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Influence of glutamate on the recovery of myocardial metabolism during early reperfusion in patients operated for unstable angina
Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
Dept. of Thoracic Physiology, Karolinska Hospital, Stockholm , Sweden.
Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background. A previous study on glutamate infusion after elective coronary bypass surgery demonstrated increased myocardial uptake of glutamate and improved lactate metabolism. The present study investigates myocardial metabolism in high-risk patients during early reperfusion and evaluates the influence of glutamate on the recovery of myocardial metabolism.

Methods. 19 patients with unstable angina requiring intravenous nitroglycerine were randomized to intravenous glutamate or saline. Myocardial metabolism during reperfusion was studied from one minute after unclamping the aorta to 15 minutes after weaning from cardiopulmonary bypass (CPB).

Results. Compared with before CPB there was a shift towards glucose uptake during early reperfusion. Immediately after unclamping there was a low oxygen extraction and a lactate release. At the end of the study period oxygen extraction had normalized but in the control group there was still no uptake of lactate. Glutamate infusion resulted in myocardial uptake of glutamate and a significant myocardial uptake of lactate was found at the end of the study period. A substantial uptake of FFAs was observed in both groups.

Conclusion. Myocardial metabolism during early reperfusion was characterized by dynamic changes including low oxygen extraction, lactate release and a shift towards increased myocardial glucose uptake. Intravenous glutamate infusion resulted in a significant uptake of glutamate, which was associated with metabolic findings suggesting earlier recovery of the oxidative metabolism during reperfusion.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-79555OAI: oai:DiVA.org:liu-79555DiVA: diva2:543486
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2012-08-08Bibliographically approved
In thesis
1. Metabolic intervention with amino acids in coronary surgery: A clinical study with special reference to effects of glutamate and aspartate on myocardial metabolism
Open this publication in new window or tab >>Metabolic intervention with amino acids in coronary surgery: A clinical study with special reference to effects of glutamate and aspartate on myocardial metabolism
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amino acids, particularly glutamate and aspartate, have been suggested to be important for the tolerance to myocardial ischemia and for the recovery of the oxidative metabolism of the heart after ischemia. The objective of the present work was to investigate myocardial metabolism and how it is influenced by intravenous supply of glutamate and aspartate in association with coronary artery bypass grafting (CABG). Three groups, comprising a total of 49 patients, were studied with classical organ balance technique. 30 patients with stable angina were studied 1-2 hour after CABG and 19 patients with unstable angina were studied before cardiopulmonary bypass (CPB) and during early reperfusion.

Glutamate infusion early after elective CABG caused a dose-dependent linear increase in arterial levels and increased myocardial uptake of glutamate. The greatest impact on myocardial glutamate uptake was achieved by increasing arterial whole blood level by less than 100 μmol/L, while a further increase of arterial level was associated with marginal effects on myocardial uptake. The fractional uptake of lactate increased during glutamate infusion, whereas myocardial exchange of other substrates remained essentially unaffected. These metabolic changes were associated with improved myocardial performance.

Aspartate infusion in the same setting resulted in a dose-dependent linear increase of both arterial aspartate level and myocardial uptake of aspartate. No positive effects on myocardial metabolism or function were demonstrated. However, considerable interactions with glutamate metabolism, compatible with competitive inhibition of myocardial glutamate uptake were observed.

In patients with unstable angina the only substrate extracted by the heart immediately before CPB was free fatty acids (FFAs). In contrast, during glutamate infusion a significant myocardial uptake of glutamate and lactate was also found. The uptake of lactate correlated with arterial levels of lactate (r0.83; p<0.01). Myocardial metabolism during early reperfusion was characterized by dynamic changes including low oxygen extraction, lactate release, a shift towards increased glucose utilization. At the end of the study period oxygen extraction had normalized but in the control group there was still no uptake of lactate. Glutamate infusion resulted in myocardial uptake of glutamate and a significant myocardial uptake of lactate was found at the end of the study period (15 minutes after weaning from CPB). A substantial uptake ofFFAs was observed in both groups.

In conclusion, this study demonstrates beneficial metabolic effects of myocardial glutamate augmentation in association with CABG. The normal lactate metabolism in patients with unstable angina before revascularization suggests enhanced myocardial tolerance to ischemia and the improved lactate metabolism during early reperfusion and after completion of surgery is compatible with improved recovery of the oxidative metabolism.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 64 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 631
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27551 (URN)12212 (Local ID)91-7219-588-6 (ISBN)12212 (Archive number)12212 (OAI)
Public defence
2000-05-26, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-08Bibliographically approved

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Vanhanen, IngemarHåkansson, ErikSvedjeholm, Rolf

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