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

The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed.
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PMID:Contribution of tissue acidosis to ischemic injury in the perfused rat heart. 0 93

Diabetes was induced in pregnant rats by administration of streptozotocin and the changes of the feto-placental unit were investigated. Dead fetuses were found in 12% of the untreated diabetic animals. In comparison to the controls, the fetal weights were significantly smaller and placental weights greater in diabetic animals. The changes were clearly characterized by the ratio fetal placental weight. Edema and cystic degeneration were characteristic of insulin treated diabetic placentas while fibrosis and ischemia were observed mainly in untreated animals. Insulin treatment resulted in hemorrhages and necrosis in the placenta of normal pregnant rats; the change is ascribed to hypoglycaemia.
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PMID:Clinical and morphological studies in streptozotocin diabetic pregnant rats. 13 71

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
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PMID:Insulin: fundamental mechanism of action and the heart. 18 67

31P NMR was used to continuously monitor ATP and inorganic phosphate levels in perfused mouse liver. Under "optimal" conditions, the time resolution of the technique was approximately 1 min. In the absence of any metabolic perturbations the ATP level remained constant for at least 2 hr and decreased by only approximately 20% in 18 hr. Both ATP and inorganic phosphate levels responded to alterations in the oxygen supply to the liver. The half-time for this response was approximately 1 min, and the response to short periods of hypoxia or ischemia was partially reversible. The addition of insulin caused only a minor decrease in the ATP level but significantly decreased the rate of response of ATP and phosphate levels to hypoxia and ischemia.
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PMID:Rapid ATP assays in perfused mouse liver by 31P NMR. 29 54

The conducting system was studied in an in situ perfused swine heart preparation with reduced coronary flow (ischemia) using perfusate containing high and low levels of glucose (26.6 versus 8.6mM) with and without insulin. Coronary flow was maintained at normal levels for 60 minutes in control hearts. In ischemic hearts flow was reduced to about 50 percent of control levels for 30 minutes. Ultrastructural studies documented only subtle modifications of Purkinje fibers in ischemic hearts. Glycogen depletion and disruption of cell junctions were observed in some fibers. One consistent finding was the activation of the lysosomal system. The outer membranes of primary lysosomes appeared herniated and in some cases disrupted, and small vesicles containing hydrolytic enzymes were seen in association with the Golgi apparatus and larger primary lysosomes. Specimens prepared for the demonstration of acid phosphatase indicated a redistribution of hydrolytic enzymes in Purkinje fibers with a depostion of acid hydrolases in smaller lysosomal vesicles, the transverse and side-to-side junctions between cells, and occasionally in the sarcoplasmic reticulum. Enriched perfusate containing high levels of glucose with insulin appeared to have no therapeutic effects in terms of the structure of the Purkinje fibers. The results suggest that alterations in the lysosomal system may be one of the earliest structural changes which occur in oxygen-deficient hearts.
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PMID:Ischemic injury to the conducting system of the heart. Involvement of myocardial lysosomes. 43 Oct 98

In an isolated rat liver perfusion system the effects of normothermal ischemia on hepatic functions were investigated. After 30 minutes of anoxy bile production and BSP elimination capacity of the liver are significantly reduced. The quantity of secreted "ascites" from the surface of the liver several times high after anoxic damage, while oxygen consumption, portal venous pressure and ammonia elimination do not differ significantly from the controls. Pretreatment with insulin plus glucose, isoproterenol, hypoxanthine, chlorpromazine and glucagon (5 micrograms/100 g i.v., or 0.2 mg/100 g s.c.) does not reduce noticeably the normothermal anoxic lesion of the liver Glucagon (50 micrograms/100 g i.v.), allopurinol, dibenzyline, ATP-MgCl2 and aspartic acid enhance significantly the ischemia-tolerance of liver in vitro.
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PMID:Ischemic damage of the liver. Part I: In vitro investigation of the prevention of the ischemic lesion of the liver. 49 24

To evaluate the influence of glucose infusate administered with insulin and potassium on left ventricular function during 4 h of ischemia, as well as mechanism of action, four groups of intact anesthetized dogs were studied. Acute regional ischemia was induced with a balloon tip catheter in the left anterior descending artery and infusates were begun after 20 min of ischemia. A threefold increase of plasma glucose concentration was associated with improved left ventricular function during ischemia, compared to animals receiving isovolumic saline. There was a significant decline of left ventricular end-diastolic pressure associated with elevation of stroke volume and ejection fraction to control levels, as determined by indicator dilution. In a separate subgroup studied by cineangiography, shortening of the ischemic anterior wall, after an initial decline, was increased in response to glucose but there was no evidence of extension of injury. Ischemic tissue exhibited a smaller gain of water as well as Na+ per gram dry weight as compared to ischemic controls. On precordial electrocardiogram mapping there was a significant decrease in the sigmaST (sum of ST elevation) as well as NST (number of ST segment elevations), but the reduction of R wave amplitude was not different from controls. To further evaluate long-term effects, eight controls and six treated animals underwent myocardial ischemia and were sacrificed after 4 mo. Calculated area and weight of scar, as well as degree of wall thinning, were similar in both groups. The glucose-treated animals had a significant decrease of plasma FFA in contrast to controls which manifested a significant rise. To examine the postulate that the decrease in FFA was important to therapeutic action, a third group was infused with Intralipid (Cutter Laboratories, Inc., Berkeley, Calif.) and heparin, simultaneously with the glucose infusate, to effect an elevation of plasma FFA during ischemia. Changes in myocardial function and electrolyte composition, as well as precordial electrocardiogram mapping, were similar to that of animals receiving glucose alone. Because serum osmolality was increased approximately 40 mosmol during the glucose infusion, the potential role of hyperosmolality was assessed by infusion of 20% mannitol during acute ischemia in a fourth group. After a transient small increase, there was a moderate decline in function by 4 h, suggesting that the response to glucose is not dependent upon extracellular osmolality. Thus, it is concluded that during the initial hours after the onset of myocardial ischemia the glucose infusate improves ventricular performance without evidence of arrhythmia induction or intensification of ischemic injury. Evolution of irreversible necrosis appears to be delayed rather than prevented under the circumstances of this study.
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PMID:Sustained effect of glucose-insulin-potassium on myocardial performance during regional ischemia. Role of free fatty acid and osmolality. 65 87

Insulin was administered to two patients whose diminished myocardial contractility made it difficult to terminate cardiopulmonary bypass. In both instances, bypass was successfully terminated shortly after the insulin injection. These clinical observations led to experiments under the controlled conditions provided by the isolated, working rat heart preparation. The recovery of contractility after 30 minutes of severe ischemia was assessed in all 11 control and 11 insulin-treated hearts. Myocardial performance, as judged by the product of heart rate and peak systolic blood pressure, was significantly greater in the insulin-treated hearts. These clinical observations and experimental findings suggest the need for more extensive study of the potential value of insulin in treating depressed contractility after prolonged myocardial ischemia.
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PMID:Insulin therapy for depressed myocardial contractility after prolonged ischemia. 66 28

The complications of ureteral ischemia make revascularization of polar vessels attractive in cadaver and live-related transplants. Thirty-two patients underwent reconstruction of polar vessels of 1.2 to 2.5 mm, in diameter after revascularization of the major vessels as follows: (1) inferior epigastric artery to polar artery, ten patients - six cadaver transplants, four living-related transplants (The vessels are spatulated and sutured precisely by microvascular techniques with Nos. 7-0 or 8-0 Tevdek); (2) polar vessel with a patch of aorta to iliac artery, one patient - living relative donor; (3) polar artery to the main renal artery or branch, 17 patients - 14 cadaver transplants, three living-related transplants [A Waters "MOX"-100 machine is used with cryoprecipitated plasma (800 mg. of SoluMedrol and 80 U. of insulin added) for preservation.]; (4) autogenous saphenous vein graft, two patients - one child receiving on adult live-related kidney and one cadaver transplant with three arteries and a stenosis of the inferior polar vessel; (5) polar artery to vein patch in iliac artery, two patients - cadaver transplants. Follow-up was done by arteriography (18 patients), direct observation (two patients), and by use of ultrasound (one patient). The remaining 11 patients have exhibited no evidence of occlusion. Twenty of 21 patients exhibited patent vessels; one thrombosed at the time of the transplant operation. Long-term patency in those patients studied was 95%. We advocate small-vessel reconstruction in human renal transplantation, either during ex vivo preservation (workbench surgery) or at the time of transplantation.
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PMID:Microvascular techniques for polar artery reconstruction in kidney transplants. 76 11

An approach to intraoperative protection of the myocardium is described that attempts to increase glucose utilization by infusion of high-energy solutions during aortic cross-clamping. Infusion of hypertonic glucose or glucose plus insulin prior to aortic cross-clamping has enhanced contractility and increased high-energy phosphate moieties in animals with induced ischemia. Recent pilot experiments in our laboratory suggest that infusions of creatine may result in increased production of creatine phosphate, which in turn induces phosphorylation of adenosine diphosphate to adenosine triphosphate, possibly enhancing myocardial contractility. The intraoperative clinical benefits of these infusions remain to be proved, however.
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PMID:Protection of the myocardium with high-energy solutions. 80 61


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