Improved Recovery After Cold Crystalloid Cardioplegia Using Low-Dose Glutamate Enrichment During Reperfusion After Aortic Unclamping: a Study in Isolated Blood-Perfused Pig Hearts

Abstract

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.

Captopril-induced glutamate release at the start of reperfusion after cold cardioplegic storage of pig hearts

“…21 In addition, we have demonstrated that glutamate enrichment during reperfusion improves postcardioplegic recovery. 22 In the present study, captopril induced a massive glutamate release during postcardioplegic reperfusion. We have previously observed a substantial loss of glutamate from pig hearts at the start of reperfusion after cold crystalloid cardioplegia.…”