Hemodynamics and metabolic effects of fructose 1–6 diphosphate in ischemia and shock — experimental and clinical observations

Markov, Angel K.

doi:10.1016/s0196-0644(86)80946-5

Cited by 70 publications

(40 citation statements)

References 15 publications

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“…Maximal protec tion of hypoxic cells occurred at 6.0 mM FDP. Lactate concentrations of the culture medium of hypoxic cells increased 2.5 times above normoxic control values when glucose was present, but neither FDP alone nor glucose reduces the tis sue damage associated with cardiac arrest (Jones et aI., 1980), myocardial infarction (Markov et aI., 1980;1986), myocardial ischemia (Marchionni et aI., 1985), and renal ischemia (Didlake et aI., 1985). It also reduces ischemic damage to skin flaps (Heckler et aI., 1984), and it increases the concen trations of ATP, phosphocreatine, and lactate in ischemic muscle (Heckler et aI., 1983).…”

Section: Discussionmentioning

confidence: 99%

“…Markov et ai. (Markov, , 1986 suggested that FDP enters cells, bypasses the reaction involving phosphofructokinase (PFK) (which is inhibited by hypoxia and acidosis) (Mansour, 1963), and in creases glycolysis and ATP production. They point out that this would effectively provide twice as much ATP as glc metabolism because the phosphor ylation steps of both glc and fru-6-P would be by passed.…”

Section: Discussionmentioning

confidence: 99%

“…Reports suggesting that it does are based on indirect evidence (Markov, 1986;Didlake et aI., 1982;Markov et aI., 1983); reports suggesting that it does not are based on e 4 C]FDP uptake stud ies in erythrocytes (Rigobello et aI., 1982;Berna sconi et aI., 1983). There are no published data on whether FDP is taken up by brain or brain cells.…”

Section: Discussionmentioning

confidence: 99%

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Fructose-1,6-Bisphosphate Protects Astrocytes from Hypoxic Damage

Gregory

Chan

1989

J Cereb Blood Flow Metab

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Summary:To determine the effects of glucose and fruc tose-l,6-bisphosphate (FDP) on hypoxic cell damage, pri mary cultures of astrocytes were incubated for 18 h in an air-tight chamber that had been flushed with 95% N2/5% CO2 for 15 min before it was sealed. Cultures containing 7. 5 mM glucose without FDP or FDP without glucose showed evidence of significant cell injury after 18 h of hypoxia (increased lactate dehydrogenase content in the culture medium; cell edema and disruption by phase contrast microscopy). Cultures exposed to glucose + FDP had normal lactate dehydrogenase concentrations and appeared normal microscopically. Maximal protec tion of hypoxic cells occurred at 6.0 mM FDP. Lactate concentrations of the culture medium of hypoxic cells increased 2.5 times above normoxic control values when glucose was present, but neither FDP alone nor glucose reduces the tis sue damage associated with cardiac arrest (Jones et aI., 1980), myocardial infarction (Markov et aI., 1980;1986), myocardial ischemia (Marchionni et aI., 1985), and renal ischemia (Didlake et aI., 1985). It also reduces ischemic damage to skin flaps (Heckler et aI., 1984), and it increases the concen trations of ATP, phosphocreatine, and lactate in ischemic muscle (Heckler et aI., 1983). We showed that hypoxic FDP-treated rabbits breathed nearly 15 times longer than glucose (glc)-treated rabbits (20.9 ± 4.9 versus 1.4 ± 0.2 min) before respiratory arrest occurred and that we could resuscitate 100% of the FDP-treated, 18% of glc-treated, and 14% of Received December 10, 1987; accepted July 26, 1988 saline-treated animals, despite the fact that the FDP-treated rabbits were much more acidotic at cardiac arrest (Farias et aI., 1986). Thirty minutes after resuscitation, FDP-treated rabbits had normal pupil and eyelid reflexes and responded normally to pain. Rabbits treated with either glc or saline had no response to pain.To eliminate the multiple factors that may affect the brain in vivo, we determined whether FDP pro tected intact, primary cultures of cortical astrocytes from hypoxic injury. This model is described in de tail in the article by Yu et a1. (1989), which demon strates the time course of hypoxic injury and its multifactorial nature. MATERIALS AND METHODS Cell culturePrimary cultures of cerebral astrocytes were prepared by the method of Yu et a1. (1986) using newborn Sprague Dawley rats (Simonsen, Gilroy, CA, U. S.A.). The cere bral hemispheres were removed from the skull aseptically 30 G. A. GREGORY ET AL. and the meninges, olfactory bulbs, basal ganglia, and hip pocampus were discarded, leaving the neopallium, i. e., the cortex dorso-lateral to the lateral ventricle. The cleaned neopallium was placed in modified Eagle's min imum essential tissue culture medium (MEM) (Hertz et al. , 1985) that contained 20% fetal calf serum (FCS) (Ster ile Systems, Logan, UT, U.S. A. ) and cut into -1 mm cubes. Tissues were disrupted by vortex-mixing for 1 min (Bullaro and Brookman, 1976) and passed through two sterile nylon Nitex sieves (L. and S. ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fructose-1,6-Bisphosphate Protects Astrocytes from Hypoxic Damage

Gregory

Chan

1989

J Cereb Blood Flow Metab

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“…The salutary effects shown by FBP might be explained considering that ischemia produces a depletion of the brain stores of ATP; and by reducing either aerobic or anaerobic metabolism, FBP might have increased ATP production throughout the glycolitic pathway as soon as recirculation has been allowed. In support of this hypo thesis, data showing the ability of FBP to increase ATP levels during ischemia or hypoperfusion in several differ ent tissues exist (2,5). The understanding of the mecha nisms by which FBP modifies ATP levels is, however, a difficult task.…”

Section: Resultsmentioning

confidence: 91%

“…It has been reported to reduce the tissue damage associated with cardiac arrest (1), myocar dial ischemia (2) and myocardial infarct (3). Didlake and colleagues (4) observed a substantial prevention of the ischemic renal injury in rats treated with FBP.…”

mentioning

confidence: 99%

Improvement of Ischemic Myocardial Dysfunction by Nisoldipine in Relation to Its Coronary Vasodilating Action

Trimarchi

Arcadi

Luca

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-We examined the protective activity of fructose l,6-bisphosphate (FBP) on mortality and delayed hippocampal cell death induced by transient cerebral ischemia in the Mongolian gerbil. Forebrain ischemia was produced by bilaterally occluding the common carotid arteries for 15 min using micro aneurysm clips; then the blood supply to the brain was restored. The number of survivors was counted for 8 days, and the histopathological damage in the CAI region of the hippocampus was scored according to the semiquantitative scale of Rudolphi and colleagues. When injected 15 min before the ischemic insult, FBP (100 and 333 mg/kg, i.v.) significantly reduced the rate of mortality during the 8-day observation period. Equivalent doses of fructose and fructose monophosphate did not improve survival, and neither did low doses (33 mg/kg) of FBP. FBP also produced a significant degree of protection against the CAI pyramidal cell loss in comparison with its vehicle (distilled water). Conversely, when we administered the compound, at the same dose, 15 min after the release of the arterial occlusion, we observed neither a significant reduc tion of mortality nor significant protection against hippocampal CAI pyramidal cell loss. These results sug gest that FBP possesses salutary properties against the damages induced by transient cerebral ischemia, although they are evident only when the compound is administered before the resolution of the ischemic injury.

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Improved Exercise Tolerance by IV Fructose‐l,6‐Diphosphate in Chronic, Stable Angina Pectoris

Marchionni

Moschi

Bari

et al. 1988

The Journal of Clinical Pharma

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The effect of IV fructose-1,6-diphosphate (FDP) on transient, reproducible myocardial ischemia was evaluated in ten patients, aged 50 to 66 years, with chronic, stable exertional angina. FDP or placebo (glucose) were administered between basal and posttreatment ergometric stress testing; an identical procedure was repeated in each patient with the second treatment on the following day according to a single-blind, cross-over design. FDP improved exercise tolerance and total work capacity, significantly delaying the onset of ST-segment depression and angina. Nevertheless, the critical level of the rate x pressure (R X P) product, causing appearance of myocardial ischemia, was not remarkably changed. However, the R X P product at same workload was significantly lower after FDP. These results suggest that improved exercise tolerance might have resulted from peripheral (increased oxygen delivery to skeletal muscle) rather than from central (cardiac) effects of FDP.

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Hemodynamics and metabolic effects of fructose 1–6 diphosphate in ischemia and shock — experimental and clinical observations

Cited by 70 publications

References 15 publications

Fructose-1,6-Bisphosphate Protects Astrocytes from Hypoxic Damage

Fructose-1,6-Bisphosphate Protects Astrocytes from Hypoxic Damage

Improvement of Ischemic Myocardial Dysfunction by Nisoldipine in Relation to Its Coronary Vasodilating Action

Improved Exercise Tolerance by IV Fructose‐l,6‐Diphosphate in Chronic, Stable Angina Pectoris

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