Improved recovery after cold crystalloid cardioplegia using low-dose glutamate enrichment during reperfusion after aortic unclamping: a study in isolated blood-perfused pig hearts.
Increased glutamate utilization is a part of the metabolic adaptation to oxygen deprivation by the heart. The effect of low-dose L-glutamate (2 mmol/L) during continuous reperfusion after aortic unclamping on postcardioplegic recovery was studied in pig hearts similar in size, anatomy, and function to the human adult heart. After cold crystalloid cardioplegic arrest (CCC) with Bretschneider solution no 3, hearts were excised from pigs weighing 70-80 kgs (heart weight, average +/- SEM: 308 +/- 4 grams), and reperfused in an isolated blood-perfused heart model for 120 minutes. Three groups of hearts were compared. One group of hearts was subjected to 30 minutes of CCC only (30 min group; n = 9), another group of hearts to 90 minutes of CCC and storage (Control group: n = 16), and a third group to 90 minutes of CCC and storage, but with L-glutamate added to the blood reperfusate (2 mmol/L) (Glutamate group: n = 18). In the Control group 14 of 16 hearts (88%) needed electrical defibrillation after start of reperfusion, significantly more (p < 0.05) than the 8 of 18 (44%) in the Glutamate group; the difference between the 30-min (2 of 9 [22%]) and the Glutamate group was not significant (p = 0.48). Developed left-ventricular pressure (DLVP) and positive dP/dtmax (+dP/dtmax) was significantly higher in the Glutamate group than in the Control group during early reperfusion (DLVP: p < 0.05: +dP/dtmax: p < 0.01) and the entire reperfusion (DLVP and +dP/dtmax: p < 0.05), while reperfusion responses in the Glutamate and 30-min groups were not significantly different. Furthermore, myocardial oxygen uptake was significantly higher in the Glutamate group than in the Control group (p < 0.001), but not higher than that in the 30-min group. Decreased lactate release was found in the Glutamate group compared to the Control group during early reperfusion (p < 0.01), and the entire reperfusion (p < 0.001). No differences were found between the Control and Glutamate groups in alanine exchange. Thus, L-glutamate has a beneficial effect in pig hearts on both functional and metabolic recovery after cold crystalloid cardioplegia and storage when present in a concentration even as low as 2 mmol/L during continuous reperfusion after aortic unclamping. A possible mechanism is a glutamate-induced stimulation of the malate-aspartate shuttle leading to increased intramyocardial lactate utilization.
Kimose
H H
HH
Department of Cardiothoracic and Vascular Surgery, Arhus University Hospital, Skejby Sygehus, Denmark.
Helligsø
P
P
Randsbaek
F
F
Kim
Y
Y
Bøtker
H E
HE
Hansen
S B
SB
Thomassen
A R
AR
Nielsen
T T
TT
D000328:Adult; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008955:Models, Cardiovascular; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
C039984:Bretschneider cardioplegic solution; D002314:Cardioplegic Solutions; D019344:Lactic Acid; D018698:Glutamic Acid; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D005947:Glucose