title: Very early administration of glucose-insulin-potassium by emergency medical service for acute coronary syndromes: Biological mechanisms for benefit in the IMMEDIATE Trial.
abstract: OBJECTIVE
  In the IMMEDIATE Trial, intravenous glucose-insulin-potassium (GIK) was started as early as possible for patients with suspected acute coronary syndrome by ambulance paramedics in communities. In the IMMEDIATE Biological Mechanism Cohort substudy, reported here, we investigated potential modes of GIK action on specific circulating metabolic components. Specific attention was given to suppression of circulating oxygen-wasting free fatty acids (FFAs) that had been posed as part of the early GIK action related to averting cardiac arrest.
  
  
  METHODS
  We analyzed the changes in plasma levels of FFA, glucose, C-peptide, and the homeostasis model assessment (HOMA) index.
  
  
  RESULTS
  With GIK, there was rapid suppression of FFA levels with estimated levels for GIK and placebo groups after 2 hours of treatment of 480 and 781 μmol/L (P<.0001), even while patterns of FFA saturation remained unchanged. There were no significant changes in the HOMA index in the GIK or placebo groups (HOMA index: placebo 10.93, GIK 12.99; P = .07), suggesting that GIK infusions were not countered by insulin resistance. Also, neither placebo nor GIK altered endogenous insulin secretion as reflected by unchanging C-peptide levels.
  
  
  CONCLUSIONS
  These mechanistic observations support the potential role of FFA suppression in very early cardioprotection by GIK. They also suggest that the IMMEDIATE Trial GIK formula is balanced with respect to its insulin and glucose composition, as it induced no endogenous insulin secretion.
authors: Institute for Clinical Research and Health Policy Study, Tufts Medical Center, Boston MA. Electronic address: hselker@tuftsmedicalcenter.org.
authors: Harry P
authors: HP
authors: Selker
authors: Department of Medicine, Sanford School of Medicine, University of South Dakota, SD.
authors: William S
authors: WS
authors: Harris
authors: Department of Medicine, Georgetown University Medical Center, Washington, DC.
authors: Charles E
authors: CE
authors: Rackley
authors: Lipid Division, Department of Medicine, Tufts Medical Center, Boston, MA.
authors: Julian B
authors: JB
authors: Marsh
authors: Institute for Clinical Research and Health Policy Study, Tufts Medical Center, Boston MA.
authors: Robin
authors: R
authors: Ruthazer
authors: Institute for Clinical Research and Health Policy Study, Tufts Medical Center, Boston MA; Regis College, Regulatory and Clinical Research Management, Weston, MA.
authors: Joni R
authors: JR
authors: Beshansky
authors: Department of Internal Medicine, Stony Brook University School of Medicine, Stony Brook, NY.
authors: Eric J
authors: EJ
authors: Rashba
authors: Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Inga
authors: I
authors: Peter
authors: Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
authors: Lionel H
authors: LH
authors: Opie
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D061345:Early Medical Intervention; D004562:Electrocardiography; D004632:Emergency Medical Services / Q000379:methods*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000627:therapeutic use*; D006323:Heart Arrest / Q000097:blood / Q000517:prevention & control*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000072658:Non-ST Elevated Myocardial Infarction / Q000097:blood / Q000188:drug therapy; D011188:Potassium / Q000627:therapeutic use*; D000072657:ST Elevation Myocardial Infarction / Q000097:blood / Q000188:drug therapy
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose; D011188:Potassium