Enhancement of Hypothermic Heart Preservation with Fructose 1,6-Diphosphate

Niu, Wenying; Zhang, Futing; Ehringer, William D.; Tseng, Micheal; Gray, Laman A.; Chien, Sufan

doi:10.1006/jsre.1999.5658

Cited by 15 publications

(7 citation statements)

References 36 publications

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“…The optimal concentration of FBP appeared to be about 5 mmol/liter, which is similar to concentrations that were protective in studies of the hypothermic preservation of intact heart. [1][2][3] These results confirm our hypothesis that effects of FBP could be observed with isolated myocytes, and suggests that biochemical characterization of the effects of FBP will be relevant to the whole organ.…”

Section: Discussionsupporting

confidence: 88%

Fructose-1,6-Bisphosphate Enhances Hypothermic Preservation of Cardiac Myocytes

Wheeler

Wiegand

Chien

2005

The Journal of Heart and Lung Transplantation

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Section: Discussionsupporting

confidence: 88%

Fructose-1,6-Bisphosphate Enhances Hypothermic Preservation of Cardiac Myocytes

Wheeler

Wiegand

Chien

2005

The Journal of Heart and Lung Transplantation

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“…Our findings indicate that one major effect of FBP is its chelation of extracellular Ca 2+ , in addition to other mechanisms. An appreciation of the ability of FBP to chelate Ca 2+ , and thus affect intracellular calcium levels, is of importance because FBP has been used for preservation of a wide variety of types of tissues [3]–[9], as well as in many other types of experiments. We used an extreme endpoint for assessing the effects of FBP (protection against cell death), but it is likely that FBP would help protect cell functions even in cases where little or no cell death is occurring.…”

Section: Discussionmentioning

confidence: 99%

“…New studies concerning benefits of FBP appear every year (e.g., [10]–[13]). Our group has characterized effects of FBP in preserving heart function during hypothermic storage [3], [14]–[15], and has demonstrated uptake of FBP by cardiac myocytes [16]–[17], even at 3°C [17]. We also showed that in an experimental model for hypothermic heart preservation, isolated cardiac myocytes maintained in ischemic suspension at 3°C, FBP greatly reduced the death rate (as measured by loss of rod-shaped morphology) and helped preserve cellular ATP [18].…”

Section: Introductionmentioning

confidence: 87%

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Protection of Rat Cardiac Myocytes by Fructose-1,6-Bisphosphate and 2,3-Butanedione

Wheeler

Chien

2012

PLoS ONE

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Earlier studies by our group showed that fructose-1,6-bisphosphate (FBP) enhances the hypothermic preservation of rat cardiac myocytes and the functional recovery of animal hearts after hypothermic storage. However, the mechanisms involved were not clear. We extended the cardiomyocyte studies by testing whether the FBP effects were due to chelation of extracellular calcium, leading to lower intracellular levels. We also tested effects of 2,3-butanedione monoxime (BDM), pyruvate, and adenine nucleotide precursors. Cardiomyocytes were incubated in ischemic suspension at 3°C, and aliquots examined over 48 to 72 hours for retention of rod-shaped morphology, a measure of viability. Cytosolic Ca2+ levels were measured in some experiments. FBP at 5 mM reduced the death rate even when added after one or two days of incubation. It caused cytosolic calcium levels that were 33% lower than controls in freshly-isolated cells and 70% lower after one day of incubation. EGTA protected against cell death similarly to FBP. These results indicated that one of the mechanisms by which FBP exerts protective effects is through chelation of extracellular calcium. BDM was strongly protective and reduced cytosolic calcium by 30% after one day of incubation. As with FBP, BDM was effective when added after one or two days of incubation. BDM may be useful in combination with FBP in preserving heart tissue. Pyruvate, adenine, and ribose provided little or no protection during hypothermia.

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“…Results from our laboratory indicated that when FBP was added to St. Thomas solution, rat heart preservation time was also increased (20,21). It is theorized that the mechanism by which FBP exerts its effects is by a direct metabolic enhancement.…”

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confidence: 93%

Destabilizing effects of fructose‐1,6‐bisphosphate on membrane bilayers

Ehringer

Chiang

et al. 2002

Lipids

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Fructose-1,6-bisphosphate (FBP) is a high-energy glycolytic intermediate that decreases the effects of ischemia; it has been used successfully in organ perfusion and preservation. How the cells utilize external FBP to increase energy production and the mechanism by which the molecule crosses the membrane bilayer are unclear. This study examined the effects ofFBP on membrane bilayer permeability, membrane fluidity, phospholipid packing, and membrane potential to determine how FBP crosses the membrane bilayer. Large unilamellar vesicles composed of egg phosphatidylcholine (Egg PC) were made and incubated with 50 mM FBP spiked with 14C-FBP at 30 degrees C. Uptake of FBP was significant (P < 0.05) and dependent on the lipid concentration, suggesting that FBP affects membrane bilayer permeability. With added calcium (10 mM), FBP uptake by lipid vesicles decreased significantly (P < 0.05). Addition of either 5 or 50 mM FBP led to a significant increase (P < 0.05) in Egg PC carboxyfluorescein leakage. We hypothesized that the membrane-permeabilizing effects of FBP may be due to a destabilization of the membrane bilayer. Small unilamellar vesicles composed of dipalmitoyl pC (DPPC) were made containing either diphenyl-1,3,5-hexatriene (DPH) or trimethylammmonia-DPH (TMA-DPH) and the effects of FBP on the fluorescence anisotropy (FA) of the fluorescent labels examined. FBP caused a significant decrease in the FA of DPH in the liquid crystalline state of DPPC (P < 0.05), had no effect on FA of TMA-DPH in the liquid crystalline state of DPPC, but increased the FA of TMA-DPH in the gel state of DPPC. From phase transition measurements with DPPC/DPH or TMA-DPH, we calculated the slope of the phase transition as an indicator of the cooperativity of the DPPC molecules. FBP significantly decreased the slope, suggesting a decrease in fatty acyl chain interaction (P< 0.05). The addition of 50 mM FBP caused a significant decrease (P< 0.05) in the liquid crystalline/gel state fluorescence ratio of merocyanine 540, indicating increased head-group packing. To determine what effects these changes would have on cellular membranes, we labeled human endothelial cells with the membrane potential probe 3,3'-dipropylthiacarbocyanine iodide (DiSC3) and then added FBP. FBP caused a significant, dose-dependent decrease in DiSC3 fluorescence, indicating membrane depolarization. We suggest that FBP destabilizes membrane bilayers by decreasing fatty acyl chain interaction, leading to significant increases in membrane permeability that allow FBP to diffuse into the cell where it can be used as a glycolytic intermediate.

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Enhancement of Hypothermic Heart Preservation with Fructose 1,6-Diphosphate

Cited by 15 publications

References 36 publications

Fructose-1,6-Bisphosphate Enhances Hypothermic Preservation of Cardiac Myocytes

Fructose-1,6-Bisphosphate Enhances Hypothermic Preservation of Cardiac Myocytes

Protection of Rat Cardiac Myocytes by Fructose-1,6-Bisphosphate and 2,3-Butanedione

Destabilizing effects of fructose‐1,6‐bisphosphate on membrane bilayers

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