Harry P Selker1, William S Harris2, Charles E Rackley3, Julian B Marsh4, Robin Ruthazer5, Joni R Beshansky6, Eric J Rashba7, Inga Peter8, Lionel H Opie9. 1. Institute for Clinical Research and Health Policy Study, Tufts Medical Center, Boston MA. Electronic address: hselker@tuftsmedicalcenter.org. 2. Department of Medicine, Sanford School of Medicine, University of South Dakota, SD. 3. Department of Medicine, Georgetown University Medical Center, Washington, DC. 4. Lipid Division, Department of Medicine, Tufts Medical Center, Boston, MA. 5. Institute for Clinical Research and Health Policy Study, Tufts Medical Center, Boston MA. 6. Institute for Clinical Research and Health Policy Study, Tufts Medical Center, Boston MA; Regis College, Regulatory and Clinical Research Management, Weston, MA. 7. Department of Internal Medicine, Stony Brook University School of Medicine, Stony Brook, NY. 8. Icahn School of Medicine at Mount Sinai, New York, NY. 9. Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
Abstract
AIMS: 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. CONCLUSION: 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.
RCT Entities:
AIMS: 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. CONCLUSION: 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: D SODI-PALLARES; M R TESTELLI; B L FISHLEDER; A BISTENI; G A MEDRANO; C FRIEDLAND; A DE MICHELI Journal: Am J Cardiol Date: 1962-02 Impact factor: 2.778
Authors: Britt N Fuglesteg; Naushaad Suleman; Crina Tiron; Tambuzai Kanhema; Lydia Lacerda; Thomas V Andreasen; Michael N Sack; Anne K Jonassen; Ole D Mjøs; Lionel H Opie; Sandrine Lecour Journal: Basic Res Cardiol Date: 2008-05-23 Impact factor: 17.165