L-glutamate and glutamine improve haemodynamic function and restore myocardial glycogen content during postischaemic reperfusion: A radioactive tracer study in the rat isolated heart.
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.
Støttrup
Nicolaj B
NB
Department of Cardiology, Skejby Sygehus, Aarhus University Hospital, Aarhus, Denmark. stoettrup@ki.au.dk
Kristiansen
Steen B
SB
Løfgren
Bo
B
Hansen
Bo Falck
BF
Kimose
Hans-Henrik
HH
Bøtker
Hans Erik
HE
Nielsen
Torsten Toftegaard
TT
D000818:Animals; D018698:Glutamic Acid / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D005973:Glutamine; D018698:Glutamic Acid; D006003:Glycogen