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

Experimental diabetes in rodents has been successfully treated by implantation of isolated islets using a syngenic system (Lewis rats). It is possible to reverse all diabetic symptoms of the animals and to prevent late complications in kidney, eye and nervous system. Although isolated islets are highly immunogenic in an allogenic system immuno-alteration techniques have been developed and succeeded in longterm survival after culture at low temperature (24 degrees C), UV-irradiation, cryopreservation, pretreatment with Ia-antibodies etc. Islet transplantation in larger animals and in man up to now has been less successful. Although in a few studies longterm survival of canine islets has been observed, other groups were less successful using dogs and pigs in auto- or allo-transplantation. In man there are reports from various institutions during the last fifteen years using adult or fetal islet material. Only in a few instances the patients came off insulin for some weeks or months. The reasons for this failure are probably manifold: low number of islets, impurity, long ischemia time before isolation, transplantation to inappropriate sites, impairment of engraftment in longterm diabetic recipients and recurrence of autoimmunity in transplanted islets. Further studies are necessary to overcome these barriers. Recent observations using a higher number of islets (> 500,000) and new immunosuppressive drugs (FK506) seem to be promising.
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PMID:Islet transplantation: clinical and experimental. 149 Jun 85

We have previously demonstrated that withdrawal of insulin treatment from BB diabetic rats for a 24-hour period will increase the failure rate of hearts subjected to low-flow ischemia. The purpose of this study was to determine if this increased severity of ischemia was related to a decrease in glycolytic rates during ischemia. Two groups of insulin-dependent diabetic BB Wistar rats were used; in one group, insulin treatment was withheld from rats 24 hours prior to study (uncontrolled), while in the second group, the daily insulin injection was not withheld (insulin-treated). Isolated working hearts obtained from these animals were perfused with 30 mmol/L (2-3H/U-14C)-glucose and 1.2 mmol/L palmitate, at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Hearts were subjected to a 15-minute aerobic perfusion followed by 60 minutes of low-flow ischemia (coronary flow, 0.5 mL/min). Under aerobic conditions, steady-state glucose oxidation rates (measured as 14CO2 production) were decreased in the uncontrolled group compared with the insulin-treated group (85.3 +/- 21.5 v 406.2 +/- 120.1 nmol/min/g dry weight, respectively; P less than .05). Steady-state glycolytic rates (measured as 3H2O production) were also decreased in the uncontrolled group compared with the insulin-treated group (1.73 +/- 0.30 v 5.57 +/- 1.26 mumol/min/g dry weight, respectively; P less than .05). During low-flow ischemia, glucose-oxidation rates markedly decreased in both groups (23.9 +/- 8.7 and 38.3 +/- 25.2 nmol/min/g dry weight in the uncontrolled and insulin-treated diabetic rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute insulin withdrawal from diabetic BB rats decreases myocardial glycolysis during low-flow ischemia. 154 73

Experiments in adult animals have indicated that hyperglycemia accentuates whereas hypoglycemia ameliorates hypoxic-ischemic brain damage. To determine whether hypoglycemia is protective or deleterious to the perinatal brain subjected to hypoxia-ischemia, 7-d postnatal rats were rendered hypoglycemic either by receiving an s.c. injection of insulin or fasting for 12 h. All rat pups underwent unilateral common carotid artery ligation followed by exposure to 8% oxygen-balance nitrogen at 37 degrees C for 2 h. Control animals (no insulin or fasting) received s.c. injections of normal saline. Mean blood glucose concentrations were 5.4 +/- 0.1, 4.3 +/- 0.2, and 3.4 +/- 0.1 mmol/L for control, insulin, and fasted animals, respectively. Blood beta-hydroxybutyrate concentrations were identical (0.5 +/- 0.1 mmol/L) for control and insulin-treated animals, but more than doubled in concentration in the fasted animals (p less than 0.001). Mortality rates during hypoxia-ischemia were higher in the insulin-treated animals (30%) than in either the fasted (4%) or control (0%) animals (p less than 0.05). Fasted animals showed a significant reduction in hypoxic-ischemic brain damage as compared with either the insulin-treated or control animals. Insulin-treated animals were not significantly different from controls. The findings indicate that 1) insulin induced hypoglycemia does not provide a protective effect on perinatal hypoxic-ischemic brain damage, as in adults; and 2) fasting adequate to produce hypoglycemia and ketonemia improved neuropathologic outcome.
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PMID:Effect of insulin-induced and fasting hypoglycemia on perinatal hypoxic-ischemic brain damage. 154 41

We have recently demonstrated that calcium channel blockers can protect the ischemic myocardium at concentrations which do not decrease myocardial workload or metabolic demand before ischemia. In this study, we extended these observations by determining what effect the calcium channel blocker, diltiazem, has on overall myocardial energy substrate metabolism in aerobic, ischemic and reperfused ischemic hearts. Isolated working rat hearts were perfused at a 11.5-mm Hg preload, 80-mm Hg afterload, with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate and 500 microU/ml insulin. Glycolysis and glucose oxidation rates were determined in aerobic and reperfused ischemic hearts perfused with [3H]/[14C]glucose, whereas fatty acid oxidation rates were determined under similar conditions in hearts perfused with [14C]palmitate. Addition of diltiazem (0.8 microM) before subjecting hearts to a 30-min period of global no-flow ischemia resulted in a significant improvement in recovery of mechanical function (heart rate x developed pressure during reperfusion recovered to 28 and 53% of preischemic levels, in control and diltiazem-treated hearts, respectively). If diltiazem was added at reperfusion, no improvement of functional recovery was seen. Addition of diltiazem before or after ischemia had no effect on palmitate or glucose oxidation during reperfusion, but did significantly decrease rates of glycolysis during reperfusion. In hearts subjected to low-flow ischemia (coronary flow = 0.5 ml/min), diltiazem significantly decreased glycolytic rates during ischemia (glycolytic rates were 2.09 +/- 0.25 and 1.58 +/- 0.28 mumol/min.g dry wt. in control and diltiazem-treated hearts, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of diltiazem on glycolysis and oxidative metabolism in the ischemic and ischemic/reperfused heart. 154 89

With the recent increase in the number of liver and pancreas transplants being performed in Europe, many groups have found it necessary to develop techniques for the combined harvesting of whole pancreaticoduodenal and liver grafts. To date we have carried out a total of 35 multiorgan procurements including liver, heart, pancreas, and kidneys. In ten cases we reconstructed the arterial supply of the pancreas with an end-to-end anastomosis between the proximal splenic artery and the distal end of the superior mesenteric artery (SMA), and in eight patients we used a donor Y-iliac graft. Patients were monitored postoperatively by determination of BUN, serum creatinine, blood glucose, serum and urinary amylase levels, and Doppler assessment of the graft was carried out at regular intervals. Mean ischemia/preservation time in both groups was 6 h. All simultaneous kidney and pancreas transplants functioned well initially with none of the patients requiring dialysis. All patients were insulin-free immediately after surgery. One patient in the splenomesenteric group developed venous thrombosis of the graft, requiring removal of the gland, but has subsequently been successfully retransplanted. All remaining patients have been insulin-free for 1-14 months. One patient in the Y-iliac group also developed venous thrombosis of the graft, but all remaining patients in this group have been insulin-free for 1-12 months after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combined whole pancreas and liver retrieval: comparison between Y-iliac graft and splenomesenteric anastomosis. 158 Sep 87

Ischemic hepatitis is not an uncommon complication of reversible severe hypotension or cardiac failure. The prognosis usually is determined by the cause of the initial hypotension or cardiac failure, rather than the subsequent hepatic dysfunction. We report a retrospective analysis of nine patients with ischemic hepatitis in which previously unreported clinical and biochemical abnormalities are noted. The clinical and biochemical course of the patients were reviewed until recovery or death from ischemic hepatitis. All the patients had a rapid striking elevation of aspartate aminotransferase, and lactic dehydrogenase, with an equally rapid resolution of these parameters. Abnormal serum glucose levels occurred in six patients (none of whom had a prior carbohydrate intolerance). Insulin therapy was given to three patients for a limited period. Renal impairment was manifest in all nine patients, and it resolved spontaneously within 10 days. Altered mental status was detected in six patients; the changes reverted to normal within 7 days of their onset. A preexisting anemia (hemoglobin less than 11.0 g/dl) was noted on admission in four patients, and it did not appear to potentiate the manifestations of the hepatic ischemia. We conclude that ischemic hepatitis should be anticipated in all patients with a recent history of systemic hypotension. It should be considered in the differential diagnosis of patients with unexplained hepatitis; the early massive rise in lactic dehydrogenase, the rapid fall in transaminases, and the early mild/moderate renal failure strongly suggest ischemic hepatitis. Patients with ischemic hepatitis can manifest reversible renal failure, mental confusion, and hyperglycemia which may require insulin for its control.
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PMID:Ischemic hepatitis: widening horizons. 848 Jul 56

Prostaglandin E1/I2 and insulin receptors of human erythrocyte and platelet are capable of modulating each other's activity. This modulation of the receptor activity and number in one system by a second receptor system in human platelet and erythrocyte seems to be beneficial. Insulin increases the PGE1 binding to platelets and thereby enhances the platelet antiaggregatory action of prostaglandin by increasing cyclic AMP levels. Similarly, PGE1 increases insulin binding to human erythrocyte, and thereby reduces the optimum concentration of insulin for a maximal reduction in membrane microviscosity. During ischemia the reduced response of platelets to the inhibitory effect of PGE1 or PGI2 relates to the impaired PGE1/I2 receptor activity. Treatment of these platelets with insulin at physiological concentrations can normalise the PGE1/I2 receptor activity. This review focuses on the relationship between the two receptor systems in human blood cells.
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PMID:Interaction of receptors for prostaglandin E1/prostacyclin and insulin in human erythrocytes and platelets. 165 91

NGF and bFGF have recently been shown to have biological activity in central neurons, but their normal functions and mechanisms of action are unknown. Since central neurons are particularly vulnerable to hypoglycemia that occurs with ischemia or insulin overdose, we tested the hypothesis that growth factors can protect neurons against hypoglycemic damage. NGF and bFGF each prevented glucose deprivation-induced neuronal damage in human cerebral cortical and rat hippocampal cell cultures (EGF was ineffective). Protection was afforded when the growth factors were administered before (NGF and bFGF) or up to 12 hr following (NGF) the onset of hypoglycemia. Direct measurements of intracellular calcium levels and manipulations of calcium influx demonstrated that sustained elevations in intracellular calcium levels mediated the hypoglycemic damage. NGF and bFGF each prevented the hypoglycemia-induced elevations of intracellular calcium. These findings indicate that growth factors can stabilize neuronal calcium homeostasis in central neurons and thereby protect them against environmental insults.
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PMID:NGF and bFGF protect rat hippocampal and human cortical neurons against hypoglycemic damage by stabilizing calcium homeostasis. 166 17

Polymorphonuclear cells and monocytes (phagocytes) are a critical component of host defense against infections. However, these cells also play a significant role in host tissue damage in many noninfectious diseases, such as ischemia-reperfusion injury syndromes and rejection of transplanted organs. The leukocyte adhesion molecule family CD11/CD18 (beta 2 integrins) is critical to the function of polymorphonuclear cells and monocytes in inflammation and injury. Inherited deficiency of CD11/CD18 impairs phagocyte chemotaxis, adhesion and transmigration across endothelium, and clearance of invading microorganisms through phagocytosis and cell-mediated killing. Furthermore, murine monoclonal antibodies directed against the CD11b/CD18 (CR3) heterodimer have been shown to reduce, by 50%-80%, phagocyte-mediated ischemia-reperfusion injury in several organ systems, such as the myocardium, liver, and gastrointestinal tract and to inhibit development of insulin-dependent diabetes mellitus in nonobese diabetic (NOD) mice. Expression of CD11b/CD18 in a soluble and functional form might therefore be potentially useful as an anti-inflammatory agent. We have now expressed a recombinant soluble heterodimeric form of this human beta 2 integrin, normally expressed as two noncovalently associated membrane-bound subunits. The secreted receptor exhibited direct and specific binding to its ligand, iC3b, the major complement C3 opsonin, and inhibited binding of polymorphonuclear cells to recombinant interleukin 1-activated endothelium.
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PMID:Expression of a soluble and functional form of the human beta 2 integrin CD11b/CD18. 167 28

Glibenclamide, a hypoglycemic sulfonylurea, is a blocker of the adenosine triphosphatase-modulated potassium ion channels. The opening of these channels in the myocardial cells, induced by acute myocardial hypoxia, can be responsible for ischemic ventricular arrhythmias. To evaluate the antiarrhythmic effects of this drug 19 non-insulin-dependent diabetic patients were selected. They had coronary artery disease and evidence on Holter monitoring of ventricular premature complexes or nonsustained ventricular tachycardia, or both, induced by transient myocardial ischemia. In all patients, 24-hour electrocardiographic monitoring was performed to evaluate the number and duration of myocardial ischemic events, the frequency of ventricular premature complexes and nonsustained ventricular tachycardia per minute of ischemia and the percentage of ventricular premature complexes versus total ischemic beats. Selected patients were classified in 2 groups: group A (9 patients) received metformin (placebo) and group B (10 patients) was treated with glibenclamide. On the fourteenth day patients underwent 24-hour control monitoring. Then a crossover between the 2 groups was made and a new Holter monitoring sequence was performed at the end of the second phase. Results indicate that glibenclamide significantly (p less than 0.001) reduced both the frequency of ventricular premature complexes and the episodes of nonsustained ventricular tachycardia during transient myocardial ischemia, but did not change the number and duration of acute myocardial ischemic attacks and did not reduce the spontaneous ventricular arrhythmias. Thus, glibenclamide appears to have an antiarrhythmic effect in preventing ventricular arrhythmias induced by transient myocardial ischemia.
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PMID:Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus. 170 21


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