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Assessment of myocardial glutamate requirements early after coronary artery bypass surgery
Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
Department of Anesthesiology, Akademiska Hospital, Uppsala.
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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.

Place, publisher, year, edition, pages
1998. Vol. 32, no 3, 145-152 p.
Keyword [en]
adverse effects, biological transport, cardiac surgery, coronary artery disease, dose-response, human glutamate, metabolism, myocardium
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14023DOI: 10.1080/14017439850140102OAI: oai:DiVA.org:liu-14023DiVA: diva2:22476
Available from: 2006-09-28 Created: 2006-09-28 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Surgery for aortic stenosis: with special reference to myocardial metabolism, postoperative heart failure and long-term outcome
Open this publication in new window or tab >>Surgery for aortic stenosis: with special reference to myocardial metabolism, postoperative heart failure and long-term outcome
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Postoperative heart failure (PHF) remains a major determinant of the outcome after cardiac surgery. However, characteristics of and risk factors for PHF after valve surgery have received little attention.

Post-ischaemic disturbances of myocardial metabolism that may contribute to PHF and are amenable to metabolic treatment have been identified early after coronary surgery (CABG). Knowledge derived from these studies may not be applicable to other patient groups. We therefore studied myocardial energy metabolism in 20 elective patients undergoing aortic valve replacement (AVR) for isolated aortic stenosis (AS). The metabolic studies indicated that myocardial oxidative metabolism had not fully recovered when the procedure was completed. Free fatty acids were the only major substrates taken up by the heart. Signs of preoperative and postoperative metabolic adaptation with substantial uptake of glutamate, previously demonstrated in patients with coronary artery disease, were found. Postoperative infusion of glutamate, (2 mL/kg body weight and hour of 0.125 M solution) based on assessment of myocardial glutamate requirements in CABG patients, resulted in a two-fold increase in myocardial glutamate uptake and a seven-fold increase in AV differences across the leg. This was associated with a significant myocardial uptake of lactate and metabolic changes in the leg suggesting mitigation of net amino acid loss and peripheral tissue lipolysis.

Characteristics of and risk factors for PHF were evaluated in 398 patients undergoing isolated AVR for AS from 1 January 1995 to 31 December 2000. These were compared with 398 patients, matched for age and sex, undergoing on-pump isolated CABG. Forty-five AVR and 47 CABG patients fulfilled criteria for PHF and these were studied in detail. PHF usually presented at weaning from cardiopulmonary bypass. After CABG it was closely associated with preoperative ischaemic events and intraoperatively acquired myocardial infarction. Potential causes and eliciting events of PHF after AVR for AS were obvious only in one-third of the patients. Risk factors for PHF after AVR for AS indicated either pre-existing myocardial dysfunction, increased right or left ventricular after-load, or intraoperatively acquired myocardial injury. PHF was associated with high early mortality after CABG, whereas the consequences of PHF after AVR for AS became evident only with time, resulting in a 42% five-year mortality. Although PHF had a different temporal impact on late mortality after CABG and AVR for AS, it emerged as the statistically most significant risk factor for mortality occurring within 5 years from surgery both after AVR for AS and after CABG. Potential implications of our findings include needs for greater focus on preoperative surveillance of patients with AS for optimal timing of surgery, mitigation of intraoperatively acquired myocardial injury and tailoring of treatment for PHF. Furthermore, the findings have implications for long-term follow up of AS patients after surgery.

Place, publisher, year, edition, pages
Institutionen för medicin och vård, 2006
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 952
Keyword
Aortic stenosis, Surgery, Postoperative heart failure, Long-term outcome, Metabolism
National Category
Clinical Science
Identifiers
urn:nbn:se:liu:diva-7471 (URN)91-85497-89-4 (ISBN)
Public defence
2006-06-09, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2006-09-28 Created: 2006-09-28 Last updated: 2012-01-30
2. 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, IngemarSvedjeholm, RolfHåkansson, ErikVánky, Farkas

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