Prolonged preservation of the blood-perfused canine heart with glycolysis-promoting solution

Takeuchi, Koh; Cao-Danh, Hung; Kawai, Akihiko; Ohkado, Akihiko; Konishi, Hiroaki; McGowan, Francis X.; Nido, Pedro J. del

doi:10.1016/s0003-4975(99)00534-2

Cited by 11 publications

(27 citation statements)

References 9 publications

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“…The diastolic dysfunction indicated by EDP increases in IA and IAA hearts, respectively (see Table 2) may reflect elevated free [ADP] near myofibrils as measured using 31 P NMR in IA-treated rat hearts (34). However, due to the importance of bound, compartmentalized CK in the myocardium (39,44), increases in measured [ADP] may not reflect changes in subcompartments (20).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies (41) have illustrated a degree of functional compartmentalization of glycolytic metabolism and energy stores plus the preferential use of glycolytic rather than oxidatively produced ATP by the sarcolemma. Whereas anaerobic glycolysis may only produce as little as 3-7% of the total ATP under aerobic conditions in ex vivo preparations (8,17), its contribution to cellular bioenergetics may increase significantly during ischemia and hypoxia (31). In addition, ATP from glycolysis may be used in the heart early during dynamic workload changes (7), as observed previously in skeletal muscle (24).…”

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confidence: 88%

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Glycolytic buffering affects cardiac bioenergetic signaling and contractile reserve similar to creatine kinase

Harrison

Wijhe²,

Groot³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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buffering affects cardiac bioenergetic signaling and contractile reserve similar to creatine kinase. Am J Physiol Heart Circ Physiol 285: H883-H890, 2003. First published April 24, 2003 10.1152/ajpheart.00725.2002 and glycolysis represent important energy-buffering processes in the cardiac myocyte. Although the role of compartmentalized CK in energy transfer has been investigated intensely, similar duties for intracellular glycolysis have not been demonstrated. By measuring the response time of mitochondrial oxygen consumption to dynamic workload jumps (t mito) in isolated rabbit hearts, we studied the effect of inhibiting energetic systems (CK and/or glycolysis) on transcytosolic signal transduction that couples cytosolic ATP hydrolysis to activation of oxidative phosphorylation. Tyrode-perfused hearts were exposed to 15 min of the following: 1) 0.4 mM iodoacetamide (IA; n ϭ 6) to block CK (CK activity Ͻ3% vs. control), 2) 0.3 mM iodoacetic acid (IAA; n ϭ 5) to inhibit glycolysis (GAPDH activity Ͻ3% vs. control), or 3) vehicle (control, n ϭ 7) at 37°C. Pretreatment t mito was similar across groups at 4.3 Ϯ 0.3 s (means Ϯ SE). No change in tmito was observed in control hearts; however, in IAA-and IA-treated hearts, t mito decreased by 15 Ϯ 3% and 40 Ϯ 5%, respectively (P Ͻ 0.05 vs. control), indicating quicker energy supply-demand signaling in the absence of ADP/ATP buffering by CK or glycolysis. The faster response times in IAA and IA groups were independent of the size of the workload jump, and the increase in myocardial oxygen consumption during workload steps was unaffected by CK or glycolysis blockade. Contractile function was compromised by IAA and IA treatment versus control, with contractile reserve (defined as increase in rate-pressure product during a standard heart rate jump) reduced to 80 Ϯ 8% and 80 Ϯ 10% of baseline, respectively (P Ͻ 0.05 vs. control), and significant elevations in end-diastolic pressure, suggesting raised ADP concentration. These results demonstrate that buffering of phosphate metabolites by glycolysis in the cytosol contributes appreciably to slower mitochondrial activation and may enhance contractile efficiency during increased cardiac workloads. Glycolysis may therefore play a role similar to CK in heart muscle. glycolysis; energy transduction; mitochondria; regulation of oxidative phosphorylation THE RELATIONSHIP BETWEEN CONTRACTILE function of the myocardium and myocyte bioenergetics is centered on the generation of ATP by oxidative phosphorylation, anaerobic glycolysis, and the conversion of phosphocreatine by creatine kinase (CK). The role of CK as an energy reserve and transfer system in the heart has been intensively studied (1,27,28,30,40), focusing on the functional significance of the compartmentation of CK isozymes to the mitochondria and myofibrils (39,44) and the regulators of CK flux during conditions of altered ATP synthesis or hydrolysis (22). Moreover, changes have been observed in CK activity and levels of its substrates and products in human patients sufferi...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 88%

Glycolytic buffering affects cardiac bioenergetic signaling and contractile reserve similar to creatine kinase

Harrison

Wijhe²,

Groot³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…It has been demonstrated (5) that the anaplerotic flux is very important in allowing cells to adjust the concentration of the Krebs' cycle intermediates in response to some metabolic conditions. The use of 13 C NMR spectroscopy to analyze tissue metabolism provides useful and important information about a wide range of metabolic rearrangements that occur in some pathological conditions, such as ischemia/reperfusion (I/R). The perfusion of 13 C-enriched substrates for the Krebs' cycle leads to dynamic changes in 13 C spectra that are dependent on the turnover of labeling patterns in the cycle, and provide an evaluation method for the cycle flux.…”

Section: Introductionmentioning

confidence: 99%

“…The use of 13 C NMR spectroscopy to analyze tissue metabolism provides useful and important information about a wide range of metabolic rearrangements that occur in some pathological conditions, such as ischemia/reperfusion (I/R). The perfusion of 13 C-enriched substrates for the Krebs' cycle leads to dynamic changes in 13 C spectra that are dependent on the turnover of labeling patterns in the cycle, and provide an evaluation method for the cycle flux. It has been shown that, in the isolated perfused heart, lactate contributes significantly more to acetyl-CoA than glucose (6), although the uptake of lactate by the in vivo heart is directly proportional to its serum concentration (7).…”

Section: Introductionmentioning

confidence: 99%

“…This being so, it is of great importance to understand and characterize the metabolic alterations that occur during I/R. In this study, we examined the metabolic fate of [U- 13 C]glucose (glucose enriched with 13 C in all carbons) and [3-13 C]lactate (lactate enriched with 13 C in carbon-3) in hearts preserved in two different cardioplegic solutions, the clinically used Celsior (Cs) and an emerging solution in clinical research, histidine buffer solution (HBS) (13,14), over 4 h (moderate ischemia) or 6 h (severe ischemia). The hearts were then perfused with a Krebs-Henseleit solution (KH) containing 5.5 mM of [U-…”

Section: Introductionmentioning

confidence: 99%

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Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender

2011

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In conditions of ischemia/reperfusion (I/R), the relative use of all available substrates by the heart has a significant effect on the recovery of the organ. This substrate preference in perfused hearts is influenced by ischemia. We followed the metabolic fate of [U-(13) C]glucose and [3-(13) C]lactate in hearts preserved in Celsior (Cs) and histidine buffer solution (HBS) for 4 or 6 h and subsequently perfused with a Krebs-Henseleit solution (KH) containing [U-(13) C]glucose and [3-(13) C]lactate. We also assessed gender-specific metabolic modulation in our I/R experimental conditions. Hearts from male and female Wistar rats (6-8 weeks) were subjected to moderate (0-240 min) or prolonged (240-360 min) cold ischemia whilst immersed in Cs and HBS, and perfused for 30 min with KH containing [U-(13) C]glucose and [3-(13) C]lactate. After perfusion, hearts were freeze-clamped and metabolites were extracted for (13) C NMR isotopomer analysis. In control conditions, there were no differences with regard to lactate origin in hearts from males and females. After 6 h of preservation in Cs, lactate origin was mostly from [U-(13) C]glucose in hearts from males and from [3-(13) C]lactate in hearts from females. During the 6 h of organ preservation in HBS, the lactate pool showed a strong contribution from unenriched sources in male hearts and from [U-(13) C]glucose in female hearts. The glutamate C2/C4 ratio was stable or increased in hearts from females after I/R, and the alanine index increased in hearts from both males and females. Octanoate was, as predicted, the preferential substrate during perfusion. Glucose and lactate suffer a distinct metabolic fate in our I/R conditions, which is related to the cardioplegic solution used during organ storage, and the gender. Hearts from females appear to be less sensitive to I/R injury, and heart preservation in HBS proved to be effective in enhancing anaplerosis during perfusion, especially in hearts from females.

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Anti-apoptotic protection afforded by cardioplegic celsior and histidine buffer solutions to hearts subjected to ischemia and ischemia/reperfusion

et al. 2011

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Cardiomyocytes undergo apoptosis in response to ischemia and ischemia/reperfusion (I/R). During heart preservation, inhibition of apoptosis is critical to avoid organ failure. We aimed to compare the protection afforded by Celsior (Cs) and Histidine buffer solution (HBS) against apoptotic signaling in hearts subjected to moderate (4 h) versus severe (6 h) ischemia alone or followed by 30 min reperfusion. The impact of gender on cardioplegic protection was also explored. Hearts from male and female Wistar-Han rats were divided by gender in distinct groups: control, perfusion_control, ischemia, and I/R. Ischemia and I/R groups were divided in subgroups Cs or HBS, and subjected to 4 or 6 h ischemia alone or followed by reperfusion. Proteins involved in apoptotic signaling (p53, Bax, Fas, FasL, and Flip) were quantified by Western blot in mitochondria and/or whole tissue. Caspases 3, 8, and 9-like activities were measured and hemodynamic parameters were monitored. Ischemia activated p53/Bax signaling. After I/R, HBS-preserved hearts had lower p53/Bax content in mitochondrial fractions than Cs-preserved hearts. The p53/Bax decrease in tissue samples was mostly observed in females. Caspase 3-like activity was increased in HBS-preserved male hearts. The heart rate was decreased in Cs and HBS-preserved hearts. Fas protein levels remained unaltered in all conditions but soluble FasL increased from 4 to 6 h preservation in Cs and HBS. Hearts from male rats were more prone to apoptosis and myocardial dysfunction. HBS and Cs were not effective in inhibiting apoptotic signaling although HBS presented best overall results. Both solutions should be improved to prevent apoptosis and myocardial dysfunction after I/R.

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Prolonged preservation of the blood-perfused canine heart with glycolysis-promoting solution

Cited by 11 publications

References 9 publications

Glycolytic buffering affects cardiac bioenergetic signaling and contractile reserve similar to creatine kinase

Glycolytic buffering affects cardiac bioenergetic signaling and contractile reserve similar to creatine kinase

Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender

Anti-apoptotic protection afforded by cardioplegic celsior and histidine buffer solutions to hearts subjected to ischemia and ischemia/reperfusion

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