for 60 min. PGE1 was administered intravenously to some dogs at a dose of 0.5 microgram/kg/min for 30 min prior to the Pringle procedure. Sham operations were performed without induction of liver ischemia in control animals. Insulin, glucagon, and glucose metabolic clearance rates were examined before and after the Pringle procedure in the control and experimental groups. Insulin and glucose metabolic clearance rates decreased 5 min after declamping in the ischemic group, while the glucagon metabolism was not affected, and lipid peroxide production increased. In contrast, hepatic insulin metabolism improved, and lipid peroxide production normalized in the ischemic group which was pretreated with PGE1. This study suggests that PGE1 prevents hepatic metabolic disturbances due to warm ischemia and subsequent reperfusion.
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PMID:Prostaglandin E1 protects liver from ischemic damage. 807 86

Insulin-like growth factors (IGFs) are involved in cell growth and differentiation. In muscle tissue they regulate axonal in growth and maintain the connection. They also play a role in regeneration of the peripheral nerve system. We hypothesized that IGFs might also be important factors in the recovery of central nervous tissue after traumatic damage such as perinatal asphyxia. Our group developed a rat model to mimic the resulting damage and test the changes of expression of IGF-1, -2 and several of their binding proteins. We also examined the influence of exogenous IGF-1 and -2 after asphyxia in the same model. Rats underwent a unilateral ligation of the A. carotis followed by a 15 or 90 min inhalational hypoxia (8% O2). The treatment resulted in a mild or severe damage in the ligated hemisphere with either selective neuronal loss or complete infarction of the volume, respectively. The treatment induced expression of both IGFs and binding protein 2, 3 and 5. Binding protein 1 is not expressed and binding protein 4 is suppressed soon after hypoxia-ischemia. We conclude that both IGFs and several of their binding proteins are involved in response and wound healing after hypoxic brain damage. This was further tested in a second experiment. Rats were injected with IGF-1 or IGF-2 intra-ventricular soon after the hypoxic damage. IGF-1 treatment significantly reduced neuronal loss, IGF-2 had no effect. Behaviour tests, however, showed no difference between IGF-1 treated rats and controls. Our studies show interesting aspects for further investigation and a possible treatment of perinatal asphyxia and traumatic damage of nerve tissue.
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PMID:[Somatomedins and their binding proteins are involved in wound healing after hypoxia of the central nervous system]. 812

High levels of fatty acids can decrease the recovery of previously ischemic hearts by inhibiting myocardial glucose use during reperfusion. We determined if this was due to a decrease in glycolysis or a decrease in glucose oxidation. Isolated working rat hearts were perfused with either 11 mM [2-3H/U-14C] glucose or 11 mM [2-3H/U-14C] glucose and 1.2 mM palmitate. In aerobically perfused hearts, the presence of fatty acids reduced glucose oxidation rates (from 1576 +/- 154 to 228 +/- 28 nmol/min.g dry weight, P < .05), with a nonsignificant reduction in glycolysis (from 3297 +/- 349 to 2798 +/- 343 nmol/min.g dry weight). If fatty acid perfused hearts were subjected to a 30-min period of ischemic function was 36%. Glucose oxidation rates during reperfusion were markedly lower than glycolytic rates (228 +/- 35 and 3096 +/- 576 nmol/min.g dry weight, respectively, P < .05). Dichloroacetate (1 mM) added during reperfusion significantly improved recovery of mechanical function to 96% of preischemic values. In these hearts, Dichloracetate increased glucose oxidation, while actually decreasing glycolytic rates (values during reperfusion were 501 +/- 136 and 1171 +/- 122 nmol/min.g dry weight, respectively). Insulin (500 microU/ml) added at reperfusion resulted in a small increase in glucose oxidation rates and a significant increase in glycolysis (375 +/- 66 and 4769 +/- 955 nmol/g dry weight.min, respectively). However, the presence of insulin at reperfusion did not improve recovery of function (hearts recovered 52% of preischemic function). We demonstrate that the detrimental effects of high concentrations of fatty acids after ischemia are primarily due to an inhibition of glucose oxidation, and not glycolysis, during the reperfusion period. Furthermore, increasing glucose oxidation during reperfusion has a beneficial effect on functional recovery of hearts.
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PMID:An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acids during aerobic reperfusion of ischemic hearts. 838 Aug 56

31P nuclear magnetic resonance spectroscopy was used to follow changes in cerebral pH and high-energy phosphate metabolites during forebrain ischemia in hypo-, normo- and hyperglycemic rats, and during reperfusion in animals in which the blood glucose level was altered post-ischemia. Pre-ischemia, no differences in the levels of inorganic phosphate (Pi) and adenosine triphosphate (ATP) relative to phosphocreatine (PCr) or in tissue pH between blood glucose groups were observed. During ischemia, the decrease in tissue pH was found to be dependent on the pre-ischemic blood glucose concentration, being greatest in hyperglycemic and least in hypoglycemic animals. The increase of Pi, a consequence of the hydrolysis of high-energy phosphate metabolites, also depended on the blood glucose concentration, being greatest in hypoglycemic and least in hyperglycemic animals. ATP and PCr decreased more rapidly in hypoglycemic rats compared to normo- or hyperglycemic animals, which showed no differences in the rates of depletion. Post-ischemic hyperglycemia resulted in delayed recovery of tissue pH in all groups and of PCr and ATP in animals hyperglycemic throughout the experiment. Insulin administration immediately following ischemia increased the rate of recovery of pH, ATP and PCr in hyperglycemic animals. ATP remained significantly below pre-ischemia level in all subgroups at 1 h post-ischemic, while PCr was lower than it was pre-ischemia only in those subgroups hyperglycemic prior to and/or following ischemia. In animals maintained severely hypoglycemic throughout the experiment, erratic blood pressure and cerebral energy failure during the reperfusion interval were observed.
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PMID:Metabolic changes associated with altering blood glucose levels in short duration forebrain ischemia. 849 63

The purpose of this investigation was to assess the effects of hyperglycemia, in the absence of changes in plasma insulin and arterial free fatty acid (FFA) levels, on interstitial glucose levels and glucose uptake across the left ventricular wall during ischemia in domestic swine. Insulin secretion was suppressed with a continuous infusion of somatostatin. Arterial FFA levels remained stable due to the suppression of insulin. Microdialysis probes were used to estimate changes in interstitial glucose and lactate, and were placed in the subepicardium and the subendocardium of the left anterior descending ([LAD] ischemic) coronary artery perfusion bed and in the midmyocardium of the circumflex ([CFX] nonischemic) perfusion bed. The LAD coronary artery was cannulated and perfused with blood from the femoral artery through an extracorporal perfusion circuit. Ischemia was induced in the LAD perfusion bed by reducing the flow of the LAD perfusion pump by 60% for 50 minutes, and was followed by 30 minutes of reperfusion. Twenty minutes into the ischemic period, seven animals were given a bolus injection of 50% glucose (200 mg/kg) followed by a glucose infusion (10 mg/kg/min), resulting in an increase in arterial glucose levels from 5 to 13 mmol/L in the hyperglycemic group. Hyperglycemia resulted in a marked increase in dialysate glucose during ischemia and a greater than twofold increase in glucose extraction and uptake. Dialysate glucose correlated with plasma glucose in all three perfusion beds. In conclusion, hyperglycemia, in the absence of an increase in insulin and a decrease in arterial FFA, resulted in a doubling of glucose extraction, delivery, and uptake, which corresponded to the twofold elevation in interstitial glucose during ischemia.
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PMID:Hyperglycemia results in an increase in myocardial interstitial glucose and glucose uptake during ischemia. 862 95


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