Myocardial Loss of Glutamate after Cold Chemical Cardioplegia and Storage in Isolated Blood-Perfused Pig Hearts

Hh, Kimose; Ravkilde, Jan; Helligsø, Per; Ma, Knudsen; Ar, Thomassen; Tt, Nielsen; Jc, Djurhuus

doi:10.1055/s-2007-1013829

Cited by 13 publications

(12 citation statements)

References 3 publications

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“…No evidence was provided that this was caused by metabolism of the amino acids. We have reported a marked release of glutamate in the first minute of reperfusion in a pig isolated heart model 13 . Bäckström et al 14 .…”

Section: Discussionmentioning

confidence: 78%

“…This may be due to increased glutamate utilization. However, we and others have reported a marked release of glutamate across the heart at the start of reperfusion, 13,14 which may contribute to low tissue glutamate levels during reperfusion. Recently, both sarcolemmal and mitochondrial Na + ‐dependent glutamate transporters, similar to those of brain tissue (excitatory amino acid transporters), have been identified in cardiomyocytes 15,16 .…”

Section: Introductionmentioning

confidence: 74%

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CARDIOPROTECTION BY l‐GLUTAMATE DURING POSTISCHAEMIC REPERFUSION: REDUCED INFARCT SIZE AND ENHANCED GLYCOGEN RESYNTHESIS IN A RAT INSULIN‐FREE HEART MODEL

Kristiansen

Løfgren

Støttrup

et al. 2008

Clin Exp Pharma Physio

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1. Previously, we found that administration of high-dose L-glutamate during postischaemic reperfusion improves haemodynamic recovery and enhances glycogen resynthesis. In the present study, we investigated whether the same effect occurs in an insulin-free model and whether glutamate administration reduces infarct size. Further, we studied whether the cardioprotective effect of glutamate depends on preserved glutamate transamination and K(ATP) channel activity. 2. In a rat isolated, insulin-free, perfused heart model, we compared the effects of administration of L-glutamate (10 mmol/L) during either 45 min no-flow regional ischaemia plus 120 min reperfusion or reperfusion alone on infarct size and left ventricular (LV) recovery. The effect of glutamate on glycogen metabolism was studied in a model of 30 min global no-flow ischaemia and 60 min reperfusion. In both models, the effects of inhibition of glutamate transamination and K(ATP) channel activity were examined by adding amino-oxyacetate (an aminotransferase inhibitor; 0.1 mmol/L) and glibenclamide (a K(ATP) blocker; 10 mmol/L), respectively. 3. Administration of L-glutamate reduced infarct size by 60% (P < 0.01) and improved postischaemic LV function (developed pressure and rate pressure product; P < 0.05). L-Glutamate increased glycogen content after 60 min reperfusion by 65% (P < 0.01). Amino-oxyacetate, as well as glibenclamide, abolished the glutamate-mediated reduction in infarct size, haemodynamic improvement and glycogen resynthesis during reperfusion. 4. In conclusion, L-glutamate administration from the start of postischaemic reperfusion exerts cardioprotective effects, including reduced infarct size, improved haemodynamic recovery and enhanced glycogen resynthesis. These effects depend on preserved transamination of glutamate and K(ATP) channel activity, but not on insulin administration.

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Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 74%

CARDIOPROTECTION BY l‐GLUTAMATE DURING POSTISCHAEMIC REPERFUSION: REDUCED INFARCT SIZE AND ENHANCED GLYCOGEN RESYNTHESIS IN A RAT INSULIN‐FREE HEART MODEL

Kristiansen

Løfgren

Støttrup

et al. 2008

Clin Exp Pharma Physio

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“…Using gas chromatography–mass spectrometry, glutamate has been shown to increase myocardial release and tissue levels of citrate by a reverse flux through the NADP + –isocitrate dehydrogense reaction in rat perfused heart exposed to low‐flow ischaemia 25 . We have reported previously increased myocardial citrate release across the postischaemic human heart 4 and during reperfusion of cardioplegic arrested pig hearts 19 . Because cytosolic citrate level is a potent inhibitor of glycolysis at the site of phosphofructokinase, 26 it seems worth considering that exogenous glutamate may mediate its enhancement of postischaemic glycogen resynthesis relative to glycolysis by this mechanism.…”

Section: Discussionmentioning

confidence: 93%

l‐GLUTAMATE AND GLUTAMINE IMPROVE HAEMODYNAMIC FUNCTION AND RESTORE MYOCARDIAL GLYCOGEN CONTENT DURING POSTISCHAEMIC REPERFUSION: A RADIOACTIVE TRACER STUDY IN THE RAT ISOLATED HEART

Støttrup¹,

Kristiansen²,

Løfgren³

et al. 2006

Clin Exp Pharma Physio

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1. L-Glutamate and glutamine have been suggested to have cardioprotective effects. However, the issue is controversial and the metabolic mechanisms underlying a beneficial effect are not well understood. 2. In the present study we investigated the effects of L-glutamate and glutamine on haemodynamic recovery, the rate of de novo glycogen synthesis and myocardial glucose uptake during postischaemic reperfusion. 3. Hearts from male Wistar rats (250-300 g) were divided into three groups as follows: (i) control (n = 12); (ii) L-glutamate (n = 12); and (iii) glutamine (n = 12). Hearts were mounted in a Langendorff preparation and perfused with oxygenated Krebs'-Henseleit solution at 80 mmHg and 37C. Global ischaemia for 20 min was followed by 15 min reperfusion, during which L-glutamate (50 mmol/L) or glutamine (20 mmol/L) were administered. Left ventricular developed pressure (LVDP), de novo synthesis of glycogen using [14C]-glucose and myocardial glucose uptake using D-[2-3H]-glucose were measured. 4. L-Glutamate and glutamine increased postischaemic LVDP (P < 0.01 vs control hearts for both). L-Glutamate and glutamine increased de novo glycogen synthesis by 78% (P < 0.001) and 55% (P < 0.01), respectively. At the end of reperfusion, total myocardial glycogen content was increased by both L-glutamate and glutamine (5.7 +/- 0.3 and 6.2 +/- 0.7 micromol/g wet weight, respectively; P < 0.05 and 0.01, respectively) compared with that in control hearts (3.6 +/- 0.4 micromol/g wet weight). Neither L-glutamate nor glutamine affected myocardial glucose uptake during reperfusion. 5. Improved postischaemic haemodynamic recovery after L-glutamate and glutamine supplementation during reperfusion is associated with increased de novo glycogen synthesis, suggesting a favourable modulation of intracellular myocardial carbohydrate metabolism.

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“…Among those, the myocardium-specific troponin T is released in reversible and irreversible cell damage [4, 5, 6, 7, 8, 9, 10, 11]. Another sensitive, although unspecific set of markers for myocardial damage is free amino acids [12, 13]. Some are released massively in response to decreased oxygen tension [14].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Amino Acids as Markers of Myocardial Ischemia during Cardioplegic Heart Arrest

Kennergren¹,

Mantovani

Lönnroth³

et al. 1999

Cardiology

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Extracellular levels of amino acids in the myocardial interstitium are sensitive indicators of myocyte function. Lowered ATP leads to a rapid extracellular appearance of amino acids with a high intra- to extracellular concentration ratio, such as taurine and glutamate. Nitrogen fluxes are reflected by glutamine, while alanine, glycine, serine and leucine are markers of proteolysis. In addition, degradation of membrane phospholipids is reflected by other primary amines, such as phosphoethanolamine. The time course of these changes was determined before, during and after cardioplegic heart arrest. Two regions of the heart were monitored in 20 patients by means of microdialysis sampling. After only 20 min of heart arrest, extracellular taurine, glutamate and phosphoethanolamine increased transiently up to 25 times the basal level. Ten–20 min later, glutamine increased by 6 times. A doubling of alanine, glycine, serine and leucine levels took place 30 min after release of the aortic cross-clamp. After 2 h, all were at levels similar to those recorded 15–30 h later. Levels of taurine and glutamate in the anterior wall of the heart correlated significantly with those of its lateral wall. The response to surgery and heart arrest was studied in a group of patients with ischemic heart disease as well as in another group of patients, who underwent heart surgery for nonischemic reasons. The response of taurine and glutamine was significantly higher for the patients with ischemic heart disease, in spite of a shorter mean time of heart arrest. No sex differences were recorded. High levels of amino acids coincided frequently with clinical events, which were suggestive of ischemia, but were also recorded in a few patients without diagnosed events. We conclude that monitoring of extracellular amino acids is valuable for evaluation and development of cardioprotective strategies.

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Myocardial Loss of Glutamate after Cold Chemical Cardioplegia and Storage in Isolated Blood-Perfused Pig Hearts

Cited by 13 publications

References 3 publications

CARDIOPROTECTION BY l‐GLUTAMATE DURING POSTISCHAEMIC REPERFUSION: REDUCED INFARCT SIZE AND ENHANCED GLYCOGEN RESYNTHESIS IN A RAT INSULIN‐FREE HEART MODEL

CARDIOPROTECTION BY l‐GLUTAMATE DURING POSTISCHAEMIC REPERFUSION: REDUCED INFARCT SIZE AND ENHANCED GLYCOGEN RESYNTHESIS IN A RAT INSULIN‐FREE HEART MODEL

l‐GLUTAMATE AND GLUTAMINE IMPROVE HAEMODYNAMIC FUNCTION AND RESTORE MYOCARDIAL GLYCOGEN CONTENT DURING POSTISCHAEMIC REPERFUSION: A RADIOACTIVE TRACER STUDY IN THE RAT ISOLATED HEART

Extracellular Amino Acids as Markers of Myocardial Ischemia during Cardioplegic Heart Arrest

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