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

Seizures are a documented complication to cerebral ischemia. After 10 min of forebrain ischemia in rats, preischemic hyperglycemia invariably leads to severe, most often fatal epileptic attacks. This outcome is related to the exaggerated lactic acidosis, which has been suggested as a possible contributor to severe membrane changes and widespread edema. To find out if circulating hormones or plasma energy substrates modulate this additive damage caused by the hyperglycemia, plasma concentrations of of corticosterone, epinephrine, norepinephrine, dopamine, glucagon, insulin, glucose, free fatty acids (FFA), 3-hydroxybutyrate, and acetoacetate were measured before and in the early recirculation period after 15 min of forebrain ischemia in the rat. Plasma corticosterone levels did not differ between the normo- and hyperglycemic groups. Although not significantly different from control, the catecholamine levels showed a tendency to be higher in the hyperglycemic groups. Therefore, because catecholamines have been reported to have a protective effect during ischemia the present result cannot explain why hyperglycemia aggravates the ischemic damage. Insulin levels seemed to increase during ischemia but not significantly. Levels quickly returned to normal after 30 min of recirculation. FFA concentrations were reduced after the induction of ischemia and appeared lower in all hyperglycemic groups. The level of one of the ketone bodies, 3-hydroxybutyrate, showed a significant decrease in hyperglycemic ischemia in all groups compared with normoglycemic ischemia. The same tendency was seen for acetoacetate. Results are compatible with a protective role of ketone bodies in ischemia. It is concluded that among the hormones and substrates studied only the ketone body concentrations qualify as a modulator of the exaggerated brain damage after ischemia in hyperglycemic subjects.
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PMID:Ischemia in normoglycemic and hyperglycemic rats: plasma energy substrates and hormones. 211 Apr 23

This study describes a procedure for large scale isolation of swine islets. The reported results are from 15 consecutive isolations. The glands were removed from live animals with no warm ischemia, and the pancreata were digested by a modification of the automated method for human islet isolation. It was possible to separate an average of 690,000 +/- 279,429 islets per pancreas corresponding to 10,360 +/- 4034 islets per gram of pancreas with a volume of 714 +/- 480 mm3. After purification the recovery was 255,000 +/- 32,407 islets corresponding to 4,000 +/- 567 islets per gram of pancreas. Purity of the final preparation was 80% to 95% islets. Insulin content resulted in an average of 146.8 +/- 78 U before purification and 71 +/- 53 U after purification. After a 10 mm3 aliquot of the final preparation was transplanted under the renal subcapsular space of seven nude mice with diabetes, normoglycemia occurred in six of the mice. Thirty days after transplantation, nephrectomy of the kidneys bearing the grafts produced a rapid return to the diabetic state in all cases. This method makes it possible to provide large numbers of intact swine islets for preliminary studies of prevention of the rejection of pig islet xenograft by immunoalteration and immunoisolation procedures.
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PMID:Isolation of the elusive pig islet. 211 87

The contribution of poor metabolic control to myocardial ischemic failure was determined in isolated working hearts from insulin-dependent BB Wistar rats. Removal of insulin treatment 24 h prior to study (uncontrolled diabetic rats) resulted in significant increases in serum glucose, serum fatty acids, and myocardial triglyceride, compared with animals in which insulin treatment was not withheld (insulin-treated diabetic rats). Isolated working hearts obtained from these two groups were subjected to a 40% reduction in coronary flow in the presence of a maintained metabolic demand (hearts were paced at 200 beats/min and perfused at an 80 mmHg (1 mmHg = 133.3 Pa) left aortic afterload, 11.5 mmHg left atrial preload). Within 15 min of ischemia, a significant deterioration of mechanical function occurred in the uncontrolled diabetic rats, whereas function was maintained in the insulin-treated diabetic rats. Oxygen consumption by the two groups of hearts was similar prior to the onset of ischemia and decreased during ischemia in parallel with the work performed by the hearts. This suggests that the accelerated failure rate in uncontrolled diabetic rat hearts is unlikely a result of an increased oxygen requirement. These data are a direct demonstration that acute changes in metabolic control of the diabetic can contribute to the severity of myocardial ischemic injury.
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PMID:Acute insulin withdrawal contributes to ischemic heart failure in spontaneously diabetic BB Wistar rats. 218 88

The recovery of both contractile performance and metabolic response of rat heart following 1 h of ischemia after equilibration with glucose + insulin (glucose-ischemia) or with pyruvate (pyruvate-ischemia), was tested in normoxic reperfusion in the presence of glucose + insulin, pyruvate, lactate or acetate. In glucose-ischemia only the reperfusion with pyruvate results in a complete recovery of the contractile force (left ventricular pressure, LVP) (170%) and good recovery of high energy phosphate compounds. Lower LVP and tissue energy charge were found in glucose reperfusion and even less in lactate and acetate reperfusion. Disappearance of the IMP accumulated during ischemia is evident only in the pyruvate reperfusion indicating a higher metabolic recovery. On the contrary in pyruvate-ischemia all types of reperfusion tested were effective in reactivating the contractile force (although acetate to a lesser extent); the contractile activity was accompanied by a good recovery of phosphocreatine, ATP, energy charge and by the decrease of IMP. Large decreases of adenine nucleotides and NADP and lower decreases of NAD are observed during ischemia/reperfusion in both systems. Pyruvate-ischemia is quite similar to, if not worse than glucose-ischemia, for all the metabolic parameters considered, but not worse for the possibility of recovery. Some specific effect of pyruvate should be exerted during the ischemic phase. The mechanism of pyruvate protection is discussed in relationship to: (i) the possible activation of pyruvate dehydrogenase, (ii) the activation of NADPH-dependent peroxide scavenging systems, (iii) the direct scavenging action of pyruvate on H2O2.
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PMID:The protective action of pyruvate on recovery of ischemic rat heart: comparison with other oxidizable substrates. 218 87

Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Insulin and atheroma. 20-yr perspective. 199 42

We have previously shown that high concentrations of fatty acids depress reperfusion recovery of ischemic rat hearts as a result of a fatty acid inhibition of glucose oxidation. In this study, we determined whether dichloroacetate, an activator of pyruvate dehydrogenase, could overcome fatty acid inhibition of glucose oxidation and thereby improve mechanical recovery of hearts reperfused after a period of transient global ischemia. Isolated working rat hearts, perfused with 11 mM glucose, 1.2 mM palmitate, and 500 microU/ml insulin, were subjected to a 30-min period of no flow ischemia, followed by a 30-min period of reperfusion. Under these conditions, control hearts recovered 37% of preischemic function. The addition of 1 mM dichloroacetate to the perfusate at reperfusion resulted in a significant improvement in recovery of mechanical function (to 73% of preischemic function). When dichloroacetate was added before the onset of ischemia, however, this protective effect was lost, and a significant increase in myocardial lactate accumulation during ischemia was observed. The effects of dichloroacetate on glucose oxidation rates in both nonischemic and reperfused ischemic hearts was determined by perfusing hearts with 11 mM [U-14C]glucose and 1.2 mM palmitate and quantitatively collecting 14CO2 produced by the heart. In nonischemic hearts, 1 mM dichloroacetate increased steady-state glucose oxidation rates from 298 +/- 69 to 1,223 +/- 135 nmol.g dry wt-1.min-1. The addition of dichloroacetate to hearts reperfused after a 25-min period of ischemia also increased glucose oxidation rates from (112 +/- 25 to 561 +/- 83 nmol.g dry wt-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts. 222 Nov 15

1. Rats which survived hypoglycemia by insulin, hypoxia by 10% O2, or ischemia by carotid ligation and hypotension to 40 mm Hg, evidenced no changes in cerebrospinal fluid (CSF) uridine. Animals which died soon after the above interventions or as a result of KCl-induced cardiac arrest had elevated CSF uridine concentrations. 2. Injection of whole blood or the soluble contents of lysed blood cells into the lateral ventricle of rats reduced CSF uridine to less than one-half normal at 24 hrs but values returned to normal 3 days later. Changes in hypoxanthine resembled those of uridine, but were less dramatic, whereas xanthine concentrations were largely unaltered. Intraventricular injection of plasma or saline did not alter CSF uridine. 3. It seems most likely that low CSF uridine concentrations previously reported in head injury patients may be secondary to the effects of blood cell contents in the cerebrospinal fluid, rather than responses to altered metabolism in neurons or glia cells.
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PMID:Opposite alterations in cerebrospinal fluid uridine after severe cerebral ischemia or intrathecal blood injection. 225 61

Sudden fissuring of an atherosclerotic plaque has been suggested as the primary trigger of transient spontaneous ischemia in both the coronary and cerebral circulation. Measurements of urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2, as well as results of Aspirin trials, have suggested that episodic platelet activation at the site of this acute vascular lesion is mediated, at least partly, by enhanced thromboxane (TX) A2 biosynthesis. Thus, episodic increases in metabolite excretion have been detected in unstable angina. Aspirin (75-325 mg/day) prevents about one third of all fatal and nonfatal thrombotic events in this setting. That a similar "dynamic" thrombotic process occurs during the early phase of acute myocardial infarction is suggested by thromboxane metabolite measurements and by the results of the ISIS-2 trial showing a similar impact of short-term Aspirin therapy to that seen in unstable angina. Percutaneous transluminal coronary angioplasty is associated with transiently enhanced TXA2 biosynthesis and Aspirin-suppressable periprocedural thrombotic complications. On the other hand, both non-insulin-dependent diabetes mellitus and type IIa hypercholesterolemia are associated with a relatively reproducible and persisting abnormality of TXA2-dependent platelet function. This association is likely to reflect a systemic rather than localized stimulus to platelet activation and a continuous rather than episodic alteration. Low-dose (50 mg/day) Aspirin can largely suppress thromboxane metabolite excretion in both diseases. Thus, low-dose Aspirin and/or selective prostaglandin H2/TXA2-receptor antagonists may be important tools to test the hypothesis that TXA2-dependent platelet activation represents an important transducer of the enhanced thrombotic risk associated with these metabolic abnormalities.
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PMID:Thromboxane biosynthesis in cardiovascular diseases. 226 Jan 37

Controversy still exists in the published literature about the need for administration of intravenous glucose during liver transplantation. The ability of the grafted liver to metabolize insulin and glucagon and the appropriateness of secretion of these hormones are addressed in the present study. Two groups of pigs received unstored liver autografts, one with free infusion of 10% glucose and the other with limited infusion of 2.5% glucose solution, while attempting to maintain plasma glucose levels less than 200 mg/100 ml. In these animals, irrespective of moderate or major hyperglycemia, serum insulin levels were appropriate for blood glucose concentrations. However, in both groups, plasma glucagon levels rose three- to fourfold more than preoperative values and were inappropriate. Although facilities for measurement of blood flow were not available, application of the technique of transhepatic sampling has revealed that hepatic handling of insulin seems to be unimpaired after autograft with limited ischemia. Pancreatic secretion of glucagon, however, appeared to increase during the period immediately after revascularization. It is suggested that transhepatic sampling methods may be used in experimental transplantation to elucidate the effects of storage for prolonged periods.
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PMID:Transhepatic sampling during experimental porcine liver autotransplantation--its application to measurements of insulin, glucagon, and glucose. 226 87

Published "normal" values of some hormones have an excessively wide range and unequal mean values because the material on which these values are based is from subjects suffering from different diseases which only apparently are not associated with the investigated hormone, or else the specimens are obtained under non-standard conditions (malnutrition, stress, alcohol etc.). This wide range of normal values may hide incipient pathological processes and is not suitable even as control group. The investigation is based on the assessment of insulin, growth hormone (GH), cortisol, thyroxine (T4) and triiodothyronine (T3) in a group of blood donors. The assembled results were compared with two other groups of blood donors and a group of obese subjects. The following findings were assembled: We recommend to lower the upper borderline of "normal" insulinaemia from the recommended value of 26 to 20 i.u./l, as the original range may comprise milder forms of hyperinsulinism which is recently assumed to participate in the genesis of type 2 diabetes, hypertension, coronary ischemia and polycystic ovaries. Elevated normal values of serum insulin may be obtained also from blood donors who usually have breakfast before the blood is collected. The wide range of cortisolaemia is due to the diurnal rhythm. The basal value is raised by a declining blood sugar level, alcohol, obesity and of course, varying forms of stress. The upper range of cortisolaemia at 8 a.m. should not be beyond the range of 140-690 nmol/l. GH secretion is governed by an individual 3.5-hour cycle as well as changes of the blood sugar level, e. g. during the OGTT: the declining blood sugar level raises the GH level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Factors affecting normal levels of insulin, cortisol, STH, thyroxine and triiodothyronine]. 226 67


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