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

This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.
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PMID:Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure. 250 26

The oxygenation of arachidonic acid by lipoxygenases results in the formation of HPETEs (hydroperoxyeicosatetraenoic acids), the first products of the LOX pathway. These compounds are short lived and are catabolised into various families of more stable compounds of which the HETEs, hepoxilins, lipoxins and leukotrienes have been identified so far. The development of new techniques have helped to identify and understand the structures of various HPETEs and only recently the biological effects of HPETEs and their various catabolites are being unraveled. Although lipoxygenases are ubiquitous, not all tissues possess the same spectrum of lipoxygenase enzymes. Hence different HPETEs can be formed in different tissues. Recent studies have revealed that HPETEs or products derived from them possess a diversity of important biological properties including the regulation of electrolyte flux and eicosanoid and corticosterone syntheses, release of histamine, regulation of oocyte maturation and release of various reproductive hormones. HPETEs appear to be involved in some pathological conditions viz, skin psoriasis, Clarkson's disease, nerve injury and spinal cord ischemia. These novel eicosanoids are associated with the release of insulin as well as renin. Recently HPETEs have been suggested to act as second messengers in the Aplysia sensory neurons and its catabolite, hepoxilin, has been demonstrated to have effects on mammalian hippocampal neurons. The purpose of this review is to provide a brief summary of the formation of the HPETEs and the various families of compounds derived from them as well as the various types of biological activities for these products described so far.
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PMID:Biosynthesis, catabolism, and biological properties of HPETEs, hydroperoxide derivatives of arachidonic acid. 251 25

A combination of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) has been used to follow the time course of changes resulting from forebrain ischemia in the rat. The 31P MRS demonstrates that the level of high energy metabolites decreases significantly during the 10 min ischemic period but returns to normal after 1 h of reperfusion. MRI shows no change after 1 h of reperfusion but significant changes in the striatum after 24 h and in the hippocampus after 48 h. These changes correlate well with histopathology. Diabetic rats have shown the effect of hyperglycemia in accentuation of ischemic and post ischemic pH changes. Conversely, diabetic rats maintained severely hypoglycemic with insulin showed little variation in pH during or following the ischemic insult. The results emphasize the importance of both MRS and MRI in following the temporal profile and distribution of ischemic neuronal injury.
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PMID:Forebrain ischemia studied using magnetic resonance imaging and spectroscopy. 264 5

More efficient methods of islet isolation must be developed for islet transplantation to become clinically routine. During collagenase dispersal of human pancreas, an amorphous, viscous, gellike material often develops and entraps large numbers of islets, thereby reducing the yield. When donor human pancreas is minced and treated with collagenase, the gel forms most abundantly if the digestion temperature is less than 35 degrees C and if pH falls below 7.2 +/- 0.2. Gel formation appears to be proportional to warm- or cold-ischemia time and may be related to tissue trauma during collection. Once gel has formed, trapped islets cannot be released by filtration, dilution, DNase, incubation temperature, or pH adjustment. These characteristics suggest that the material is gelatin derived from collagen released enzymatically from pancreatic stroma. We demonstrate that gelation is greatly reduced or eliminated when 1) the incubation medium includes glycerol--a common gelatin solvent--at 5% (vol/vol), 2) the minced tissue-to-total incubation volume ratio is greater than or equal to 1:10, 3) free-islet exposure to pancreatic digestion products is minimized by frequent separation of islets, and 4) collagenase concentration is optimized by titration. Gelation is also minimized by maintaining 5) incubation temperature at 38 +/- 1 degree C and 6) pH in the range 7.7-7.9. Variations in these physical and chemical conditions were analyzed by determining islet yields (stereoscopic microscope counts of serially diluted samples) and by insulin radioimmunoassay of acid alcohol extracts of isolated islets after separation through discontinuous Ficoll gradients. When isolation conditions are optimized as stated, we typically recover 3.3 +/- 1.0 x 10(4) islets/g pancreas, corresponding to greater than 10(6) islets per donor.
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PMID:Factors influencing isolation of islets of Langerhans. 264 35

We studied the effects of insulin with and without food deprivation on experimental cerebral ischemia in 197 gerbils. Ischemia was induced by unilateral common carotid artery occlusion for 4 hours. Gerbils were divided into four experimental groups and were studied for up to 1 week of survival: Group A (n = 50) was fed but received no insulin, Group B (n = 50) was deprived of food for 24 hours before surgery but received no insulin, Group C (n = 49) was fed and received daily injections of 0.1 IU lente insulin for 3 days before surgery, and Group D (n = 48) was deprived of food and received daily insulin injections. Insulin treatment was continued in Groups C and D after surgery. Blood glucose levels of all gerbils were determined before treatment (overall mean +/- SEM 88.0 +/- 12.4 mg/dl) and before carotid artery occlusion (Group A 92.2 +/- 18.3 mg/dl, Group B 81.4 +/- 11.7 mg/dl [p less than 0.05 different from before treatment], Group C 92.8 +/- 22.3 mg/dl, and Group D 66.1 +/- 24.0 mg/dl [p less than 0.001 different from before treatment]). Among the four groups, 52 gerbils died within 1 week. Neurologic deficits were scored and histologic evidence of the infarcts was graded in survivors at 1 week. Group C gerbils had the best stroke index scores. Histologic evaluation revealed that 35.9% of Group A, 21.1% of Group B, 13.9% of Group C (p less than 0.05 compared with Group A), and 28.1% of Group D survivors developed cerebral infarcts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of insulin on acute experimental cerebral ischemia in gerbils. 268 48

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

We investigated the ability of postischemic insulin administration to modify the structural and neurobehavioral consequences of cerebral ischemia in rats. Forebrain ischemia was induced in fed rats by combining controlled systemic hypotension with bilateral carotid artery clamping for 10 1/2 minutes. Following clamp release, one group of six rats [corrected] was given insulin (2 IU/kg s.c. b.i.d.) for 1 week. An ischemic-control group of five rats [corrected] received no postischemic treatment. A sham-ischemia group of rats was used as a behavioral control. Throughout the recovery period until sacrifice, the drinking water of all rats was supplemented with 25% glucose. Rats were trained on two water maze place navigation tasks 1-2 months after ischemia. Escape latencies and swim patterns were recorded. Performance in the insulin-treated group was better than that in the ischemic-control group (p less than 0.05) on both tasks and did not differ significantly from that of the sham-ischemia group. Improvement in behavior correlated with a significant reduction in CA1 hippocampal necrosis in the insulin-treated group (p less than 0.05). Our findings demonstrate that postischemic treatment with insulin improves neurobehavioral performance in addition to lessening ischemic neuronal necrosis.
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PMID:Postischemic insulin reduces spatial learning deficit following transient forebrain ischemia in rats. 265 86

Hyperglycemia worsens ischemic injury in several ischemic models. To determine whether renal lactate accumulation was associated with hyperglycemia-exacerbated postischemic renal dysfunction and mortality, halothane-anesthetized rats underwent right nephrectomy and 45 min of left renal artery and vein occlusion. Prior to ischemia, rats received saline (n = 22), glucose (2 g/kg, n = 22), or insulin (4 U/kg, n = 18). Sham-operated glucose-treated rats (2 g/kg, n = 4) underwent right nephrectomy and no vascular occlusion. As anticipated, glucose pretreatment elevated plasma glucose, while insulin pretreatment lowered plasma glucose; both were significantly different from values in saline controls. Creatinine was unchanged in sham-operated rats but was significantly higher in glucose-treated rats at 24 and 48 hr postischemia compared to saline controls. No statistical differences in creatinine were found when comparing saline controls to insulin-treated rats. Eighteen percent of glucose-treated rats survived to 72 hr postocclusion, while 45% of insulin-treated rats, 73% of saline control rats, and 100% of sham-operated rats survived this period. In a separate but identical treatment protocol, renal tissue was serially sampled and lactate content was determined in rats pretreated with saline (n = 7), glucose (n = 6) or insulin (n = 6) or sham-operated (n = 2) and receiving identical operation. Tissue lactate concentration did not change during serial sampling in the sham group. During ischemia, lactate was significantly higher in glucose-treated rats and significantly lower in insulin-treated rats as compared to saline controls. The adverse effects of exogenous glucose and attendant hyperglycemia on renal function during normothermic renal ischemia are demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperglycemia exacerbates and insulin fails to protect in acute renal ischemia in the rat. 265 96

To assess the effects of insulin in stable coronary artery disease (CAD), 2 U i.v. insulin was given to 9 control and 10 CAD patients during coronary sinus catheterization. Hemodynamic and metabolic data were obtained before and for 90 min after insulin injection. Insulin induced no changes in heart rate, mean aortic pressure, rate-pressure product, coronary sinus flow, or coronary resistance. Metabolic changes were similar in both groups and included 1) 30% decrease of arterial glucose (P less than .001) and 3-fold increase of myocardial glucose uptake (P less than .001), 2) 1.5- to 2.5-fold elevation of arterial lactate (P less than .001) and myocardial lactate usage (P less than .001), respectively, 3) 50-70% suppression of arterial levels (P less than .001) and myocardial uptake of free fatty acids (P less than .01), and 4) 10% reduction of myocardial net oxygen consumption (P less than .05). Myocardial citrate efflux increased in the CAD patients (P less than .05), whereas alanine release rose only in control patients (P less than .01), suggesting that glucose enters glycogen production in the CAD patients and pyruvate production in the control patients to a high degree. Myocardial glutamate uptake remained unchanged. In conclusion, insulin sensitivity was not altered in CAD. The insulin-induced shift from myocardial free fatty acid to carbohydrate usage may be beneficial to the ischemic heart by increasing glycogen stores, saving oxygen, and inhibiting an excess free-fatty acid concentration, which may be toxic during ischemia.
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PMID:Cardiac metabolic and hemodynamic effects of insulin in patients with coronary artery disease. 267 Jun 46

We present a general review of the literature concerning the role of the 31 P spectroscopy in studying the metabolic effects of drugs like verapamil, chlorpromazin, propranolol, acebutolol, 2-mercaptopropionylglycine, insulin, 2-deoxyglucose, cardioplegic solutions, as well as perfluorocarbon solutions on the energy status of the ischemic myocardium. Using 31 P spectroscopy several important results have been found concerning the changes of the concentration of the high energy phosphates and of the intracellular pH during myocardial ischemia. It is now possible to gain interesting insights into the metabolic effects of different drugs. By using these drugs, changes in the high energy phosphates, as PCr and ATP were attenuated during the myocardial ischemia. A better recovery of the PCr and ATP contents during reperfusion was noted. The myocardial pH changes during ischemia are attenuated compared to controls. A good correlation between the preservation of the high energy phosphates and myocardial pH and the recovery of the ventricular function was described. An in vivo documentation of the mitochondrial oxidative phosphorylation is now possible. A short overview is presented about the phosphorylation potential and its prognostic value for various cardiac diseases. The 31 P spectroscopy successfully shifted the research interest towards biochemical processes at the cellular level in the diagnosis and therapy monitoring. It extends our knowledge on the pathophysiology of the myocardium.
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PMID:[Possibilities of phosphorus 31 spectroscopy in assessing the therapeutic effects on cellular energy metabolism of the myocardium]. 267 15


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