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Metabolic intervention with amino acids in coronary surgery: A clinical study with special reference to effects of glutamate and aspartate on myocardial metabolism
Linköping University, Department of Medicine and Care, Thoracic Surgery. Linköping University, Faculty of Health Sciences.
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: urn:nbn:se:liu:diva-27551Local ID: 12212ISBN: 91-7219-588-6 (print)OAI: oai:DiVA.org:liu-27551DiVA: diva2:248103
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
List of papers
1. Metabolic and hemodynamic effects of intravenous glutamate infusion early after coronary operations
Open this publication in new window or tab >>Metabolic and hemodynamic effects of intravenous glutamate infusion early after coronary operations
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1996 (English)In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 112, no 6, 1468-1477 p.Article in journal (Refereed) Published
Abstract [en]

Amino acids, particularly glutamate, have been proposed to play an important role in the recovery of cardiac oxidative metabolism after ischemia. In this investigation, the metabolic and hemodynamic effects of glutamate infusion after coronary operations were studied. From 220 to 240 ml 0.1 mol/L l-glutamic acid solution was infused in 10 patients during 1 hour starting 2 hours after operation. A control group of 10 patients received an infusion of 240 ml saline solution. During glutamate infusion, there were significant increases in the uptake of glutamate (from 0.7 ± 0.2 μmol/min in the basal state to a peak of 5.7 ± 1.2 μmol/min at 20 minutes) and lactate (from 4.9 ± 2.0 μmol/min in the basal state to 14.1 ± 4.4 μmol/min at 60 minutes; p < 0.01), whereas the uptake and release of other substrates remained essentially unaffected. Arterial glutamate levels (in whole blood) increased from 103 ± 10 μmol/L to 394 ± 20 μmol/L at 60 minutes. Thirty minutes after discontinuation of the glutamate infusion, arterial levels had decreased to 129 ± 17 μmol/L. The markedly improved utilization of lactate and the unchanged release of alanine together suggest that the oxidative metabolism of the heart was stimulated by glutamate. The metabolic changes were associated with improved myocardial performance. Left ventricular stroke work index increased from 26.8 ± 2.1 gm · beat-1· m-2body surface area to 31.3 ± 3.1 gm · beat-1· m-2body surface area during glutamate infusion. Metabolic support with amino acids may provide a means to improve recovery of metabolic and hemodynamic function of the heart early after cardiac operations.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79552 (URN)10.1016/S0022-5223(96)70005-3 (DOI)
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2017-12-07Bibliographically approved
2. Assessment of myocardial glutamate requirements early after coronary artery bypass surgery
Open this publication in new window or tab >>Assessment of myocardial glutamate requirements early after coronary artery bypass surgery
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1998 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 32, no 3, 145-152 p.Article in journal (Refereed) Published
Abstract [en]

Glutamate is an important substrate for the intermediary metabolism of the heart, particularly in association with ischemia. Early after coronary artery bypass surgery (CABG) myocardial uptake of glutamate seems to be limited by substrate availability (arterial levels). However, glutamate is not an innocuous substrate. As arterial levels of glutamate are important both for myocardial uptake and adverse effects, an attempt was made to determine a minimum dose of glutamate sufficient to supply the needs of the heart after CABG. Ten patients received and infusion of 220-240 ml of 0.1 M L-glutamic acid solution at varying rates during two 30-min periods, starting 2 h after uncomplicated elective CABG. Intravenous glutamate infusion caused a dose-dependent linear increase in arterial glutamate and an increased myocardial uptake of glutamate. However, myocardial uptake of glutamate correlated with arterial levels only at lower infusion rates. Although maximal peak uptake in individual patients (6.6 ± 1.1 μmol/min) occurred at an average increase of arterial whole blood glutamate of 172 ± 34 μmol/L, the greatest impact on myocardial glutamate uptake was achieved by increasing arterial whole blood glutamate by less than 100 μmol/L. This implies that an infusion rate of 30-40 mg glutamate/kg BW/h could suffice to achieve a maximal or near maximal myocardial glutamate uptake in most patients after CABG. The adequacy of this dosage remains to be confirmed in high-risk patients.

Keyword
adverse effects, biological transport, cardiac surgery, coronary artery disease, dose-response, human glutamate, metabolism, myocardium
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14023 (URN)10.1080/14017439850140102 (DOI)
Available from: 2006-09-28 Created: 2006-09-28 Last updated: 2017-12-13Bibliographically approved
3. Intravenous Aspartate Infusion After a Coronary Operation: Effects on Myocardial Metabolism and Hemodynamic State
Open this publication in new window or tab >>Intravenous Aspartate Infusion After a Coronary Operation: Effects on Myocardial Metabolism and Hemodynamic State
1998 (English)In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 65, no 5, 1296-1302 p.Article in journal (Refereed) Published
Abstract [en]

Background. In a previous study glutamate infusion after coronary artery bypass grafting was associated with beneficial effects on myocardial metabolism and myocardial performance. It has been claimed that aspartate is more important than glutamate for the recovery of myocardial metabolism after cardioplegic arrest. Therefore, the metabolic and hemodynamic effects of aspartate were studied after coronary artery bypass grafting.

Methods. Fifty to 240 mL of a 0.1 mol/L aspartic acid solution was infused intravenously during 60 minutes in 10 patients early after coronary artery bypass grafting. Myocardial metabolism was studied using the coronary sinus catheter technique.

Results. Aspartate infusion caused a significant increase in the arterial levels of both aspartate and glutamate. This was associated with a significant increase in myocardial uptake of aspartate and a decrease in myocardial uptake of glutamate. Myocardial exchange of other substrates remained unaffected. There were no changes in hemodynamic state except an increase of heart rate and pulmonary vascular resistance.

Conclusions. Interactions with glutamate metabolism, compatible with competitive inhibition of myocardial glutamate uptake, which may have outweighed potential effects of aspartate, were observed. Recognition of these amino acid interactions is important as they are used together as additives in cardioplegic solutions.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79553 (URN)10.1016/S0003-4975(98)00155-6 (DOI)
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2017-12-07Bibliographically approved
4. Myocardial metabolism during the early phase of urgent coronary surgery and effects of glutamate infusion
Open this publication in new window or tab >>Myocardial metabolism during the early phase of urgent coronary surgery and effects of glutamate infusion
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background. Glutamate has been reported to improve myocardial tolerance to ischemia. As preoperative ischemia remains a major risk factor for myocardial injury in coronary surgery we decided to investigate the impact of intravenous glutamate infusion in patients operated for unstable angina.

Methods. 19 patients with unstable angina requiring intravenous nitroglycerine were randomized to intravenous glutamate (30mg/kg (body weight • hour)) or saline. The infusion was started when the patient arrived to the operation theater. Metabolic studies were done just before cardiopulmonary bypass (CPB).

Results. The only major substrates that were extracted by the heart in the control group were free fatty acids. In the glutamate group there was also a significant uptake of glutamate and lactate. Furthermore, there was a positive correlation between arterial level and uptake oflactate (r=0.83; p<0.01).

Conclusion. The results show an unfavorable metabolic situation for the heart immediately before CPB, which in combination with ischemia could be deleterious. Glutamate infusion was associated with a normal lactate metabolism suggesting that preoperative ischemia was better tolerated.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79554 (URN)
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2012-08-08Bibliographically approved
5. Influence of glutamate on the recovery of myocardial metabolism during early reperfusion in patients operated for unstable angina
Open this publication in new window or tab >>Influence of glutamate on the recovery of myocardial metabolism during early reperfusion in patients operated for unstable angina
(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:nbn:se:liu:diva-79555 (URN)
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2012-08-08Bibliographically approved

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