Glutamate for metabolic intervention in coronary surgery: with special reference to the GLUTAMICS-trial

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Glutamate for metabolic intervention in coronary surgery : with special reference to the GLUTAMICS-trial

Vidlund, Mårten, 1968- (author): Örebro universitet,Hälsoakademin

Svedjeholm, Rolf, Professor (thesis advisor): Universitetssjukhuset i Linköping, Thorax-kärlkliniken

Ivert, Torbjörn, Professor (opponent): Karolinska universitetssjukhuset, Thoraxkliniken

(creator_code:org_t)

ISBN 9789176688243
Örebro : Örebro universitet, 2011
English 87 s.
Series: Örebro Studies in Medicine, 1652-4063 ; 58

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Doctoral thesis (other academic/artistic)

Abstract Subject headings

Myocardial ischemia is a major cause of postoperative heart failure and adverse outcome in coronary artery bypass graft surgery (CABG). Conventional treatment of postoperative heart failure with inotropic drugs may aggravate underlying ischemic injury. Glutamate has been claimed to increase myocardial tolerance to ischemia and promote metabolic and hemodynamic recovery after ischemia. The aim of this work was to investigate if intravenous glutamate infusion given in association with CABG for acute coronary syndrome can reduce mortality and prevent or mitigate myocardial injury and postoperative heart failure. We also wanted to assess neurological safety issues, as a concern with the use of glutamate is that it may act as an excitotoxin under certain conditions.A metabolic strategy for perioperative care was assessed in an observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. Based on encouraging clinical results, unsurpassed in the literature, the GLUTAMICS-trial was initiated. 861 patients undergoing CABG for acute coronary syndrome were randomly allocated to blinded intravenous infusion of L-glutamicacid solution or saline. The primary endpoint was a composite of postoperative mortality (≤30 days), perioperative myocardial infarction and left ventric ular heart failure in association with weaning from cardiopulmonary bypass. Secondary endpoints included neurological safety issues, degree of myocardial injury,postoperative hemodynamic state, use of circulatory support and cardiac mortality.The event rate was lower than anticipated and the primary endpoint did not differ significantly between the groups. Regarding secondary endpoints there were significant differences compatible with a beneficial effect of glutamate on post-ischemic myocardial recovery. The putative effect of glutamate infusion was seen in more ischemic patients (CCS class IV) and in patients with evident or anticipated LV-failure on weaning from CPB. No evidence for increased incidence of clinical or subclinical neurological injury was found. In conclusion, intravenous glutamate infusion is safe in the dosages employed and could provide a novel and important way of promoting myocardial recovery after ischemic injury.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)

Keyword

myocardial ischemia
coronary artery bypass
cardiac surgery
acute coronary syndrome
glutamate
metabolic intervention
postoperative heart failure
myocardial recovery
Surgery
Kirurgi

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vet (subject category)
dok (subject category)

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