The effect of glutamate infusion on cardiac performance is independent of changes in metabolism in patients undergoing routine coronary artery bypass surgery

Abstract

In a double-blind randomized placebo-controlled study, the effects of intravenous glutamate infusion on myocardial haemodynamics and metabolism were studied in 22 patients undergoing routine coronary artery bypass graft (CABG) surgery. Immediately after aortic cross-clamp release, an intravenous infusion of a solution of glutamate (125 mmol x l(-1)) at a rate of 1.5 ml x h(-1) x kg(-1) was given over 1 h to 11 patients (G group). The other 11 patients received a placebo infusion (0.9% NaCl) (P group). Haemodynamic functions and rates of exchange of glucose, non-esterified fatty acids and lactic acid over the heart were measured before sternotomy (T1), 40 min after cross-clamp release (T2) and 4 h after cross-clamp release (T3). At T2, decreases were seen in comparison with T1 in systemic vascular resistance index, and increases were seen in cardiac index and coronary sinus flow. All of these changes were greater in the G group than in the P group (P<0.05). Myocardial glutamate consumption increased 2-fold after glutamate administration. No significant changes were observed in the myocardial utilization of glucose, lactate or non-esterified fatty acids between the P and the G groups at T1, T2 or T3. These data show that an intravenous glutamate infusion after routine CABG surgery significantly improved cardiac haemodynamic performance without direct effects on cardiac substrate metabolism. This suggests that a reduction of the afterload via a peripheral vasodilatory effect is the main mechanism leading to the observed changes in haemodynamics. Earlier claims that patients with post-operative cardiac failure show metabolic benefits from the glutamate infusion do not seem to apply to patients undergoing routine CABG surgery.

Identification of Potential Pharmacological Targets by Analysis of the Comprehensive G Protein-Coupled Receptor Repertoire in the Four Cardiac Chambers

“…The main known physiological function of glutamate in the heart, where it has a high intra-(millimolar range) to extracellular (Ͻ1 M range) concentration ratio, is to regulate energy metabolism by maintaining the levels of Krebs cycle intermediates, an effect independent of glutamate receptor activation. This process, known as anaplerosis, has been proposed to be the basis for the cardioprotective effects of glutamate (Langenberg et al, 2001). On the other hand, glutamate may also have toxic effects at supraphysiological concentrations (Gill et al, 2007).…”

NT-proBNP as a marker of postoperative heart failure in adult cardiac surgery

“…Glutamate's effect is dependent on whether there is a metabolic derangement which glutamate can facilitate the recovery of 92,100,120 . As might be expected such an effect could not be detected in low-risk patients with no or minimal metabolic derangement 121 . In the GLUTAMICS-trial, a high proportion of low-risk patients were included 102 .…”

The impact of glutamate infusion on postoperative NT-proBNP in patients undergoing coronary artery bypass surgery: a randomized study

“…The second mechanism, enhancement of postischemic recovery of myocardial metabolism has been shown in patients with proven metabolic disturbances [19,20]. As might be expected such an effect could not be detected in low risk patients with no or minimal metabolic derangement [33].…”